1. A 64-year-old woman presented to the hospital with 3 days of abdominal pain, nausea, vomiting and profuse watery diarrhoea. She was recently discharged from the hospital for a urinary tract infection following a successful renal transplant from her son with excellent function. She is currently on Tacrolimus (trough level 9 ng/ml), Myfortic (720 mg bd) and prednisolone (15 mg od). She had just completed a 14-day course of ciprofloxacin.
On admission to the hospital, the blood pressure was 65/41 mmHg. Hypothermia was present. The temperature was 35.8°C. She was obese and appeared in mild distress. Her abdomen was mildly distended, with silent bowel sounds. There was tenderness in the lower quadrants without rebound tenderness.
The WBC was 53.9 109 /L with 84% neutrophils. The Hct was 36.1%. There was severe metabolic acidosis with an anion gap of 19, bicarbonate level of 12 mmol/ L, and lactic acid level of 3.6 mmol/L. The arterial blood gas demonstrated a pH of 7.11, CO2 of 16, and O2 of 150 on 2 litres of oxygen via nasal cannula. The serum creatinine was 1051 μmol/L. The K+ was 2.5 mmol/L, and Mg++ of 0.24 mmol/L. The INR was 2.1. The patient was resuscitated with IV fluids and placed on dopamine and later norepinephrine. She was also given intravenous ciprofloxacin 500 mg every 12 h, oral vancomycin 250 mg every 6 h and IV metronidazole 500 mg every 6 h. A CT of the abdomen and pelvis demonstrated circumferential wall thickening of the colon consistent with pan colitis (see below). The transverse colon was dilated to 5.8 cm. The colonoscopy is shown below.
The patient did not improve despite treatment over the next 36 h. The WBC rose to 62.4 109 /L with a more tender abdomen. A repeat CT scan showed transverse colon was dilated to 8.7cm. There was no other source of infection. Blood, urine, and stool cultures were negative.
Screening by fecal enzyme immunoassay, real-time PCR & confirmed by C.difficile toxin ELISA or a tissue culture cytotoxicity assay.
Mx: Resuscitate the patient. Start antimicrobial therapy( Metronidazole/ vancomycin), start RRT & surgical decompression is needed. Colonoscopy should be avoided due to risk of perforation.
Pseudo-membranous Colitis with Toxic Megacolon possibly due to C. difficile
Inflammatory bowel disease: Ulcerative colitis or Crohn’s disease
How would you confirm the diagnosis?
Detection C. difficile toxin in stool by Enzyme-Immuno-Assay (EIA) PCR for C. difficilein stool
How would manage this patient?
Resuscitation with IV fluids and inotropes
Withdraw immunosuppression
Oral vancomycin (500 mg 4 times/day) or oral fidaxomicin.
NG suction for decompression of the stomach
Fecal Microbiota Transplant is an option
Surgery if abdominal compartment syndrome or colon perforation
How would you confirm it is C Def colitis? PCR or Nucleic acid amplification test (NAAT) for C.difficle
Enzyme immuno-assay (EIA) for C. difficile toxins A & B
2. If you have this CT image with the abovementioned history, would you go for a colonoscopy?
Colonoscopy is contraindicated.
References:
Skomorochow E, Pico J. Toxic Megacolon. In: Stat Pearls [Internet, Updated 2022 Jul 5]. Treasure Island (FL): Stat Pearls Publishing; 2023 Jan
Trudel JL, Deschênes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous enterocolitis. Diseases of the colon and rectum. 1995 Oct;38(10):1033-8. PubMed PMID: 7555415. Epub 1995/10/01.
1. What is the differential diagnosis? 64 yr female, recent post-renal transplant, from son – probably no induction. Had UTI – received 14 days ciprofloxacin presented with abdominal pain, watery diarrhoea, vomiting, dehydration, septic shock, severe metabolic acidosis, AKI. CT abdomen – dilated colon (8cm) suggestive of Toxic Megacolon. F From typical history, clinical picture, with CT imaging à most probable diagnosis is Pseudo-membranous Enterocolitis due to Clostridium difficile (most common cause following prolonged antibiotic therapy), with Toxic Megacolon, Septic Shock and AKI. Toxic Megacolon – diagnostic criteria: Ø Radiologic (CT) e/o colonic dilatation >6cm Ø + 3 of the following: fever, tachycardia, leuko-cytosis, anaemia Ø + at least 1 of the following: dehydration, hypotension, altered sensorium, dys-electrolytemia Other infectious causes: Ø Salmonella Ø Shigella Ø Campylobacter colitis Ø Enterohemorrhagic / enteroaggregative E Coli – O157 (can lead to HUS) Ø Adeno-virus, Rota virus, Norovirus, Cytomegalovirus Ø Entamoeba histolytica Ø Inflammatory: Ulcerative colitis, Crohn’s disease, Ischemic Colitis. Factors that can precipitate toxic megacolon include, (but not limited to):
Hypokalemia
Drug induced (antimotility agents, opiates, anticholinergics, antidepressants)
Barium enema, bowel preparations, Colonoscopy
2. How would you confirm the diagnosis? F Typical history, clinical picture, with CT imaging F no other source of infection; blood, urine and stool cultures were negative Toxic Megacolon – diagnostic criteria: Ø Radiologic (CT) e/o colonic dilatation >6cm Ø + 3 of the following: fever, tachycardia, leuko-cytosis, anaemia Ø + at least 1 of the following: dehydration, hypotension, altered sensorium, dys-electrolytemia F Abdominopelvic CT scan with oral + IV contrast – to establish the diagnosis, exclude other complications that require urgent surgery. Serial Xray-abdomen, thereafter, to monitor colonic dilatation. F Diagnosis of C. difficile by detection of its toxin in stool (Enzyme-Immuno-Assay), or by positive nucleic acid amplification test (NAAT) for C. difficile toxin gene. 3. how would manage this patient? F ICU admission and Resuscitation – IV fluid, Noradrenalin, IV Hydrocortisone – correction of acidosis, electrolytes – may need CVVH due to AKI. – monitor kidney function, urine output, ABG, sepsis marker and CBC. F Stop immunosuppression – Hydrocortisone to continue for septic shock (100mg tid) · Broad spectrum IV antibiotics – commonly used are metronidazole or vancomycin. – Antibiotics of choice for C. difficile: oral vancomycin (500 mg 4 times /day) or oral fidaxomicin. If those are not available, IV metronidazole is an alternative. – In case of ileus, megacolon, per-rectal Vancomycin + Fidaxomicin may be tried. – Tigecycline is used for refractory cases. · Rest to bowel: reduce inflammation, avoid need for surgery Ø NPO, NG tube aspiration can decompress the stomach, but not the colon à rectal tube may be helpful for that. PC Enema and intermittent rolling / knee-elbow position – help redistribute, expel colonic gas. Ø Parenteral nutrition + micronutrients supplement – K, Cal, Mg, zinc, selenium, multivitamin. Ø Once the patient improves, gradual enteral feed may promote healing, reduce gut-sepsis, stimulates motility. · To stop medications that affect GI motility – anticholinergics, opiates. Patient did not improve despite 36 hours treatment – Rising WBC 51K à 63.4K/L, abdomen became more tender, increased Colon dilation 5.8 à 8.7cm on CT… all indicates towards worsening abdomen.
Colonic decompression by bedside flexible sigmoidoscopy is helpful in certain scenarios, but is dangerous in sick and acutely ill patients like the index case; with high risk of perforation – so, it should be avoided. Surgical treatment: (GI Surgery consultation) F Indications for surgery: intrabdominal hypertension, abdominal compartment syndrome, colonic perforation / necrosis, full thickness ischemia, peritonitis, worsening abdominal findings (tenderness/ distension/ colonic dilation on Xray/ CT), organ failure requiring vasopressors, AKI, intubation-mechanical ventilation. Surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy (+Hartmann pouch / Sigmoidostomy). Diversion ileostomy with colonic lavage may be tried in selected sick patients. Ø This index patient is very sick, with life-threatening complications – not fit to undergo any surgical procedure – high risk of mortality (60-90%) with or without surgery. If the patient survives and improves Fecal Microbiota Transplant (FMT, per rectal) or rectal Vancomycin, may be tried. Recurrent CDI à fidaxomicin + vancomycin + rifaximin 400mg TID x 20days, Bezlotoxumab may be tried. There is some role for fecal microbiota transplantation. Support your answer — References: 1) Sartelli M, Malangoni MA, Abu-Zidan FM, et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World Journal of Emergency Surgery (2015) 10:38 DOI 10.1186/s13017-015-0033-6 2) Skomorochow E, Pico J. Toxic Megacolon. In: Stat Pearls [Internet, Updated 2022 Jul 5]. Treasure Island (FL): Stat Pearls Publishing; 2023 Jan 3) Trudel JL, Deschênes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous enterocolitis. Diseases of the colon and rectum. 1995 Oct;38(10):1033-8. PubMed PMID: 7555415. Epub 1995/10/01. 4) Autenrieth DM, Baumgart DC. Toxic megacolon. Inflammatory bowel diseases. 2012 Mar;18(3):584-91. PubMed PMID: 22009735. Epub 2011/10/20. 5) Johal SS1, Hammond J, Solomon K,et al. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004 May; 53(5): 673-7. DOI: 10.1136/gut.2003.028803. PMID: 15082585 PMCID: PMC1774022 6) Louie TJ. Treatment of first recurrences of Clostridium difficile-associated disease: waiting for new treatment options. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2006 Mar 15;42(6):765-7. PubMed PMID: 16477550. Epub 2006/02/16.
Prof. Ahmed Halawa
Tutor
1 month ago Dear All How would you confirm it is C Def colitis? If you have this CT image with the above mentioned history, would you go for a colonoscopy? 1. How would you confirm it is C Def colitis? C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation, particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age) [1]. Diagnosis of CDI requires demonstration of C. difficile toxin(s) or detection of organism in diarrhoeal stool sample. A number of lab tests (stool) are available, can be used alone or in combination as part of diagnostic algorithm: 1) Nucleic acid amplification test (NAAT) for C.difficle – sensitive and specific in detecting gene for C Def toxins – rapid, false negative results can occur in patients receiving empirical antibiotics, or with delayed collection. 2) PCR are highly sensitive, greater than EIA and comparable with cytotoxicity assay; can’t differentiate asymptomatic carriers from disease state. 3) Enzyme immunoassay (EIA) for C. difficile toxins A & B – highly sensitive, rapid (result within an hour), highly specific 99%. 4) Enzyme immunoassay EIA for C. difficile GDH: cannot distinguish between toxigenic and nontoxigenic strains, so it has to be done along with EIA for toxins A&B. 5) Cell culture cytotoxicity assay the gold standard test for diagnosis – time taking. 6) Selective anaerobic culture – sensitive, cannot distinguish toxin-producing strains from non-toxin-producing strains, second test is required to detect toxin. 2. If you have this CT image with the abovementioned history, would you go for a colonoscopy? Colonoscopy is generally not required routinely when typical signs and laboratory tests. In such sick patients, it can’t be performed (sedation or anesthesia is dangerous) and has high risk of perforation. For decompression of colon, other measures (NPO + NG tube + rectal tube) should be done, in place of flexible sigmoidoscopy. References: 1) Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149. 2) McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085. PMID: 29462280; PMCID: PMC6018983.
3) Sartelli M, Malangoni MA, Abu-Zidan FM, et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World Journal of Emergency Surgery (2015) 10:38 DOI 10.1186/s13017-015-0033-6
4) Johal SS1, Hammond J, Solomon K,et al. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004 May; 53(5): 673-7. DOI: 10.1136/gut.2003.028803. PMID: 15082585 PMCID: PMC1774022
· What is the differential diagnosis? The DD of diarrhea in this immunosuppressed 65 lady include: Infectious causes: Bacterial: Salmonella, Campylobacter, bacterial over growth, E. coli. Virus: CMV, norovirus, rotavirus and adenovirus, Parasites: Guardia, entamoeba. and cryptosporidiosis, Noninfectious:
Drug related: immunosuppressive drugs (MMF, CNI, mTOR-I) and non –immunosuppressive drugs including antibacterial medications(pseudo-membranous colitis), laxatives anti-arrhythmic, hypoglycemic drug, , PPI
IBD
PTLD
GVHD
Bowel malignancy
PTLD
GVHD
However, in this scenario, his lady received ciprofloxacin for UTI in first month post-transplant. Accordingly, the most probable cause of diarrhea is C. difficile infection-(antibiotic related diarrhea- fluoroquinolone) which is an opportunistic infection that can occur in first month post transplantation.
· How would you confirm the diagnosis?
· The diagnosis is based on the clinical features(diarrhea in the context of recent antibiotic use coupled with toxic mega-colon that appeared in CT. However, Colonoscopy was not required as it increases the risk bowel perforation.
· Confirm the diagnosis by stool toxin assay to detect C Diff toxin rather than doing cultures. However, stool culture is still required to exclude another enteric pathogens Who would manage this patient? Substantiate your answer!
· MDT approach including the transplant team and thegastroenterologist, infectious disease with ICU team. This patient has multiple poor prognostic indicators including septic shock, significant metabolic derangement, graft dysfunction, poor response to medical therapy with disease progression.
· ICU admission for cardio ventilator support, fluid resuscitation, correction of electrolytes, improve nutritional status as the patient will need to stop enteral feeding and start parenteral nutrition. CRRT may be required in the context of newly developing AKI and shock.
· Stop Ciprofloxacin. Continue on vancomycin and metronidazole. Liaise with the ID team for any required antibiotics.
· Immunosuppression management: Stop MMF, reduce tacrolimus to keep a trough level between 5-8 ng/ml. Use IV hydrocortisone to replace prednisolone initially.
· Decompression of the dilated colon with nasogastric tube.
· Holding medications that slow intestinal motility (anticholinergics, antidepressants, anti-diarrheal, and narcotics)
· Monitor the patient clinical improvement or response to treatment, consider discussing with the surgical treatment. Only 1 % of all patients with clostridium defficile infection(CDI) and 30 % with severe disease will require emergency surgery. The overall mortality with severe Clostridium difficile colitis with toxic mega-colon was 64- 67%, and 71 to 100 % for surgically treated patients. .
· Early surgical consultation and timely and decisive operative management is the key for survival of patients with severe or fulminant C. difficile colitis. The surgical treatment is total abdominal colectomy but a diverting loop ileostomy and colonic lavage may be an alternative. References: 1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493.. 2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7.
· What is the differential diagnosis? The DD of diarrhea in this immunosuppressed 65 lady include: Infectious causes: Bacterial: Salmonella, Campylobacter, bacterial over growth, E. coli. Virus: CMV, norovirus, rotavirus and adenovirus, Parasites: Guardia, entamoeba. and cryptosporidiosis, Noninfectious:
Drug related: immunosuppressive drugs (MMF, CNI, mTOR-I) and non –immunosuppressive drugs including antibacterial medications(pseudo-membranous colitis), laxatives anti-arrhythmic, hypoglycemic drug, , PPI
IBD
PTLD
GVHD
Bowel malignancy
PTLD
GVHD
However, in this scenario, his lady received ciprofloxacin for UTI in first month post-transplant. Accordingly, the most probable cause of diarrhea is C. difficile infection-(antibiotic related diarrhea- fluoroquinolone) which is an opportunistic infection that can occur in first month post transplantation.
· How would you confirm the diagnosis?
· The diagnosis is based on the clinical features(diarrhea in the context of recent antibiotic use coupled with toxic mega-colon that appeared in CT. However, Colonoscopy was not required as it increases the risk bowel perforation.
· Confirm the diagnosis by stool toxin assay to detect C Diff toxin rather than doing cultures. However, stool culture is still required to exclude another enteric pathogens Who would manage this patient? Substantiate your answer!
· MDT approach including the transplant team and thegastroenterologist, infectious disease with ICU team. This patient has multiple poor prognostic indicators including septic shock, significant metabolic derangement, graft dysfunction, poor response to medical therapy with disease progression.
· ICU admission for cardio ventilator support, fluid resuscitation, correction of electrolytes, improve nutritional status as the patient will need to stop enteral feeding and start parenteral nutrition. CRRT may be required in the context of newly developing AKI and shock.
· Stop Ciprofloxacin. Continue on vancomycin and metronidazole. Liaise with the ID team for any required antibiotics.
· Immunosuppression management: Stop MMF, reduce tacrolimus to keep a trough level between 5-8 ng/ml. Use IV hydrocortisone to replace prednisolone initially.
· Decompression of the dilated colon with nasogastric tube.
· Holding medications that slow intestinal motility (anticholinergics, antidepressants, anti-diarrheal, and narcotics)
· Monitor the patient clinical improvement or response to treatment, consider discussing with the surgical treatment. Only 1 % of all patients with clostridium defficile infection(CDI) and 30 % with severe disease will require emergency surgery. The overall mortality with severe Clostridium difficile colitis with toxic mega-colon was 64- 67%, and 71 to 100 % for surgically treated patients. .
· Early surgical consultation and timely and decisive operative management is the key for survival of patients with severe or fulminant C. difficile colitis. The surgical treatment is total abdominal colectomy but a diverting loop ileostomy and colonic lavage may be an alternative. References: 1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493.. 2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7.
Q1: Differential diagnosis:
1.Infectious diarrhea:
Bacterial: clostridium difficile (most probable due to recent antibiotic therapy), salmonella,
E. coli, shigella, campylobacter, Yersinia
Viral: Norovirus, rotavirus, CMV, adenovirus
Protozoa: cryptosporidium, giardia, ameloidosis
2.Non-infectious:
Drug induced by MMF, Laxatives
Q2: Diagnosis:
Stool exam and stool culture for bacterial or protozoal infection, clostridium difficile toxin determination by ELIZA, EIA or PCR
PCR for viral infections (CMV and others)
Q3: This patient has toxic mega colon with a critical condition and needs ICU admission and multi-disciplinary approach (intensivist, nephrologist, infectious disease and surgical consultation)
Volume repletion with IV hydration and replacement fluids and inotrope), reduction of immunosuppressive drugs (especially stop MMF and steroids with stress dose) are needed. She should be NPO and have NG tube and rectal tube to decompress GI tract. Start IV metronidazole and oral vancomycin and broad spectrum anti-biotic. Close monitoring for vital signs, electrolytes, acid-base, CBC-diff, LFT and RFT. Start CRRT and consult with surgeons if suspect to perforation or peritonitis for total colectomy and ileostomy.
· What is the differential diagnosis?
C difficile infection is top on this case scenario, with immunosuppression status, recent prolong antibiotic use and history of diarrhea.
Other differential: Infectious and non infectious causes of diarrhea. Like bacteria ( dysentery, Salmonella, etc), parasitic Giardia, amoeba, etc), viral ( CMV).
· How would you confirm the diagnosis?
ds
Test for C Diff toxin
Cell culture
NAAT
Who would manage this patient?
This patient needs:
Admission to ICU, isolation.
Aggressive fluid resuscitation with fluids and electrolytes replacement (replace potassium before considering bicarbonate).
Reduction of immunosuppression, cut MPA by 50% and hold it no high risk for rejection or no improvement after initial resuscitation.
Change prednisone to hydrocortisone stress dose.
Check FK level and keep it at target.
Antibiotic coverage with oral vancomycin and IV metronidazole.
We need to avoid colonoscopy if possible because of perforation risk.
Transplant recipient, received 14 day course of ciprofloxacin for UTI presented with abdominal pain , watery diarrhea , vomiting , septic shock and, metabolic acidosis AKI. CT abdomen showed dilated colon picture suggestive of Toxic Megacolon. Causes : The most common cause following antibiotic for long time is Clostridium difficile Other infectious causes: · Salmonella · Shigella · Campylobacter colitis · Enterohemorrhagic or enteroaggregative Escherichia coli O157 (can lead to hemolytic-uremic syndrome) · Cytomegalovirus · Entamoeba
. How would you confirm the diagnosis? Diagnosis of C. difficile by detection of its toxin in stool, or by positive nucleic acid amplification test (NAAT) for C. difficile toxin gene
how would manage this patient? -ICU admission with fluid resuscitation, iv fluid, correction of electrolytes , correction of acidosis, fluid chart , monitor kidney function , urine out put , ABG , sepsis marker and CBC. – antibiotics, especially if an infectious cause is suspected. The most commonly used antibiotics are metronidazole or vancomycin. -If cytomegalovirus is the suspected cause, then gancyclovir should be given. Antibiotics of choice for C. difficile are oral vancomycin (500 mg 4 times /day) or oral fidaxomicin. If those are not available, oral metronidazole is an alternative.
Tigecycline is used for refractory cases.
-patients must be on bowel rest. A nasogastric tube can be inserted to help decompress the stomach, but it will not decompress the colon. As the patient continues to improve, they can gradually start eating to promote gut healing
-Surgical Management, in case intervention might be necessary. The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
Reference Skomorochow E, Pico J. Toxic Megacolon. [Updated 2022 Jul 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan
Patient admitted with acute diarrhea after hospitalization with manifestations of organ dysfunction and sepsis. In this situation, the most pathogenic agent is Clostridium difficile inducing pseudomembranous colitis developed fulminant colitis complicated with toxic megacolon.
Despite this, there is the possibility of differential diagnoses of infectious and non-infectious etiology.
Infectious: E. coli, Campylobacter, Salmonella, CMV, Rotavirus, Enterovirus,
Non-infectious: immunosuppressive drugs.
• How would you confirm the diagnosis?
For the diagnosis of acute diarrhea, we could start with:
– C. difficile PCR in stool
– CMV qPCR/NAT in blood/serum
– Bacterial culture or PCR for bacterial pathogen in stool
– Multiplex PCR if available in stool
• Who would manage this patient?
Faced with renal dysfunction with acidosis and loss of electrolytes, volume expansion and electrolyte replacement is necessary as performed.
Start of broad-spectrum antibiotic (ciprofloxacin) and specific for C. difficile due to its greater pathogenicity (oral Vanco + IV Metronidazole)
I would avoid colonoscopy because of the risk of perforation.
Early use of amines, with weaning as there was a response to volume expansion.
• Substantiate your answer!
– Amin K, Choksi V, Farouk SS, Sparks MA. Diarrhea in a Patient With Combined Kidney-Pancreas Transplant. Am J Kidney Dis. 2021 Aug;78(2):A13-A16. doi: 10.1053/j.ajkd.2021.01.023. PMID: 34303438.
– Angarone, M, Snydman, DR; on behalf of the AST ID Community of Practice. Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13550. https://doi.org/10.1111/ctr.13550
Patient is a recent renal transplant recipient with normal graft function…She is on triple immunosuppression…She has been treated for UTI with ciprofloxacin recently for 14 days…
She has presented to ER with septic shock…there was pancolitis with elevated WBC count which has progressed into septic shock requiring inotropes…Patient also has hypokalemia with hypomagnesemia which was corrected..IV fluids were given…The patient has progressed to toxic megacolon…
The patient needs IV fluids as per surviving sepsis guidelines….IV electrolytes correction has to be given…Colonoscopy is not indicated now as there is risk of perforation with toxic megacolon….IV antibiotics preferably third generation cephalosporin or meropenem with IV metronidazole is needed…Basic lab work up has to be done daily to monitor the renal functions, complete blood count…I would stop all immunosuppression and keep the patient on low dose steroids….
Stool for C diff toxin can be done to prove the diagnosis….culture and blood tests for C.Diff are not helpful in diagnosis
The DDx include infectious causes and non infectious causes
Infectious causes include:
Bacterial like
C.difficile , C. Perfrangins , E.Coli, Salmonella spp.
Viral like
Rotavirus, adenovirus
Parasitic like
Giardiasis and amebeoasis
The non infectious causes include
Drug induced
IBS
Inflammatory bowel syndrome
Caeliac disease
The most likely diagnosis here is Toxic megacolon secondary to fulminating colitis and pseudo membranous colitis . The diagnosis can be confirmed by:
1-NAAT for toxin gene
2-Stool for enzyme immune assay
3-Cell based cytotoxicity test.
Colonoscopy is contraindicated in this case The management plan include:
Admission to ICU
MDT including transplant nephrologist
Intravenous fluid rehydration
Abdominal decompression
NPO
Stop MMP, decrease CNIs by 50%
Sress dose steroid
Medical treatment and if not improved within 24 hrs then go for surgical intervention by total colectomy and illieostomy.
What is the differential diagnosis?In this scenario, the likely cause is infective causes diarrhoea. The patient is currently in septic shock in DIVC (coagulopathy), complicated by AKI and toxic megacolon. This is also compounded by electrolyte imbalance due to severe diarrhoea (hyponatraemia, hypomagnesemia) and metabolic acidosis (lactic acidosis).
Differential diagnosis
Bacterial causes:
1) Clostridium difficile (provisional diagnosis)
2) Salmonella
3) E.Coli
4) Campylobacter
Virus causes:
1) CMV
2) Norovirus
3) Adenovirus
Parasite:
1) Giardia
2) Cryptosporidium
3) Microsporadium
4) Isospora How would you confirm the diagnosis?1) Stool examination for clostridium difficile (toxin, culture,nucleic acid amplification test (NAAT) or enzyme immunoassay to detect glutamate dehydrogenase (EIA GDH) Who would manage this patient?1) Aggressive fluid resuscitation
2) NG tube for bowel decompression
3) Electrolytes correction (potassium and magnesium)
4) Withhold MMF and advagraf (may need to restart once infection is improving)
5) Switch prednisolone to hydrocortisone 100 mg TDS
6) Switch oral vancomycin (poor absorption in this case to Fidaxomicin
7) If failed to consider faecal microbiota (FMT)
8) Other novel alternative therapy is Bezlotoxumab
References
1.Infectious Diseases Society of America (IDSA) 2.Society for Healthcare Epidemiology of America (SHEA)
3.van Prehn, J.; Reigadas, E.; Vogelzang, E.H.; Bouza, E.; Hristea, A.; Guery, B.; Krutova, M.; Norén, T.; Allerberger, F.; Coia, J.E.; et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin. Microbiol. Infect. 2021, 27 (Suppl. S2), S1–S21.
it is mostly toxic megacolon due to C. difficile toxins
Diagnosis:
stool cultures for c.difficile
c.difficile PCR
Colonoscopy is contraindicated due to high risk of perforation
The management:
ICU admission
resuscitation
correct electrolytes
NPO
stop myfortic and reduction of CNI dose by 50%
change steroid to IV
oral vancomycin or IV metronidazole
Pseudomembranous colitis brought on by Clostridium difficile progressed to fulminant colitis worsened by toxic megacolon.There are additional infectious and non-infectious causes of diarrhea.
E. choli, Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp. are among the bacteria that can cause infectious diarrhea. Rotavirus, adenovirus, and sapovirus are viruses. Giardia, cryptosporidium, microsporidium, and Entamoeba are parasites.
Non-infectious diarrhea; immune suppressive medications, including tacrolimus, cyclosporin, and sirolimus; non-immune suppressive medications, such as antibiotics and PPIs; and other conditions, such as GVHD, PTLD, post-infectious irritable bowel syndrome, inflammatory bowel disease, celiac disease, and microscopic colitis.
2. Substantiate the diagnosis?
Toxin culture and cell cytotoxicity are the gold standard tests for diagnosing C. difficile, but because they require 24 to 48 hours, they are not suited for this critically ill patient.
-C. difficile real-time PCR (high sensitivity and specificity, 90%) or fecal enzyme immune assay.
The index instance does not require a colonoscopy due to the possibility of perforation.
3. Who is to treat the patient?
This patient should be admitted to the intensive care unit with a multidisciplinary team.
Supportive therapy, including intravenous rehydration and replenishment with electrolyte replacements
Stop MMf, lower the CNI dose, and perhaps raise the stress dose of steroids.
-Close monitoring of liver function, CBC, venous blood gases, and electrolytes in addition to graft performance
Aggressive medicinal therapy may help avoid surgical intervention in toxic megacolon caused by C. difficile in up to 50% of cases.
Because of insufficient intestinal motility, oral vancomycin may not produce adequate intracolonic concentrations of the antibiotic.
Vancomycin enemas have been advised as a result; however, they might not be effective for treating colon disease on the right side.
Nasogastric suction and regular patient positional changes may help to relieve the pressure on the dilated colon. Some writers advise lying on one’s back for 10 to 15 minutes every two to three hours to allow flatus to pass.
Holding off on using drugs that reduce intestinal motility is another aspect of managing toxic megacolon. These drugs include opioids, anticholinergics, antidepressants, and antidiarrheals.
Up to 80% of patients with toxic megacolon caused by C. difficile colitis may require surgical intervention.
Surgery is advised in cases of perforation, progressive colon dilatation, failure to improve clinically during the first 48–72 hours, and uncontrolled bleeding.
A 64-year-old woman presented to the hospital with 3 days of abdominal pain, nausea, vomiting and profuse watery diarrhoea. She was recently discharged from the hospital for a urinary tract infection following a successful renal transplant from her son with excellent function. She is currently on Tacrolimus (trough level 9 ng/ml), Myfortic (720 mg bd) and prednisolone (15 mg od). She had just completed a 14-day course of ciprofloxacin. On admission to the hospital, the blood pressure was 65/41 mmHg. Hypothermia was present. The temperature was 35.8°C. She was obese and appeared in mild distress. Her abdomen was mildly distended, with silent bowel sounds. There was tenderness in the lower quadrants without rebound tenderness. The WBC was 53.9 109 /L with 84% neutrophils. The Hct was 36.1%. There was severe metabolic acidosis with an anion gap of 19, bicarbonate level of 12 mmol/ L, and lactic acid level of 3.6 mmol/L. The arterial blood gas demonstrated a pH of 7.11, CO2 of 16, and O2 of 150 on 2 litres of oxygen via nasal cannula. The serum creatinine was 1051 μmol/L. The K+ was 2.5 mmol/L, and Mg++ of 0.24 mmol/L. The INR was 2.1.The patient was resuscitated with IV fluids and placed on dopamine and later norepinephrine. She was also given intravenous ciprofloxacin 500 mg every 12 h, oral vancomycin 250 mg every 6 h and IV metronidazole 500 mg every 6 h. A CT of the abdomen and pelvis demonstrated circumferential wall thickening of the colon consistent with pan colitis (see below). The transverse colon was dilated to 5.8 cm. The colonoscopy is shown below. The patient did not improve despite treatment over the next 36 h. The WBC rose to 62.4 109 /L with a more tender abdomen. A repeat CT scan showed transverse colon was dilated to 8.7cm. There was no other source of infection. Blood, urine, and stool cultures were negative. DDX;
Septic shock with pre renal AKI from possibly;
Toxic megacolon from C.difficile.
IBD
Other infectious causes of diarrhea- E. coli,S aureus,Klebsiella,C perfringens,Salmonella,CMV etc.
Non infectous causes ; MMF,CNI,KS etc
Confirm diagnosis;
NAAT for difficile toxin gene or +ve stool test for C. difficile toxin.
EIA for C. difficile GDH antigen.
EIA for C.difficile toxins A and B.
Criteria for toxic megacolon in our case above; colonic dilatation >6.cm,fever >38.5,Tachycardia >120,neutrophil count> 10000/m ,hypotension ,electrolyte imbalance and altered sensorium.
Management;
Admit in ICU for resp and hemodynamic support.
Get an ID expert on board + transplant nephrologist.
Adequate IV fluids and ionotropic support to reverse shock.
RRT as needed.
RIS- stop MMF and decease CNI by 50% and increase steroids to stress doses. Monitor graft function.
This is a fulminant case as we have hypotension, shock and electrolyte imbalance; Vancomycin 500mg PO or via NGT QID +flagyl 500mg IV TDS,if ileus develops, Fidaxomicin (PR) or PR vancomycin as a retention enema 500mg in 100mls NS per rectum QID.
Sx review in the event we have a perforation, severe sepsis, resp failure needing vent support, worsening end organ failure or abd compartment syndrome.
Substantiate answer.
Uptodate; C .difficile infection in adults ;Treatment and Prevention.
Hrebinko et al;C.difficile; What the surgeon needs to know.Semincolon rectal surg 2018;29;28
Sheth SG et al;Toxin Megacolon.Lancet 1998 feb 14.351(9101);509-13
1. Issues/ concerns
– 64yo woman, 3/7 hx of abdominal pain, nausea, vomiting, profuse watery diarrhoea
– recently discharged from the hospital for a UTI
– successful LDKT, donor son, excellent kidney function
– medication: tacrolimus (trough level 9ng/ml), myfortic 720mg BD, prednisone 15mg OD
– has just completed 14 days of ciprofloxacin
– at admission: hypotensive BP 65/41, hypothermia 35.8, obese, mild distress, mild abdominal distension, silent bowel sounds, tenderness in the lower quadrants with no rebound tenderness
– WBC 53.9/L, neutrophils 84%, Hct 36.1%
– severe metabolic acidosis, AG 19, bicarb 12mmol/l, lactate 3.6 mmol/L, pH 7.11, CO₂ 16, O₂ 150 on 2L/min oxygen via nasal canula
– sCR 1051 μmol/L, K+ 2.5 mmol/L, Mg 0.24 mmol/L, INR 2.1
– patient resuscitated with IVF, placed on dopamine and later norepinephrine
– was given ciprofloxacin 500mg IV BD, vancomycin 250mg every 6hours, metronidazole 500mg IV TID
– Abdominopelvic CT scan done demonstrated pan colitis (circumferential wall thickening of the colon), transverse colon was dilated to 5.8cm
– patient did not improve despite treatment over the next 36 hours
– WBC increased to 63.4/L, abdomen was more tender, repeat CT scan showed transverse colon was dilated to 8.7cm
– no other source of infection, blood, urine and stool cultures were negative
What is the differential diagnosis? (1, 2)
– Sepsis, septic shock
– E. coli can cause hemorrhagic colitis and hemolytic uremic syndrome which can result in toxic megacolon
– use of loperamide in fulminant amoebic colitis can precipitate toxic megacolon
How would you confirm the diagnosis? (3-5)
– history and physical examination: malaise, abdominal pain, bloody diarrhoea, abdominal distension, drug history (antibiotics, antimotility drugs, chemotherapy), fever, tachycardia, hypotension, altered mental status, distended abdomen
– diagnostic criteria for toxic megacolon: –
· radiologic evidence of colonic dilatation i.e., diameter >6cm
· plus at least 3 of the following: fever >38, HR >120, leukocytosis >10,500microL, anaemia
· plus at least 1 of the following: dehydration, electrolyte disturbances, hypotension, altered sensorium
– initial abdominopelvic CT scan with oral and IV contrast to establish the diagnosis and exclude complications that require urgent surgery
– thereafter, serial plain abdominal radiographs to monitor progression of colonic dilatation
– laboratory studies: CBC, UECs, LFTs, ESR, CRP, procalcitonin, stool for m/c/s and C. difficile toxin, CMV PCR, stool bacterial and viral PCR
· neutrophilia (especially with C. difficile), neutropenia (in sepsis, immunocompromised patients)
· anaemia due to GI blood loss
· hypokalemia and metabolic alkalosis due to diarrhoea and colonic inflammation
· metabolic acidosis suggests ischaemic colitis
· hypoalbuminemia due to protein loss, chronic inflammation, malnutrition
– colonoscopy indicated for selected patients – it is best avoided due to the risk of colonic perforation, worsening ileus, distension
– biopsy and histology: characteristic findings in C. difficile (pseudomembranous appearance), amoebic colitis (presence of trophozoites, punched-out ulcers), CMV colitis (inclusion bodies)
– assess for risk factors for development of severe colitis in patients with C. difficile infection: immunosuppressive therapy, kidney failure, exposure to clindamycin, anti-peristaltic drugs, malignancy, COPD
– hypokalemia, antimotility drugs, abrupt cessation of steroids can precipitate toxic megacolon
Who would manage this patient? (4, 6-8)
– aim of treatment is to reduce colonic inflammation, restore normal colonic motility, reduce likelihood of colonic perforation
– initial management is supportive and medical, prevents surgery in 50% of the patients
– however, delaying surgery can increase the risk of complications like abdominal compartment syndrome, bowel perforation leading to poor prognosis
– hold immunosuppressants (tacrolimus, myfortic and prednisone), maintain on hydrocortisone 100mg IV TID until she is stable
– supportive management:
· ICU monitoring due to systemic toxicity
· fluid therapy – IVF
· correct electrolyte imbalances
· broad-spectrum antibiotics for management of sepsis
· in case of colonic perforation administer H₂ blockers or PPIs for GI prophylaxis, DVT prophylaxis
· complete bowel rest and NGT bowel decompression initially then
· enteral feeding – it hastens mucosal healing, stimulates normal motility, can be started as soon as the patient improves
· consider TPN for patients who cannot tolerate enteral nutrition
· stop medications that can affect colonic motility e.g., anticholinergics, opiates
· maneuvers to redistribute and expel gas in the colon – intermittent rolling or the knee-elbow position
· surgical consultation
– definitive management:
· Medications are 1st line therapy
· Indications for surgery: intrabdominal hypertension, abdominal compartment syndrome, colonic perforation, necrosis, full thickness ischemia, peritonitis, worsening abdominal examination, organ failure requiring vasopressors, intubation, mechanical ventilation, AKI
· Surgical options: total abdominal colectomy, diverting ileostomy with colonic lavage
– C. difficile infection (CDI) management
· stop inciting antibiotics
· avoid steroids in infectious colitis
Non-fulminant disease· initial episode of non-severe disease (WBC <15,000 cells/mL, sCr <1.5mg/dL) or severe disease (WBC >15,000 cells/ mL, sCr >1.5mg/dL): –
– give Fidaxomicin 200mg PO BD 10/7 or Vancomycin 125mg PO QID 10/7 or Metronidazole 400mg PO TID 10-14/7
· recurrent episode of CDI – initiate antibiotics and add bezlotoxumab 10mg/kg IV stat
· first recurrence of CDI – fidaxomicin, vancomycin, bezlotuxumab
· second or subsequent recurrence of CDI – fidaxomicin, vancomycin + rifaximin 400mg TID 20/7, bezlotoxumab; there is a role for fecal microbiota transplantation
Fulminant disease as evidenced by hypotension or shock, ileus, megacolon- absence of ileus – Vancomycin 500mg PO/ NGT QID and metronidazole 500mg IV TID
– ileus present – FMT (per rectal) or rectal vancomycin
Substantiate your answer
References
1. Rubin MS, Bodenstein LE, Kent KC. Severe Clostridium difficile colitis. Diseases of the colon and rectum. 1995 Apr;38(4):350-4. PubMed PMID: 7720439. Epub 1995/04/01. eng.
2. Hommes DW, Sterringa G, van Deventer SJ, Tytgat GN, Weel J. The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research. Inflammatory bowel diseases. 2004 May;10(3):245-50. PubMed PMID: 15290919. Epub 2004/08/05. eng.
3. Trudel JL, Deschênes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous enterocolitis. Diseases of the colon and rectum. 1995 Oct;38(10):1033-8. PubMed PMID: 7555415. Epub 1995/10/01. eng.
4. Autenrieth DM, Baumgart DC. Toxic megacolon. Inflammatory bowel diseases. 2012 Mar;18(3):584-91. PubMed PMID: 22009735. Epub 2011/10/20. eng.
5. Jalan KN, Sircus W, Card WI, Falconer CW, Bruce CB, Crean GP, et al. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology. 1969 Jul;57(1):68-82. PubMed PMID: 5305933. Epub 1969/07/01. eng.
6. Louie TJ. Treatment of first recurrences of Clostridium difficile-associated disease: waiting for new treatment options. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2006 Mar 15;42(6):765-7. PubMed PMID: 16477550. Epub 2006/02/16. eng.
7. Sheth SG, LaMont JT. Toxic megacolon. Lancet (London, England). 1998 Feb 14;351(9101):509-13. PubMed PMID: 9482465. Epub 1998/03/03. eng.
This seems to be toxic megacolon due to C, Def
ICU stay , involvement of surgical gastro with aim to avoid colonic perforation which is likely with colonoscopy
diagnosis-
C def toxin in stool – quick test
culture
serology like EIA
· What is the differential diagnosis?Septic shock 2ry to toxic megacolon & perforation complicated by AKI & metabolic acidosis.DD: C.diff , IBD & CMV colitis. · How would you confirm the diagnosis?– C.diff toxin in stool- CMV PCR- Colonoscopy is not appropriate due to risk of perforation.· Who would manage this patient?MDT with involvement in ICU setting with transplant team, ID team & surgical team.· Substantiate your answer!Management is:1- Supportive measures: inotropes keeping MAP above 65mmgh, good hydration by IV fluids, IV antibiotics 2- Management of immunosuppression: hold MMF temporarily, decrease tacrolimus by 50 % with trough level monitoring around 63- Management of C.diff by ID protocols4- Surgical team has the upper hand to decide for urgent colectomy
The clinical picture is highly suggestive of fulminant C diff colitis with shock and toxic megacolon
AKI secondary to volume depletion
Electrolyte disturbance secondary to GI loss
The diagnosis can be confirmed by NAAT Enzyme immunoassay for C. difficile toxins A and B Cell culture cytotoxicity assay
Management
Need ICU admission for circulatory support, fluid resuscitation and inotropes
Correction of electrolyte
Withhold MMF and Tac for now, continue steroid
Discontinue causative antibiotics
Might need CVVH in the acute setting
Vancomycin, metronidazole +/- fidaxomicin which has the same efficiency as vancomycin but less associate with less recurrence
Early surgical review and assessment, Once stabilised, might need colectomy of no improvement although surgical mortality is high
Faecal transplant is an alternative
What is the differential diagnosis?
· This patient has Toxic megacolon mostly due to C.difficile infection.
· immunosuppressive therapy and antibiotic treatment are considered important risk factors for C.difficile infection DIFFERENTIAL DIAGNOSIS
· Ogilvie’s syndrome (colonic pseudo-obstruction), volvulus, or ischemia
· Infectious diarrhea – due to Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp
· Inflammatory bowel disease How would you confirm the diagnosis?
· Toxic megacolon should be suspected in patients with abdominal distension and diarrhea.
· Criteria for toxic megacolon diagnosis:
1) Radiographic evidence of colonic dilation (diameter >6 cm) 2) PLUS at least three of the following:
•Fever >38ºC •Heart rate >120 beats/min •Neutrophilic leukocytosis >10,500/microL •Anemia 3) PLUS at least one of the following:
Manifestations of Severe and fulminant colitis due to Clostridioides difficile infection:
diarrhea, lower quadrant or diffuse abdominal pain, abdominal distention, fever, hypovolemia, lactic acidosis, hypoalbuminemia, elevated creatinine concentration, and marked leukocytosis (white blood cell count 40,000 cells/microL or higher)
· Fulminant colitis (previously referred to as severe, complicated C.difficile Infection) may be characterized by hypotension or shock, ileus, or megacolon
· The diagnosis of CDI is established via either a positive NAAT for C. difficile toxin gene or a positive stool test for C. difficile toxin(s). Who would manage this patient?
· Supportive therapy in intensive care because of systemic toxicity. Treatment of Fulminant disease of Clostridioides difficile infection (CDI) in adults · Absence of ileus: Enteric vancomycin plus parenteral metronidazole:
Vancomycin 500 mg orally or via nasogastric tube 4 times daily, AND
Metronidazole 500 mg intravenously every 8 hours
· If ileus is present, additional considerations include:
· Fecal microbiota transplantation FMT (administered rectally) OR
· Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours) Indications for operative management in patients with CDI
· A diagnosis of CDI as determined by one of the following:
1) Positive laboratory assay for C. difficile
2) Colonoscopic findings consistent with C. difficile colitis
3) CT scan findings consistent with C. difficile colitis (pancolitis with or without ascites)
· Plus any one of the following criteria:
1) Peritonitis
2) Colonic perforation or full-thickness ischemia
3) Sepsis
4) Respiratory failure requiring intubation and mechanical ventilation
5) Vasopressor requirement after resuscitation
6) Mental status changes attributable to C. difficile colitis
7) Clinical deterioration despite adequate medical management
8) Acute renal failure (or other worsening end-organ failure)
9) Serum lactate level >5 mmol/L
10) White blood cell counts greater than or equal to 50,000 cells/mL
11) Abdominal compartment syndrome or intra-abdominal hypertension Substantiate your answer! https://www.uptodate.com/contents/toxic-megacolon?search=toxic%20megacolon&source=search_result&selectedTitle=1~104&usage_type=default&display_rank=1#H12:~:text=Back-,Toxic%20megacolon,-Topic
This is a case of toxic mega colon caused by either infection (bacterial or viral) or inflammation but more compatible to C.def. Because of history of taking of quinolones for treatment of UTI.
How would you confirm the diagnosis?
C.def toxin in stool
Radiological: mega colon
Clinical: sever abdominal pain with abdominal distension and toxic picture after antibiotics administration
Management
1. surgical by Urgent total if one of the following is present:
· Evidence of perforation, peritonitis acute compartmental syndrome
· Severe sepsis with end organ damage
2. Conservative treatment in the form of
· Caution decompression because of risk of perforation.
· Metronidazole or oral vancomycin.
· Hydrocortisone IV
· Correction of dehydration and electrolytes disturbances References
1- Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351:509.
2- Fazio VW. Toxic megacolon in ulcerative colitis and Crohn’s colitis. Clin Gastroenterol 1980; 9:389.
3- Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology 1969; 57:68.
4- Ahmed N, Kuo YH. Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection. South Med J 2020; 113:345.
Clostridium Difficile induced pseudomembranous colitis developed fulminant colitis complicated with toxic megacolon.
Other infectious and noninfectious causes of diarrhea. Infectious diarrhea;
Bacterial; E choli, Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp.
Viruses; Rotavirus, adenovirus, sapovirus
Parasites; Giardia, cryptosporidium, Microsporidium, Entameoba Non-infectious diarrhea;
Immune suppressive drugs; MMF, tacrolimus, cyclosporin, sirolimus
Non-immune suppressive drugs e.g antibiotics, PPI, antidiabetic
How would you confirm the diagnosis?
History: Details History of prolonged Ab Course.
Examination: Vital signs (Hypotension, Fever, Tachycardia, tachypneic, obtunded, and physical findings may be minimal due to high-dose steroids to r/o toxic megacolon.
toxin culture & cell-cytotoxicity but it takes 24-48 hours, so it is not appropriate test for this critical ill patient.
Fecal enzyme immune assay or real-time C. difficile PCR (with high sensitivity & specificity (90%).
Colonoscopy is not indicated due to the risk of perforation.
Who would manage this patient?
NPO / NGT (bowel rest)
ABCD/ICU Support
Aggressive IV fluids, O2 to prevent AKI
Antibiotics should be given if an infectious cause is suspected.
Discontinue MMF or Myfortic
Hydrocortisone stress dose
Steroids should be given hydrocortisone 100 mg over 6 hours or methylprednisone 60 mg daily for 5 days.
Tacrolimus level can be reduced, levels should be monitored during metronidazole treatment to avoid toxicity.
the treatment of severe forum of C difficle with toxic megacolon.
Metronidazole 500mg IV TID and Oral vancomycin 125 mg to 500 mg QID (if tolerated) for 14 days or fidaxomicin 20 mg two times per day for 10 days.
Prevention and treatment of relapsing and refractory forms is difficult
Fidaxomicin, ramoplanin and tigecycline are effective for the treatment of severe
or recurrent disease.
IVIG 250-500mg/kg IV x1
human monoclonal antibodies against C. difficile toxins A and B
Fecal microbiota transplantation (FMT) in refractory cases but under trial.
Ciprofloxacin was just finished so no introduction of other antibiotics except those for C difficle
The treatment of MMF colitis includes a reduction or, in more severe forms, complete discontinuation of MPA.
Indications for surgical consultation in the management of C. DIFF Infection after stabilizing your patients:
Any one of the following: Hypotension with or without required use of vasopressors.
Fever ≥38.5°C
Ileus or significant abdominal distention
Peritonitis or significant abdominal tenderness
Mental status changes
WBC ≥20,000 cells/mL
Serum lactate levels >2.2 mmol/L
Admission to intensive care unit for CDI
End organ failure (mechanical ventilation, renal failure, etc.)
Failure to improve after three to five days of maximal medical therapy.
References
Clostridioides difficile infection in adults: Treatment and prevention(UpToDate)
Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130
Bagdasarian N., Rao K. and Malani P. Diagnosis and Treatment of Clostridium difficile in Adults: A Systemic Review. JAMA, 2015;313(4):398-408.
-Valey A and Ferrada P. Role of Surgery in Clostridium difficile Infection. Clin. Colon Rectal Surgery, 2020;33(2):87-91.
What is the differential diagnosis?In this scenario, the likely cause is infective causes diarrhoea. The patient is currently in septic shock in DIVC (coagulopathy), complicated by AKI and toxic megacolon. This is also compounded by electrolyte imbalance due to severe diarrhoea (hyponatraemia, hypomagnesemia) and metabolic acidosis (lactic acidosis).
How would you confirm the diagnosis?1) Stool examination for clostridium difficile (toxin, culture,nucleic acid amplification test (NAAT) or enzyme immunoassay to detect glutamate dehydrogenase (EIA GDH)
Who would manage this patient?1) Aggressive fluid resuscitation
2) NG tube for bowel decompression
3) Electrolytes correction (potassium and magnesium)
4) Withhold MMF and advagraf (may need to restart once infection is improving)
5) Switch prednisolone to hydrocortisone 100 mg TDS
6) Switch oral vancomycin (poor absorption in this case to Fidaxomicin
7) If failed to consider faecal microbiota (FMT)
8) Other novel alternative therapy is Bezlotoxumab
References
1.Infectious Diseases Society of America (IDSA) 2.Society for Healthcare Epidemiology of America (SHEA)
3.van Prehn, J.; Reigadas, E.; Vogelzang, E.H.; Bouza, E.; Hristea, A.; Guery, B.; Krutova, M.; Norén, T.; Allerberger, F.; Coia, J.E.; et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin. Microbiol. Infect. 2021, 27 (Suppl. S2), S1–S21.
What is the differential diagnosis
This is a case of post transplantation diarrhea and acute colitis
I- Infectious causes
1- Viral
CMV
Norvovirus
1- Bacterial :
Cl. Difficile , Campylobacter
2- Protozoa
3- Fungal
II- Non infectious causes:
Mostly related to drugs specially MMF and combined MMF with TAC DD for acute colitis
1-Infectoius causes : Cl difficile ,salmonella typhea and paratyphea.
2-Non infectious causes
-IBD
-Drug induced colitis
– ischemic colitis
This patient is still in early posttransplantation period so CMV possibility is uncommon. She received 14 day course of cipro followed by development of diarrhea ,so she most likely has pseudomembranous colitis.
· B- How would you confirm the diagnosis?The gold standard tests for diagnosing Cl difficle infection are to detect Cl difficle toxins in stool through
– Enzyme Immune assay : most commonly used in clinical settings
– toxigenic culture : consist of standard stool cultures from diarrheal stool to identify both toxigenic and non toxigenic strains. But has long turn around and delayed results
– – cytotoxin neutralizing assay : based on detection of the cytopathic effect of toxin B preoduced by Cl difficle on cells and the neutralizating its effect by antitoxin
· Real time PCR assay to detect cl difficile genr toxins
· Colonoscopy : not routinely recommended and very high risk in our current case due to risk of perforation.
· CT
· C- How would manage this patient?This patient presented with septic shock complicated with AKI toxic megacolon.
–Diagnostic criteria of septic shock are ( persistent hypotension reqiring vasopressor agent and serum lacticacid more than 2 mmol).
– Diagnostic criteria of toxic megacolon :
Radiological evidence of dilated colon > 6 cm , plus 3 of the following
1- Fever >38.6 C
2- Tachycardia > 120 b/min
3- Leukocytosis or anemia
4- Any of the following : altered mental status ,hypovolemia, hypotension or electrolytes disturbance Initial treament
1- Stabilize the patient : bowel rest , nasogastric tube insertion to relieve upper GIT distension , repositioning the patient to decompress the colon by moving the air to the desending colon and rectum through rolling maneuvers and prone knee –elbow position.
2- correct hypovolemia and replace electrolytes deficit
3- Adjust IS dose : stop MMF and reduce Tac dose by 50% . Specific treatment for Cl . difficile :
Start with oral vancomycin in severe cases as such patient plus metronidazole ,followed by rifixin if no response to vancomycin
If initial management fail, other potential options include fecal transplantation ,IVIG.
Shelter et al recommended colonoscopic decompression and intracolonic vancomycin administarion.
Ref
1-Johnson TA, Tabbut BR, Page CO. Treatment of antibiotic-associated pseudomembranous colitis with metronidazole. Am J Hosp Pharm. 1981 Jul;38(7):1034-5. PMID: 7258204. 2-Buxey KN, Sia C, Bell S, Wale R, Wein D, Warrier SK. Clostridium colitis: challenges in diagnosis and treatment. ANZ J Surg. 2017 Apr. 87(4):227-31. 3-Shetler K, Nieuwenhuis R, Wren SM, Triadafilopoulos G. Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis. Surg Endosc. 2001 Jul. 15(7):653-9.
What is the differential diagnosis?Clostridium difficile associated diarrhoea is the most likely cause in a patient with prior history of antibiotic use and presence of toxic megacolon. Also CDAD is most likely associated with fluroquionolones which the patient had history of use.
Other differentials:
Viral: CMV, rotavirus, Noravirus
Bacterial: Campylobacter, shigella, salmonella
Protozoa: Giardia, cryptosporidium
Fungal
Non-infectious: crohns disease
How would you confirm the diagnosis?Nucleic acid amplification test-can detect both toxin A and B. They have high sensitivity though do not differentiate disease from colonisation.
Toxin EIA: they are high specific though they lack sensitivity
Cell culture neutralisation assay: it has high sensitivity for the B toxin however is not routinely available on all cell centers.
Culture can be done though there is delay of results for uptown 1 week.
Colonoscopy in this patient is contraindicated due to risk of perforation. Who would manage this patient?This patient requires management in an ICU setup.
She requires fluids and electrolyte replacement as she is hypotensive with electrolyte imbalances.
The management of pseudomembranous colitis include oral vancomycin/ IV metronidazole/ Oral fidaxomicin; fluid and electrolyte replacement and cessation of the causative antibiotic.
Oral vancomycin is not absorbed in the GIT hence leading to concentration in the gut however should be avoided when there is perforation.
The patient also requires surgical consult due to the megacolon, the colon can be decompressed with nasogastric suction.
References
Laboratory Tests for the Diagnosis of Clostridium difficileKaren C. Carroll, MD and Masako Mizusawa, MD, PhD, MS
Pseudomembranous Colitis Surgery Treatment & ManagementSaid Fadi Yassin, MD; Chief Editor: John Geibel, MD, MSc, DSc, AGAF
Current and Future Treatment Modalities for Clostridium difficile-Associated Disease
Jennifer Halsey, M.S., Pharm.D
1-What is the differential diagnosis? *Clostridium Difficile induced pseudomembranous colitisdeveloped fulminant colitis complicated with toxic megacolon. *Other infectious and noninfectious causes of diarrhea. Infectious diarrhea; *Bacterial; E choli, Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp. *Viruses; Rotavirus, adenovirus, sapovirus * Parasites; Giardia, cryptosporidium, Microsporidium, Entameoba Non-infectious diarrhea; *Immune suppressive drugs; MPA, tacrolimus, cyclosporin, sirolimus *Non-immune suppressive drugs e.g antibiotics, PPI, antidiabetic *Others e.g., GVHD, PTLD, Post-infectious irritable bowel syndrome, inflammatory bowel disease, celiac disease, and microscopic colitis. 2-To confirm the diagnosis? -The gold standard test for C. difficile diagnosis are toxin culture & cell-cytotoxicity but it takes 24-48 hours, so it is not appropriate test for this critical ill patient. -Fecal enzyme immune assay or real-time C. difficile PCR (with high sensitivity & specificity (90%). –Colonoscopy is not indicated in the index case due to the risk of perforation. 3-Who would manage this patient? -This critically ill patient with septic shock should be admitted under ICU with MDT (Intensivist, Nephrologist, Infectious disease specialist and Surgeon). -Counseling her family regarding critical condition of having high mortality. -Supportive therapy; Resuscitation & replenishment with intravenous fluids and electrolytes replacements. -Stop MMf and decrease CNI dose, may increase steroids dose to stress dose. -Close monitoring of graft function, liver function ,CBC ,venous blood gases and electrolytes. -In the treatment of C. difficile related toxic megacolon, aggressive medical therapy may help prevent surgical intervention in up to 50% of cases. -Adequate intracolonic concentrations of vancomycin may not be achieved with oral vancomycin because of poor intestinal motility. -Therefore, vancomycin enemas have been recommended; however enemas may fail to treat right-sided disease of the colon. -The dilated colon may be decompressed with nasogastric suction and frequent repositioning of the patient, some authors recommend prone positioning for 10 to 15 min every 2 to 3 h allowing the passage of flatus. -Management of toxic megacolon also includes with holding medications that slow intestinal motility. These medications include anticholinergics, antidepressants, antidiarrheals, and narcotics. -Surgical intervention may be necessary in up to 80% of patients with toxic megacolon due to C. difficile colitis. -Surgery indicated in such situations; perforation, progressive dilation of the colon, lack of clinical improvement over the first 48-72 h and uncontrolled bleeding. References; -Bagdasarian N., Rao K. and Malani P. Diagnosis and Treatment of Clostridium difficile in Adults: A Systemic Review. JAMA, 2015;313(4):398-408. -Valey A and Ferrada P. Role of Surgery in Clostridium difficile Infection. Clin. Colon Rectal Surgery, 2020;33(2):87-91. -Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130.
What is the differential diagnosis? The infectious diarrhea post-transplant with leucocytosis and sepsis usually caused by severe Clostridium difficile infection. The infectious diarrhea post-transplant with leucocytosis and sepsis after prolonged course of antibiotics in this post kidney transplant patient is also consistent with Pseudomembranous colitis caused by severe Clostridium difficile infection. The colonoscopy image shows raised elevated yellow-white nodules or plaques forming mucosal pseudomembranous that are characteristic of pseudomembranous colitis, commonly a manifestation of severe colonic disease that is usually associated with Clostridium difficile infection because of the prolonged use of broad-spectrum antibiotics. Any broad-spectrum antibiotics can cause pseudomembranous colitis – especially clindamycin and ampicillin.
Diarrhea because of pseudomembranous colitis occurs in about 3-10% of adults receiving antibiotics.
Pseudomembranous colitis can be life-threatening and possible complications include:
Toxic megacolon which is complicating the case in this scenario, as by CT image.
AKI, Sepsis, Dehydration and electrolytes disturbance from colonic perforation.
Immunosuppressive related diarrhea(MPA-colitis) Large-Bowel Obstruction
How would you confirm the diagnosis?
History: Details History of prolonged Ab Course,
Examination: Vital signs (Hypotension, Fever, Tachycardia, tachypneic, obtunded, and physical findings may be minimal due to high-dose steroids to r/o toxic megacolon
The most common criteria used to diagnose toxic megacolon are radiographic evidence of colonic dilatation, fever, tachycardia, neutrophilic leukocytosis, anemia, dehydration, altered mental status, electrolyte abnormality, or hypotension.
Peritoneal signs of perforation include rebound, rigidity, and irritation.
CBC, Lytes, ABGs, CRP,
Stool studies should include culture, O&P, and C difficile toxin testing.
C difficile is a clinical diagnosis with lab confirmation.
It is highly suspicious in the presence of severe diarrhea after antibiotic course complicated by toxic megacolon as per the findings.
A Positive Nucleic Acid Amplification Test For C. difficle Toxin Gene.
A Positive Stool Test for C. difficle.
Cell Culture Cytotoxicity Assay.
Selective Anaerobic Culture.
Toxin enzyme ELISA is specific, less sensitive as some can identify Toxin A only, inexpensive, easy, rapid.
PCR test Rapid, high sensitivity, simple, costly
Cytotoxicity cell assay is specific, sensitivity, time consuming and expensive.
Stool multiplex PCR
Stool culture is the most sensitive, for strain typing, expensive, does not determine if isolate is toxigenic, ≥ 48 hours for results. Histology: Toxic megacolon demonstrates acute inflammation, necrosis, and infiltration of inflammatory cells. Radiography; is essential for diagnosis and management of toxic megacolon, with air-fluid levels in the colon, deep mucosal ulcerations, air in the small bowel, segmental parietal thinning, and comparison with old baseline films.
Radiographic evidence of dilation of the colon, greater than 6 cm and fever, heart rate, neutrophilic leukocytosis, anemia, dehydration, altered sensorium, electrolyte disturbances, and hypotension are all signs of anemia.
CT scanning is useful for diagnosing toxic megacolon and is more accurate than plain radiography in detecting severe colitis.
It can show diffuse colonic wall thickening, accordion sign, multilayered appearance, and peri colic stranding. Colonoscopy is not indicated in our case due to the risk of perforation. Disease severity can be divided into 3 categories for treatment considerations:
Mild or moderate: diarrhea and abdominal cramping without systemic symptoms.
Severe: profuse diarrhea, abdominal pain, Leucocytosis and fever, or other systemic symptoms.
Severe disease with complications: life-threatening conditions such as paralytic ileus, toxic megacolon and multiorgan failure.
Who would manage this patient? NPO / NGT (bowel rest)
ABCD/ICU Support
Aggressive IV fluids, O2 to prevent AKI
Antibiotics should be given if an infectious cause is suspected.
Discontinue MMF or Myfortic
Hydrocortisone stress dose
Steroids should be given hydrocortisone 100 mg over 6 hours or methylprednisone 60 mg daily for 5 days. Tacrolimus level can be reduced, levels should be monitored during metronidazole treatment to avoid toxicity.
the treatment of severe forum of C difficle with toxic megacolon. Metronidazole 500mg IV TID and Oral vancomycin 125 mg to 500 mg QID (if tolerated) for 14 days or fidaxomicin 20 mg two times per day for 10 days.
Prevention and treatment of relapsing and refractory forms is difficult Fidaxomicin, ramoplanin and tigecycline are effective for the treatment of severe or recurrent disease.
IVIG 250-500mg/kg IV x1 human monoclonal antibodies against C. difficile toxins A and B
Fecal microbiota transplantation (FMT) in refractory cases but under trial.
Ciprofloxacin was just finished so no introduction of other antibiotics except those for C difficle
The treatment of MMF colitis includes a reduction or, in more severe forms, complete discontinuation of MPA.
Indications for surgical consultation in the management of C. DIFF Infection after stabilizing your patients:
Any one of the following: Hypotension with or without required use of vasopressors. Fever ≥38.5°C Ileus or significant abdominal distention Peritonitis or significant abdominal tenderness Mental status changes WBC ≥20,000 cells/mL Serum lactate levels >2.2 mmol/L Admission to intensive care unit for CDI End organ failure (mechanical ventilation, renal failure, etc.) Failure to improve after three to five days of maximal medical therapy. Reference;
Clostridioides difficile infection in adults: Treatment and prevention(UpToDate)
Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130
Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14. 351(9101):509-13. Marshak RH, Lester LJ. Megacolon a complication of ulcerative colitis. Gastroenterology. 1950 Dec. 16(4):768-72.
Ausch C, Madoff RD, Gnant M, Rosen HR, Garcia-Aguilar J, Hölbling N, Herbst F, Buxhofer V, Holzer B, Rothenberger DA, Schiessel R. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
Moulin V, Dellon P, Laurent O, Aubry S, Lubrano J, Delabrousse E. Toxic megacolon in patients with severe acute colitis: computed tomographic features. Clin Imaging. 2011 Nov-Dec. 35(6):431-6. Sarah E. Ward and Erik R. Dubberke, Clostridium difficile Infection in Solid Organ Transplant Patients, Antimicrobe/Transplant Infection
Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections [published correction appears in Am J Gastroenterol. 2022 Feb 1;117(2):358]. Am J Gastroenterol. 2021;116(6):1124-1147.
What is the differential diagnosis?This patient has severe colonic dilatation due to C difficiel infection
to detect C diff , will do PCR test to detect the organism, and it is highly sensitive while
This patient has Toxic megacolon with severe septic shock due to C difficile toxicity.
At the time of severe dilatation, better to avoid colonoscopy as it carries a high risk of perforation.
This patient first needs full resuscitation and decompression measure.
ALL IS should hold and continue will steroids only.
-Selective anaerobic culture highly sensitive and cannot distinguish toxin-producing strains from non-toxin-producing strains, a second test is required to detect toxin.
The pathologic appearance of toxic megacolon associated with other disorders is as follows: ●In toxic megacolon secondary to C. difficile (or, rarely, ischemia), the characteristic pathologic features include diffuse ulcerations, raised mucosal nodules, yellowish-white superficial plaques with normal intervening mucosa (typical “pseudomembrane” appearance), and extensive denudation .
Narrative
Recent Tx (Tac, MMF, Steroid) had UTI ttt with Abx presented with diarrhea, septic shock and AKI
DD:
A) Sepsis for DD most likely diarrhea related
infection diarrhea, C Diff, Norovirus, Cambylobacter, CMV, or other infectious agents.Non infectionous, think graft versus host reaction, IBD, drug relatedB) AKI for DD which is multifactorial
Sepsis: needs work up and tttHypovoelmic: needs correctionToxins: recent Abx (Cipro) if newly started think TIN as associate culprit. CNI in DD however in this case levels was appropriateObstruction: Needs to role out BOO after UTIParenchyma: Rejection needs to be aleays in DD given early tx and recent UTIIntra abdominal compartment syndromeConfirm diagnosis:
1- sepsis work up
Cutlures (blood, urine , stool) reported as negativeStool test for C-Diff antigens and toxinsCMV2- Discuss with gastroenterolgist for their input
3- CT scan that was done and would show if there is urinary obstruction
************
Management
ressucitation in ITU setting with fluids, inotrops, CRRTcorrect electrolytesttt C-Diff infection per local guidlines Oral Vanc and metronidazole and consider Fidaxomicin and discuss with micro teamdiscuss with gastro if scope will be helpfulToxic mega colon has developed unfurtnatly and patient has approached criria for colectomyIndications for operative management in patients with CDI
A diagnosis of CDI as determined by one of the following:
Positive laboratory assay for C.difficileColonoscopic findings consistent with C. difficile colitisCT scan findings consistent with C. difficile colitis (pancolitis with or without ascites)Plus any one of the following criteria:
PeritonitisColonic perforation or full-thickness ischemiaSepsisRespiratory failure requiring intubation and mechanical ventilationVasopressor requirement after resuscitationMental status changes attributable to C. difficile colitisClinical deterioration despite adequate medical managementAcute renal failure (or other worsening end-organ failure)Serum lactate level >5 mmol/LWhite blood cell count greater than or equal to 50,000 cells/mLAbdominal compartment syndrome or intra-abdominal hypertension
Reference :
Uptodate Toxic megacolon accessed 1 April 23
Who would manage this patient? MDT of transplant physician, general surgeon, intensivist, radiologist, microbiologist, gastroenterologist, nursing care
ICU admission
Intravenous fluid, monitor with IVC measurement/cvp, fluid status, not responding start inotropes keep MAP>65 mmhg
Npo and N.G tube insertion for decompression
Oral vancomycin/ iv metronidazole
Correction of electrolytes; magnesium, potassium, bicarbonate supplements to treat acidosis.
Reduction of immunosuppression, reduce MMF and tacrolimus
Renal function and infection monitoring
RRT for refractory electrolyte, fluid and acidosis.
DVT prophylaxis
Monitoring of abdominal colonic diameter by x ray/CT, to alert for perforation/impending perforation- needing surgical intervension
Reference
Moulin V, Dellon P, Laurent O, Aubry S, Lubrano J, Delabrousse E. Toxic megacolon in patients with severe acute colitis: computed tomographic features. Clin Imaging. 2011 Nov-Dec. 35(6):431-6.
Marshak RH, Lester LJ. Megacolon a complication of ulcerative colitis. Gastroenterology. 1950 Dec. 16(4):768-72.
Boutros M, Al-Shaibi M, Chan G, Cantarovich M, Rahme E, Paraskevas S, et al. Clostridium difficile colitis. Transplantation. 2012;93(10):1051–7
In this septic patient with shock, combined with leukocytosis and neutrophilia, history of antibiotic use, immunosuppression, MMF, and other medications, the first thing coming to mind is clostridium difficult rather than drug or viral infection. Empirical therapy as done, and searching for c.difficile tıxins (according to availability in the hospital: we have toxins A and B) should be done. Other factors can be taken in the differential diagnosis, like smv, etc. but the lab. Findings are not consistent (the differential CBC); combined etiologies can occur simultaneously
Thanks All This patient needs resuscitation to avoid AKI due to dehydration and electrolyte disturbance. Colonoscopy is not indicated in the index case due to the risk of perforation. We always look for C Def toxins rather than culture. Of course culture for other organisms as a part of the differential diagnosis.
What is the differential diagnosis?C. difficile must be distinguished from other infectious and noninfectious causes of diarrhea.
●Infectious diarrhea – Other organisms that have been implicated as causes of antibiotic-associated diarrhea include Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp
The clinical manifestations are similar to those of CDI; the diagnosis is distinguished by stool culture and/or stool multiplex nucleic acid testing.
●Noninfectious diarrhea –
Causes of noninfectious diarrhea that may mimic CDI include postinfectious irritable bowel syndrome, inflammatory bowel disease, celiac disease, and microscopic colitis.
Enteric infections account for about 10 percent of symptomatic relapses in patients with IBD; C. difficile accounts for about half of these infections
•Microscopic colitis – Microscopic colitis is a chronic inflammatory disease of the colon characterized by chronic watery diarrhea. The diagnosis is established by histopathology following colonoscopy with biopsy. •Celiac disease is a small bowel disease associated with dietary gluten exposure intolerance; gastrointestinal symptoms including chronic or recurrent diarrhea, malabsorption, weight loss, and abdominal distension or bloating. The diagnosis is established via serology and/or biopsy. How would you confirm the diagnosis?The diagnosis of C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation, particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age) Patients with suspected C. difficile infection should be placed on contact precautions preemptively pending diagnostic evaluation
A number of laboratory stool tests are available alone or in combination as part of a diagnostic algorithm: ●NAAT ●Enzyme immunoassay for C. difficile GDH ●Enzyme immunoassay for C. difficile toxins A and B ●Cell culture cytotoxicity assay ●Selective anaerobic culture
Who would manage this patient?
Admission ICU
SURGERY
CRRT
In the treatment of C. difficile related toxic megacolon, aggressive medical therapy may help prevent surgical intervention in up to 50% of cases
The medical management of toxic megacolon includes
oral vancomycin, IV metronidazole, bowel rest, bowel decompression, and replacement of fluids and electrolytes
adequate intracolonic concentrations of vancomycin may not be achieved with oral vancomycin because of poor intestinal motility. Therefore, vancomycin enemas have been recommended; however enemas may fail to treat right-sided disease of the colon.
Other alternatives include direct instillation of vancomycin by colonoscopy, colostomy or ileostomy
The dilated colon may be decompressed with nasogastric suction and frequent repositioning of the patient[
Some authors recommend prone positioning for 10 to 15 min every 2 to 3 h allowing the passage of flatus.
Management of toxic megacolon also includes with holding medications that slow intestinal motility. These medications include anticholinergics, antidepressants, antidiarrheals, and narcotics
Surgical intervention may be necessary in up to 80% of patients with toxic megacolon due to C. difficile colitis
Surgery should be considered if there is progressive colonic dilation or if clinical improvement is not noted within 2 to 3 d.
Indications for surgery include: perforation, progressive dilation of the colon, lack of clinical improvement over the first 48-72 h and uncontrolled bleeding
total colectomy resulted in a lower mortality rate (11%) compared to those with a left hemicolectomy (100%).
Patients with an ileus should be given rectal vancomycin as well – even though there is a lack of evidence-based studies to confirm its efficacy.
Substantiate your answerIMPRESSION SEPTIC SHOCK -AKI
NOT IMPROVED NEED SURGICAL INTERVENTIONAL
Most antibiotic-associated diarrhea is not attributable to CDI (but rather to osmotic mechanisms), whereas antibiotic-associated diarrhea associated with colitis is nearly always due to CDI.Acute abdomen – CDI may present as abdominal distension mimicking small bowel ileus, Ogilvie’s syndrome (colonic pseudo-obstruction), volvulus, or ischemia
●Shock – Severe hypotension may occur in the setting of fulminant CDI and/or in the setting of bowel perforation with peritonitis. In addition, CDI may develop during antibiotic treatment for septic shock caused by a separate bacterial infection. Shock due to other causes (such as septic shock or cardiogenic shock) must be distinguished from severe hypotension due to CDI via cardiac and hemodynamic assessment.
Excellent Hamada Yes, you have addressed the clinical condition very well including his fluid resuscitation, the electrolyte imbalance and the need for ICU treatment.
How to confirm diagnosis
The diagnosis is made based on clinical signs of systemic toxicity combined with radiographic evidence of colonic dilatation (diameter >6 cm) The most widely used criteria are
Radiographic evidence of colonic dilation (diameter >6 cm)
PLUS at least three of the following:
Fever >38ºC
Heart rate >120 beats/min
Neutrophilic leukocytosis >10,500/microL
Anemia
PLUS at least one of the following:
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension
For c diff diagnosis
Diagnosis
•
The diagnosis of CDI is established via a positive nucleic acid amplification test (NAAT) for C. difficile toxin gene or a positive stool test for C. difficile toxin(s).
Management
General Management where we have to do basic resuscitation
Specific Management is according to cause.
This patient if confirmed with C diff colitis , fulfills the criteria of Fulminant colitis
Management of fulminant colitis consists of antibiotic therapy, supportive care, and close monitoring; in addition, patients should be assessed for surgical indications.
Antibiotic therapy — The approach to antibiotic therapy depends on whether concomitant ileus is present. Absence of ileus — For treatment of patients with fulminant colitis but without ileus, we suggest oral (or per nasogastric tube) vancomycin (500 mg four times daily) plus parenteral metronidazole (500 mg every 8 hours)
In the setting of ileus, we suggest addition of FMT (administered via enema), rather than rectal vancomycin (Grade 2C). However, given risk of colonic perforation, this approach should be restricted to patients who are not responsive to standard antibiotic therapy and performed only by personnel with appropriate expertise.(up to date)
1. Clostridium difficile
2. Campylobacter sp
3. Bacterial over growth
4. Rota, adenovirus and CMV
5. Giardia and Cryptosporidium
6. CNI, MMF
7. IBD, PTLD
How would you confirm the diagnosis?
Could be confirmed by;
1. Hx of broad-spectrum antibiotics(cipro in this case) 2. Labs work like TLC, elevated Neutrophils and ESR 3. NAAT 4. Enzyme immunoassay for C difficile 5. Cell culture cytotoxicity assay 6. Selective anaerobic culture 7. Radiographic imaging(colonic dilatation of >7cm) 8. Endoscopy NOT warranted in this case
· Who would manage this patient?
· Explain the condition and usual prognosis of this patient to family and involvement of multidiscipline like GI and GI surgeon.
· Intensive care
· Stop offending agents like cipro
· Stop IS like MMF and CNIs
· Address metabolic derangements, patient would need RRT either CRRT/Prolong intermittent renal replacement therapy(PIRRT)
· Oral vancomycin 500mg QID, or may consider rectally
· May consider her for Bezlotoxumab or add fidaxomicin(lack evidence in such casese)
· References 1. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections [published correction appears in Am J Gastroenterol. 2022 Feb 1;117(2):358]. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278 2. Apisarnthanarak A, Razavi B, Mundy LM. Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature. Clin Infect Dis. 2002;35(6):690-696. doi:10.1086/342334 3. Nathanson DR, Sheahan M, Chao L, Wallack MK. Intracolonic use of vancomycin for treatment of clostridium difficile colitis in a patient with a diverted colon: report of a case. Dis Colon Rectum. 2001;44(12):1871-1872. doi:10.1007/BF02234471
The patient was admitted previously for UTI and was treated with ciprofloxacin.
Now she is admitted with toxic megacolon< evidenced by
Radiographic evidence of colonic dilation (diameter >6 cm)
PLUS at least three of the following:
Fever >38ºC
Heart rate >120 beats/min
Neutrophilic leukocytosis >10,500/microL
Anaemia
PLUS at least one of the following
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension
Differential diagnosis will be:
C. difficile pseudomembranous colitis
E.coli,
Salmonella, Shigella, Campylobacter, Yersinia
CMV colitis
Norovirus
I would confirm my diagnosis by investigations:
to rule out CD:Clostridium difficile PCR or enzyme immunoassay for C. difficile toxin A &B
To rule out CMV: CMV PCR.
Stool analysis (WBCs and cultures)
Stool for PCR, ova, and parasite evaluation, giardia, and cryptosporidium enzyme immunoassay.
Colonoscopy should be avoided in patients with toxic megacolon because the risk of colonic perforation.
This patient should be managed by MDT, surgical team, gastroenterologist, infectious disease, Transplant physician and intensivist
Require ICU admission due to Toxic megacolon and septic shock
Rapid correction of volume status: fluid resusctitaion 30mls/kg then start inotrope if BP persistently low
Correct electrolytes and acid-base disturbances
Require CKRT for metabolic acidosis and AKI
Continue vancomycin and metronidazole.
Stop MPA , reduce tacrolimus level to 5-6
IV hydrocortisone 100mg TDS
Close monitoring and low threshold for surgery
The surgical indications are:
Colonic perforation or full-thickness ischemia
Abdominal compartment syndrome
Cardiopulmonary deterioration with ongoing or escalating need for vasopressor support despite adequate fluid resuscitation.
Respiratory failure requiring intubation and mechanical ventilation.
Worsening end organ failure, most notably acute renal failure.
Clinical signs of peritonitis or worsening abdominal exam despite adequate medical treatment.
References
Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14. 351(9101):509-13.
Marshak RH, Lester LJ. Megacolon a complication of ulcerative colitis. Gastroenterology. 1950 Dec. 16(4):768-72.
Ausch C, Madoff RD, Gnant M, Rosen HR, Garcia-Aguilar J, Hölbling N, Herbst F, Buxhofer V, Holzer B, Rothenberger DA, Schiessel R. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
⭐ Differential diagnosis:
_infectious diarrhea (most probably here is clostridium difficile (old age, recent hx of 2 weeks treatment with ciprofloxacin )).
_otger infections as (viral infections as Norovirus, Rita and adenovirus, bacterial infections as salmonella and ECOLi, protozoa as cryptosporidium and giardia)
_non infectious as MMF induced or other drugs as (laxatives, PPI or anti arrhthmics).
⭐ to confirm the diagnosis:
_intital stool examination and culture for bacterial infection or ptozoa identification.
_identification of Cl difficile by ELISA or PCR for it’s toxin is more commonly used.
_CMV PCR.
⭐ Management:
_continue in supportive therapy (IV fluids resuscitation, fluid replacement and postive inotropes) .
_patient must be manged in ICU setting with MDT (intensivist, nephrologist, infectious disease specialist and surgeon).
_Gut decompression through NGT and NPO, plus rectal tube decompression.
_reduce IS (stop MMf and decrease CNI dose, may increase steroids dose to stress dose (to guard against adrenal crisis in such critical case and to prevent development of AR in the context of IS reduction)).
_care of critically ill patient (start IV PPI, close monitoring of vital signs and random glucose ).
_start treatment with oral vancomycin for 14 days (I think no role of IV metronidazole in such critically ill patient).
_close monitoring of graft function, liver function, CBC،venous blood gases and electrolytes is essential.
_surgical intervention is warranted if any evidence of perforation, severe cases with peritonitis) in which colonectomy and peritoneal toilet are indicated.
DD/Toxic megacolon Inflammatory Ulcerative colitis Crohn’s colitis Infectious Bacterial Clostridioides difficile pseudomembranous colitis Salmonella – typhoid and nontyphoid Shigella Campylobacter Yersinia Parasitic Entameba histolytica Cryptosporidium Viral CMV colitis Self-limited colitis (culture negative) A diagnosis of CDI as determined by one of the following Positive laboratory assay for C.difficile Colonoscopic findings consistent with C. difficile colitis (raised yellowish white 2-10 mm plaques overlying erythematous edematous mucosa ,psausomebrane 3.CT scan findings consistent with C. difficile colitis (pancolitis with or without ascites Patient is classified as fulminant disease /shock /ileus /megacolon Treatment of fulminant disease Absence of ileus: Enteric vancomycin plus parenteral metronidazole Vancomycin500 mg orally or via nasogastric tube 4 times daily, AND Metronidazole 500 mg intravenously every 8 hours If ileus is present, additional considerations include: FMT (administered rectally) OR Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)¶ Given potential risk of colonic perforation in setting of CDI, rectal vancomycin instillation should be performed by personnel with appropriate expertise. Consider operative management Indication of operative management Peritonitis Colonic perforation or full-thickness ischemia Sepsis Respiratory failure requiring intubation and mechanical ventilation Vasopressor requirement after resuscitation Mental status changes attributable to C. difficilecolitis Clinical deterioration despite adequate medical management Acute renal failure (or other worsening end-organ failure) Serum lactate level >5 mmol/L White blood cell count greater than or equal to 50,000 cells/mL Abdominal compartment syndrome or intra-abdominal hypertension
The criteria proposed for defining fulminant CDI are based on expert opinion 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 24:ciab549. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124. Hrebinko K, Zuckerbraun BS. Clostridium difficile: What the surgeon needs to know. Semin Colon Rectal Surg 2018; 29:28. Table used with the permission of Elsevier Inc. All rights reserved.
DD/Toxic megacolon Inflammatory Ulcerative colitis Crohn’s colitis Infectious Bacterial Clostridioides difficile pseudomembranous colitis Salmonella – typhoid and nontyphoid Shigella Campylobacter Yersinia Parasitic Entameba histolytica Cryptosporidium Viral CMV colitis Self-limited colitis (culture negative) A diagnosis of CDI as determined by one of the following Positive laboratory assay for C.difficile Colonoscopic findings consistent with C. difficile colitis (raised yellowish white 2-10 mm plaques overlying erythematous edematous mucosa ,psausomebrane 3.CT scan findings consistent with C. difficile colitis (pancolitis with or without ascites Patient is classified as fulminant disease /shock /ileus /megacolon Treatment of fulminant disease Absence of ileus: Enteric vancomycin plus parenteral metronidazole†: Vancomycin500 mg orally or via nasogastric tube 4 times daily, AND Metronidazole 500 mg intravenously every 8 hours If ileus is present, additional considerations include: FMT (administered rectally) OR Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)¶ Given potential risk of colonic perforation in setting of CDI, rectal vancomycin instillation should be performed by personnel with appropriate expertise. Consider operative management Indication of operative management Peritonitis Colonic perforation or full-thickness ischemia Sepsis Respiratory failure requiring intubation and mechanical ventilation Vasopressor requirement after resuscitation Mental status changes attributable to C. difficilecolitis Clinical deterioration despite adequate medical management Acute renal failure (or other worsening end-organ failure) Serum lactate level >5 mmol/L White blood cell count greater than or equal to 50,000 cells/mL Abdominal compartment syndrome or intra-abdominal hypertension
The criteria proposed for defining fulminant CDI are based on expert opinion 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 24:ciab549. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124. Hrebinko K, Zuckerbraun BS. Clostridium difficile: What the surgeon needs to know. Semin Colon Rectal Surg 2018; 29:28. Table used with the permission of Elsevier Inc. All rights reserved.
What is the differential diagnosis?–
this patient probably had features of C.difficile infections and risk factors for it could be;
Previous fluroquinolones treatment for UTI
Age >55
Immune suppressive therapy for transplant
-She is critically unwell, having septic shock, worsening toxic mega colon and pan colitis
-Allograft dysfunction with Metabolic derangement and not responding to initial treatment due to the toxic mega colon needing a surgical opnion.
-She also had poor prognostic features including raising WCC, with septic shock features.
Differential Diagnosis of diarrhea in posttransplant is wide and may include: A. Infection
What is the differential diagnosis?1.infectious colitis
bacterial : c.diificile, salmonella, compaylobacter, e coli
viral : CMV,rota virus, norovirus
parasitic : Giardia, entamoeba
fungal
2.immunosuppreesion related ,mostly MMF
3.denove or exacerbating existing IBD
4.GVHD
5.ischaemic colitis especially in those who have AF
How would you confirm the diagnosis?require work up for each category ,starting from the most likely diagnosis
in this case scenario…..clinical presentation with history of recent antibiotic usage .on the top of the list pseudomembranous colitis with toxic megacolon
diagnosis:
NAAT
EIA for toxin A & B
toxigenic culture (SN & SP around 95% but require 3-5 days0
Who would manage this patient?
first resuscitation and admission in ICU
stop previous AB
start iv metronidazole and oral vancomycin
toxic megacolon……as soon as general surgeon consultation discussing about requiring colectomy
note:
if radiological finding of toxic megacolon …..better to avoid colonoscopy as delaying the surgical intervention and risk of perforation and sepsis
Differential diagnosis This is a Toxic megacolon due to C.dificile infection. Other possibilities Infectious causes;
CMV colitis
E.coli infection.
Rotavirus.
Giardia.
Entameba.
Non-infectious causes
MMF can cause a de novo pathway of purine synthesis for growth and proliferation, and they’re vulnerable to MPA inhibition and diarrhea.
TAC is proposed due to macrolide structure which may stimulate intestinal motility.
Sirolimus, due to villous atrophy.
ATG causes diarrhea and resolves spontaneously.
Confirmation of the diagnosis
Fecal enzyme immunoassay.
Real-time PCR.
A cell-based cytotoxicity assay for C.dificile.
All the above tests are highly sensitive and specific.
Management of C.dificile infection.
C.dificile treatment includes; fidaxomicin, metronidazole (70% response), and vancomycin in severe cases.
Fidaxomicin, ramoplanin, and tigecycline are effective in treating severe or recurrent diseases.
The human monoclonal antibody has encouraging results against C.dificile toxins A and B.
Bowel rest and bowel decompression, help to remove gas and filling substances.
IV fluid and electrolytes correction.
Surgery if the condition does not improve after 2-3 days (total or subtotal colectomy).
References
Ekberg H, Kyllonen L, Madsen S, et al. Clinicians underestimate gastrointestinal symptoms and overestimate quality of life in renal transplant recipients: a multinational survey of nephrologists. Transplantation 2007; 84:1052–1054. The study describes the extent to which posttransplant diarrhea is often under-recognized by practitioners.
Bunnapradist S, Neri L, Wong W, et al. Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality. Am J Kidney Dis 2008; 51:478–486. The authors demonstrate the incidence and risk factors for diarrhea following kidney transplantation.
Rankin AC, Walsh SB, Summers SA, et al. Acute oxalate nephropathy causes late renal transplant dysfunction due to enteric hyperoxaluria. Am J Transplant 2008; 8:1755–1758.
Roos-Weil D, Ambert-Balay K, Lanternier F, et al. Impact of norovirus/sapovirus-related diarrhea in renal transplant recipients hospitalized for diarrhea. Transplantation 2011; 92:61–69. 5. Pant C, Deshpande A, Larson A, et al. Diarrhea in solid-organ transplant recipients: a review of the evidence. Curr Med Res Opin
Well done all. Clearly colonscopy is contraindicated because of the perforation risk although this patient did have colonscopy. Confirmation is by detection of C diff toxin as mentioned by most of you.
Were there any risk factors for this patient to develop C diff colitis?
What do you think the appropriate course of treatment here after she did receive both oral vancomycin and IV metronidazole, and the reasons behind your decision?
This post kidney transplant patient developed severe sepsis and septic shock imaging showed features of colitis and toxic megacolon he has history of UTI for which she completed 2 weeks course of ciprofloxacin the most likely diagnosis clostridium difficile pseudomembranous colitis complicated with toxic megacolon other differentials :
CMV colitis
Inflammatory bowel disease ulcerative colitis
Dysentery (bacillary, amoebic )
Ischemic colitis
– How would you confirm the diagnosis?
ELISA to detect C. difficile toxins. this test specificity is generally greater than 90%, but a disadvantage is a decreased sensitivity (70%-80%)
Gold standard test to detect C. difficile toxin is the cytotoxicity cell assay, but its use is limited because it is technically demanding and costly.
Real-time PCR detects toxigenic C. difficile in stool in a few hours with higher sensitivity than toxin ELISAs and cytotoxicity cell assays.
Stool culture, when properly performed, is the most sensitive method to detect C. difficile. but,stool culture is expensive and impractical ,time consuming may take >48 hours, in addition it does not differentiate toxigenic and nontoxigenic strains
C. difficile glutamate dehydrogenase (GDH) assay is inexpensive, rapid, and easy to perform. but it has poor specificity (~50%) and also does not differentiate between toxin producing and non-toxin producing strains of C. difficile.
– Who would manage this patient?
She is critically ill patient she needs:
ICU admission
Supportive treatment : Ventilatory support if needed hemodynamic stabilization ,and antipyretic
Early surgical assessment
Antibiotics treatment :
The offending antibiotic is already discontinued
Oral vancomycin is the only FDA-approved treatment of C. difficile, but mitronidazole has considerable historical use.
In such severe cases the efficacy of oral vancomycin might be limited by ileus so higher doses of oral vancomycin may be indicated .
If the patient is intolerant to oral therapy intracolonic administration of vancomycin can be used.in addition intravenous metronidazole .
Surgical intervention :May be needed in such severe cases , up to 20% of cases of fulminant infection require surgery, but mortality remains high at 35% to 80%.
Reference: 1. J. Clin. Med. 2022, 11, 4365. https://doi.org/10.3390/jcm11154365 2. Ann Intern Med. 2009 Aug 4;151(3):176-9. doi: 10.7326/0003-4819-151-3-200908040-00005. 3. Identification of a pseudo-outbreak of Clostridium difficile infection (CDI) and the effect of repeated testing, sensitivity, and specificity on perceived prevalence of CDI. Infect Control Hosp Epidemiol. 2009; (30):1166–1171. 4. Louie T, Gerson M, Grimard D, et al. Results of a phase III trial comparing tolevamar, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhea (CDAD). In: Proceedings of the 47th Annual ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy. 2007. Chicago 5. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comprison of vancomycin and metronidazole for the treatment of Clostridium-difficile associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007; 45(3): 302-7.
This patient receive ciprofloxacin for UTI infection in first post transplant month, so the most probable cause of diarrhea is C. difficile infection(opportunistic infection can occur in first month post transplantation, & the most common cause is antibiotic use especially fluoroquinolone).
Confirm diagnosis of C. difficile:
The gold standard test for C. difficile diagnosis are toxin culture & cell-cytotoxicity but it takes 24-48 hours, so it is not appropriate test for this critical ill patient.
Fecal enzyme immunoassay, RT-PCR, & NAAT are easier, less expensive & rapid test for C. difficile infection diagnosis with high sensitivity & specificity(90%).
Management:
This patient had fulminant pseudomembranous colitis with megacolon & sepsis.
Fidaxomicin 200mg twice daily for 10days is effective for severe disease treatment with same efficacy to vancomycin & lower risk of relapse.
Fulminant disease can be treated with oral vancomycin & IV metronidazole.
Tigecycline 50mg iv twice a day used for refractory cases.
Urgent surgical consultation is mandatory because surgical treatment is essential for fulminant C. difficile colitis(hypotension or shock, ileum or megacolon). Surgery in critical ill patient may be too late & associated with high mortality.
References:
Bagdasarian N., Rao K. and Malani P. Diagnosis and Treatment of Clostridium difficile in Adults: A Systemic Review. JAMA, 2015;313(4):398-408.
Shin H. and Chandrraker A. Causes and management of post renal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Current. Open Nephrol Hypertensive, 2017.
UpTodate
Valey A and Ferrada P. Role of Surgery in Clostridium difficile Infection. Clin. Colon Rectal Surgery, 2020;33(2):87-91.
What is the differential diagnosis?
The most likely diagnosis in this case scenario is infectious post transplant diarrhea due to leucocytosis and sepsis caused by severe Clostridium difficile infection complicated by toxic megacolon secondary to immunosuppression and receiving antimicrobial therapy for recent UTI episode
DD
Bacteria :Clostridium difficile ,Salmonella,Campylobacter ,Ecoli
Viral ;CMV,HSV,Norovirus ,sapovirus
Parasitic ; Giardia ,Entameba ,Cryptosporidium
Ischemic colitis
Immunosuppressive related diarrhea How would you confirm the diagnosis?
C difficile is a clinical diagnosis with lab confirmation.
It is highly suspicious in the presence of severe diarrhea after antibiotic course complicated by toxic megacolon as per the findings .
· Toxin enzyme ELISA is specific, less sensitive as some can identify Toxin A only ,inexpensive, easy , rapid.
· PCR test Rapid, high sensitivity, simple ,costy
· Cytotoxicity cell assay is specific, sensitivity, time consuming and expensive
· Stool multiplex PCR
· Stool culture is the most sensitive, for strain typing ,expensive, does not determine if isolate is toxigenic, ≥ 48 hours for results
Who would manage this patient?
The patient resuscitation need to be continued with replacement of electrolyte deficiencies that can worsen the condition
As for the treatment of the severe forum of Cdifficle with toxic megacolon
-Metronidazole 500mg IV TID and Oral vancomycin 125 mg to 500 mg qid (if tolerated) for 10–14 days or fidaxomicin 20 mg two times per day for 10 days
Prevention and treatment of relapsing and refractory forms is difficult
Fidaxomicin, ramoplanin and tigecycline are effective for the treatment of severe
or recurrent disease .
-Surgical consultation
-IVIG 250-500mg/kg IV x1
human monoclonal antibodies against C. difficile toxins A and B
fecal microbiota transplantation (FMT) in refractory cases but under trial.
Myfortic should be suspended
Tacrolimus level can be reduced , levels should be monitored during metronidazole treatment in order to avoid toxicity
Ciprofloxacin was just finished so no introduction of other antibiotics except those for C difficle
Substantiate your answer!
-Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130
-Shin SH et al.Causes and management of post renal transplant diarrhea:an underappreciated cause of transplant associated morbidity. Curr Opin Nephrol Hypertens 2017 26(6) 484 -493
-Pant C etal.Diarrhea in solid organ transplant recipients :a review of the evidence. Curr Med Res Opin 2013 ,29(10) :1315-1328.
– Gunderson CC, Gupta MR, Lopez F, Lombard GA, LaPlace SG, Taylor DE, Dhillon GS, Valentine VG. Clostridium difficile colitis in lung tranplantation.Transpl Infect Dis. 2008; 10(4):245-51.
Differential diagnosis of post-transplant diarrhea in the above patient are broad:
It can be infectious and non-infectious –In infectious causes- bacterial(C. difficile, Campylobacter ssp, salmonella species, ) , viruses(Rotavirus, adenovirus,CMV),parasites( Giardia, cryptosporidium, isosopora Cyclospora, Microsporidium )should be considered.In non-infectious causes-drugs like MPA, tacrolimus, cyclosporin, sirolimus, antibiotics, PPI).Likely diagnosis in the above is Toxic megacoln with fulminant colitis secondary to C. difficile infection as patient has history of recent antibiotic use, severe metabolic acidosis with septic shock requiring vasopressors ,CT abdomen showing dilated transverse colon and colonoscopy revealing edematous mucosa with yellowish plaques. DIAGNOSIS: Diagnosis is made on the basis of clinical features and colonic dilation (diameter >6 cm) on CT scan Abdomen.Stool analysis for C. Difficile toxin either by Fecal enzyme immunoassays , Real-time PCR test or Cytotoxicity assay .CT scan Abdomen more better than X-ray Abdomen. Colonoscopy is recommended in the above due to high chances of perforation and rarely helpful in diagnosis. TREATMENT:
Patient should be admitted –Gastroenterologist and Surgical specialist should be taken into loop and immediately supportive measures i.e., I/V Fluids, acid base disturbances and electrolytes(hypokalemia and hypomagnesemia correction and broad spectrum antibiotics along with metronidazole(first episode and mild cases in a dose of 500 TDS for 10-14 days or oral vancomycin, fidaxomicin for severe cases. Antimetabolite i.e., MMF and oral steroids should be stopped and I/V hydrocortisone to be started and Tac level to be maintained around 6-7ng/ml.Patient also need dialysis support . Fecal microbiota transplantation in resistant cases. Surgery in the form of total colectomy with ileostomy needed REFERENCES: Angarone M, Snydman DR; AST ID Community of Practice. Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13550
*The systemic toxicity and radiological findings suggestive for Fulminant colitis;Toxic megacolon secondary to C. difficile- related pseudomembranous colitis.
*The single most important risk factor for the development of CDI is recent antibiotic use(patient was on ciprofloxacin). Others include being immunocompromised and age >55.
*It is a life-threatening complication of inflammatory or infectious colitis that is characterized by total or segmental nonobstructive colonic dilatation plus systemic toxicity.
*Toxic megacolon should be suspected in patients with abdominal distension and diarrhea. The diagnosis is made based on: – clinical signs of systemic toxicity – combined with radiographic evidence of colonic dilatation (diameter >6 cm). The most widely used criteria are : -Radiographic evidence of colonic dilation (diameter >6 cm) -PLUS at least three of the following: •Fever >38ºC •Heart rate >120 beats/min •Neutrophilic leukocytosis >10,500/microL •Anemia -PLUS at least one of the following: •Dehydration •Altered sensorium •Electrolyte disturbances •Hypotension
Differential diagnosis:
Toxic megacolon can occur with many infectious or inflammatory etiologies *Infectious colitis: Bacterial C. difficile pseudomembranous colitis, E.Coli, Salmonella, Shigella, Campylobacter, Yersinia Viral: CMV colitis (tissue invasive) Parasitic: Entameba histolytica, Cryptosporidium
*Ischemic colitis complicated with infection.
* Post-transplant IBD. Confirm the diagnosis:
– Clostridium difficile PCR or enzyme immunoassay for C. difficile toxin A &B
– CMV PCR.
– Stoll analysis (WBCs and culturs).
– Stool multiplex PCR, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay. -Colonoscopy should generally be avoided in patients with toxic megacolon because the risk of colonic perforation. Management: This patient should be co-managed by transplant nephrologist, surgical team, gastroenterologist, infectious disease with ICU team. Medical management: – ICU admission for cardiac and respiratory support. – Correct volume status; fluid and inotropes. – Correct electrolytes and acid-base disturbances. – May need CRRT. – Should be kept NOP and start parenteral nutrition. – Stop Ciprofloxacin. – Broad spectrum antibiotic; meropenem ( liaise with ID team). – Continue on vancomycin and metronidazole. – Fidaxomcin – Stop myfortic, reduce tacrolimus level to 5-6 – IV hydrocortisone.
– If CMV highly suspected start ganciclovir.
*Monitor patient response: clinical , radiologically and assess the response if deteriorated or no response with days of therapy, might consider discussing surgical treatment.
*CDI is predominantly treated medically. Only 1 % of all patients with CDI and 30 % with severe disease will require emergency surgery.
* The overall mortality from severe C. difficile colitis/toxic megacolon was 64 to 67%, and 71 to 100 % for surgically treated patients.
*Patient has poor prognostic signs includes: septic shock, significant metabolic derangement, graft dysfunction, poor response to medical therapy with disease progression.
The surgical indications includes:
-Colonic perforation or full-thickness ischemia
-Abdominal compartment syndrome
-Cardiopulmonary deterioration with ongoing or escalating need for vasopressor support despite adequate fluid resuscitation.
-Respiratory failure requiring intubation and mechanical ventilation.
-Worsening end organ failure, most notably acute renal failure.
-Clinical signs of peritonitis or worsening abdominal exam despite adequate medical treatment.
Surgical options and the timing of the surgery (discussed with the surgical team)
-Early surgical consultation as well as timely and decisive operative management as the timing of surgical intervention is the key for survival of patients with severe or fulminant C. difficile colitis.
-Options: Total abdominal colectomy, diverting loop ileostomy/colonic lavage is an alternative
-hin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
What is the differential diagnosis?
o Axial CT abdomen showed dilated transverse colon and colonoscopy revealed pseudomembraneous colitis (edematous mucosa with yellowish plaques). This diagnosis is C. difficile associated toxic megacolon
o The incidence of C. difficile infection (CDI) in transplanted patients is approximately 3.5–4.5%
o The mortality rate of toxic megacolon secondary to C. difficile colitis varies from 38-80%
o The single most important risk factor for the development of CDI is recent antibiotic use (recent fluoroquinolones for UTI are associated with the highest risk).
Other differential diagnoses include:
1. Inflammatory bowel disease
2. Ischemic colitis
3. Infectious colitis (CMV is the commonest)
4. Malignancy
How would you confirm the diagnosis?1. Fecal enzyme immunoassays
2. Real-time PCR test
3. Cytotoxicity assay for C. difficile on stool: The gold standard for C. difficile detection
Endoscopy is rarely used to confirm the diagnosis of C. difficile related toxic megacolon (the diagnosis can be made by a combination of immunotoxin assay, clinical findings and imaging). An endoscopy may be dangerous, especially in a setting of fulminant colitis due to the increased risk of perforation
Diagnostic criteria for toxic megacolon:
Colonic dilation (CT) PLUS 3 of the following 4 criteria (Jalan et al): fever > 101.5 F, HR > 120 beats/min, WBC > 10 500/mm, and anemia with hemoglobin or hematocrit level less than 60% of normal PLUS any one of the following four clinical findings: dehydration, electrolyte disturbance, hypotension or changes in mental status
Endoscopy is recommended for the diagnosis of C. difficile toxic colitis in:
1. When there is a high level of clinical suspicion for C. difficile despite repeated negative laboratory assays
2. When a prompt diagnosis is needed before laboratory results can be obtained
3. When C. difficile infection fails to respond to antibiotic therapy
4. For atypical presentations of C. difficile colitis (patients who present with ileus, acute abdomen, or leukocytosis without diarrhea)
Who would manage this patient?o Aggressive medical therapy (prevent surgical intervention in up to 50% of cases)
o Stop ciprofloxacin
o Oral vancomycin (vancomycin enemas are better but may fail to treat right-sided disease of the colon/ intracolonic perfusion of vancomycin), IV metronidazole, bowel rest, bowel decompression, and replacement of fluids and electrolytes
o Decompression of the dilated colon with nasogastric suction and frequent repositioning of the patient (prone positioning for 10 to 15 min every 2 to 3 h allowing the passage of flatus)
o Colonic decompression with a colonoscopy
o Holding medications that slow intestinal motility (anticholinergics, antidepressants, antidiarrheals, and narcotics)
Surgical intervention (may be indicated in up to 80% of patients). Indications include:
1. Perforation
2. Progressive dilation of the colon
3. Lack of clinical improvement over the first 48-72 h and uncontrolled bleeding
The surgical procedure of choice is total colectomy with preservation of rectum and diverting ileostomy
References
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
What is the differential diagnosis?
The clinical scenario of this patient is highly suggestive of severe C.difficile infection causing colitis and toxic megacolon as appeared on the colonoscopy(haemorrhagic colitis) and CT abdomen( dilatation of the transverse colon). This severe form of infection is complicated with severe metabolic acidosis, septic shock and DIC.
The differential diagnosis is as follows:
a) Clostridium difficile infection.
b) CMV- Tissue invasive disease.
c) Infection with enterotoxin-producing E.Coli
d) Ischemic colitis complicated with infection.
e) Inflammatory bowel disease(IBD).
How would you confirm the diagnosis? To confirm diagnosis of C.difficile(1):
1. The gold standard for C. difficile detection is the cell-based cytotoxicity assay.
2. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR)(2). Fecal enzyme immunoassays or real-time PCR test are mostly used by many laboratories.
Who would manage this patient?
1. In general, initial treatment of C.difficile infection in this patient include:
a) Supportive measure and adequate hydration to maintain BP and MAP within perfusion capability as well as correction of acid base disorder and managing DIC state.
b) fidaxomicin, metronidazole or vancomycin, with vancomycin preferred for cases of more severe infection(1):
a. First episode: metronidazole 500mg three times per day for 10–14 days.
b. Severe disease: vancomycin oral four times per day for 10–14 days fidaxomicin 20 mg two times per day for 10 days.
c. First relapse: same for first episode.
d. Second relapse: vancomycin taper with pulse.
e. third relapse: consider fecal microbiota transplantation, prolonged oral vancomycin.
2. In this case; early surgical consultation and intervention is crucial. Colectomy is likely considered to control sepsis and to save the patient.
3. Tacrolimus levels should be closely monitored and to be targeted at 5-7 ng/ml.
4. Reducing myfortic dosage to 360/360.
References 1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048. 2. Amin K, Choksi V, Farouk SS, Sparks MA. Diarrhea in a Patient With Combined Kidney-Pancreas Transplant. Am J Kidney Dis. 2021 Aug;78(2):A13-A16. doi: 10.1053/j.ajkd.2021.01.023. PMID: 34303438.
Obviously, this patient has infectious diarrhoea considering her signs and symptoms. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common.
Diagnosis: Identification of a specific pathogen or cause for the diarrhea allows for focused treatment and monitoring for improvement.
· Stool testing for a microbial pathogen. As per American Society of Transplantation Infectious Diseases recommendation:
· Initial testing for SOT recipients with diarrhea should include testing for C difficile and bacterial pathogens in the stool and CMV PCR testing in the serum. In addition, all patients with diarrhea should have their medications reviewed for potential causes of diarrhea and unnecessary agents should be stopped (strong, moderate)
· Persistent diarrhea should prompt testing for norovirus and parasitic causes for diarrhea
· Colonoscopy with or without biopsy should be performed on SOT recipients with chronic diarrhea that have had a negative infectious evaluation or for those not responding to targeted therapy
· If available, multiplex PCR testing for stool pathogens should be performed on all SOT recipients presenting with diarrhea
For management: As per American Society of Transplantation Infectious Diseases recommendation:
· Empiric antimotility therapy should be considered in SOT recipients with diarrhea that is negative for C difficile and where there is no evidence of megacolon or inflammatory diarrhea
· SOT recipients with diarrhea and mild to moderate dehydration should be given reduced osmolarity rehydration fluids.
· Isotonic intravenous fluids should be administered for those with severe dehydration, shock, altered mental status, or ileus
· Antimicrobial therapy should be modified to target any identified pathogen suspected to be the cause of the diarrhea
Angarone M, Snydman DR, AST ID Community of Practice. Diagnosis and management of diarrhea in solid‐organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation. 2019 Sep;33(9):e13550.
CDI is diagnosed by confirming the presence of toxigenic C. difficile or one of its toxins in the stool .
The laboratory gold standard for C. difficile toxin detection is the cytotoxicity cell assay,however its use is also limited due to the cost and the delay of at least 24h before interpretation.
ELISAs for C. difficile toxin detection,these assays have a rapid turnaround and are relatively inexpensive. ELISAs are generally only 60–90% sensitive compared with cytotoxicity assays, but newer assays continue to improve detection rates.
Currently, commercially available PCR-based assays are several times more expensive than toxin ELISAs and require specialized equipment.
Who would manage this patient?
Oral metronidazole and oral vancomycin are the accepted first line antimicrobial agents for treatment of CDI in both immunocompetent and SOT recipients. Only oral vancomycin is FDA approved treatment for C. difficile.
Higher doses of oral vancomycin may be warranted in an attempt to increase the probability that adequate levels of vancomycin will be achieved in the colon as quickly as possible. Several case reports also support the use of vancomycin administered by enema in cases of ileus.
Antimicrobial therapy alone may be insufficient treatment in patients with severe CDI and surgical intervention may be a necessary addition. Less than 3% of immuncompetent patients with CDI develop fulminant pseudomembranous colitis that requires colectomy.
Intravenous immunoglobulin (IVIG) has been attempted with variable success in the treatment of CDI. IVIG is known to contain C. difficile antitoxin antibodies; but its use is supported only by case studies and series.
This a case of toxic megacolon due to Pseudomembranous Colitis
Other differentials include :
Inflammatory Causes
Ulcerative colitis
Crohn disease
Infectious Causes
Clostridium difficile
Salmonella
Shigella
Campylobacter colitis
Enterohemorrhagic or enteroaggregative Escherichia coli O157
Cytomegalovirus
Entamoeba
Ischemic Colitis
How would you confirm the diagnosis?
The diagnostic basis is the patient’s systemic symptoms and greater than 6 cm dilation of the colon seen on radiographic images.
Below are the most commonly used diagnostic criteria for toxic megacolon (by Jalan et al.)
Radiographic evidence of the dilation of the colon greater than 6 cm AND:
At least three of the following:
Fever over 38 degrees C
Heart rate greater than 120 beats/min
Neutrophilic leukocytosis exceeding 10500/micro/L
Anemia
At least one of the following:
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension
Colonoscopy to be avoided due to high perforation risk
Who would manage this patient?
Initial treatment involves supportive therapy and resuscitation . Patients should be admitted to the intensive care unit.
Checking complete blood count, abdominal films, and electrolytes should take place
All the medications which can aggravate the megacolon, such as opioids, anticholinergics, etc., should be stopped.
Patients should be started on IV fluids to provide adequate hydration
The most commonly used antibiotics are metronidazole or vancomycin.
If cytomegalovirus is the suspected cause, then gancyclovir should be given. Antibiotics of choice for C. difficile are oral vancomycin or oral fidaxomicin. If those are not available, oral metronidazole is an alternative.
Surgical Treatment
Urgent Surical Consult required. The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
Substantiate your answer!
Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015 Jan 27;313(4):398-408.
Vardakas KZ, Polyzos KA, Patouni K, Rafailidis PI, Samonis G, Falagas ME. Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence. Int J Antimicrob Agents. 2012 Jul;40(1):1-8.
The most likely diagnosis for this patient is severe Clostridium Difficile pseudomembranous colitis – she has the risk factor of fluoroquinolone use. She has now developed fulminant colitis as evidenced by: Hypotension requiring pressors, severe metabolic acidosis, marked leucocytosis, toxic megacolon
The other differential diagnosis includes:
Salmonella typhi
Campylobacter jejunii infection
Enterotoxigenic E.coli
Bacterial overgrowth syndrome
Novo virus
Rota virus
Adenovirus
CMV colitis – less likely as it was a recent transplant
Giardiasis
Cryptosporiodosis
Microsporidiosis
Non-infectious causes – myfortic induced diarrhea
Diagnosis
The diagnosis is confirmed by:
Clostridium difficile stool antigen test – This can give false negatives depending on the assay used
Enzyme immunoassay for C.difficile GDH
Selective anaerobic culture – rarely employed as it takes several days to get a result
Stool biofire panel – Has a higher sensitivity in detecting C.difficile
Adjunctive diagnostic tests can be used:
Colonoscopy – normally not required to make a diagnosis. Used if the stool tests are negative and there is a high index of suspicion in a symptomatic patient – Patient will have bowel wall edema, erythema, friability and inflammation. There will also be pseudomembranes on the inflammed mucosal surface – pseudomembranous colitis which can be missed on the stool tests
Management:
This patient has fulminant severe Clostridium difficile colitis with a toxic megacolon and electrolyte imbalance with graft dysfunction
The patient will require surgery – urgent surgical consult
Keep the patient NPO
Aggressive fluid rehydration with strict fluid input-output monitoring
Correct the electrolytes – hypokalemia and hypomagnesemia
Due to the severe metabolic acidosis and graft dysfunction – may require dialysis
Continue with the IV metronidazole
May require fecal microbiota transplant if the fidaxomicin does not work
Stop the tacrolimus, myfortic and prednisolone – as the patient is going to be NPO
IV hydrocortisone 100 mg eight hourly
Shin Ho et al. Curr Opin Nephrol Hypertens 2017, 26:000–000
To confirm the diagnosis of c.def colitis: -A positive nucleic acid amplification test (NAAT) for C. difficile toxin gene -a positive stool test for C. difficile toxins. –Cell culture cytotoxicity assay.
-Selective anaerobic culture.
Colonoscopy is absolutely contraindicated to avoid colonic perforation.
To confirm C. difficile colitis: fecal enzyme immunoassays or real-time PCR test
The risk of perforation is high and colonoscopy is contraindicated here
Diagnosis should be confirmed with a positive stool test for toxigenic C. difficile or its toxins.
colonoscopy should be avoided esp. with the presence of dilated colon like this patient for fear of perforation.
Nucleic acid amplification test (NAAT) for C.difficle – sensitive and specific in detecting toxins, rapid false negative results can occur in patients receiving empirical antibiotics, or with delayed collection.
EIA for C. difficile toxins A and B: highly sensitive result within an hour, highly specific 99%, with variable sensitivity.
If you have this CT image with the abovementioned history, would you go for a colonoscopy?
Colonoscopy is dangerous in such a case with high risk of perforation, decompression measures should be done and keeping patienT NPO.
1. Fecal enzyme immunoassays
2. Real-time PCR test
3. Cytotoxicity assay for C. difficile on stool: The gold standard for C. difficile detection
Endoscopy is rarely used to confirm the diagnosis of C. difficile related toxic megacolon (the diagnosis can be made by a combination of immunotoxin assay, clinical findings and imaging). An endoscopy may be dangerous, especially in a setting of fulminant colitis due to the increased risk of perforation
Diagnostic criteria for toxic megacolon:
Colonic dilation (CT) PLUS 3 of the following 4 criteria (Jalan et al): fever > 101.5 F, HR > 120 beats/min, WBC > 10 500/mm, and anemia with hemoglobin or hematocrit level less than 60% of normal PLUS any one of the following four clinical findings: dehydration, electrolyte disturbance, hypotension or changes in mental status
Endoscopy is recommended for the diagnosis of C. difficile toxic colitis in:
1. When there is a high level of clinical suspicion for C. difficile despite repeated negative laboratory assays
2. When a prompt diagnosis is needed before laboratory results can be obtained
3. When C. difficile infection fails to respond to antibiotic therapy
4. For atypical presentations of C. difficile colitis (patients who present with ileus, acute abdomen, or leukocytosis without diarrhea)
References
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
if you have this CT image with the abovementioned history, would you go for a colonoscopy?
No, I wouldn’t go for colonoscopy because it is an invasive intervention and may precipitate colonic perforation in such friable colon.
References 1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
colonscopy will end up with perforation and better to avoid . This is toxic megacolon(TM) in a very sick patient in septic shock due to sever acute coltitis likley pseudomembrnous coltitis ,not responding to medical therapy .Computed tomography( CT) is useful in distinguishing patients with TM from patients with SAC but no TM as a complication. The association of air-filled colonic distension >6 cm, abnormal haustral pattern and segmental colonic parietal thinning seems pathognomonic of TM and should lead to rapid surgery(1). TM couild be localized or diffuse complication of ischaemic or infectious inflammation like pseudomembranous colitis. This patient need urgent surgical intervention with total colectomy and ileostomy ,parentral nutrition ,supportive CRRT with electrolytes correction and broad sepctrum AB with stress dose of steriod only , stop all immunsuppressive therapy toxic megacolon very serious complication and is life threatening infection with high mortality rate. Reference 1.Moulin V, Dellon P, Laurent O, Aubry S, Lubrano J, Delabrousse E. Toxic megacolon in patients with severe acute colitis: computed tomographic features. Clin Imaging. 2011 Nov-Dec;35(6):431-6. doi: 10.1016/j.clinimag.2011.01.012. PMID: 22040786.
2.Ruf G. Toxisches Megakolon–Chirurgische Sicht [Toxic megacolon–surgical point of view]. Praxis (Bern 1994). 2006 Nov 1;95(44):1727-30. German. doi: 10.1024/1661-8157.95.44.1727. PMID: 17111883.
Laboratory diagnosis of CDI requires demonstration ofC. difficiletoxin(s) or detection oforganism(s):
-PCR are highly sensitive; greater than EIA and comparable with cytotoxicity assay, cant differentiate asymptomatic carriers from disease state.
-Enzyme immunoassay EIA forC. difficileGDH: cannot distinguish between toxigenic and nontoxigenic strains
-Enzyme immunoassay EIA forC. difficiletoxins A and B
-Cell culture cytotoxicity assay the gold standard test for diagnosis.
-Selective anaerobic culturehighly sensitive, cannot distinguish toxin-producing strains from non-toxin-producing strains , second test is required to detect toxin
Endoscopy generally is not required routinely when typical signs and laboratory tests and patient is at high risk of perforation. References: – Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085. PMID: 29462280; PMCID: PMC6018983.
-stool toxigenic bacterial culture ,NAT, cell culture cytotoxicity neutralising test , toxin assay ,multiple tests can be done together to confirm
-Shetler et al demonstrated that colonoscopic decompression and intracolonic vancomycin administration in the management of severe, toxic megacolon is feasible, safe, and effective in approximately 57-71% of these cases. Reference
Shetler K etal . Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.Surgical Endoscopy 2001 July
👉 confirm diagnosis by Cl difficile toxin identification by ELISA or detection of gene responsible for toxin by PCR.
👉 Colonscopy is better avoided in case of toxic megacolon for fear of perforation.
I wouldn’t go for colonoscoy; this is a critically ill or actually dying patient , her diagnosis is very obvious and it is clear that she had a very poor prognosis. It would be irrational to subject her to invasive investigation with high risk of complications and a little or no gain. The unfortunate story is that , she may even be too late for surgery, which is by far more important for her than any colosocopy
Cell-based cytotoxicity detects C. difficile.
Clostridium difficile detection by a polymerase chain reaction.
It is very risky to proceed with a colonoscopy with this fragile colon.
The diagnosis of C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation, particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age) [1]. Patients with suspected C. difficile infection should be placed on contact precautions preemptively pending diagnostic evaluation
A number of laboratory stool tests are available alone or in combination as part of a diagnostic algorithm: ●NAAT ●Enzyme immunoassay for C. difficile GDH ●Enzyme immunoassay for C. difficile toxins A and B ●Cell culture cytotoxicity assay ●Selective anaerobic culture
Endoscopy is seldom used to confirm the diagnosis of C. difficile related toxic megacolon since the diagnosis can be made by a combination of immunotoxin assay, clinical findings and imaging. An endoscopy may be dangerous, especially in a setting of fulminant colitis due to the increased risk of perforation.
A study by Johal et al however encouraged the use of flexible sigmoidoscopy as a tool for the diagnosis of C. difficile toxic colitis when stool assays are negative. In their study 52% of patients who tested negative for C. difficile toxin assay had pseudomembranous colitis on flexible sigmoidoscopy.
Endoscopy is recommended for the diagnosis of C. difficile toxic colitis under the following conditions:
(1) when there is a high level of clinical suspicion for C. difficile despite repeated negative laboratory assays;
(2) when a prompt diagnosis is needed before laboratory results can be obtained;
(3) when C. difficile infection fails to respond to antibiotic therapy or
(4) for atypical presentations of C. difficile colitis such as in patients who present with ileus, acute abdomen, or leukocytosis without diarrhea
Confirm diagnosis by Cl difficile toxin identification by ELISA or detection of gene responsible for toxin by PCR
Colonscopy is better avoided in case of toxic megacolon for fear of perforation.
Q1: Stool examination for C.difficile toxins by ELIZA/EIA or PCR.
Q2: Colonoscopy is contraindicated in toxic megacolon due to the risk of perforation.
This is a case of pseudomembranous colitis complicated by toxic megacolon and DIC
Other less likely causes includes bacterial gastroenteritis and CMV colitis
How would you confirm the diagnosis?
Pseudomembranous colitis is diagnosed by the presence of abdominal pain, severe diarrhea after taking broad spectrum antibiotics, which can be treated by metronidazole and if no improvement an oral vancomycin should be tried.
Toxic megacolon is an emergency life threatening condition occurring as a result of infections or inflammatory colitis. The most common causes of toxic megacolon includes IBD and CD colitis
Toxic megacolon is characterized by by non obstructive, segmental, colonic dilatation (megacolon) together with systemic septicemia (toxic) (1, 2)
Clinically it presents with
Severe diarrhea (most commonly bloody)
Severe abdominal distention
Diffuse colonic tenderness
Fever, may be signs of septicemia such as tachycardia, hypotension and organ hypoperfusion (AKI, DLC)
Diagnosis of toxic megacolon
Risk factors of toxic megacolon such as previous intake of broad spectrum antibiotics
Clinical manifestations including local colonic manifestation (diarrhea, abdominal pain, abdominal distention, and diffuse colonic tenderness) and systemic toxicity (fever)
Laboratory investigations which show leukocytosis, increase CRP, electrolyte disturbance, elevation of serum creatinine
Radiologically a transverse colon diameter exceeding 6 cm is consistent with toxic megacolon either in plain XR abdomen but better with Abdominopelvic CT with oral and intravenous contrast for assessment of complications and the need for urgent surgery
The diagnosis is settled if all the following criteria are met (3)
A- Radiographic evidence of colonic dilation (diameter >6 cm)
B- At least three of the following:
Fever >38ºC (hypothermia is a criteria of severe septic shock)
Tachycardia with HR >120 beats/min
WBCS >10,500/microL, with neutrophilia
Anemia
C- At least one of the following:
Dehydration
Hypotension
DLC (disturbed level of consciousness)
Electrolyte disturbances
Management
1- Urgent total colectomy with ileostomy after resuscitation (fluids, packed RBCS, FFP, correction of metabolic acidosis) is indicated in case of toxic megacolon if one of the following is present:
If there is evidence of perforation, necrosis, full thickness ischemia, peritonitis or increase intra-abdominal pressure (IAH, compartmental syndrome)
Severe sepsis (requirement for vasopressors, WBCS > 50,000 cell/Ml, LDH >5 mmol/L)
The presence of end organ damage (mechanical ventilation or ARF).
Early colectomy before the development of septic shock was shown to reduce 30 days mortality from 45% top 21%(4)
2- Decompression either by rectal tube or endoscopic is contraindicated since there is high risk of perforation, but decompression using nasogastric tube can be tried
3- Give hydrocortisone IV in a dose of 100 mg every 8 hours in the day of operation and from day 1 the dose is halved and the oral preoperative dose of prednisolone can be resumed on day 2 post-operative together with other immunosuppressive therapy
4- Post operative correction of dehydration anemia, DIC and any electrolyte disturbance, and renal failure (RRT) as indicated
6- Broad spectrum antibiotics.
References
1- Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351:509.
2- Fazio VW. Toxic megacolon in ulcerative colitis and Crohn’s colitis. Clin Gastroenterol 1980; 9:389.
3- Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology 1969; 57:68.
4- Ahmed N, Kuo YH. Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection. South Med J 2020; 113:345.
Toxic megacolon; with colon diameter >6cm & colonic parietal thinking on CT scan
Crohn’s disease
Antibiotics-related pseudomembranous colitis
CMV colitis
Clostridium Defficile, Campylobacter spp, and Salmonella infection
Ulcerative colitis
How would you confirm the diagnosis?
Detail history of antibiotic use, hospital admission, travel, donor, and recipient CMV status, past history of chronic diarrhea, use of laxatives
Physical examination
Plain abdominal radiographic finding like air-filled colonic distention >6cm (especially transverse colon), abnormal haustral pattern, and colonic parietal thining is highly diagnostic of toxic megacolon plus the following
PLUS at least three of the following:
Fever >38ºC
Heart rate >120 beats/min
Neutrophilic leukocytosis >10,500/microL
Anemia
PLUS at least one of the following:
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension
Who would manage this patient?
The treatment of the above patient will be aimed at reducing colonic inflammation, restoring normal colonic motility, and decreasing the possibility of colon perforation which is the main goal of medical therapy. The management will be comprised of a transplant physician, general surgeon, intensivist, radiologist, microbiologist, gastroenterologist, and the ICU nurses
admit the patient to ICU
Nil per oral and pass N.G tube for decompression
Intravenous fluid
Correction of electrolytes; magnesium, potassium
Reduce the dose of myfortic to 360mg BID
Aim trough level of tacrolimus at 5-8ng/ml
Inotropic support until MAP >85mmHg
Close kidney function monitoring
Over CRRT, if the kidney function and acid-base is not improving within 48 hours
Avoid medication that can impede colonic motility
Use of DVT stocking
regular abdominal imaging follow-up every 24 hours to watch out for increased dilatation or perforation
The following is the indication for surgery if the above failed
Frank intraperitoneal perforation
Life-threatening hemorrhage or increasing transfusion requirements
Differential diagnoses
Septic shock
Toxic megacolon, Ulcerative colitis or Crohn disease.
ischemic, infectious, pseudomembranous colitis
Cytomegalovirus Colitis, Diverticulitis, Clostridium difficile SalmonellaShigella How to confirm diagnosis
A thorough history may show recent travel, the use of antibiotics, chemotherapy, occupational exposure, or immunosuppression.
Patients typically exhibit severe symptoms, including fever, tachycardia, hypotension, abdominal distention, and discomfort.
Radiological findings of colonic dilatation is toxic megacolon. Further blood tests are;
CBC , Electroloytes, CRP, ESR, immunosupression drug level, blood C/S.
Stool R/E and eytology.
CT and endoscopy shows dilated gut loos and psudomemebranuos colitis Management
Medical management includes;
Replacement of fluid, inotropic support , correction of electrolytes and acidosis, and treatment of suspected infection with antiobiotis,
When tolerated, patients may consume a typical, low-residue diet (to reduce stool frequency and volume).
Toxic megacolon may be the culprit if diarrhea and abdominal distention get better.
Graft fuction motoring.
Collective team work with surgeon, gastroenterologist.
Early surgical consultation enables quick operative care if a patient’s condition worsens.
Surgery for C. difficile colitis is better when done quickly.
For severe or complex CDI, society’s recommendations urge early surgical consultation.
Patients with acute diarrhea (three or more loose stools in 24 hours) should have their diagnosis of C. difficile infection considered, especially if there are any pertinent risk factors present (including recent antibiotic use, hospitalization, and advanced age)
A number of laboratory stool tests are available alone or in combination; NAAT
If the collection of the stool sample is delayed and the patient has received empirical treatment for suspected CD, the NAAT results may be falsely negative.
A 64-year-old woman presented to the hospital with abdominal pain, nausea, vomiting and profuse watery diarrhoea. She was discharged from the hospital for a urinary tract infection following a successful renal transplant. On admission, the blood pressure was 65/41 mmHg, hypothermia was present, and the WBC was 53.9 109 /L with 84% neutrophils. There was severe metabolic acidosis with an anion gap of 19, bicarbonate level of 12 mmol/L, and lactic acid level of 3.6 mmol/L. The patient was resuscitated with IV fluids and placed on dopamine and norepinephrine.
She was given intravenous ciprofloxacin 500 mg every 12 h, oral vancomycin 250 mg every 6 h, and IV metronidazole 500 mg every 6 h. A CT scan showed circumferential wall thickening of the colon consistent with pan colitis. The patient did not improve despite treatment over the next 36 h. Blood, urine, and stool cultures
Toxic megacolon is distinct from other conditions that present with colon dilatation without systemic toxicity.
Patients with toxic megacolon typically have signs and symptoms of acute colitis, including diarrhea, abdominal pain, rectal bleeding, tenesmus, vomiting, and fever.
Patients may be ill due to recent exposure or immunosuppression.
Vital signs of toxic megacolon include tachycardia, fever, hypotension, tachypneic, obtundeic, and physical findings may be minimal due to high-dose steroids.
Peritoneal signs of perforation include rebound, rigidity, and irritation.
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The most common criteria used to diagnose toxic megacolon are radiographic evidence of colonic dilatation, fever, tachycardia, neutrophilic leukocytosis, anemia, dehydration, altered mental status, electrolyte abnormality, or hypotension.
Complete blood cell (CBC) count
The presence of an abnormally low WBC count does not rule out toxic megacolon, as it may be normal or low in immunosuppressed or extremely toxic patients.
Chemistry panel
Electrolyte disturbances are common in toxic megacolon due to inflammatory diarrhea, steroid use, and gastrointestinal losses.
Nutrition and coagulation panels
Nutrition and coagulation panels should be ordered to assess the patient’s nutritional status.
Hypoalbuminemia is common due to protein wasting, decreased production, and inflammation.
ESR and CRP
Elevated ESR and CRP levels may support toxic megacolon diagnosis.
Histology
Toxic megacolon demonstrates acute inflammation, necrosis, and infiltration of inflammatory cells.
Stool studies
Stool studies should include culture, O&P, and C difficile toxin testing.
Radiography
Radiography is essential for diagnosis and management of toxic megacolon, with air-fluid levels in the colon, deep mucosal ulcerations, air in the small bowel, segmental parietal thinning, and comparison with old baseline films.
Radiographic evidence of dilation of the colon, greater than 6 cm and fever, heart rate, neutrophililic leukocytosis, anemia, dehydration, altered sensorium, electrolyte disturbances, and hypotension are all signs of anemia.
Computed Tomography Scanning
CT scanning is useful for diagnosing toxic megacolon and is more accurate than plain radiography in detecting severe colitis.
It can show diffuse colonic wall thickening, accordion sign, multilayered appearance, and peri colic stranding.
Endoscopy
Endoscopy can be used to identify CMV or pseudomembranous colitis, but it should be limited to the sigmoid colon and air insufflation should be minimal.
Perforation is a potential complication of this approach.
The main goal of treatment for toxic megacolon is to control the severity of the colitis and restore colon function as soon as possible.
Electrolyte abnormalities must be addressed aggressively, medications must be discontinued, bowel rest is recommended, nasogastric tube placement is recommended, rolling maneuvers and a prone knee-elbow position are suggested, DVT prophylaxis is recommended, and broad-spectrum antibiotics are recommended.
Enteral feeding should be started as soon as the patient shows clinical improvement.
Medical Management
Initial treatment involves supportive therapy and medical management, which is usually successful in about half of the patients.
Patients should receive admission to the intensive care unit, check complete blood count, abdominal films, and electrolytes every 12 hours, and start on IV fluids.
Antibiotics should be given if an infectious cause is suspected.
Steroids should be given hydrocortisone 100 mg over 6 hours or methylprednisone 60 mg daily for 5 days.
Cyclosporine and infliximab should not be used as part of the treatment.
Bowel rest is also recommended.
Surgical Management
Surgery should be considered in cases of acute, severe ulcerative colitis that fail to respond to steroid therapy within 3 to 5 days.
Poor nutritional status is associated with increased mortality and morbidity.
Indications for surgery include colon perforation, colon-wall full-thickness ischemia, necrosis, increased intra-abdominal pressure, or abdominal compartment syndrome, signs of peritonitis, end-organ failure, and severe leukocytosis with a WBC count over 50,000 cells/mL and serum lactate levels above 5 mmol/L.
The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
Turnbull’s method was associated with increased bleeding and high mortality, while total proctocolectomy and the Turnbull method were associated with increased bleeding and high mortality.
Surgeons and hospitalists need to work together to assess the patient on a daily basis.
That is a high quality well referenced reply.
Rather than stating ‘surgeons and hospitalists need to work together’, I would say that it is essential to have close liaison between GI surgeon and gastro-enterology team.
While it is not sensible to go for sub-total colectomy in someone who might respond to medical management, it is is not safe to delay surgery for whom this is the only option.
What is the differential diagnosis?toxic megacolon, cute mesenteric ischemia; colonic pseudo-obstruction; large bowel obstruction, and CMV colitis.
How would you confirm the diagnosis?commercial multiplex PCR assays to examine the presence of enteric bacteria, parasites, and viruses in the feces of diarrheal kidney transplant recipients. CMV PCR C.defecile toxins OGD with tissue biopsy and culture
Who would manage this patient?
The prevalence of the difficult form of CDI, defined by a high white blood cell count (>25,000/KL) and pancolitis on CT scan, averaged from 2.5% to 5% but reached as high as 12.4% in 165 SOT patients infected with the extremely virulent strain NAP1/BI/027.
Toxigenic Clostridium infections have a high rate of recurrence and a high level of resistance to therapy, making it very difficult to eradicate them. In two case studies, fecal microbiota transplantation has recently been shown to be an effective and safe treatment for SOT patients with refractory C. difficile infection. Acute CDI patients may develop systemic toxicity with or without diarrhea, requiring hospitalization, intensive care, or emergency surgery.
Reduce the immunosuppressive dose (d/c MMF). Discontinue inciting antibiotic agent(s) — An important initial step in the treatment of CDI is the discontinuation of the inciting antibiotic agent(s) as soon as possible
Supportive care with attention to the correction of fluid losses and electrolyte imbalances is important.
Patients may have a regular, low-residue diet as tolerated (to reduce stool frequency and volume). If abdominal distention and diarrhea decrease, toxic megacolon may be the cause. Early surgical consultation is warranted for patients with CDI who meet one or more of the following clinical indicators that have been associated with poor prognosis(hypotension, lactate>2,2, wbc> 15,000)
If a patient worsens, earlier surgical consultation allows for prompt operational care. Timely surgery for C. difficile colitis improves outcomes. Society recommendations recommend early surgical consultation for severe or complicated CDI.
If Ileus is present, additional considerations include:
Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)
Subtotal colectomy can be lifesaving, but the optimal timing is difficult to establish. Early surgical consultation when the fulminant or refractory disease is suspected is highly recommended.
References:
1- Boutros M, Al-Shaibi M, Chan G, Cantarovich M, Rahme E, Paraskevas S, et al. Clostridium difficile colitis. Transplantation. 2012;93(10):1051–7
Similar to your sensible approach, I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment that may include surgical option in subset of patients.
What is the differential diagnosis?
Toxic megacolon secondary to Pseudomembranous colitis (Clostridium difficile).
Inflammatory Causes such as Ulcerative colitis or Crohn disease. Infectious Causes (Clostridium difficile, Salmonella, Shigella, Campylobacter colitis, Enter hemorrhagic or enter aggregative Escherichia coli O157 (can lead to hemolytic-uremic syndrome), Cytomegalovirus and Entamoeba). Ischemia . How would you confirm the diagnosis?
The most commonly used diagnostic criteria for toxic megacolon (by Jalan et al.) : Radiographic evidence of the dilation of the colon greater than 6 cm AND🙁 here in our case 8.7 cm). At least three of the following: Fever over 38 degrees C (patient in shocked status). Heart rate greater than 120 beats/min (patient in shocked status). Neutrophilic leukocytosis exceeding 10500/micro/L(in our case WBC was 53.9 109 /L). Anemia At least one of the following: Dehydration Altered sensorium Electrolyte disturbances Hypotension ((in our case blood pressure was 65/41 mmHg).). Colonoscopy is not necessary for diagnosis. Therefore, colonoscopy is discouraged due to the high risk of perforation. Who would manage this patient?
Our patient status is critical and need urgent surgical intervention to avoid colonic perforation because some studies conclude favorable outcomes in patients where surgical intervention is done soon after making the diagnosis of toxic megacolon.
The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
It is important to start with initial treatment involves supportive therapy and medical management.
Should be started on IV fluid.
The most commonly used antibiotics are metronidazole or vancomycin for C,difficle.
If cytomegalovirus is the suspected cause, then ganciclovir should be given.
TTT of the associated IBD. Patients must be on bowel rest and a nasogastric tube can be inserted to help decompress the stomach, but it will not decompress the colon. References:
1- Skomorochow E, Pico J. Toxic Megacolon. [Updated 2022 Jul 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547679/.
2- Mukhopadhya A, Samal SC, Patra S, et al. Toxic megacolon in a renal allograft recipient with cytomegalovirus colitis. Indian J Gastroenterol. 2001;20(3):114-115.
Similar to your sensible approach, I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment that may include surgical option in subset of patients.
complicated pseudomembranous colitis with life-threatening toxic megacolon in an old kidney transplant patient recently treated with ciprofloxacin and on intense triple immunosuppression she is in septic shock with lower BP despite inotrope support, dilated bowel > 6cm, indication for urgent surgical intervention and get MDT approach, surgery, transplant physician and infectious disease team in board with stopping all current immunosuppression and continue on stress dose of hydrocortisone along with broad-spectrum antibiotics to cover gram-positive, negative and anaerobic bacteria, parenteral feeding and hemicolectomy based on the gross appearance upon surgery
I wonder in such cases of toxic megacolon is it reasonable to go with colonoscopy as it carries a high risk of perforation and preferred to send for clostridia toxin and CT imaging
What is the differential diagnosis?-Unforfortnately this monther had features of C.difficile infections and her risk factors are;
Exposure to fluroquinolones for treatment of UTI
Age >55
Immune suppression
-She is critically ill, in florid sepsis, haemodynamically unstable, worsening toxic mega colon and pan colitis
-Allograft dysfunction
-Metabolic derangement
-Not responding to the initial treatment due to the toxic mega colon which is purely a surgical problem
-She had poor prognostic features including raising WCC
-Risk of mortality is high
-The differential diagnosis of diarrhea in posttransplant is wide and may include:
A. Infection
Fecal enzyme immune assay or real-time C.difficile PCR
-How would manage this patient?
Counseling the family & care taker that their relative in a critical condition and requires urgent surgery. Mortality may be high and the medical team are going to do their best but she may or may not make it
Obtained a high risk consent form
Admit to Surgical ICU
Stop all the immune suppression by now except the steroid
Mobilize the team ; Run to the on call surgeon, anesthetist, infectious disease specialist
Urgent surgical review
Continue inotropic support, adrenaline may be added if needed
IV fluid resuscitation by balanced electrolytes solution
Correction of electrolytes by giving IV magnesium and potassium
Cardiac monitor
Respiratory support
Stop the ongoing ciprofloxacin
Add meropenem
Add fidaxomicin
Continue Vancomycin
Organized renal replacement therapy in form of CRRT
Close monitoring & follow up post-opt
Updates the family
Source
Hand book of kidney transplantation, 6 th edition
Causes and managment of posttransplant diarrhea by Ho Sik Shin and Anil Chandraker
pseudomembranous colitis induced Toxic megacolon 1– is a life-threatening condition characterized by 2– nonobstructive 3– segmental or pancolonic 4– dilatation of at least 6 cm 5– with systemic toxicity
Although (IBD) is a common reason for toxic megacolon, other etiologies including infections (CMV) , inflammation, bowel ischemia, radiation, and certain medications can lead to the development of this condition
Some antibiotics are more commonly linked to pseudomembranous colitis than others, including: Fluoroquinolones, such as ciprofloxacin (Cipro) and levofloxacin
Colonoscopy may be not necessary for diagnosis. Therefore, colonoscopy is discouraged due to the high risk of perforation.
management
in our patient , the case wasn’t improved after supportive treatment. Therefore surgical management is considered
Surgical Management
●A surgeon should be involved in the patient’s care from day 1
●The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
●Previously there were two additional surgical methods used: total proctocolectomy and the Turnbull method.
●The exact time of surgery in toxic megacolon patients is still unclear.
●If there is perforation, bleeding, or clinical deterioration of a patient, surgical intervention is unavoidable.
Indications for surgical consultation in the management of CDI
Any one of the following:Hypotension with or without required use of vasopressors
Fever ≥38.5°C
Ileus or significant abdominal distention
Peritonitis or significant abdominal tenderness
Mental status changes
WBC ≥20,000 cells/mL
Serum lactate levels >2.2 mmol/L
Admission to intensive care unit for CDI
End organ failure (mechanical ventilation, renal failure, etc.)
Failure to improve after three to five days of maximal medical therapy
Medical Management
○This approach is usually successful in about half of the patients. But not in our patient.
○ admission to the ICU
CBC Electrolytes
AXR
○the medications which can aggravate the megacolon, should be stopped.
○IV fluids to provide adequate hydration.
○The most commonly used antibiotics are metronidazole or vancomycin
○If CMV is the suspected cause, then gancyclovir should be given. And perform PCR (CMV)
○ bowel rest. NGT
REFERENCES
1– Clostridioides difficile infection in adults: Treatment and prevention(UpToDate)
2– Toxic Megacolon. Skomorochow E, Pico J.
3– Diarrhea in a Patient With Combined Kidney-Pancreas Transplant. Krunal Amin.
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment that may include surgical option in subset of patients.
-Toxic megacolon can be suspected in patients with abdominal distension and diarrhea. The diagnosis is made based on clinical signs of systemic toxicity combined with imaging evidence of colonic dilatation (colonic diameter >6 cm).
The toxic megacolon is most commonly considered a complication of inflammatory bowel disease, especially ulcerative colitis but can be a complication of almost any inflammatory or infectious condition of the colon can lead to toxic dilatation, in our transplant patient it can be secondary to:
-Clostridioides difficile pseudomembranous colitis (patient had UTI post transplantation and received wide spectrum antibiotic for 14 days.
-CMV colitis.
–Cryptosporidium.
-Other chronic nontoxic processes leading to colonic dilatation by its inflammatory trigger like:
Congenital megacolon (Hirschsprung’s disease). Acquired megacolon (eg, due to chronic constipation). Chagas megacolon. Colonic pseudo-obstruction. Diffuse gastrointestinal dysmotility.
How would you confirm the diagnosis? The diagnosis is made based on clinical signs combined with imaging evidence of colonic dilatation (diameter >6 cm). The used criteria are:
-Radiographic evidence of colonic dilation (diameter >6 cm) PLUS at least three of the following:Fever >38ºC,Heart rate >120 beats/min,Neutrophilic leukocytosis >10,500/microL and Anemia
Who would manage this patient? Patient not responding to extensive medical treatment, Surgery is indicated in view of deterioration and signs of end-organ failure (eg, vasopressor requirement, intubation and mechanical ventilation, or acute renal failure). In addition, WBCs count >50,000 cell/mL and serum lactate level of >5 mmol/L. Early colectomy before the onset of septic shock was associated with a reduction of 30 day mortality from 45 to 21 percent.
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment. I appreciate surgery in small subset of patients such as, as I quote you, “Early colectomy before the onset of septic shock was associated with a reduction of 30 day mortality from 45 to 21 percent.”
What is the differential diagnosis? Toxic megacolon: C.difficle colitis Other infectious colitis: Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp. Non- infectious: Inflammatory bowel syndrome, microscopic colilitis, and celiac disease.
How would you confirm the diagnosis?
Nucleic acid amplification test (NAAT) for C.difficle – sensitive and specific in detecting toxins, rapid false negative results can occur in patients receiving empirical antibiotics, or with delayed collection.
EIA for C. difficile GDH antigen: cannot distinguish between toxigenic and non toxigenic strains, has good sensitivity, result comes less than one hour.
EIA for C. difficile toxins A and B: highly sensitive result within an hour, highly specific 99%, with variable sensitivity.
Selective anaerobic culture: unable to differentiate between strains that produce toxins and those that do not, require days to get the result.
Cell culture cytotoxicity assay: time-intensive but sensitive and specific; it is not a standard clinical diagnostic procedure, he gold standard test for diagnosing C. difficile, and highly sensitive.
Serology for other disease entities, and PCR .
Who would manage this patient?
Detailed history including previous episodes and full examination.
Laboratory as highlighted in the index scenario.
Treatment includes:
1- Admission to ICU, with close monitoring, Vigorous iv fluid management, with electrolytes correction magnesium sulfate and potassium. 2- Iv antibiotics covering the highly suspected CDI. 3- Stop antimetabolites MMF, reduce the tacrolimus level to 5-8 ng/dl, but keep on steroid in a stress dose. 4- Immediate surgical consultation- evaluation and surgery if needed: indications for surgical intervention are: · Hypotension
· Fever ≥38.5°C · Ileus or significant abdominal distention · Peritonitis or significant abdominal tenderness · Altered mental status · White blood cell count ≥20,000 cells/mL · Serum lactate levels >2.2 mmol/L · Admission to intensive care unit · End organ failure (eg, requiring mechanical ventilation, renal failure) · Failure to improve after three to five days of maximal medical therapy
Impression: Fulminant colitis (previously referred to as severe, complicated CDI) – Hypotension or shock, ileus, or megacolon Patients with ileus may benefit from using a rectal swab for a toxin assay or anaerobic culture as a diagnostic technique. Treatment of C.diff. (patients with typical manifestations of CDI (acute diarrhea [≥3 loose stools in 24 hours] with no obvious alternative explanation) and a positive diagnostic laboratory assay): Systemic vancomycin or fidaxomicin for 14 days combination metronidazole, vancomycin and rifampicin, can be used Metronidazole can be used but has a high resistance rate. In the indexed case surgical intervention is the best treatment option. Fecal transplant cane be implemented with data in good response rate and decreased mortality in severe disease.
References: (1) Killeen S, Martin ST, Hyland J, O’ Connell PR, Winter DC. Clostridium difficile enteritis: a new role for an old foe. Surgeon. 2014 Oct;12(5):256-62. doi: 10.1016/j.surge.2014.01.008. Epub 2014 Mar 4. PMID: 24618362. (2) UpToDate – clostridium difficle treatment and prevention, and outcome.
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment.
The colonoscopy shows raised elevated yellow-white nodules or plaques forming mucosal pseudomembranes that are characteristic of pseudomembranous colitis.
The H/O prolonged course of antibiotics in this post KTX patient is also consistent with this diagnosis. Pseudomembranous colitis is commonly a manifestation of severe colonic disease that is usually associated with Clostridium difficile infection as a result of the use of broad-spectrum antibiotics. Any broad spectrum antibiotics can cause pseudomembranous colitis – especially clindamycin & ampiciliin. Diarrhea as a result of pseudomembranous colitis occurs in about 3-10% of adults receiving antibiotics.
Pseudomembranous colitis can be life-threatening & possible complications include:
Toxic megacolon which is complicating the case in this scenario, and it is confirmed by the accompanying CT that is shown here.
Dehydration and electrolytes disturbance
Acute kidney failure from dehydration & sepsis, as it happened in this scenario.
========================= How would you confirm the diagnosis?
There is no agreement on the clinical & histological features of post-transplant colitis, & its clinical symptoms are non-specific & may overlap with those of graft-versus-host and MMF colitis.
Stool for Clostridium difficile toxins (detecte by ELISAs) may be positive in cases of pseudomembranous colitis. However, its use is limited because it is technically demanding, costly, & requires 24–48 h wait for results.
Histopathological examination:
MMF/MPA/colitis has non-specific endoscopic & histological characteristics that may resemble those of IBD, graft-versus-host disease, & ischemic colitis. Extensive crypt atrophy & mild to severe eosinophil or plasma cell infiltrates are frequent histological findings.
Histological findings in CMV colitis include increased enterocyte apoptosis, which is caused by viral infection; however, it is difficult to distinguish CMV colitis from GVHD on gastrointestinal biopsy, so the definitive diagnosis in KTX patients requires histologic findings of characteristic inclusion bodies on H & E staining.
========================= Who would manage this patient? Substantiate your answer!
Immunosuppression (MMF) reduction, or even withdrawal, is the main stay of management in post-transplant colitis.
In addition to rehydration & other conservative measuremrnts, surgical complications like the one occurring in this scenario needs prompt surgical consultation & interventions to save the life of the patient.
Oral vancomycin is the only FDA-approved treatment of C. difficile, but metronidazole has considerable historical use.
The efficacy of oral vancomycin might be limited by ileus in cases of severe disease with complications. Higher doses of oral vancomycin may be needed & intracolonic administration of vancomycin may be tried. Intracolonic vancomycin use, however, might increase risk for bloodstream infections due to colonic flora. In life-threatening complications, intravenous metronidazole is given in addition to enteral vancomycin. However, in severe cases, like in this scenario, antimicrobial therapy alone might not be curative & it is important to consider surgical consultation.
Therapeutic use of IVIG has been tried with variable success. IVIG contains C. difficile antitoxin antibodies; however, its use is supported by only case studies & series.
Disease severity can be divided into 3 categories for treatment considerations:
Mild or moderate: diarrhea & abdominal cramping without systemic symptoms.
Severe: profuse diarrhea, abdominal pain, leukocytosis, & fever or other systemic symptoms.
Severe disease with complications: life-threatening conditions such as paralytic ileus, toxic megacolon, & multiorgan failure.
Mesalazine and cortico-steroids are the mainstays of treatment of de novo IBD even in transplant patients.
Anti-TNFα antibodies are suggested in patients refractory to standard therapy.
The treatment of MMF colitis includes a reduction or, in more severe forms, complete discontinuation of MPA.
Reference
Rossella Gioco, Lidia Puzzo, Marco Patanè, Daniela Corona, Giuseppe Trama, Pierfrancesco Veroux, Massimiliano Veroux, Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features, AGING 2020, Vol. 12, No. 24
Sarah E. Ward and Erik R. Dubberke, Clostridium difficile Infection in Solid Organ Transplant Patients, Antimicrobe/Transplant Infection
If non-invasive treatments fail to reduce the size of the toxic megacolon within 2 to 3 days, surgery may be needed to remove part or all of the colon.
Yes, it can be cultured from stool, though cultures are not widely used by most laboratories. However, it might be needed in certain situations, for example some patients with disease do not have detectable levels of toxin in their stool.
Toxic mega colon with impending perforation complicated by septic shock, metabolic acidosis and peritonitis, underlying colitis might be resultant from acute exacerbation of chronic inflammatory bowel disease Ulcerative colitis vs Crohn’s disease. infective process mediated by bacterial infection such as clostridium difficile or HIV infection might be the culprit as well. However, Cultures were negative.
Urgent management must be implemented with surgical team taking over, as there is an impending perforation with complicated peritonitis,
surgical management with colectomy must be first line of management.
Antibiotic cover.
correction of volume status.
electrolytes correction.
diagnosis of underlying IBD.
plan for long term management.
Yes , it can be C.def-induced pseudomembranous colitis complicated by toxic megacolon, its rarely occuring.
Stool culture is the most sensitive tool, but time consuming. EIA is the mostly used test for detection of C.def. toxins.
Screening by fecal enzyme immunoassay, real-time PCR & confirmed by C.difficile toxin ELISA or a tissue culture cytotoxicity assay.
Mx: Resuscitate the patient. Start antimicrobial therapy( Metronidazole/ vancomycin), start RRT & surgical decompression is needed. Colonoscopy should be avoided due to risk of perforation.
What are the differential diagnoses?
How would you confirm the diagnosis?
Detection C. difficile toxin in stool by Enzyme-Immuno-Assay (EIA)
PCR for C. difficile in stool
How would manage this patient?
Resuscitation with IV fluids and inotropes
Withdraw immunosuppression
Oral vancomycin (500 mg 4 times/day) or oral fidaxomicin.
NG suction for decompression of the stomach
Fecal Microbiota Transplant is an option
Surgery if abdominal compartment syndrome or colon perforation
How would you confirm it is C Def colitis?
PCR or Nucleic acid amplification test (NAAT) for C.difficle
Enzyme immuno-assay (EIA) for C. difficile toxins A & B
2. If you have this CT image with the abovementioned history, would you go for a colonoscopy?
Colonoscopy is contraindicated.
References:
Skomorochow E, Pico J. Toxic Megacolon. In: Stat Pearls [Internet, Updated 2022 Jul 5]. Treasure Island (FL): Stat Pearls Publishing; 2023 Jan
Trudel JL, Deschênes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous enterocolitis. Diseases of the colon and rectum. 1995 Oct;38(10):1033-8. PubMed PMID: 7555415. Epub 1995/10/01.
Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
DD:C.fiff
colonoscy congtraindicate
1. What is the differential diagnosis?
64 yr female, recent post-renal transplant, from son – probably no induction. Had UTI – received 14 days ciprofloxacin
presented with abdominal pain, watery diarrhoea, vomiting, dehydration, septic shock, severe metabolic acidosis, AKI.
CT abdomen – dilated colon (8cm) suggestive of Toxic Megacolon.
F From typical history, clinical picture, with CT imaging à most probable diagnosis is Pseudo-membranous Enterocolitis due to Clostridium difficile (most common cause following prolonged antibiotic therapy), with Toxic Megacolon, Septic Shock and AKI.
Toxic Megacolon – diagnostic criteria:
Ø Radiologic (CT) e/o colonic dilatation >6cm
Ø + 3 of the following: fever, tachycardia, leuko-cytosis, anaemia
Ø + at least 1 of the following: dehydration, hypotension, altered sensorium, dys-electrolytemia
Other infectious causes:
Ø Salmonella
Ø Shigella
Ø Campylobacter colitis
Ø Enterohemorrhagic / enteroaggregative E Coli – O157 (can lead to HUS)
Ø Adeno-virus, Rota virus, Norovirus, Cytomegalovirus
Ø Entamoeba histolytica
Ø Inflammatory: Ulcerative colitis, Crohn’s disease, Ischemic Colitis.
Factors that can precipitate toxic megacolon include, (but not limited to):
2. How would you confirm the diagnosis?
F Typical history, clinical picture, with CT imaging
F no other source of infection; blood, urine and stool cultures were negative
Toxic Megacolon – diagnostic criteria:
Ø Radiologic (CT) e/o colonic dilatation >6cm
Ø + 3 of the following: fever, tachycardia, leuko-cytosis, anaemia
Ø + at least 1 of the following: dehydration, hypotension, altered sensorium, dys-electrolytemia
F Abdominopelvic CT scan with oral + IV contrast – to establish the diagnosis, exclude other complications that require urgent surgery. Serial Xray-abdomen, thereafter, to monitor colonic dilatation.
F Diagnosis of C. difficile by detection of its toxin in stool (Enzyme-Immuno-Assay), or by positive nucleic acid amplification test (NAAT) for C. difficile toxin gene.
3. how would manage this patient?
F ICU admission and Resuscitation – IV fluid, Noradrenalin, IV Hydrocortisone
– correction of acidosis, electrolytes – may need CVVH due to AKI.
– monitor kidney function, urine output, ABG, sepsis marker and CBC.
F Stop immunosuppression – Hydrocortisone to continue for septic shock (100mg tid)
· Broad spectrum IV antibiotics – commonly used are metronidazole or vancomycin.
– Antibiotics of choice for C. difficile: oral vancomycin (500 mg 4 times /day) or oral fidaxomicin. If those are not available, IV metronidazole is an alternative.
– In case of ileus, megacolon, per-rectal Vancomycin + Fidaxomicin may be tried.
– Tigecycline is used for refractory cases.
· Rest to bowel: reduce inflammation, avoid need for surgery
Ø NPO, NG tube aspiration can decompress the stomach, but not the colon à rectal tube may be helpful for that. PC Enema and intermittent rolling / knee-elbow position – help redistribute, expel colonic gas.
Ø Parenteral nutrition + micronutrients supplement – K, Cal, Mg, zinc, selenium, multivitamin.
Ø Once the patient improves, gradual enteral feed may promote healing, reduce gut-sepsis, stimulates motility.
· To stop medications that affect GI motility – anticholinergics, opiates.
Patient did not improve despite 36 hours treatment
– Rising WBC 51K à 63.4K/L, abdomen became more tender, increased Colon dilation 5.8 à 8.7cm on CT… all indicates towards worsening abdomen.
Colonic decompression by bedside flexible sigmoidoscopy is helpful in certain scenarios, but is dangerous in sick and acutely ill patients like the index case; with high risk of perforation – so, it should be avoided.
Surgical treatment: (GI Surgery consultation)
F Indications for surgery: intrabdominal hypertension, abdominal compartment syndrome, colonic perforation / necrosis, full thickness ischemia, peritonitis, worsening abdominal findings (tenderness/ distension/ colonic dilation on Xray/ CT), organ failure requiring vasopressors, AKI, intubation-mechanical ventilation.
Surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy (+Hartmann pouch / Sigmoidostomy). Diversion ileostomy with colonic lavage may be tried in selected sick patients.
Ø This index patient is very sick, with life-threatening complications – not fit to undergo any surgical procedure – high risk of mortality (60-90%) with or without surgery.
If the patient survives and improves
Fecal Microbiota Transplant (FMT, per rectal) or rectal Vancomycin, may be tried.
Recurrent CDI à fidaxomicin + vancomycin + rifaximin 400mg TID x 20days, Bezlotoxumab may be tried. There is some role for fecal microbiota transplantation.
Support your answer — References:
1) Sartelli M, Malangoni MA, Abu-Zidan FM, et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World Journal of Emergency Surgery (2015) 10:38 DOI 10.1186/s13017-015-0033-6
2) Skomorochow E, Pico J. Toxic Megacolon. In: Stat Pearls [Internet, Updated 2022 Jul 5]. Treasure Island (FL): Stat Pearls Publishing; 2023 Jan
3) Trudel JL, Deschênes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous enterocolitis. Diseases of the colon and rectum. 1995 Oct;38(10):1033-8. PubMed PMID: 7555415. Epub 1995/10/01.
4) Autenrieth DM, Baumgart DC. Toxic megacolon. Inflammatory bowel diseases. 2012 Mar;18(3):584-91. PubMed PMID: 22009735. Epub 2011/10/20.
5) Johal SS 1, Hammond J, Solomon K,et al. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004 May; 53(5): 673-7. DOI: 10.1136/gut.2003.028803. PMID: 15082585 PMCID: PMC1774022
6) Louie TJ. Treatment of first recurrences of Clostridium difficile-associated disease: waiting for new treatment options. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2006 Mar 15;42(6):765-7. PubMed PMID: 16477550. Epub 2006/02/16.
Prof. Ahmed Halawa
Tutor
1 month ago
Dear All
How would you confirm it is C Def colitis?
If you have this CT image with the above mentioned history, would you go for a colonoscopy?
1. How would you confirm it is C Def colitis?
C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation, particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age) [1].
Diagnosis of CDI requires demonstration of C. difficile toxin(s) or detection of organism in diarrhoeal stool sample.
A number of lab tests (stool) are available, can be used alone or in combination as part of diagnostic algorithm:
1) Nucleic acid amplification test (NAAT) for C.difficle – sensitive and specific in detecting gene for C Def toxins – rapid, false negative results can occur in patients receiving empirical antibiotics, or with delayed collection.
2) PCR are highly sensitive, greater than EIA and comparable with cytotoxicity assay; can’t differentiate asymptomatic carriers from disease state.
3) Enzyme immunoassay (EIA) for C. difficile toxins A & B – highly sensitive, rapid (result within an hour), highly specific 99%.
4) Enzyme immunoassay EIA for C. difficile GDH: cannot distinguish between toxigenic and nontoxigenic strains, so it has to be done along with EIA for toxins A&B.
5) Cell culture cytotoxicity assay the gold standard test for diagnosis – time taking.
6) Selective anaerobic culture – sensitive, cannot distinguish toxin-producing strains from non-toxin-producing strains, second test is required to detect toxin.
2. If you have this CT image with the abovementioned history, would you go for a colonoscopy?
Colonoscopy is generally not required routinely when typical signs and laboratory tests.
In such sick patients, it can’t be performed (sedation or anesthesia is dangerous) and has high risk of perforation.
For decompression of colon, other measures (NPO + NG tube + rectal tube) should be done, in place of flexible sigmoidoscopy.
References:
1) Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
2) McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085. PMID: 29462280; PMCID: PMC6018983.
3) Sartelli M, Malangoni MA, Abu-Zidan FM, et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World Journal of Emergency Surgery (2015) 10:38 DOI 10.1186/s13017-015-0033-6
4) Johal SS 1, Hammond J, Solomon K,et al. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004 May; 53(5): 673-7. DOI: 10.1136/gut.2003.028803. PMID: 15082585 PMCID: PMC1774022
· What is the differential diagnosis?
The DD of diarrhea in this immunosuppressed 65 lady include:
Infectious causes:
Bacterial: Salmonella, Campylobacter, bacterial over growth, E. coli.
Virus: CMV, norovirus, rotavirus and adenovirus,
Parasites: Guardia, entamoeba. and cryptosporidiosis,
Noninfectious:
However, in this scenario, his lady received ciprofloxacin for UTI in first month post-transplant. Accordingly, the most probable cause of diarrhea is C. difficile infection-(antibiotic related diarrhea- fluoroquinolone) which is an opportunistic infection that can occur in first month post transplantation.
· How would you confirm the diagnosis?
· The diagnosis is based on the clinical features(diarrhea in the context of recent antibiotic use coupled with toxic mega-colon that appeared in CT. However, Colonoscopy was not required as it increases the risk bowel perforation.
· Confirm the diagnosis by stool toxin assay to detect C Diff toxin rather than doing cultures. However, stool culture is still required to exclude another enteric pathogens
Who would manage this patient? Substantiate your answer!
· MDT approach including the transplant team and the gastroenterologist, infectious disease with ICU team. This patient has multiple poor prognostic indicators including septic shock, significant metabolic derangement, graft dysfunction, poor response to medical therapy with disease progression.
· ICU admission for cardio ventilator support, fluid resuscitation, correction of electrolytes, improve nutritional status as the patient will need to stop enteral feeding and start parenteral nutrition. CRRT may be required in the context of newly developing AKI and shock.
· Stop Ciprofloxacin. Continue on vancomycin and metronidazole. Liaise with the ID team for any required antibiotics.
· Immunosuppression management: Stop MMF, reduce tacrolimus to keep a trough level between 5-8 ng/ml. Use IV hydrocortisone to replace prednisolone initially.
· Decompression of the dilated colon with nasogastric tube.
· Holding medications that slow intestinal motility (anticholinergics, antidepressants, anti-diarrheal, and narcotics)
· Monitor the patient clinical improvement or response to treatment, consider discussing with the surgical treatment. Only 1 % of all patients with clostridium defficile infection(CDI) and 30 % with severe disease will require emergency surgery. The overall mortality with severe Clostridium difficile colitis with toxic mega-colon was 64- 67%, and 71 to 100 % for surgically treated patients. .
· Early surgical consultation and timely and decisive operative management is the key for survival of patients with severe or fulminant C. difficile colitis. The surgical treatment is total abdominal colectomy but a diverting loop ileostomy and colonic lavage may be an alternative.
References:
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493..
2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7.
· What is the differential diagnosis?
The DD of diarrhea in this immunosuppressed 65 lady include:
Infectious causes:
Bacterial: Salmonella, Campylobacter, bacterial over growth, E. coli.
Virus: CMV, norovirus, rotavirus and adenovirus,
Parasites: Guardia, entamoeba. and cryptosporidiosis,
Noninfectious:
However, in this scenario, his lady received ciprofloxacin for UTI in first month post-transplant. Accordingly, the most probable cause of diarrhea is C. difficile infection-(antibiotic related diarrhea- fluoroquinolone) which is an opportunistic infection that can occur in first month post transplantation.
· How would you confirm the diagnosis?
· The diagnosis is based on the clinical features(diarrhea in the context of recent antibiotic use coupled with toxic mega-colon that appeared in CT. However, Colonoscopy was not required as it increases the risk bowel perforation.
· Confirm the diagnosis by stool toxin assay to detect C Diff toxin rather than doing cultures. However, stool culture is still required to exclude another enteric pathogens
Who would manage this patient? Substantiate your answer!
· MDT approach including the transplant team and the gastroenterologist, infectious disease with ICU team. This patient has multiple poor prognostic indicators including septic shock, significant metabolic derangement, graft dysfunction, poor response to medical therapy with disease progression.
· ICU admission for cardio ventilator support, fluid resuscitation, correction of electrolytes, improve nutritional status as the patient will need to stop enteral feeding and start parenteral nutrition. CRRT may be required in the context of newly developing AKI and shock.
· Stop Ciprofloxacin. Continue on vancomycin and metronidazole. Liaise with the ID team for any required antibiotics.
· Immunosuppression management: Stop MMF, reduce tacrolimus to keep a trough level between 5-8 ng/ml. Use IV hydrocortisone to replace prednisolone initially.
· Decompression of the dilated colon with nasogastric tube.
· Holding medications that slow intestinal motility (anticholinergics, antidepressants, anti-diarrheal, and narcotics)
· Monitor the patient clinical improvement or response to treatment, consider discussing with the surgical treatment. Only 1 % of all patients with clostridium defficile infection(CDI) and 30 % with severe disease will require emergency surgery. The overall mortality with severe Clostridium difficile colitis with toxic mega-colon was 64- 67%, and 71 to 100 % for surgically treated patients. .
· Early surgical consultation and timely and decisive operative management is the key for survival of patients with severe or fulminant C. difficile colitis. The surgical treatment is total abdominal colectomy but a diverting loop ileostomy and colonic lavage may be an alternative.
References:
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493..
2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7.
Q1: Differential diagnosis:
1.Infectious diarrhea:
Bacterial: clostridium difficile (most probable due to recent antibiotic therapy), salmonella,
E. coli, shigella, campylobacter, Yersinia
Viral: Norovirus, rotavirus, CMV, adenovirus
Protozoa: cryptosporidium, giardia, ameloidosis
2.Non-infectious:
Drug induced by MMF, Laxatives
Q2: Diagnosis:
Stool exam and stool culture for bacterial or protozoal infection, clostridium difficile toxin determination by ELIZA, EIA or PCR
PCR for viral infections (CMV and others)
Q3: This patient has toxic mega colon with a critical condition and needs ICU admission and multi-disciplinary approach (intensivist, nephrologist, infectious disease and surgical consultation)
Volume repletion with IV hydration and replacement fluids and inotrope), reduction of immunosuppressive drugs (especially stop MMF and steroids with stress dose) are needed. She should be NPO and have NG tube and rectal tube to decompress GI tract. Start IV metronidazole and oral vancomycin and broad spectrum anti-biotic. Close monitoring for vital signs, electrolytes, acid-base, CBC-diff, LFT and RFT. Start CRRT and consult with surgeons if suspect to perforation or peritonitis for total colectomy and ileostomy.
· What is the differential diagnosis?
C difficile infection is top on this case scenario, with immunosuppression status, recent prolong antibiotic use and history of diarrhea.
Other differential: Infectious and non infectious causes of diarrhea. Like bacteria ( dysentery, Salmonella, etc), parasitic Giardia, amoeba, etc), viral ( CMV).
· How would you confirm the diagnosis?
ds
Test for C Diff toxin
Cell culture
NAAT
Who would manage this patient?
This patient needs:
Admission to ICU, isolation.
Aggressive fluid resuscitation with fluids and electrolytes replacement (replace potassium before considering bicarbonate).
Reduction of immunosuppression, cut MPA by 50% and hold it no high risk for rejection or no improvement after initial resuscitation.
Change prednisone to hydrocortisone stress dose.
Check FK level and keep it at target.
Antibiotic coverage with oral vancomycin and IV metronidazole.
We need to avoid colonoscopy if possible because of perforation risk.
Transplant recipient, received 14 day course of ciprofloxacin for UTI presented with abdominal pain , watery diarrhea , vomiting , septic shock and, metabolic acidosis AKI.
CT abdomen showed dilated colon picture suggestive of Toxic Megacolon.
Causes :
The most common cause following antibiotic for long time is Clostridium difficile
Other infectious causes:
· Salmonella
· Shigella
· Campylobacter colitis
· Enterohemorrhagic or enteroaggregative Escherichia coli O157 (can lead to hemolytic-uremic syndrome)
· Cytomegalovirus
· Entamoeba
Inflammatory causes: Ulcerative colitis, Crohn’s colitis
Ischemia
Factors that can precipitate toxic megacolon include, but are not limited to :
. How would you confirm the diagnosis?
Diagnosis of C. difficile by detection of its toxin in stool, or by positive nucleic acid amplification test (NAAT) for C. difficile toxin gene
how would manage this patient?
-ICU admission with fluid resuscitation, iv fluid, correction of electrolytes , correction of acidosis, fluid chart , monitor kidney function , urine out put , ABG , sepsis marker and CBC.
– antibiotics, especially if an infectious cause is suspected. The most commonly used antibiotics are metronidazole or vancomycin.
-If cytomegalovirus is the suspected cause, then gancyclovir should be given.
Antibiotics of choice for C. difficile are oral vancomycin (500 mg 4 times /day) or oral fidaxomicin. If those are not available, oral metronidazole is an alternative.
Tigecycline is used for refractory cases.
-patients must be on bowel rest. A nasogastric tube can be inserted to help decompress the stomach, but it will not decompress the colon. As the patient continues to improve, they can gradually start eating to promote gut healing
-Surgical Management, in case intervention might be necessary. The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and
either a Hartmann pouch, sigmoidostomy, or rectostomy.
Reference
Skomorochow E, Pico J. Toxic Megacolon. [Updated 2022 Jul 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan
• What is the differential diagnosis?
Patient admitted with acute diarrhea after hospitalization with manifestations of organ dysfunction and sepsis. In this situation, the most pathogenic agent is Clostridium difficile inducing pseudomembranous colitis developed fulminant colitis complicated with toxic megacolon.
Despite this, there is the possibility of differential diagnoses of infectious and non-infectious etiology.
Infectious: E. coli, Campylobacter, Salmonella, CMV, Rotavirus, Enterovirus,
Non-infectious: immunosuppressive drugs.
• How would you confirm the diagnosis?
For the diagnosis of acute diarrhea, we could start with:
– C. difficile PCR in stool
– CMV qPCR/NAT in blood/serum
– Bacterial culture or PCR for bacterial pathogen in stool
– Multiplex PCR if available in stool
• Who would manage this patient?
Faced with renal dysfunction with acidosis and loss of electrolytes, volume expansion and electrolyte replacement is necessary as performed.
Start of broad-spectrum antibiotic (ciprofloxacin) and specific for C. difficile due to its greater pathogenicity (oral Vanco + IV Metronidazole)
I would avoid colonoscopy because of the risk of perforation.
Early use of amines, with weaning as there was a response to volume expansion.
• Substantiate your answer!
– Amin K, Choksi V, Farouk SS, Sparks MA. Diarrhea in a Patient With Combined Kidney-Pancreas Transplant. Am J Kidney Dis. 2021 Aug;78(2):A13-A16. doi: 10.1053/j.ajkd.2021.01.023. PMID: 34303438.
– Angarone, M, Snydman, DR; on behalf of the AST ID Community of Practice. Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13550. https://doi.org/10.1111/ctr.13550
What is the differential diagnosis?
The differential diagnosis is of Toxic megacolon due to Clostridium difficile infection.
How would you confirm the diagnosis?
Stool test for C. difficile presence.
Who would manage this patient?
Reduction in the levels of Tacrolimus
Oral Vancomycin (500 mg four times/day for 10 days)/ Vancomycin (Pulse dosage or tapered vancomycin administration)
Fidaxomicin (200 mg two times/day for 10 days) in case patient is resistant to metronidazole.
Fecal Microbiota Transplantation in severe case.
Substantiate your answer!
Goudarzi M, Seyedjavadi SS, Goudarzi H, Mehdizadeh Aghdam E, Nazeri S. Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options. Scientifica (Cairo). 2014;2014:916826.
Patient is a recent renal transplant recipient with normal graft function…She is on triple immunosuppression…She has been treated for UTI with ciprofloxacin recently for 14 days…
She has presented to ER with septic shock…there was pancolitis with elevated WBC count which has progressed into septic shock requiring inotropes…Patient also has hypokalemia with hypomagnesemia which was corrected..IV fluids were given…The patient has progressed to toxic megacolon…
The patient needs IV fluids as per surviving sepsis guidelines….IV electrolytes correction has to be given…Colonoscopy is not indicated now as there is risk of perforation with toxic megacolon….IV antibiotics preferably third generation cephalosporin or meropenem with IV metronidazole is needed…Basic lab work up has to be done daily to monitor the renal functions, complete blood count…I would stop all immunosuppression and keep the patient on low dose steroids….
Stool for C diff toxin can be done to prove the diagnosis….culture and blood tests for C.Diff are not helpful in diagnosis
The DDx include infectious causes and non infectious causes
Infectious causes include:
Bacterial like
C.difficile , C. Perfrangins , E.Coli, Salmonella spp.
Viral like
Rotavirus, adenovirus
Parasitic like
Giardiasis and amebeoasis
The non infectious causes include
Drug induced
IBS
Inflammatory bowel syndrome
Caeliac disease
The most likely diagnosis here is Toxic megacolon secondary to fulminating colitis and pseudo membranous colitis .
The diagnosis can be confirmed by:
1-NAAT for toxin gene
2-Stool for enzyme immune assay
3-Cell based cytotoxicity test.
Colonoscopy is contraindicated in this case
The management plan include:
Admission to ICU
MDT including transplant nephrologist
Intravenous fluid rehydration
Abdominal decompression
NPO
Stop MMP, decrease CNIs by 50%
Sress dose steroid
Medical treatment and if not improved within 24 hrs then go for surgical intervention by total colectomy and illieostomy.
What is the differential diagnosis?In this scenario, the likely cause is infective causes diarrhoea. The patient is currently in septic shock in DIVC (coagulopathy), complicated by AKI and toxic megacolon. This is also compounded by electrolyte imbalance due to severe diarrhoea (hyponatraemia, hypomagnesemia) and metabolic acidosis (lactic acidosis).
Differential diagnosis
Bacterial causes:
1) Clostridium difficile (provisional diagnosis)
2) Salmonella
3) E.Coli
4) Campylobacter
Virus causes:
1) CMV
2) Norovirus
3) Adenovirus
Parasite:
1) Giardia
2) Cryptosporidium
3) Microsporadium
4) Isospora
How would you confirm the diagnosis?1) Stool examination for clostridium difficile (toxin, culture,nucleic acid amplification test (NAAT) or enzyme immunoassay to detect glutamate dehydrogenase (EIA GDH)
Who would manage this patient?1) Aggressive fluid resuscitation
2) NG tube for bowel decompression
3) Electrolytes correction (potassium and magnesium)
4) Withhold MMF and advagraf (may need to restart once infection is improving)
5) Switch prednisolone to hydrocortisone 100 mg TDS
6) Switch oral vancomycin (poor absorption in this case to Fidaxomicin
7) If failed to consider faecal microbiota (FMT)
8) Other novel alternative therapy is Bezlotoxumab
References
1.Infectious Diseases Society of America (IDSA)
2.Society for Healthcare Epidemiology of America (SHEA)
3.van Prehn, J.; Reigadas, E.; Vogelzang, E.H.; Bouza, E.; Hristea, A.; Guery, B.; Krutova, M.; Norén, T.; Allerberger, F.; Coia, J.E.; et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin. Microbiol. Infect. 2021, 27 (Suppl. S2), S1–S21.
DD may be infectious causes or non infectious causes:
*infectious as:
-Bacterial ( C. Difficile, E. Coli, salmonella)
-viral ( Rota virus
-parasite (giardiasis ,amebesis)
*non infectious:
-drug induced
-Inflammatory bowel disease
it is mostly toxic megacolon due to C. difficile toxins
Diagnosis:
stool cultures for c.difficile
c.difficile PCR
Colonoscopy is contraindicated due to high risk of perforation
The management:
ICU admission
resuscitation
correct electrolytes
NPO
stop myfortic and reduction of CNI dose by 50%
change steroid to IV
oral vancomycin or IV metronidazole
Surgical intervention for colectomy
1. What are the possible diagnoses?
Pseudomembranous colitis brought on by Clostridium difficile progressed to fulminant colitis worsened by toxic megacolon.There are additional infectious and non-infectious causes of diarrhea.
E. choli, Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp. are among the bacteria that can cause infectious diarrhea. Rotavirus, adenovirus, and sapovirus are viruses. Giardia, cryptosporidium, microsporidium, and Entamoeba are parasites.
Non-infectious diarrhea; immune suppressive medications, including tacrolimus, cyclosporin, and sirolimus; non-immune suppressive medications, such as antibiotics and PPIs; and other conditions, such as GVHD, PTLD, post-infectious irritable bowel syndrome, inflammatory bowel disease, celiac disease, and microscopic colitis.
2. Substantiate the diagnosis?
Toxin culture and cell cytotoxicity are the gold standard tests for diagnosing C. difficile, but because they require 24 to 48 hours, they are not suited for this critically ill patient.
-C. difficile real-time PCR (high sensitivity and specificity, 90%) or fecal enzyme immune assay.
The index instance does not require a colonoscopy due to the possibility of perforation.
3. Who is to treat the patient?
This patient should be admitted to the intensive care unit with a multidisciplinary team.
Supportive therapy, including intravenous rehydration and replenishment with electrolyte replacements
Stop MMf, lower the CNI dose, and perhaps raise the stress dose of steroids.
-Close monitoring of liver function, CBC, venous blood gases, and electrolytes in addition to graft performance
Aggressive medicinal therapy may help avoid surgical intervention in toxic megacolon caused by C. difficile in up to 50% of cases.
Because of insufficient intestinal motility, oral vancomycin may not produce adequate intracolonic concentrations of the antibiotic.
Vancomycin enemas have been advised as a result; however, they might not be effective for treating colon disease on the right side.
Nasogastric suction and regular patient positional changes may help to relieve the pressure on the dilated colon. Some writers advise lying on one’s back for 10 to 15 minutes every two to three hours to allow flatus to pass.
Holding off on using drugs that reduce intestinal motility is another aspect of managing toxic megacolon. These drugs include opioids, anticholinergics, antidepressants, and antidiarrheals.
Up to 80% of patients with toxic megacolon caused by C. difficile colitis may require surgical intervention.
Surgery is advised in cases of perforation, progressive colon dilatation, failure to improve clinically during the first 48–72 hours, and uncontrolled bleeding.
A 64-year-old woman presented to the hospital with 3 days of abdominal pain, nausea, vomiting and profuse watery diarrhoea. She was recently discharged from the hospital for a urinary tract infection following a successful renal transplant from her son with excellent function. She is currently on Tacrolimus (trough level 9 ng/ml), Myfortic (720 mg bd) and prednisolone (15 mg od). She had just completed a 14-day course of ciprofloxacin.
On admission to the hospital, the blood pressure was 65/41 mmHg. Hypothermia was present. The temperature was 35.8°C. She was obese and appeared in mild distress. Her abdomen was mildly distended, with silent bowel sounds. There was tenderness in the lower quadrants without rebound tenderness.
The WBC was 53.9 109 /L with 84% neutrophils. The Hct was 36.1%. There was severe metabolic acidosis with an anion gap of 19, bicarbonate level of 12 mmol/ L, and lactic acid level of 3.6 mmol/L. The arterial blood gas demonstrated a pH of 7.11, CO2 of 16, and O2 of 150 on 2 litres of oxygen via nasal cannula. The serum creatinine was 1051 μmol/L. The K+ was 2.5 mmol/L, and Mg++ of 0.24 mmol/L. The INR was 2.1.The patient was resuscitated with IV fluids and placed on dopamine and later norepinephrine. She was also given intravenous ciprofloxacin 500 mg every 12 h, oral vancomycin 250 mg every 6 h and IV metronidazole 500 mg every 6 h. A CT of the abdomen and pelvis demonstrated circumferential wall thickening of the colon consistent with pan colitis (see below). The transverse colon was dilated to 5.8 cm. The colonoscopy is shown below.
The patient did not improve despite treatment over the next 36 h. The WBC rose to 62.4 109 /L with a more tender abdomen. A repeat CT scan showed transverse colon was dilated to 8.7cm. There was no other source of infection. Blood, urine, and stool cultures were negative.
DDX;
Confirm diagnosis;
Criteria for toxic megacolon in our case above; colonic dilatation >6.cm,fever >38.5,Tachycardia >120,neutrophil count> 10000/m ,hypotension ,electrolyte imbalance and altered sensorium.
Management;
Substantiate answer.
1. Issues/ concerns
– 64yo woman, 3/7 hx of abdominal pain, nausea, vomiting, profuse watery diarrhoea
– recently discharged from the hospital for a UTI
– successful LDKT, donor son, excellent kidney function
– medication: tacrolimus (trough level 9ng/ml), myfortic 720mg BD, prednisone 15mg OD
– has just completed 14 days of ciprofloxacin
– at admission: hypotensive BP 65/41, hypothermia 35.8, obese, mild distress, mild abdominal distension, silent bowel sounds, tenderness in the lower quadrants with no rebound tenderness
– WBC 53.9/L, neutrophils 84%, Hct 36.1%
– severe metabolic acidosis, AG 19, bicarb 12mmol/l, lactate 3.6 mmol/L, pH 7.11, CO₂ 16, O₂ 150 on 2L/min oxygen via nasal canula
– sCR 1051 μmol/L, K+ 2.5 mmol/L, Mg 0.24 mmol/L, INR 2.1
– patient resuscitated with IVF, placed on dopamine and later norepinephrine
– was given ciprofloxacin 500mg IV BD, vancomycin 250mg every 6hours, metronidazole 500mg IV TID
– Abdominopelvic CT scan done demonstrated pan colitis (circumferential wall thickening of the colon), transverse colon was dilated to 5.8cm
– patient did not improve despite treatment over the next 36 hours
– WBC increased to 63.4/L, abdomen was more tender, repeat CT scan showed transverse colon was dilated to 8.7cm
– no other source of infection, blood, urine and stool cultures were negative
What is the differential diagnosis? (1, 2)
– Sepsis, septic shock
– Toxic megacolon
– Infectious: –
· Bacterial: C. difficile pseudomembranous colitis, salmonella (typhoid and nontyphoid), shigella, campylobacter, yersinia, E. coli
· Parasitic: Entamoeba histolytica, cryptosporidium
· Viral: CMV colitis (disseminated CMV infection)
· Self-limited colitis (culture negative)
– Inflammatory: –
· Ulcerative colitis
· Crohn’s colitis
– Other: –
· Kaposi sarcoma
– E. coli can cause hemorrhagic colitis and hemolytic uremic syndrome which can result in toxic megacolon
– use of loperamide in fulminant amoebic colitis can precipitate toxic megacolon
How would you confirm the diagnosis? (3-5)
– history and physical examination: malaise, abdominal pain, bloody diarrhoea, abdominal distension, drug history (antibiotics, antimotility drugs, chemotherapy), fever, tachycardia, hypotension, altered mental status, distended abdomen
– diagnostic criteria for toxic megacolon: –
· radiologic evidence of colonic dilatation i.e., diameter >6cm
· plus at least 3 of the following: fever >38, HR >120, leukocytosis >10,500microL, anaemia
· plus at least 1 of the following: dehydration, electrolyte disturbances, hypotension, altered sensorium
– initial abdominopelvic CT scan with oral and IV contrast to establish the diagnosis and exclude complications that require urgent surgery
– thereafter, serial plain abdominal radiographs to monitor progression of colonic dilatation
– laboratory studies: CBC, UECs, LFTs, ESR, CRP, procalcitonin, stool for m/c/s and C. difficile toxin, CMV PCR, stool bacterial and viral PCR
· neutrophilia (especially with C. difficile), neutropenia (in sepsis, immunocompromised patients)
· anaemia due to GI blood loss
· hypokalemia and metabolic alkalosis due to diarrhoea and colonic inflammation
· metabolic acidosis suggests ischaemic colitis
· hypoalbuminemia due to protein loss, chronic inflammation, malnutrition
– colonoscopy indicated for selected patients – it is best avoided due to the risk of colonic perforation, worsening ileus, distension
– biopsy and histology: characteristic findings in C. difficile (pseudomembranous appearance), amoebic colitis (presence of trophozoites, punched-out ulcers), CMV colitis (inclusion bodies)
– assess for risk factors for development of severe colitis in patients with C. difficile infection: immunosuppressive therapy, kidney failure, exposure to clindamycin, anti-peristaltic drugs, malignancy, COPD
– hypokalemia, antimotility drugs, abrupt cessation of steroids can precipitate toxic megacolon
Who would manage this patient? (4, 6-8)
– aim of treatment is to reduce colonic inflammation, restore normal colonic motility, reduce likelihood of colonic perforation
– initial management is supportive and medical, prevents surgery in 50% of the patients
– however, delaying surgery can increase the risk of complications like abdominal compartment syndrome, bowel perforation leading to poor prognosis
– hold immunosuppressants (tacrolimus, myfortic and prednisone), maintain on hydrocortisone 100mg IV TID until she is stable
– supportive management:
· ICU monitoring due to systemic toxicity
· fluid therapy – IVF
· correct electrolyte imbalances
· broad-spectrum antibiotics for management of sepsis
· in case of colonic perforation administer H₂ blockers or PPIs for GI prophylaxis, DVT prophylaxis
· complete bowel rest and NGT bowel decompression initially then
· enteral feeding – it hastens mucosal healing, stimulates normal motility, can be started as soon as the patient improves
· consider TPN for patients who cannot tolerate enteral nutrition
· stop medications that can affect colonic motility e.g., anticholinergics, opiates
· maneuvers to redistribute and expel gas in the colon – intermittent rolling or the knee-elbow position
· surgical consultation
– definitive management:
· Medications are 1st line therapy
· Indications for surgery: intrabdominal hypertension, abdominal compartment syndrome, colonic perforation, necrosis, full thickness ischemia, peritonitis, worsening abdominal examination, organ failure requiring vasopressors, intubation, mechanical ventilation, AKI
· Surgical options: total abdominal colectomy, diverting ileostomy with colonic lavage
– C. difficile infection (CDI) management
· stop inciting antibiotics
· avoid steroids in infectious colitis
Non-fulminant disease· initial episode of non-severe disease (WBC <15,000 cells/mL, sCr <1.5mg/dL) or severe disease (WBC >15,000 cells/ mL, sCr >1.5mg/dL): –
– give Fidaxomicin 200mg PO BD 10/7 or Vancomycin 125mg PO QID 10/7 or Metronidazole 400mg PO TID 10-14/7
· recurrent episode of CDI – initiate antibiotics and add bezlotoxumab 10mg/kg IV stat
· first recurrence of CDI – fidaxomicin, vancomycin, bezlotuxumab
· second or subsequent recurrence of CDI – fidaxomicin, vancomycin + rifaximin 400mg TID 20/7, bezlotoxumab; there is a role for fecal microbiota transplantation
Fulminant disease as evidenced by hypotension or shock, ileus, megacolon- absence of ileus – Vancomycin 500mg PO/ NGT QID and metronidazole 500mg IV TID
– ileus present – FMT (per rectal) or rectal vancomycin
Substantiate your answer
References
1. Rubin MS, Bodenstein LE, Kent KC. Severe Clostridium difficile colitis. Diseases of the colon and rectum. 1995 Apr;38(4):350-4. PubMed PMID: 7720439. Epub 1995/04/01. eng.
2. Hommes DW, Sterringa G, van Deventer SJ, Tytgat GN, Weel J. The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research. Inflammatory bowel diseases. 2004 May;10(3):245-50. PubMed PMID: 15290919. Epub 2004/08/05. eng.
3. Trudel JL, Deschênes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous enterocolitis. Diseases of the colon and rectum. 1995 Oct;38(10):1033-8. PubMed PMID: 7555415. Epub 1995/10/01. eng.
4. Autenrieth DM, Baumgart DC. Toxic megacolon. Inflammatory bowel diseases. 2012 Mar;18(3):584-91. PubMed PMID: 22009735. Epub 2011/10/20. eng.
5. Jalan KN, Sircus W, Card WI, Falconer CW, Bruce CB, Crean GP, et al. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology. 1969 Jul;57(1):68-82. PubMed PMID: 5305933. Epub 1969/07/01. eng.
6. Louie TJ. Treatment of first recurrences of Clostridium difficile-associated disease: waiting for new treatment options. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2006 Mar 15;42(6):765-7. PubMed PMID: 16477550. Epub 2006/02/16. eng.
7. Sheth SG, LaMont JT. Toxic megacolon. Lancet (London, England). 1998 Feb 14;351(9101):509-13. PubMed PMID: 9482465. Epub 1998/03/03. eng.
–
This seems to be toxic megacolon due to C, Def
ICU stay , involvement of surgical gastro with aim to avoid colonic perforation which is likely with colonoscopy
diagnosis-
C def toxin in stool – quick test
culture
serology like EIA
· What is the differential diagnosis?Septic shock 2ry to toxic megacolon & perforation complicated by AKI & metabolic acidosis.DD: C.diff , IBD & CMV colitis. · How would you confirm the diagnosis?– C.diff toxin in stool- CMV PCR- Colonoscopy is not appropriate due to risk of perforation.· Who would manage this patient?MDT with involvement in ICU setting with transplant team, ID team & surgical team.· Substantiate your answer!Management is:1- Supportive measures: inotropes keeping MAP above 65mmgh, good hydration by IV fluids, IV antibiotics 2- Management of immunosuppression: hold MMF temporarily, decrease tacrolimus by 50 % with trough level monitoring around 63- Management of C.diff by ID protocols4- Surgical team has the upper hand to decide for urgent colectomy
The clinical picture is highly suggestive of fulminant C diff colitis with shock and toxic megacolon
AKI secondary to volume depletion
Electrolyte disturbance secondary to GI loss
The diagnosis can be confirmed by
NAAT
Enzyme immunoassay for C. difficile toxins A and B
Cell culture cytotoxicity assay
Management
Need ICU admission for circulatory support, fluid resuscitation and inotropes
Correction of electrolyte
Withhold MMF and Tac for now, continue steroid
Discontinue causative antibiotics
Might need CVVH in the acute setting
Vancomycin, metronidazole +/- fidaxomicin which has the same efficiency as vancomycin but less associate with less recurrence
Early surgical review and assessment, Once stabilised, might need colectomy of no improvement although surgical mortality is high
Faecal transplant is an alternative
What is the differential diagnosis?
· This patient has Toxic megacolon mostly due to C. difficile infection.
· immunosuppressive therapy and antibiotic treatment are considered important risk factors for C. difficile infection
DIFFERENTIAL DIAGNOSIS
· Ogilvie’s syndrome (colonic pseudo-obstruction), volvulus, or ischemia
· Infectious diarrhea – due to Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp
· Inflammatory bowel disease
How would you confirm the diagnosis?
· Toxic megacolon should be suspected in patients with abdominal distension and diarrhea.
· Criteria for toxic megacolon diagnosis:
1) Radiographic evidence of colonic dilation (diameter >6 cm)
2) PLUS at least three of the following:
•Fever >38ºC
•Heart rate >120 beats/min
•Neutrophilic leukocytosis >10,500/microL
•Anemia
3) PLUS at least one of the following:
•Dehydration
•Altered sensorium
•Electrolyte disturbances
•Hypotension
Manifestations of Severe and fulminant colitis due to Clostridioides difficile infection:
diarrhea, lower quadrant or diffuse abdominal pain, abdominal distention, fever, hypovolemia, lactic acidosis, hypoalbuminemia, elevated creatinine concentration, and marked leukocytosis (white blood cell count 40,000 cells/microL or higher)
· Fulminant colitis (previously referred to as severe, complicated C.difficile Infection) may be characterized by hypotension or shock, ileus, or megacolon
· The diagnosis of CDI is established via either a positive NAAT for C. difficile toxin gene or a positive stool test for C. difficile toxin(s).
Who would manage this patient?
· Supportive therapy in intensive care because of systemic toxicity.
Treatment of Fulminant disease of Clostridioides difficile infection (CDI) in adults
· Absence of ileus: Enteric vancomycin plus parenteral metronidazole:
· If ileus is present, additional considerations include:
· Fecal microbiota transplantation FMT (administered rectally) OR
· Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)
Indications for operative management in patients with CDI
· A diagnosis of CDI as determined by one of the following:
1) Positive laboratory assay for C. difficile
2) Colonoscopic findings consistent with C. difficile colitis
3) CT scan findings consistent with C. difficile colitis (pancolitis with or without ascites)
· Plus any one of the following criteria:
1) Peritonitis
2) Colonic perforation or full-thickness ischemia
3) Sepsis
4) Respiratory failure requiring intubation and mechanical ventilation
5) Vasopressor requirement after resuscitation
6) Mental status changes attributable to C. difficile colitis
7) Clinical deterioration despite adequate medical management
8) Acute renal failure (or other worsening end-organ failure)
9) Serum lactate level >5 mmol/L
10) White blood cell counts greater than or equal to 50,000 cells/mL
11) Abdominal compartment syndrome or intra-abdominal hypertension
Substantiate your answer!
https://www.uptodate.com/contents/toxic-megacolon?search=toxic%20megacolon&source=search_result&selectedTitle=1~104&usage_type=default&display_rank=1#H12:~:text=Back-,Toxic%20megacolon,-Topic
https://www.uptodate.com/contents/clostridioides-difficile-infection-in-adults-clinical-manifestations-and-diagnosis?sectionName=Endoscopy&search=toxic%20megacolon&topicRef=1381&anchor=H4904350&source=see_link#:~:text=Clostridioides%20difficile%20infection%20in%20adults%3A%20Clinical%20manifestations%20and%20diagnosis
What is the differential diagnosis?
How would you confirm the diagnosis?
Management
1. surgical by Urgent total if one of the following is present:
· Evidence of perforation, peritonitis acute compartmental syndrome
· Severe sepsis with end organ damage
2. Conservative treatment in the form of
· Caution decompression because of risk of perforation.
· Metronidazole or oral vancomycin.
· Hydrocortisone IV
· Correction of dehydration and electrolytes disturbances
References
1- Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351:509.
2- Fazio VW. Toxic megacolon in ulcerative colitis and Crohn’s colitis. Clin Gastroenterol 1980; 9:389.
3- Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology 1969; 57:68.
4- Ahmed N, Kuo YH. Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection. South Med J 2020; 113:345.
What is the differential diagnosis?
Clostridium Difficile induced pseudomembranous colitis developed fulminant colitis complicated with toxic megacolon.
Other infectious and noninfectious causes of diarrhea.
Infectious diarrhea;
Bacterial; E choli, Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp.
Viruses; Rotavirus, adenovirus, sapovirus
Parasites; Giardia, cryptosporidium, Microsporidium, Entameoba
Non-infectious diarrhea;
Immune suppressive drugs; MMF, tacrolimus, cyclosporin, sirolimus
Non-immune suppressive drugs e.g antibiotics, PPI, antidiabetic
How would you confirm the diagnosis?
History: Details History of prolonged Ab Course.
Examination: Vital signs (Hypotension, Fever, Tachycardia, tachypneic, obtunded, and physical findings may be minimal due to high-dose steroids to r/o toxic megacolon.
toxin culture & cell-cytotoxicity but it takes 24-48 hours, so it is not appropriate test for this critical ill patient.
Fecal enzyme immune assay or real-time C. difficile PCR (with high sensitivity & specificity (90%).
Colonoscopy is not indicated due to the risk of perforation.
Who would manage this patient?
NPO / NGT (bowel rest)
ABCD/ICU Support
Aggressive IV fluids, O2 to prevent AKI
Antibiotics should be given if an infectious cause is suspected.
Discontinue MMF or Myfortic
Hydrocortisone stress dose
Steroids should be given hydrocortisone 100 mg over 6 hours or methylprednisone 60 mg daily for 5 days.
Tacrolimus level can be reduced, levels should be monitored during metronidazole treatment to avoid toxicity.
the treatment of severe forum of C difficle with toxic megacolon.
Metronidazole 500mg IV TID and Oral vancomycin 125 mg to 500 mg QID (if tolerated) for 14 days or fidaxomicin 20 mg two times per day for 10 days.
Prevention and treatment of relapsing and refractory forms is difficult
Fidaxomicin, ramoplanin and tigecycline are effective for the treatment of severe
or recurrent disease.
IVIG 250-500mg/kg IV x1
human monoclonal antibodies against C. difficile toxins A and B
Fecal microbiota transplantation (FMT) in refractory cases but under trial.
Ciprofloxacin was just finished so no introduction of other antibiotics except those for C difficle
The treatment of MMF colitis includes a reduction or, in more severe forms, complete discontinuation of MPA.
Indications for surgical consultation in the management of C. DIFF Infection after stabilizing your patients:
Any one of the following: Hypotension with or without required use of vasopressors.
Fever ≥38.5°C
Ileus or significant abdominal distention
Peritonitis or significant abdominal tenderness
Mental status changes
WBC ≥20,000 cells/mL
Serum lactate levels >2.2 mmol/L
Admission to intensive care unit for CDI
End organ failure (mechanical ventilation, renal failure, etc.)
Failure to improve after three to five days of maximal medical therapy.
References
Clostridioides difficile infection in adults: Treatment and prevention(UpToDate)
Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130
Bagdasarian N., Rao K. and Malani P. Diagnosis and Treatment of Clostridium difficile in Adults: A Systemic Review. JAMA, 2015;313(4):398-408.
-Valey A and Ferrada P. Role of Surgery in Clostridium difficile Infection. Clin. Colon Rectal Surgery, 2020;33(2):87-91.
What is the differential diagnosis?In this scenario, the likely cause is infective causes diarrhoea. The patient is currently in septic shock in DIVC (coagulopathy), complicated by AKI and toxic megacolon. This is also compounded by electrolyte imbalance due to severe diarrhoea (hyponatraemia, hypomagnesemia) and metabolic acidosis (lactic acidosis).
Differential diagnosis
Bacterial causes:
1) Clostridium difficile (provisional diagnosis)
2) Salmonella
3) E.Coli
4) Campylobacter
Virus causes:
1) CMV
2) Norovirus
3) Adenovirus
Parasite:
1) Giardia
2) Cryptosporidium
3) Microsporadium
4) Isospora
How would you confirm the diagnosis?1) Stool examination for clostridium difficile (toxin, culture,nucleic acid amplification test (NAAT) or enzyme immunoassay to detect glutamate dehydrogenase (EIA GDH)
Who would manage this patient?1) Aggressive fluid resuscitation
2) NG tube for bowel decompression
3) Electrolytes correction (potassium and magnesium)
4) Withhold MMF and advagraf (may need to restart once infection is improving)
5) Switch prednisolone to hydrocortisone 100 mg TDS
6) Switch oral vancomycin (poor absorption in this case to Fidaxomicin
7) If failed to consider faecal microbiota (FMT)
8) Other novel alternative therapy is Bezlotoxumab
References
1.Infectious Diseases Society of America (IDSA)
2.Society for Healthcare Epidemiology of America (SHEA)
3.van Prehn, J.; Reigadas, E.; Vogelzang, E.H.; Bouza, E.; Hristea, A.; Guery, B.; Krutova, M.; Norén, T.; Allerberger, F.; Coia, J.E.; et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin. Microbiol. Infect. 2021, 27 (Suppl. S2), S1–S21.
What is the differential diagnosis
This is a case of post transplantation diarrhea and acute colitis
I- Infectious causes
1- Viral
CMV
Norvovirus
1- Bacterial :
Cl. Difficile , Campylobacter
2- Protozoa
3- Fungal
II- Non infectious causes:
Mostly related to drugs specially MMF and combined MMF with TAC
DD for acute colitis
1-Infectoius causes : Cl difficile ,salmonella typhea and paratyphea.
2-Non infectious causes
-IBD
-Drug induced colitis
– ischemic colitis
This patient is still in early posttransplantation period so CMV possibility is uncommon. She received 14 day course of cipro followed by development of diarrhea ,so she most likely has pseudomembranous colitis.
· B- How would you confirm the diagnosis?The gold standard tests for diagnosing Cl difficle infection are to detect Cl difficle toxins in stool through
– Enzyme Immune assay : most commonly used in clinical settings
– toxigenic culture : consist of standard stool cultures from diarrheal stool to identify both toxigenic and non toxigenic strains. But has long turn around and delayed results
– – cytotoxin neutralizing assay : based on detection of the cytopathic effect of toxin B preoduced by Cl difficle on cells and the neutralizating its effect by antitoxin
· Real time PCR assay to detect cl difficile genr toxins
· Colonoscopy : not routinely recommended and very high risk in our current case due to risk of perforation.
· CT
· C- How would manage this patient?This patient presented with septic shock complicated with AKI toxic megacolon.
–Diagnostic criteria of septic shock are ( persistent hypotension reqiring vasopressor agent and serum lacticacid more than 2 mmol).
– Diagnostic criteria of toxic megacolon :
Radiological evidence of dilated colon > 6 cm , plus 3 of the following
1- Fever >38.6 C
2- Tachycardia > 120 b/min
3- Leukocytosis or anemia
4- Any of the following : altered mental status ,hypovolemia, hypotension or electrolytes disturbance
Initial treament
1- Stabilize the patient : bowel rest , nasogastric tube insertion to relieve upper GIT distension , repositioning the patient to decompress the colon by moving the air to the desending colon and rectum through rolling maneuvers and prone knee –elbow position.
2- correct hypovolemia and replace electrolytes deficit
3- Adjust IS dose : stop MMF and reduce Tac dose by 50% .
Specific treatment for Cl . difficile :
Start with oral vancomycin in severe cases as such patient plus metronidazole ,followed by rifixin if no response to vancomycin
If initial management fail, other potential options include fecal transplantation ,IVIG.
Shelter et al recommended colonoscopic decompression and intracolonic vancomycin administarion.
Ref
1-Johnson TA, Tabbut BR, Page CO. Treatment of antibiotic-associated pseudomembranous colitis with metronidazole. Am J Hosp Pharm. 1981 Jul;38(7):1034-5. PMID: 7258204.
2-Buxey KN, Sia C, Bell S, Wale R, Wein D, Warrier SK. Clostridium colitis: challenges in diagnosis and treatment. ANZ J Surg. 2017 Apr. 87(4):227-31.
3-Shetler K, Nieuwenhuis R, Wren SM, Triadafilopoulos G. Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis. Surg Endosc. 2001 Jul. 15(7):653-9.
What is the differential diagnosis?Clostridium difficile associated diarrhoea is the most likely cause in a patient with prior history of antibiotic use and presence of toxic megacolon. Also CDAD is most likely associated with fluroquionolones which the patient had history of use.
Other differentials:
Viral: CMV, rotavirus, Noravirus
Bacterial: Campylobacter, shigella, salmonella
Protozoa: Giardia, cryptosporidium
Fungal
Non-infectious: crohns disease
How would you confirm the diagnosis?Nucleic acid amplification test-can detect both toxin A and B. They have high sensitivity though do not differentiate disease from colonisation.
Toxin EIA: they are high specific though they lack sensitivity
Cell culture neutralisation assay: it has high sensitivity for the B toxin however is not routinely available on all cell centers.
Culture can be done though there is delay of results for uptown 1 week.
Colonoscopy in this patient is contraindicated due to risk of perforation.
Who would manage this patient?This patient requires management in an ICU setup.
She requires fluids and electrolyte replacement as she is hypotensive with electrolyte imbalances.
The management of pseudomembranous colitis include oral vancomycin/ IV metronidazole/ Oral fidaxomicin; fluid and electrolyte replacement and cessation of the causative antibiotic.
Oral vancomycin is not absorbed in the GIT hence leading to concentration in the gut however should be avoided when there is perforation.
The patient also requires surgical consult due to the megacolon, the colon can be decompressed with nasogastric suction.
References
Laboratory Tests for the Diagnosis of Clostridium difficileKaren C. Carroll, MD and Masako Mizusawa, MD, PhD, MS
Pseudomembranous Colitis Surgery Treatment & ManagementSaid Fadi Yassin, MD; Chief Editor: John Geibel, MD, MSc, DSc, AGAF
Current and Future Treatment Modalities for Clostridium difficile-Associated Disease
Jennifer Halsey, M.S., Pharm.D
1-What is the differential diagnosis?
*Clostridium Difficile induced pseudomembranous colitis developed fulminant colitis complicated with toxic megacolon.
*Other infectious and noninfectious causes of diarrhea.
Infectious diarrhea;
*Bacterial; E choli, Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp.
*Viruses; Rotavirus, adenovirus, sapovirus
* Parasites; Giardia, cryptosporidium, Microsporidium, Entameoba
Non-infectious diarrhea;
*Immune suppressive drugs; MPA, tacrolimus, cyclosporin, sirolimus
*Non-immune suppressive drugs e.g antibiotics, PPI, antidiabetic
*Others e.g.,
GVHD, PTLD, Post-infectious irritable bowel syndrome, inflammatory bowel disease, celiac disease, and microscopic colitis.
2-To confirm the diagnosis?
-The gold standard test for C. difficile diagnosis are toxin culture & cell-cytotoxicity but it takes 24-48 hours, so it is not appropriate test for this critical ill patient.
-Fecal enzyme immune assay or real-time C. difficile PCR (with high sensitivity & specificity (90%).
–Colonoscopy is not indicated in the index case due to the risk of perforation.
3-Who would manage this patient?
-This critically ill patient with septic shock should be admitted under ICU with MDT (Intensivist, Nephrologist, Infectious disease specialist and Surgeon).
-Counseling her family regarding critical condition of having high mortality.
-Supportive therapy; Resuscitation & replenishment with intravenous fluids and electrolytes replacements.
-Stop MMf and decrease CNI dose, may increase steroids dose to stress dose.
-Close monitoring of graft function, liver function ,CBC ,venous blood gases and electrolytes.
-In the treatment of C. difficile related toxic megacolon, aggressive medical therapy may help prevent surgical intervention in up to 50% of cases.
-Adequate intracolonic concentrations of vancomycin may not be achieved with oral vancomycin because of poor intestinal motility.
-Therefore, vancomycin enemas have been recommended; however enemas may fail to treat right-sided disease of the colon.
-The dilated colon may be decompressed with nasogastric suction and frequent repositioning of the patient, some authors recommend prone positioning for 10 to 15 min every 2 to 3 h allowing the passage of flatus.
-Management of toxic megacolon also includes with holding medications that slow intestinal motility. These medications include anticholinergics, antidepressants, antidiarrheals, and narcotics.
-Surgical intervention may be necessary in up to 80% of patients with toxic megacolon due to C. difficile colitis.
-Surgery indicated in such situations; perforation, progressive dilation of the colon, lack of clinical improvement over the first 48-72 h and uncontrolled bleeding.
References;
-Bagdasarian N., Rao K. and Malani P. Diagnosis and Treatment of Clostridium difficile in Adults: A Systemic Review. JAMA, 2015;313(4):398-408.
-Valey A and Ferrada P. Role of Surgery in Clostridium difficile Infection. Clin. Colon Rectal Surgery, 2020;33(2):87-91.
-Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130.
What is the differential diagnosis?
The infectious diarrhea post-transplant with leucocytosis and sepsis usually caused by severe Clostridium difficile infection.
The infectious diarrhea post-transplant with leucocytosis and sepsis after prolonged course of antibiotics in this post kidney transplant patient is also consistent with Pseudomembranous colitis caused by severe Clostridium difficile infection.
The colonoscopy image shows raised elevated yellow-white nodules or plaques forming mucosal pseudomembranous that are characteristic of pseudomembranous colitis, commonly a manifestation of severe colonic disease that is usually associated with Clostridium difficile infection because of the prolonged use of broad-spectrum antibiotics.
Any broad-spectrum antibiotics can cause pseudomembranous colitis – especially clindamycin and ampicillin.
Diarrhea because of pseudomembranous colitis occurs in about 3-10% of adults receiving antibiotics.
Pseudomembranous colitis can be life-threatening and possible complications include:
Toxic megacolon which is complicating the case in this scenario, as by CT image.
AKI, Sepsis, Dehydration and electrolytes disturbance from colonic perforation.
Broad Differential Diagnosis.
Bacteria: Clostridium difficile, Salmonella, Shigella Campylobacter, Ecoli….
Viral: CMV, HSV, Norovirus, sapovirus
Parasitic; Giardia, Entamoeba ,Cryptosporidium
Ischemic colitis, Ulcerative Colitis, Crohn Disease, Diverticulitis
Immunosuppressive related diarrhea(MPA-colitis)
Large-Bowel Obstruction
How would you confirm the diagnosis?
History: Details History of prolonged Ab Course,
Examination: Vital signs (Hypotension, Fever, Tachycardia, tachypneic, obtunded, and physical findings may be minimal due to high-dose steroids to r/o toxic megacolon
The most common criteria used to diagnose toxic megacolon are radiographic evidence of colonic dilatation, fever, tachycardia, neutrophilic leukocytosis, anemia, dehydration, altered mental status, electrolyte abnormality, or hypotension.
Peritoneal signs of perforation include rebound, rigidity, and irritation.
CBC, Lytes, ABGs, CRP,
Stool studies should include culture, O&P, and C difficile toxin testing.
C difficile is a clinical diagnosis with lab confirmation.
It is highly suspicious in the presence of severe diarrhea after antibiotic course complicated by toxic megacolon as per the findings.
A Positive Nucleic Acid Amplification Test For C. difficle Toxin Gene.
A Positive Stool Test for C. difficle.
Cell Culture Cytotoxicity Assay.
Selective Anaerobic Culture.
Toxin enzyme ELISA is specific, less sensitive as some can identify Toxin A only, inexpensive, easy, rapid.
PCR test Rapid, high sensitivity, simple, costly
Cytotoxicity cell assay is specific, sensitivity, time consuming and expensive.
Stool multiplex PCR
Stool culture is the most sensitive, for strain typing, expensive, does not determine if isolate is toxigenic, ≥ 48 hours for results.
Histology: Toxic megacolon demonstrates acute inflammation, necrosis, and infiltration of inflammatory cells.
Radiography; is essential for diagnosis and management of toxic megacolon, with air-fluid levels in the colon, deep mucosal ulcerations, air in the small bowel, segmental parietal thinning, and comparison with old baseline films.
Radiographic evidence of dilation of the colon, greater than 6 cm and fever, heart rate, neutrophilic leukocytosis, anemia, dehydration, altered sensorium, electrolyte disturbances, and hypotension are all signs of anemia.
CT scanning is useful for diagnosing toxic megacolon and is more accurate than plain radiography in detecting severe colitis.
It can show diffuse colonic wall thickening, accordion sign, multilayered appearance, and peri colic stranding.
Colonoscopy is not indicated in our case due to the risk of perforation.
Disease severity can be divided into 3 categories for treatment considerations:
Mild or moderate: diarrhea and abdominal cramping without systemic symptoms.
Severe: profuse diarrhea, abdominal pain, Leucocytosis and fever, or other systemic symptoms.
Severe disease with complications: life-threatening conditions such as paralytic ileus, toxic megacolon and multiorgan failure.
Who would manage this patient?
NPO / NGT (bowel rest)
ABCD/ICU Support
Aggressive IV fluids, O2 to prevent AKI
Antibiotics should be given if an infectious cause is suspected.
Discontinue MMF or Myfortic
Hydrocortisone stress dose
Steroids should be given hydrocortisone 100 mg over 6 hours or methylprednisone 60 mg daily for 5 days.
Tacrolimus level can be reduced, levels should be monitored during metronidazole treatment to avoid toxicity.
the treatment of severe forum of C difficle with toxic megacolon.
Metronidazole 500mg IV TID and Oral vancomycin 125 mg to 500 mg QID (if tolerated) for 14 days or fidaxomicin 20 mg two times per day for 10 days.
Prevention and treatment of relapsing and refractory forms is difficult
Fidaxomicin, ramoplanin and tigecycline are effective for the treatment of severe
or recurrent disease.
IVIG 250-500mg/kg IV x1
human monoclonal antibodies against C. difficile toxins A and B
Fecal microbiota transplantation (FMT) in refractory cases but under trial.
Ciprofloxacin was just finished so no introduction of other antibiotics except those for C difficle
The treatment of MMF colitis includes a reduction or, in more severe forms, complete discontinuation of MPA.
Indications for surgical consultation in the management of C. DIFF Infection after stabilizing your patients:
Any one of the following: Hypotension with or without required use of vasopressors.
Fever ≥38.5°C
Ileus or significant abdominal distention
Peritonitis or significant abdominal tenderness
Mental status changes
WBC ≥20,000 cells/mL
Serum lactate levels >2.2 mmol/L
Admission to intensive care unit for CDI
End organ failure (mechanical ventilation, renal failure, etc.)
Failure to improve after three to five days of maximal medical therapy.
Reference;
Clostridioides difficile infection in adults: Treatment and prevention(UpToDate)
Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130
Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14. 351(9101):509-13.
Marshak RH, Lester LJ. Megacolon a complication of ulcerative colitis. Gastroenterology. 1950 Dec. 16(4):768-72.
Ausch C, Madoff RD, Gnant M, Rosen HR, Garcia-Aguilar J, Hölbling N, Herbst F, Buxhofer V, Holzer B, Rothenberger DA, Schiessel R. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
Moulin V, Dellon P, Laurent O, Aubry S, Lubrano J, Delabrousse E. Toxic megacolon in patients with severe acute colitis: computed tomographic features. Clin Imaging. 2011 Nov-Dec. 35(6):431-6.
Sarah E. Ward and Erik R. Dubberke, Clostridium difficile Infection in Solid Organ Transplant Patients, Antimicrobe/Transplant Infection
Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections [published correction appears in Am J Gastroenterol. 2022 Feb 1;117(2):358]. Am J Gastroenterol. 2021;116(6):1124-1147.
What is the differential diagnosis?This patient has severe colonic dilatation due to C difficiel infection
to detect C diff , will do PCR test to detect the organism, and it is highly sensitive while
This patient has Toxic megacolon with severe septic shock due to C difficile toxicity.
At the time of severe dilatation, better to avoid colonoscopy as it carries a high risk of perforation.
This patient first needs full resuscitation and decompression measure.
ALL IS should hold and continue will steroids only.
-Selective anaerobic culture highly sensitive and cannot distinguish toxin-producing strains from non-toxin-producing strains, a second test is required to detect toxin.
The pathologic appearance of toxic megacolon associated with other disorders is as follows:
●In toxic megacolon secondary to C. difficile (or, rarely, ischemia), the characteristic pathologic features include diffuse ulcerations, raised mucosal nodules, yellowish-white superficial plaques with normal intervening mucosa (typical “pseudomembrane” appearance), and extensive denudation .
references
uptodate
Narrative
Recent Tx (Tac, MMF, Steroid) had UTI ttt with Abx presented with diarrhea, septic shock and AKI
DD:
A) Sepsis for DD most likely diarrhea related
infection diarrhea, C Diff, Norovirus, Cambylobacter, CMV, or other infectious agents.Non infectionous, think graft versus host reaction, IBD, drug relatedB) AKI for DD which is multifactorial
Sepsis: needs work up and tttHypovoelmic: needs correctionToxins: recent Abx (Cipro) if newly started think TIN as associate culprit. CNI in DD however in this case levels was appropriateObstruction: Needs to role out BOO after UTIParenchyma: Rejection needs to be aleays in DD given early tx and recent UTIIntra abdominal compartment syndromeConfirm diagnosis:
1- sepsis work up
Cutlures (blood, urine , stool) reported as negativeStool test for C-Diff antigens and toxinsCMV2- Discuss with gastroenterolgist for their input
3- CT scan that was done and would show if there is urinary obstruction
************
Management
ressucitation in ITU setting with fluids, inotrops, CRRTcorrect electrolytesttt C-Diff infection per local guidlines Oral Vanc and metronidazole and consider Fidaxomicin and discuss with micro teamdiscuss with gastro if scope will be helpfulToxic mega colon has developed unfurtnatly and patient has approached criria for colectomyIndications for operative management in patients with CDI
A diagnosis of CDI as determined by one of the following:
Positive laboratory assay for C. difficileColonoscopic findings consistent with C. difficile colitisCT scan findings consistent with C. difficile colitis (pancolitis with or without ascites)Plus any one of the following criteria:
PeritonitisColonic perforation or full-thickness ischemiaSepsisRespiratory failure requiring intubation and mechanical ventilationVasopressor requirement after resuscitationMental status changes attributable to C. difficile colitisClinical deterioration despite adequate medical managementAcute renal failure (or other worsening end-organ failure)Serum lactate level >5 mmol/LWhite blood cell count greater than or equal to 50,000 cells/mLAbdominal compartment syndrome or intra-abdominal hypertension
Reference :
Uptodate Toxic megacolon accessed 1 April 23
What is the differential diagnosis?
How would you confirm the diagnosis?
Who would manage this patient?
MDT of transplant physician, general surgeon, intensivist, radiologist, microbiologist, gastroenterologist, nursing care
Reference
In this septic patient with shock, combined with leukocytosis and neutrophilia, history of antibiotic use, immunosuppression, MMF, and other medications, the first thing coming to mind is clostridium difficult rather than drug or viral infection. Empirical therapy as done, and searching for c.difficile tıxins (according to availability in the hospital: we have toxins A and B) should be done. Other factors can be taken in the differential diagnosis, like smv, etc. but the lab. Findings are not consistent (the differential CBC); combined etiologies can occur simultaneously
Thanks All
This patient needs resuscitation to avoid AKI due to dehydration and electrolyte disturbance.
Colonoscopy is not indicated in the index case due to the risk of perforation.
We always look for C Def toxins rather than culture. Of course culture for other organisms as a part of the differential diagnosis.
Confirm diagnosis by Cl difficile toxin identification by ELISA or detection of gene responsible for toxin by PCR
Colonscopy is better avoided in case of toxic megacolon for fear of perforation.
Dear prof, thank you
attached proposed plan for C.difficile
What is the differential diagnosis?C. difficile must be distinguished from other infectious and noninfectious causes of diarrhea.
●Infectious diarrhea – Other organisms that have been implicated as causes of antibiotic-associated diarrhea include Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp
The clinical manifestations are similar to those of CDI; the diagnosis is distinguished by stool culture and/or stool multiplex nucleic acid testing.
●Noninfectious diarrhea –
Causes of noninfectious diarrhea that may mimic CDI include postinfectious irritable bowel syndrome, inflammatory bowel disease, celiac disease, and microscopic colitis.
Enteric infections account for about 10 percent of symptomatic relapses in patients with IBD; C. difficile accounts for about half of these infections
•Microscopic colitis – Microscopic colitis is a chronic inflammatory disease of the colon characterized by chronic watery diarrhea. The diagnosis is established by histopathology following colonoscopy with biopsy.
•Celiac disease is a small bowel disease associated with dietary gluten exposure intolerance; gastrointestinal symptoms including chronic or recurrent diarrhea, malabsorption, weight loss, and abdominal distension or bloating. The diagnosis is established via serology and/or biopsy.
How would you confirm the diagnosis?The diagnosis of C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation, particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age) Patients with suspected C. difficile infection should be placed on contact precautions preemptively pending diagnostic evaluation
A number of laboratory stool tests are available alone or in combination as part of a diagnostic algorithm:
●NAAT
●Enzyme immunoassay for C. difficile GDH
●Enzyme immunoassay for C. difficile toxins A and B
●Cell culture cytotoxicity assay
●Selective anaerobic culture
Who would manage this patient?
Admission ICU
SURGERY
CRRT
In the treatment of C. difficile related toxic megacolon, aggressive medical therapy may help prevent surgical intervention in up to 50% of cases
The medical management of toxic megacolon includes
oral vancomycin, IV metronidazole, bowel rest, bowel decompression, and replacement of fluids and electrolytes
adequate intracolonic concentrations of vancomycin may not be achieved with oral vancomycin because of poor intestinal motility. Therefore, vancomycin enemas have been recommended; however enemas may fail to treat right-sided disease of the colon.
Other alternatives include direct instillation of vancomycin by colonoscopy, colostomy or ileostomy
The dilated colon may be decompressed with nasogastric suction and frequent repositioning of the patient[
Some authors recommend prone positioning for 10 to 15 min every 2 to 3 h allowing the passage of flatus.
Management of toxic megacolon also includes with holding medications that slow intestinal motility. These medications include anticholinergics, antidepressants, antidiarrheals, and narcotics
Surgical intervention may be necessary in up to 80% of patients with toxic megacolon due to C. difficile colitis
Surgery should be considered if there is progressive colonic dilation or if clinical improvement is not noted within 2 to 3 d.
Indications for surgery include: perforation, progressive dilation of the colon, lack of clinical improvement over the first 48-72 h and uncontrolled bleeding
total colectomy resulted in a lower mortality rate (11%) compared to those with a left hemicolectomy (100%).
Patients with an ileus should be given rectal vancomycin as well – even though there is a lack of evidence-based studies to confirm its efficacy.
Substantiate your answerIMPRESSION SEPTIC SHOCK -AKI
NOT IMPROVED NEED SURGICAL INTERVENTIONAL
Most antibiotic-associated diarrhea is not attributable to CDI (but rather to osmotic mechanisms), whereas antibiotic-associated diarrhea associated with colitis is nearly always due to CDI.Acute abdomen – CDI may present as abdominal distension mimicking small bowel ileus, Ogilvie’s syndrome (colonic pseudo-obstruction), volvulus, or ischemia
●Shock – Severe hypotension may occur in the setting of fulminant CDI and/or in the setting of bowel perforation with peritonitis. In addition, CDI may develop during antibiotic treatment for septic shock caused by a separate bacterial infection. Shock due to other causes (such as septic shock or cardiogenic shock) must be distinguished from severe hypotension due to CDI via cardiac and hemodynamic assessment.
Excellent Hamada
Yes, you have addressed the clinical condition very well including his fluid resuscitation, the electrolyte imbalance and the need for ICU treatment.
Diagnosis
Toxic Megacolon
Inflammatory Ulcerative colitis Crohn’s colitis
Infectious Bacterial Clostridioides difficile
pseudomembranous colitis
Salmonella – typhoid and nontyphoid
ShigellaCampylobacter
YersiniaParasitic
Entameba histolytica
Cryptosporidium
ViralCMV colitis
Self-limited colitis (culture negative)
CMV: cytomegalovirus.
How to confirm diagnosis
The diagnosis is made based on clinical signs of systemic toxicity combined with radiographic evidence of colonic dilatation (diameter >6 cm) The most widely used criteria are
Radiographic evidence of colonic dilation (diameter >6 cm)
PLUS at least three of the following:
Fever >38ºC
Heart rate >120 beats/min
Neutrophilic leukocytosis >10,500/microL
Anemia
PLUS at least one of the following:
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension
For c diff diagnosis
Diagnosis
•
The diagnosis of CDI is established via a positive nucleic acid amplification test (NAAT) for C. difficile toxin gene or a positive stool test for C. difficile toxin(s).
Management
General Management where we have to do basic resuscitation
Specific Management is according to cause.
This patient if confirmed with C diff colitis , fulfills the criteria of Fulminant colitis
Management of fulminant colitis consists of antibiotic therapy, supportive care, and close monitoring; in addition, patients should be assessed for surgical indications.
Antibiotic therapy — The approach to antibiotic therapy depends on whether concomitant ileus is present.
Absence of ileus — For treatment of patients with fulminant colitis but without ileus, we suggest oral (or per nasogastric tube) vancomycin (500 mg four times daily) plus parenteral metronidazole (500 mg every 8 hours)
In the setting of ileus, we suggest addition of FMT (administered via enema), rather than rectal vancomycin (Grade 2C). However, given risk of colonic perforation, this approach should be restricted to patients who are not responsive to standard antibiotic therapy and performed only by personnel with appropriate expertise.(up to date)
Excellent Zahid
Yes, he needs proper supportive measures as you mentioned and ICU support.
What is the differential diagnosis?
1. Clostridium difficile
2. Campylobacter sp
3. Bacterial over growth
4. Rota, adenovirus and CMV
5. Giardia and Cryptosporidium
6. CNI, MMF
7. IBD, PTLD
How would you confirm the diagnosis?
Could be confirmed by;
1. Hx of broad-spectrum antibiotics(cipro in this case)
2. Labs work like TLC, elevated Neutrophils and ESR
3. NAAT
4. Enzyme immunoassay for C difficile
5. Cell culture cytotoxicity assay
6. Selective anaerobic culture
7. Radiographic imaging(colonic dilatation of >7cm)
8. Endoscopy NOT warranted in this case
· Who would manage this patient?
· Explain the condition and usual prognosis of this patient to family and involvement of multidiscipline like GI and GI surgeon.
· Intensive care
· Stop offending agents like cipro
· Stop IS like MMF and CNIs
· Address metabolic derangements, patient would need RRT either CRRT/Prolong intermittent renal replacement therapy(PIRRT)
· Oral vancomycin 500mg QID, or may consider rectally
· May consider her for Bezlotoxumab or add fidaxomicin(lack evidence in such casese)
· References
1. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections [published correction appears in Am J Gastroenterol. 2022 Feb 1;117(2):358]. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
2. Apisarnthanarak A, Razavi B, Mundy LM. Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature. Clin Infect Dis. 2002;35(6):690-696. doi:10.1086/342334
3. Nathanson DR, Sheahan M, Chao L, Wallack MK. Intracolonic use of vancomycin for treatment of clostridium difficile colitis in a patient with a diverted colon: report of a case. Dis Colon Rectum. 2001;44(12):1871-1872. doi:10.1007/BF02234471
Excellent Faraman
Yes, he needs proper supportive measures as you mentioned and ICU support.
The patient was admitted previously for UTI and was treated with ciprofloxacin.
Now she is admitted with toxic megacolon< evidenced by
Radiographic evidence of colonic dilation (diameter >6 cm)
PLUS at least three of the following:
PLUS at least one of the following
Differential diagnosis will be:
I would confirm my diagnosis by investigations:
This patient should be managed by MDT, surgical team, gastroenterologist, infectious disease, Transplant physician and intensivist
The surgical indications are:
References
⭐ Differential diagnosis:
_infectious diarrhea (most probably here is clostridium difficile (old age, recent hx of 2 weeks treatment with ciprofloxacin )).
_otger infections as (viral infections as Norovirus, Rita and adenovirus, bacterial infections as salmonella and ECOLi, protozoa as cryptosporidium and giardia)
_non infectious as MMF induced or other drugs as (laxatives, PPI or anti arrhthmics).
⭐ to confirm the diagnosis:
_intital stool examination and culture for bacterial infection or ptozoa identification.
_identification of Cl difficile by ELISA or PCR for it’s toxin is more commonly used.
_CMV PCR.
⭐ Management:
_continue in supportive therapy (IV fluids resuscitation, fluid replacement and postive inotropes) .
_patient must be manged in ICU setting with MDT (intensivist, nephrologist, infectious disease specialist and surgeon).
_Gut decompression through NGT and NPO, plus rectal tube decompression.
_reduce IS (stop MMf and decrease CNI dose, may increase steroids dose to stress dose (to guard against adrenal crisis in such critical case and to prevent development of AR in the context of IS reduction)).
_care of critically ill patient (start IV PPI, close monitoring of vital signs and random glucose ).
_start treatment with oral vancomycin for 14 days (I think no role of IV metronidazole in such critically ill patient).
_close monitoring of graft function, liver function, CBC،venous blood gases and electrolytes is essential.
_surgical intervention is warranted if any evidence of perforation, severe cases with peritonitis) in which colonectomy and peritoneal toilet are indicated.
Excellent Mai
Yes, he needs proper supportive measures as you mentioned and ICU support.
Thanks dear professor
DD/Toxic megacolon
Inflammatory
Ulcerative colitis
Crohn’s colitis
Infectious
Bacterial
Clostridioides difficile pseudomembranous colitis
Salmonella – typhoid and nontyphoid
Shigella
Campylobacter
Yersinia
Parasitic
Entameba histolytica
Cryptosporidium
Viral
CMV colitis
Self-limited colitis (culture negative)
A diagnosis of CDI as determined by one of the following
Positive laboratory assay for C. difficile
Colonoscopic findings consistent with C. difficile colitis (raised yellowish white 2-10 mm plaques overlying erythematous edematous mucosa ,psausomebrane
3.CT scan findings consistent with C. difficile colitis (pancolitis with or without ascites
Patient is classified as fulminant disease /shock /ileus /megacolon
Treatment of fulminant disease
Absence of ileus: Enteric vancomycin plus parenteral metronidazole
Vancomycin 500 mg orally or via nasogastric tube 4 times daily, AND
Metronidazole 500 mg intravenously every 8 hours
If ileus is present, additional considerations include:
FMT (administered rectally) OR
Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)¶
Given potential risk of colonic perforation in setting of CDI, rectal vancomycin instillation should be performed by personnel with appropriate expertise.
Consider operative management
Indication of operative management
Peritonitis
Colonic perforation or full-thickness ischemia
Sepsis
Respiratory failure requiring intubation and mechanical ventilation
Vasopressor requirement after resuscitation
Mental status changes attributable to C. difficilecolitis
Clinical deterioration despite adequate medical management
Acute renal failure (or other worsening end-organ failure)
Serum lactate level >5 mmol/L
White blood cell count greater than or equal to 50,000 cells/mL
Abdominal compartment syndrome or intra-abdominal hypertension
The criteria proposed for defining fulminant CDI are based on expert opinion
2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 24:ciab549.
Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124.
Hrebinko K, Zuckerbraun BS. Clostridium difficile: What the surgeon needs to know. Semin Colon Rectal Surg 2018; 29:28. Table used with the permission of Elsevier Inc. All rights reserved.
He needs also ICU support to correct his fluid and electrolyte abnormalities before operating on him
DD/Toxic megacolon
Inflammatory
Ulcerative colitis
Crohn’s colitis
Infectious
Bacterial
Clostridioides difficile pseudomembranous colitis
Salmonella – typhoid and nontyphoid
Shigella
Campylobacter
Yersinia
Parasitic
Entameba histolytica
Cryptosporidium
Viral
CMV colitis
Self-limited colitis (culture negative)
A diagnosis of CDI as determined by one of the following
Positive laboratory assay for C. difficile
Colonoscopic findings consistent with C. difficile colitis (raised yellowish white 2-10 mm plaques overlying erythematous edematous mucosa ,psausomebrane
3.CT scan findings consistent with C. difficile colitis (pancolitis with or without ascites
Patient is classified as fulminant disease /shock /ileus /megacolon
Treatment of fulminant disease
Absence of ileus: Enteric vancomycin plus parenteral metronidazole†:
Vancomycin 500 mg orally or via nasogastric tube 4 times daily, AND
Metronidazole 500 mg intravenously every 8 hours
If ileus is present, additional considerations include:
FMT (administered rectally) OR
Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)¶
Given potential risk of colonic perforation in setting of CDI, rectal vancomycin instillation should be performed by personnel with appropriate expertise.
Consider operative management
Indication of operative management
Peritonitis
Colonic perforation or full-thickness ischemia
Sepsis
Respiratory failure requiring intubation and mechanical ventilation
Vasopressor requirement after resuscitation
Mental status changes attributable to C. difficilecolitis
Clinical deterioration despite adequate medical management
Acute renal failure (or other worsening end-organ failure)
Serum lactate level >5 mmol/L
White blood cell count greater than or equal to 50,000 cells/mL
Abdominal compartment syndrome or intra-abdominal hypertension
The criteria proposed for defining fulminant CDI are based on expert opinion
2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 24:ciab549.
Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124.
Hrebinko K, Zuckerbraun BS. Clostridium difficile: What the surgeon needs to know. Semin Colon Rectal Surg 2018; 29:28. Table used with the permission of Elsevier Inc. All rights reserved.
He needs also ICU support to correct his fluid and electrolyte abnormalities before operating on him
What is the differential diagnosis?–
this patient probably had features of C.difficile infections and risk factors for it could be;
-She is critically unwell, having septic shock, worsening toxic mega colon and pan colitis
-Allograft dysfunction with Metabolic derangement and not responding to initial treatment due to the toxic mega colon needing a surgical opnion.
-She also had poor prognostic features including raising WCC, with septic shock features.
Differential Diagnosis of diarrhea in posttransplant is wide and may include:
A. Infection
B. Non-infection
-To confirm the diagnosis?
-Managing this patient?
Source
Excellent Ahmedzeb
Yes, he needs proper supportive measures as you mentioned and ICU support.
What is the differential diagnosis?1.infectious colitis
2.immunosuppreesion related ,mostly MMF
3.denove or exacerbating existing IBD
4.GVHD
5.ischaemic colitis especially in those who have AF
How would you confirm the diagnosis?require work up for each category ,starting from the most likely diagnosis
in this case scenario…..clinical presentation with history of recent antibiotic usage .on the top of the list pseudomembranous colitis with toxic megacolon
diagnosis:
Who would manage this patient?
note:
if radiological finding of toxic megacolon …..better to avoid colonoscopy as delaying the surgical intervention and risk of perforation and sepsis
Excellent Dalshad
Yes, he needs proper supportive measures as you mentioned and ICU support.
Differential diagnosis
This is a Toxic megacolon due to C.dificile infection.
Other possibilities
Infectious causes;
Non-infectious causes
Confirmation of the diagnosis
Management of C.dificile infection.
References
He needs also ICU support to correct his fluid and electrolyte abnormalities before operating on him
Well done all. Clearly colonscopy is contraindicated because of the perforation risk although this patient did have colonscopy. Confirmation is by detection of C diff toxin as mentioned by most of you.
Were there any risk factors for this patient to develop C diff colitis?
What do you think the appropriate course of treatment here after she did receive both oral vancomycin and IV metronidazole, and the reasons behind your decision?
Thank you Prof ElKossi
the risk factors is
surgery may be an option if the condition is not responded
What is the differential diagnosis?
This post kidney transplant patient developed severe sepsis and septic shock imaging showed features of colitis and toxic megacolon he has history of UTI for which she completed 2 weeks course of ciprofloxacin the most likely diagnosis clostridium difficile pseudomembranous colitis complicated with toxic megacolon other differentials :
– How would you confirm the diagnosis?
– Who would manage this patient?
She is critically ill patient she needs:
Reference:
1. J. Clin. Med. 2022, 11, 4365. https://doi.org/10.3390/jcm11154365
2. Ann Intern Med. 2009 Aug 4;151(3):176-9. doi: 10.7326/0003-4819-151-3-200908040-00005.
3. Identification of a pseudo-outbreak of Clostridium difficile infection (CDI) and the effect of repeated testing, sensitivity, and specificity on perceived prevalence of CDI. Infect Control Hosp Epidemiol. 2009; (30):1166–1171.
4. Louie T, Gerson M, Grimard D, et al. Results of a phase III trial comparing tolevamar, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhea (CDAD). In: Proceedings of the 47th Annual ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy. 2007. Chicago
5. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comprison of vancomycin and metronidazole for the treatment of Clostridium-difficile associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007; 45(3): 302-7.
Excellent Nada
Yes, he needs proper supportive measures as you mentioned and ICU support.
Differential diagnosis (post transplant diarrhea):
(A) Infectious;
(B) Non infectious:
This patient receive ciprofloxacin for UTI infection in first post transplant month, so the most probable cause of diarrhea is C. difficile infection(opportunistic infection can occur in first month post transplantation, & the most common cause is antibiotic use especially fluoroquinolone).
Confirm diagnosis of C. difficile:
Management:
References:
He needs also ICU support to correct his fluid and electrolyte abnormalities before operating on him
What is the differential diagnosis?
The most likely diagnosis in this case scenario is infectious post transplant diarrhea due to leucocytosis and sepsis caused by severe Clostridium difficile infection complicated by toxic megacolon secondary to immunosuppression and receiving antimicrobial therapy for recent UTI episode
DD
Bacteria :Clostridium difficile ,Salmonella,Campylobacter ,Ecoli
Viral ;CMV,HSV,Norovirus ,sapovirus
Parasitic ; Giardia ,Entameba ,Cryptosporidium
Ischemic colitis
Immunosuppressive related diarrhea
How would you confirm the diagnosis?
C difficile is a clinical diagnosis with lab confirmation.
It is highly suspicious in the presence of severe diarrhea after antibiotic course complicated by toxic megacolon as per the findings .
· Toxin enzyme ELISA is specific, less sensitive as some can identify Toxin A only ,inexpensive, easy , rapid.
· PCR test Rapid, high sensitivity, simple ,costy
· Cytotoxicity cell assay is specific, sensitivity, time consuming and expensive
· Stool multiplex PCR
· Stool culture is the most sensitive, for strain typing ,expensive, does not determine if isolate is toxigenic, ≥ 48 hours for results
Who would manage this patient?
The patient resuscitation need to be continued with replacement of electrolyte deficiencies that can worsen the condition
As for the treatment of the severe forum of Cdifficle with toxic megacolon
-Metronidazole 500mg IV TID and Oral vancomycin 125 mg to 500 mg qid (if tolerated) for 10–14 days or fidaxomicin 20 mg two times per day for 10 days
Prevention and treatment of relapsing and refractory forms is difficult
Fidaxomicin, ramoplanin and tigecycline are effective for the treatment of severe
or recurrent disease .
-Surgical consultation
-IVIG 250-500mg/kg IV x1
human monoclonal antibodies against C. difficile toxins A and B
fecal microbiota transplantation (FMT) in refractory cases but under trial.
Myfortic should be suspended
Tacrolimus level can be reduced , levels should be monitored during metronidazole treatment in order to avoid toxicity
Ciprofloxacin was just finished so no introduction of other antibiotics except those for C difficle
Substantiate your answer!
-Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020;15(1):623-634. Published 2020 Jul 11. doi:10.1515/med-2020-0130
-Shin SH et al.Causes and management of post renal transplant diarrhea:an underappreciated cause of transplant associated morbidity. Curr Opin Nephrol Hypertens 2017 26(6) 484 -493
-Pant C etal.Diarrhea in solid organ transplant recipients :a review of the evidence. Curr Med Res Opin 2013 ,29(10) :1315-1328.
– Gunderson CC, Gupta MR, Lopez F, Lombard GA, LaPlace SG, Taylor DE, Dhillon GS, Valentine VG. Clostridium difficile colitis in lung tranplantation.Transpl Infect Dis. 2008; 10(4):245-51.
Excellent Doaa
Yes, he needs proper supportive measures as you mentioned and ICU support.
Differential diagnosis of post-transplant diarrhea in the above patient are broad:
It can be infectious and non-infectious –In infectious causes- bacterial(C. difficile, Campylobacter ssp, salmonella species, ) , viruses(Rotavirus, adenovirus,CMV),parasites( Giardia, cryptosporidium, isosopora Cyclospora, Microsporidium )should be considered.In non-infectious causes-drugs like MPA, tacrolimus, cyclosporin, sirolimus, antibiotics, PPI).Likely diagnosis in the above is Toxic megacoln with fulminant colitis secondary to C. difficile infection as patient has history of recent antibiotic use, severe metabolic acidosis with septic shock requiring vasopressors ,CT abdomen showing dilated transverse colon and colonoscopy revealing edematous mucosa with yellowish plaques.
DIAGNOSIS: Diagnosis is made on the basis of clinical features and colonic dilation (diameter >6 cm) on CT scan Abdomen.Stool analysis for C. Difficile toxin either by Fecal enzyme immunoassays , Real-time PCR test or Cytotoxicity assay .CT scan Abdomen more better than X-ray Abdomen. Colonoscopy is recommended in the above due to high chances of perforation and rarely helpful in diagnosis.
TREATMENT:
Patient should be admitted –Gastroenterologist and Surgical specialist should be taken into loop and immediately supportive measures i.e., I/V Fluids, acid base disturbances and electrolytes(hypokalemia and hypomagnesemia correction and broad spectrum antibiotics along with metronidazole(first episode and mild cases in a dose of 500 TDS for 10-14 days or oral vancomycin, fidaxomicin for severe cases. Antimetabolite i.e., MMF and oral steroids should be stopped and I/V hydrocortisone to be started and Tac level to be maintained around 6-7ng/ml.Patient also need dialysis support . Fecal microbiota transplantation in resistant cases. Surgery in the form of total colectomy with ileostomy needed
REFERENCES:
Angarone M, Snydman DR; AST ID Community of Practice. Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13550
Excellent Batool
Yes, needs proper supportive measures as you mentioned and ICU support.
*The systemic toxicity and radiological findings suggestive for Fulminant colitis;Toxic megacolon secondary to C. difficile- related pseudomembranous colitis.
*The single most important risk factor for the development of CDI is recent antibiotic use(patient was on ciprofloxacin). Others include being immunocompromised and age >55.
*It is a life-threatening complication of inflammatory or infectious colitis that is characterized by total or segmental nonobstructive colonic dilatation plus systemic toxicity.
*Toxic megacolon should be suspected in patients with abdominal distension and diarrhea. The diagnosis is made based on:
– clinical signs of systemic toxicity
– combined with radiographic evidence of colonic dilatation (diameter >6 cm).
The most widely used criteria are :
-Radiographic evidence of colonic dilation (diameter >6 cm)
-PLUS at least three of the following:
•Fever >38ºC
•Heart rate >120 beats/min
•Neutrophilic leukocytosis >10,500/microL
•Anemia
-PLUS at least one of the following:
•Dehydration
•Altered sensorium
•Electrolyte disturbances
•Hypotension
Differential diagnosis:
Toxic megacolon can occur with many infectious or inflammatory etiologies
*Infectious colitis:
Bacterial C. difficile pseudomembranous colitis, E.Coli, Salmonella, Shigella, Campylobacter, Yersinia
Viral: CMV colitis (tissue invasive)
Parasitic: Entameba histolytica, Cryptosporidium
*Ischemic colitis complicated with infection.
* Post-transplant IBD.
Confirm the diagnosis:
– Clostridium difficile PCR or enzyme immunoassay for C. difficile toxin A &B
– CMV PCR.
– Stoll analysis (WBCs and culturs).
– Stool multiplex PCR, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay.
-Colonoscopy should generally be avoided in patients with toxic megacolon because the risk of colonic perforation.
Management:
This patient should be co-managed by transplant nephrologist, surgical team, gastroenterologist, infectious disease with ICU team.
Medical management:
– ICU admission for cardiac and respiratory support.
– Correct volume status; fluid and inotropes.
– Correct electrolytes and acid-base disturbances.
– May need CRRT.
– Should be kept NOP and start parenteral nutrition.
– Stop Ciprofloxacin.
– Broad spectrum antibiotic; meropenem ( liaise with ID team).
– Continue on vancomycin and metronidazole.
– Fidaxomcin
– Stop myfortic, reduce tacrolimus level to 5-6
– IV hydrocortisone.
– If CMV highly suspected start ganciclovir.
*Monitor patient response: clinical , radiologically and assess the response if deteriorated or no response with days of therapy, might consider discussing surgical treatment.
*CDI is predominantly treated medically. Only 1 % of all patients with CDI and 30 % with severe disease will require emergency surgery.
* The overall mortality from severe C. difficile colitis/toxic megacolon was 64 to 67%, and 71 to 100 % for surgically treated patients.
*Patient has poor prognostic signs includes: septic shock, significant metabolic derangement, graft dysfunction, poor response to medical therapy with disease progression.
The surgical indications includes:
-Colonic perforation or full-thickness ischemia
-Abdominal compartment syndrome
-Cardiopulmonary deterioration with ongoing or escalating need for vasopressor support despite adequate fluid resuscitation.
-Respiratory failure requiring intubation and mechanical ventilation.
-Worsening end organ failure, most notably acute renal failure.
-Clinical signs of peritonitis or worsening abdominal exam despite adequate medical treatment.
Surgical options and the timing of the surgery (discussed with the surgical team)
-Early surgical consultation as well as timely and decisive operative management as the timing of surgical intervention is the key for survival of patients with severe or fulminant C. difficile colitis.
-Options: Total abdominal colectomy, diverting loop ileostomy/colonic lavage is an alternative
References:
– Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
-hin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
Excellent Hadeel
Yes, needs a proper supportive measures as you mentioned and ICU support.
What is the differential diagnosis?
o Axial CT abdomen showed dilated transverse colon and colonoscopy revealed pseudomembraneous colitis (edematous mucosa with yellowish plaques). This diagnosis is C. difficile associated toxic megacolon
o The incidence of C. difficile infection (CDI) in transplanted patients is approximately 3.5–4.5%
o The mortality rate of toxic megacolon secondary to C. difficile colitis varies from 38-80%
o The single most important risk factor for the development of CDI is recent antibiotic use (recent fluoroquinolones for UTI are associated with the highest risk).
Other differential diagnoses include:
1. Inflammatory bowel disease
2. Ischemic colitis
3. Infectious colitis (CMV is the commonest)
4. Malignancy
How would you confirm the diagnosis?1. Fecal enzyme immunoassays
2. Real-time PCR test
3. Cytotoxicity assay for C. difficile on stool: The gold standard for C. difficile detection
Endoscopy is rarely used to confirm the diagnosis of C. difficile related toxic megacolon (the diagnosis can be made by a combination of immunotoxin assay, clinical findings and imaging). An endoscopy may be dangerous, especially in a setting of fulminant colitis due to the increased risk of perforation
Diagnostic criteria for toxic megacolon:
Colonic dilation (CT)
PLUS 3 of the following 4 criteria (Jalan et al): fever > 101.5 F, HR > 120 beats/min, WBC > 10 500/mm, and anemia with hemoglobin or hematocrit level less than 60% of normal
PLUS any one of the following four clinical findings: dehydration, electrolyte disturbance, hypotension or changes in mental status
Endoscopy is recommended for the diagnosis of C. difficile toxic colitis in:
1. When there is a high level of clinical suspicion for C. difficile despite repeated negative laboratory assays
2. When a prompt diagnosis is needed before laboratory results can be obtained
3. When C. difficile infection fails to respond to antibiotic therapy
4. For atypical presentations of C. difficile colitis (patients who present with ileus, acute abdomen, or leukocytosis without diarrhea)
Who would manage this patient?o Aggressive medical therapy (prevent surgical intervention in up to 50% of cases)
o Stop ciprofloxacin
o Oral vancomycin (vancomycin enemas are better but may fail to treat right-sided disease of the colon/ intracolonic perfusion of vancomycin), IV metronidazole, bowel rest, bowel decompression, and replacement of fluids and electrolytes
o Decompression of the dilated colon with nasogastric suction and frequent repositioning of the patient (prone positioning for 10 to 15 min every 2 to 3 h allowing the passage of flatus)
o Colonic decompression with a colonoscopy
o Holding medications that slow intestinal motility (anticholinergics, antidepressants, antidiarrheals, and narcotics)
Surgical intervention (may be indicated in up to 80% of patients). Indications include:
1. Perforation
2. Progressive dilation of the colon
3. Lack of clinical improvement over the first 48-72 h and uncontrolled bleeding
The surgical procedure of choice is total colectomy with preservation of rectum and diverting ileostomy
References
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
Thanks
He needs also resuscitation and may be ICU support
What is the differential diagnosis?
The clinical scenario of this patient is highly suggestive of severe C.difficile infection causing colitis and toxic megacolon as appeared on the colonoscopy(haemorrhagic colitis) and CT abdomen( dilatation of the transverse colon). This severe form of infection is complicated with severe metabolic acidosis, septic shock and DIC.
The differential diagnosis is as follows:
a) Clostridium difficile infection.
b) CMV- Tissue invasive disease.
c) Infection with enterotoxin-producing E.Coli
d) Ischemic colitis complicated with infection.
e) Inflammatory bowel disease(IBD).
How would you confirm the diagnosis?
To confirm diagnosis of C.difficile(1):
1. The gold standard for C. difficile detection is the cell-based cytotoxicity assay.
2. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR)(2). Fecal enzyme immunoassays or real-time PCR test are mostly used by many laboratories.
Who would manage this patient?
1. In general, initial treatment of C.difficile infection in this patient include:
a) Supportive measure and adequate hydration to maintain BP and MAP within perfusion capability as well as correction of acid base disorder and managing DIC state.
b) fidaxomicin, metronidazole or vancomycin, with vancomycin preferred for cases of more severe infection(1):
a. First episode: metronidazole 500mg three times per day for 10–14 days.
b. Severe disease: vancomycin oral four times per day for 10–14 days fidaxomicin 20 mg two times per day for 10 days.
c. First relapse: same for first episode.
d. Second relapse: vancomycin taper with pulse.
e. third relapse: consider fecal microbiota transplantation, prolonged oral vancomycin.
2. In this case; early surgical consultation and intervention is crucial. Colectomy is likely considered to control sepsis and to save the patient.
3. Tacrolimus levels should be closely monitored and to be targeted at 5-7 ng/ml.
4. Reducing myfortic dosage to 360/360.
References
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
2. Amin K, Choksi V, Farouk SS, Sparks MA. Diarrhea in a Patient With Combined Kidney-Pancreas Transplant. Am J Kidney Dis. 2021 Aug;78(2):A13-A16. doi: 10.1053/j.ajkd.2021.01.023. PMID: 34303438.
Excellent Safi
You are the first one who mentioned hydration, and other supportive measures.
Obviously, this patient has infectious diarrhoea considering her signs and symptoms. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common.
Diagnosis: Identification of a specific pathogen or cause for the diarrhea allows for focused treatment and monitoring for improvement.
· Stool testing for a microbial pathogen.
As per American Society of Transplantation Infectious Diseases recommendation:
· Initial testing for SOT recipients with diarrhea should include testing for C difficile and bacterial pathogens in the stool and CMV PCR testing in the serum. In addition, all patients with diarrhea should have their medications reviewed for potential causes of diarrhea and unnecessary agents should be stopped (strong, moderate)
· Persistent diarrhea should prompt testing for norovirus and parasitic causes for diarrhea
· Colonoscopy with or without biopsy should be performed on SOT recipients with chronic diarrhea that have had a negative infectious evaluation or for those not responding to targeted therapy
· If available, multiplex PCR testing for stool pathogens should be performed on all SOT recipients presenting with diarrhea
For management:
As per American Society of Transplantation Infectious Diseases recommendation:
· Empiric antimotility therapy should be considered in SOT recipients with diarrhea that is negative for C difficile and where there is no evidence of megacolon or inflammatory diarrhea
· SOT recipients with diarrhea and mild to moderate dehydration should be given reduced osmolarity rehydration fluids.
· Isotonic intravenous fluids should be administered for those with severe dehydration, shock, altered mental status, or ileus
· Antimicrobial therapy should be modified to target any identified pathogen suspected to be the cause of the diarrhea
Angarone M, Snydman DR, AST ID Community of Practice. Diagnosis and management of diarrhea in solid‐organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation. 2019 Sep;33(9):e13550.
Thanks
He needs also resuscitation and may be ICU support
Thanks, Mohamed
He needs also resuscitation and may be ICU support
What is the differential diagnosis?
This a case of toxic megacolon due to Pseudomembranous Colitis
Other differentials include :
Inflammatory Causes
Ulcerative colitis
Crohn disease
Infectious Causes
Clostridium difficile
Salmonella
Shigella
Campylobacter colitis
Enterohemorrhagic or enteroaggregative Escherichia coli O157
Cytomegalovirus
Entamoeba
Ischemic Colitis
How would you confirm the diagnosis?
The diagnostic basis is the patient’s systemic symptoms and greater than 6 cm dilation of the colon seen on radiographic images.
Below are the most commonly used diagnostic criteria for toxic megacolon (by Jalan et al.)
Radiographic evidence of the dilation of the colon greater than 6 cm AND:
At least three of the following:
Fever over 38 degrees C
Heart rate greater than 120 beats/min
Neutrophilic leukocytosis exceeding 10500/micro/L
Anemia
At least one of the following:
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension
Colonoscopy to be avoided due to high perforation risk
Who would manage this patient?
Initial treatment involves supportive therapy and resuscitation . Patients should be admitted to the intensive care unit.
Checking complete blood count, abdominal films, and electrolytes should take place
All the medications which can aggravate the megacolon, such as opioids, anticholinergics, etc., should be stopped.
Patients should be started on IV fluids to provide adequate hydration
The most commonly used antibiotics are metronidazole or vancomycin.
If cytomegalovirus is the suspected cause, then gancyclovir should be given. Antibiotics of choice for C. difficile are oral vancomycin or oral fidaxomicin. If those are not available, oral metronidazole is an alternative.
Surgical Treatment
Urgent Surical Consult required. The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
Substantiate your answer!
Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015 Jan 27;313(4):398-408.
Ewelina Skomorochow; Jose Pico. Toxic Megacolon. Stat pearles- https://www.ncbi.nlm.nih.gov/books/NBK547679/
Vardakas KZ, Polyzos KA, Patouni K, Rafailidis PI, Samonis G, Falagas ME. Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence. Int J Antimicrob Agents. 2012 Jul;40(1):1-8.
Thanks, Dr Khan
He needs also resuscitation and may be ICU support
The most likely diagnosis for this patient is severe Clostridium Difficile pseudomembranous colitis – she has the risk factor of fluoroquinolone use. She has now developed fulminant colitis as evidenced by: Hypotension requiring pressors, severe metabolic acidosis, marked leucocytosis, toxic megacolon
The other differential diagnosis includes:
Diagnosis
The diagnosis is confirmed by:
Adjunctive diagnostic tests can be used:
Colonoscopy – normally not required to make a diagnosis. Used if the stool tests are negative and there is a high index of suspicion in a symptomatic patient – Patient will have bowel wall edema, erythema, friability and inflammation. There will also be pseudomembranes on the inflammed mucosal surface – pseudomembranous colitis which can be missed on the stool tests
Management:
This patient has fulminant severe Clostridium difficile colitis with a toxic megacolon and electrolyte imbalance with graft dysfunction
Shin Ho et al. Curr Opin Nephrol Hypertens 2017, 26:000–000
Thanks, Hussein
He needs also resuscitation and may be ICU support
Dear All
How would you confirm it is C Def colitis?
If you have this CT image with the abovementioned history, would you go for a colonoscopy?
A colonoscopy is contraindicated due to the risk of perforation
Thanks, see my answer above.
Thanks prof.
Send stool sample for C.diff.
and Better to avoid colonoscopy with our case due to risk of perforation.
Thanks, see my answer above.
To confirm the diagnosis of c.def colitis:
-A positive nucleic acid amplification test (NAAT) for C. difficile toxin gene
-a positive stool test for C. difficile toxins.
–Cell culture cytotoxicity assay.
-Selective anaerobic culture.
Colonoscopy is absolutely contraindicated to avoid colonic perforation.
Thanks, see my answer above.
To confirm C. difficile colitis: fecal enzyme immunoassays or real-time PCR test
The risk of perforation is high and colonoscopy is contraindicated here
Thanks, see my answer above.
CONTAINDICATED PROF
Thanks, see my answer above.
Diagnosis should be confirmed with a positive stool test for toxigenic C. difficile or its toxins.
colonoscopy should be avoided esp. with the presence of dilated colon like this patient for fear of perforation.
Thanks, see my answer above.
How would you confirm it is C Def colitis?
If you have this CT image with the abovementioned history, would you go for a colonoscopy?
Colonoscopy is dangerous in such a case with high risk of perforation, decompression measures should be done and keeping patienT NPO.
Thanks, see my answer above.
1. Fecal enzyme immunoassays
2. Real-time PCR test
3. Cytotoxicity assay for C. difficile on stool: The gold standard for C. difficile detection
Endoscopy is rarely used to confirm the diagnosis of C. difficile related toxic megacolon (the diagnosis can be made by a combination of immunotoxin assay, clinical findings and imaging). An endoscopy may be dangerous, especially in a setting of fulminant colitis due to the increased risk of perforation
Diagnostic criteria for toxic megacolon:
Colonic dilation (CT)
PLUS 3 of the following 4 criteria (Jalan et al): fever > 101.5 F, HR > 120 beats/min, WBC > 10 500/mm, and anemia with hemoglobin or hematocrit level less than 60% of normal
PLUS any one of the following four clinical findings: dehydration, electrolyte disturbance, hypotension or changes in mental status
Endoscopy is recommended for the diagnosis of C. difficile toxic colitis in:
1. When there is a high level of clinical suspicion for C. difficile despite repeated negative laboratory assays
2. When a prompt diagnosis is needed before laboratory results can be obtained
3. When C. difficile infection fails to respond to antibiotic therapy
4. For atypical presentations of C. difficile colitis (patients who present with ileus, acute abdomen, or leukocytosis without diarrhea)
References
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
2. Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
Thanks, see my answer above.
How would you confirm it is C Def colitis?
To confirm diagnosis of C.difficile(1):
1. The gold standard for C. difficile detection is the cell-based cytotoxicity assay.
2. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR)(2).
if you have this CT image with the abovementioned history, would you go for a colonoscopy?
No, I wouldn’t go for colonoscopy because it is an invasive intervention and may precipitate colonic perforation in such friable colon.
References
1. Shin HS, Chandraker A. Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):484-493. doi: 10.1097/MNH.0000000000000368. PMID: 28863048.
Thanks, see my answer above.
colonscopy will end up with perforation and better to avoid . This is toxic megacolon(TM) in a very sick patient in septic shock due to sever acute coltitis likley pseudomembrnous coltitis ,not responding to medical therapy .Computed tomography( CT) is useful in distinguishing patients with TM from patients with SAC but no TM as a complication. The association of air-filled colonic distension >6 cm, abnormal haustral pattern and segmental colonic parietal thinning seems pathognomonic of TM and should lead to rapid surgery(1). TM couild be localized or diffuse complication of ischaemic or infectious inflammation like pseudomembranous colitis. This patient need urgent surgical intervention with total colectomy and ileostomy ,parentral nutrition ,supportive CRRT with electrolytes correction and broad sepctrum AB with stress dose of steriod only , stop all immunsuppressive therapy toxic megacolon very serious complication and is life threatening infection with high mortality rate.
Reference
1.Moulin V, Dellon P, Laurent O, Aubry S, Lubrano J, Delabrousse E. Toxic megacolon in patients with severe acute colitis: computed tomographic features. Clin Imaging. 2011 Nov-Dec;35(6):431-6. doi: 10.1016/j.clinimag.2011.01.012. PMID: 22040786.
2.Ruf G. Toxisches Megakolon–Chirurgische Sicht [Toxic megacolon–surgical point of view]. Praxis (Bern 1994). 2006 Nov 1;95(44):1727-30. German. doi: 10.1024/1661-8157.95.44.1727. PMID: 17111883.
Thanks, see my answer above.
Laboratory diagnosis of CDI requires demonstration of C. difficile toxin(s) or detection of organism(s):
-PCR are highly sensitive; greater than EIA and comparable with cytotoxicity assay, cant differentiate asymptomatic carriers from disease state.
-Enzyme immunoassay EIA for C. difficile GDH: cannot distinguish between toxigenic and nontoxigenic strains
-Enzyme immunoassay EIA for C. difficile toxins A and B
-Cell culture cytotoxicity assay the gold standard test for diagnosis.
-Selective anaerobic culture highly sensitive, cannot distinguish toxin-producing strains from non-toxin-producing strains , second test is required to detect toxin
Endoscopy generally is not required routinely when typical signs and laboratory tests and patient is at high risk of perforation.
References:
– Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc. 2010 Aug 16;2(8):293-7. doi: 10.4253/wjge.v2.i8.293. PMID: 21160629; PMCID: PMC2999149.
McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085. PMID: 29462280; PMCID: PMC6018983.
Thanks, see my answer above.
-stool toxigenic bacterial culture ,NAT, cell culture cytotoxicity neutralising test , toxin assay ,multiple tests can be done together to confirm
-Shetler et al demonstrated that colonoscopic decompression and intracolonic vancomycin administration in the management of severe, toxic megacolon is feasible, safe, and effective in approximately 57-71% of these cases.
Reference
Shetler K etal . Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.Surgical Endoscopy 2001 July
Thanks, see my answer above.
Diagnosis of C. difficile test include:
The patient had severely dialed colon & need urgently surgical consultation, colonoscopy contraindicated.
severe dilated colon
Thank you. Can you please specify what do you mean by EIA?
Enzyme immunoassay
to confirm / C Def toxin in stool
Colonoscopy is contraindicated /due to risk of perforation
Thanks, see my answer above.
C.dificile can be diagnosed by
Colonoscopy should be avoided, (fear of rupture), but bowel decompression is vital.
Thanks, see my answer above.
Colonoscopy is contraindicated due to high risk of perforation,
Thanks, see my answer above.
👉 confirm diagnosis by Cl difficile toxin identification by ELISA or detection of gene responsible for toxin by PCR.
👉 Colonscopy is better avoided in case of toxic megacolon for fear of perforation.
Thanks, see my answer above.
Thnxs, prof
Thanks, see my answer above.
No
Colonoscopy is relative contraindication in this condition
Thanks, see my answer above.
Cell-based cytotoxicity detects C. difficile.
Clostridium difficile detection by a polymerase chain reaction.
It is very risky to proceed with a colonoscopy with this fragile colon.
Thanks, see my answer above.
The diagnosis of C. difficile infection should be suspected in patients with acute diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation, particularly in the setting of relevant risk factors (including recent antibiotic use, hospitalization, and advanced age) [1]. Patients with suspected C. difficile infection should be placed on contact precautions preemptively pending diagnostic evaluation
A number of laboratory stool tests are available alone or in combination as part of a diagnostic algorithm:
●NAAT
●Enzyme immunoassay for C. difficile GDH
●Enzyme immunoassay for C. difficile toxins A and B
●Cell culture cytotoxicity assay
●Selective anaerobic culture
Endoscopy is seldom used to confirm the diagnosis of C. difficile related toxic megacolon since the diagnosis can be made by a combination of immunotoxin assay, clinical findings and imaging. An endoscopy may be dangerous, especially in a setting of fulminant colitis due to the increased risk of perforation.
A study by Johal et al however encouraged the use of flexible sigmoidoscopy as a tool for the diagnosis of C. difficile toxic colitis when stool assays are negative. In their study 52% of patients who tested negative for C. difficile toxin assay had pseudomembranous colitis on flexible sigmoidoscopy.
Endoscopy is recommended for the diagnosis of C. difficile toxic colitis under the following conditions:
(1) when there is a high level of clinical suspicion for C. difficile despite repeated negative laboratory assays;
(2) when a prompt diagnosis is needed before laboratory results can be obtained;
(3) when C. difficile infection fails to respond to antibiotic therapy or
(4) for atypical presentations of C. difficile colitis such as in patients who present with ileus, acute abdomen, or leukocytosis without diarrhea
Sayedy L, Kothari D, Richards RJ. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc 2010; 2(8): 293-297 [PMID: 21160629 DOI: 10.4253/wjge.v2.i8.293]
Excellent Hamada, but we should not do a colonoscopy in the index case. The risk of perforation is high.
THANK YOU Prof. Ahmed Halawa
NOTED
Colonoscopy should not be done because of bowel tissue friability and risk of perforation
Confirm by ;NAAT for difficile toxin.
Colonoscopy not done due to high risk of perforation.
– colonoscopy should be avoided due to the increased risk of perforation (the transverse colon is now dilated at 8.7cm)
– confirmatory test for C. difficile colitis: toxin test which uses antibodies to detect the presence of C. difficile toxin A and/ or toxin
– it has a high specificity, low turn around time, low cost
Confirm diagnosis by Cl difficile toxin identification by ELISA or detection of gene responsible for toxin by PCR
Colonscopy is better avoided in case of toxic megacolon for fear of perforation.
Q1: Stool examination for C.difficile toxins by ELIZA/EIA or PCR.
Q2: Colonoscopy is contraindicated in toxic megacolon due to the risk of perforation.
What is the differential diagnosis?
How would you confirm the diagnosis?
Clinically it presents with
Diagnosis of toxic megacolon
The diagnosis is settled if all the following criteria are met (3)
A- Radiographic evidence of colonic dilation (diameter >6 cm)
B- At least three of the following:
C- At least one of the following:
Management
1- Urgent total colectomy with ileostomy after resuscitation (fluids, packed RBCS, FFP, correction of metabolic acidosis) is indicated in case of toxic megacolon if one of the following is present:
Early colectomy before the development of septic shock was shown to reduce 30 days mortality from 45% top 21%(4)
2- Decompression either by rectal tube or endoscopic is contraindicated since there is high risk of perforation, but decompression using nasogastric tube can be tried
3- Give hydrocortisone IV in a dose of 100 mg every 8 hours in the day of operation and from day 1 the dose is halved and the oral preoperative dose of prednisolone can be resumed on day 2 post-operative together with other immunosuppressive therapy
4- Post operative correction of dehydration anemia, DIC and any electrolyte disturbance, and renal failure (RRT) as indicated
6- Broad spectrum antibiotics.
References
1- Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351:509.
2- Fazio VW. Toxic megacolon in ulcerative colitis and Crohn’s colitis. Clin Gastroenterol 1980; 9:389.
3- Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology 1969; 57:68.
4- Ahmed N, Kuo YH. Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection. South Med J 2020; 113:345.
Could it be a C. def-induced pseudomembranous colitis?
If yes, is it diagnosed by stool culture?
Yes, it is the most propable organism in this setting.
It is diagnosed by CD toxin in stool, and not detected by stool culture
Thanks, Sherif
What is the differential diagnosis?
How would you confirm the diagnosis?
PLUS at least three of the following:
PLUS at least one of the following:
Who would manage this patient?
The treatment of the above patient will be aimed at reducing colonic inflammation, restoring normal colonic motility, and decreasing the possibility of colon perforation which is the main goal of medical therapy. The management will be comprised of a transplant physician, general surgeon, intensivist, radiologist, microbiologist, gastroenterologist, and the ICU nurses
The following is the indication for surgery if the above failed
Reference
Could it be a C. def-induced pseudomembranous colitis?
If yes, is it diagnosed by stool culture?
Differential diagnoses
Septic shock
Toxic megacolon, Ulcerative colitis or Crohn disease.
ischemic, infectious, pseudomembranous colitis
Cytomegalovirus Colitis, Diverticulitis, Clostridium difficile
Salmonella Shigella
How to confirm diagnosis
A thorough history may show recent travel, the use of antibiotics, chemotherapy, occupational exposure, or immunosuppression.
Patients typically exhibit severe symptoms, including fever, tachycardia, hypotension, abdominal distention, and discomfort.
Radiological findings of colonic dilatation is toxic megacolon.
Further blood tests are;
CBC , Electroloytes, CRP, ESR, immunosupression drug level, blood C/S.
Stool R/E and eytology.
CT and endoscopy shows dilated gut loos and psudomemebranuos colitis
Management
Medical management includes;
Replacement of fluid, inotropic support , correction of electrolytes and acidosis, and treatment of suspected infection with antiobiotis,
When tolerated, patients may consume a typical, low-residue diet (to reduce stool frequency and volume).
Toxic megacolon may be the culprit if diarrhea and abdominal distention get better.
Graft fuction motoring.
Collective team work with surgeon, gastroenterologist.
Early surgical consultation enables quick operative care if a patient’s condition worsens.
Surgery for C. difficile colitis is better when done quickly.
For severe or complex CDI, society’s recommendations urge early surgical consultation.
1-Toxic Megacolon; Fadi Alali, MD, Burt Cagir, MD, FACS
2-Toxic megacolon in patients with severe acute colitis: computed tomographic features
Véronique Moulin 1 , Perrine Dellon, Olivia Laurent, Sébastien Aubry, Jean Lubrano, Eric Delabrousse
3-Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: A case report
Joon Hyun Cho and Joon Hyuk Choi
Could it be a C. def-induced pseudomembranous colitis?
If yes, is it diagnosed by stool culture?
Patients with acute diarrhea (three or more loose stools in 24 hours) should have their diagnosis of C. difficile infection considered, especially if there are any pertinent risk factors present (including recent antibiotic use, hospitalization, and advanced age)
A number of laboratory stool tests are available alone or in combination;
NAAT
If the collection of the stool sample is delayed and the patient has received empirical treatment for suspected CD, the NAAT results may be falsely negative.
●Enzyme immunoassay for C. difficile GDH
All C. difficile isolates produce the necessary enzyme GDH antigen, however its detection cannot differentiate between toxic and nontoxic strains.
Results from the GDH antigen test are available in less than an hour and have an excellent sensitivity.
●Enzyme immunoassay for C. difficile toxins A and B
Although certain strains of C. difficile only generate one toxin, the majority of strains produce both toxins A and B .
EIA testing is more sensitive when both toxins are present than when only one toxin is present. As 100 to 1000 pg of toxin must be present for the test to be positive, there is a substantial false-negative rate.
As a result, GDH antigen testing and toxin EIA are frequently combined. adjudication with NAAT is advantageous if the GDH is positive but the toxin EIA is negative.
●Cell culture cytotoxicity assay
The cell culture cytotoxicity assay is resource- and time-intensive, sensitive, and specific, but it is not a standard clinical diagnostic test.
●Selective anaerobic culture
Rectal swab for toxin assay or anaerobic culture can be a useful diagnostic tool for patients with ileus and suspected CDI.
McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66:e1.
Sunkesula VC, Kundrapu S, Muganda C, et al. Does empirical Clostridium difficile infection (CDI) therapy result in false-negative CDI diagnostic test results? Clin Infect Dis 2013; 57:494.
Fenner L, Widmer AF, Goy G, et al. Rapid and reliable diagnostic algorithm for detection of Clostridium difficile. J Clin Microbiol 2008; 46:328.
Wilkins TD, Lyerly DM. Clostridium difficile testing: after 20 years, still challenging. J Clin Microbiol 2003; 41:531.
Limaye AP, Turgeon DK, Cookson BT, Fritsche TR. Pseudomembranous colitis caused by a toxin A(-) B(+) strain of Clostridium difficile. J Clin Microbiol 2000; 38:1696.
Thanks, Mohamed
We do not need the detail of the test as this is not required. We need to know the principle of management ONLY.
A 64-year-old woman presented to the hospital with abdominal pain, nausea, vomiting and profuse watery diarrhoea. She was discharged from the hospital for a urinary tract infection following a successful renal transplant. On admission, the blood pressure was 65/41 mmHg, hypothermia was present, and the WBC was 53.9 109 /L with 84% neutrophils. There was severe metabolic acidosis with an anion gap of 19, bicarbonate level of 12 mmol/L, and lactic acid level of 3.6 mmol/L. The patient was resuscitated with IV fluids and placed on dopamine and norepinephrine.
She was given intravenous ciprofloxacin 500 mg every 12 h, oral vancomycin 250 mg every 6 h, and IV metronidazole 500 mg every 6 h. A CT scan showed circumferential wall thickening of the colon consistent with pan colitis. The patient did not improve despite treatment over the next 36 h. Blood, urine, and stool cultures
====================================================================
====================================================================
What is the differential diagnosis?
Differential Diagnoses
Including ischemic, infectious, pseudomembranous, ulcerative, etc.
===================================================================
Infectious Causes
====================================================================
How would you confirm the diagnosis?
History
=============================================
Physical Examination
================================================
The most common criteria used to diagnose toxic megacolon are radiographic evidence of colonic dilatation, fever, tachycardia, neutrophilic leukocytosis, anemia, dehydration, altered mental status, electrolyte abnormality, or hypotension.
Complete blood cell (CBC) count
Chemistry panel
Nutrition and coagulation panels
ESR and CRP
Histology
Stool studies
Radiography
Computed Tomography Scanning
Endoscopy
=============================================================
Who would manage this patient?
Medical Management
Surgical Management
====================================================================
Reference
That is a high quality well referenced reply.
Rather than stating ‘surgeons and hospitalists need to work together’, I would say that it is essential to have close liaison between GI surgeon and gastro-enterology team.
While it is not sensible to go for sub-total colectomy in someone who might respond to medical management, it is is not safe to delay surgery for whom this is the only option.
What is the differential diagnosis?toxic megacolon, cute mesenteric ischemia; colonic pseudo-obstruction; large bowel obstruction, and CMV colitis.
How would you confirm the diagnosis?commercial multiplex PCR assays to examine the presence of enteric bacteria, parasites, and viruses in the feces of diarrheal kidney transplant recipients.
CMV PCR
C.defecile toxins
OGD with tissue biopsy and culture
Who would manage this patient?
The prevalence of the difficult form of CDI, defined by a high white blood cell count (>25,000/KL) and pancolitis on CT scan, averaged from 2.5% to 5% but reached as high as 12.4% in 165 SOT patients infected with the extremely virulent strain NAP1/BI/027.
Toxigenic Clostridium infections have a high rate of recurrence and a high level of resistance to therapy, making it very difficult to eradicate them. In two case studies, fecal microbiota transplantation has recently been shown to be an effective and safe treatment for SOT patients with refractory C. difficile infection. Acute CDI patients may develop systemic toxicity with or without diarrhea, requiring hospitalization, intensive care, or emergency surgery.
Reduce the immunosuppressive dose (d/c MMF).
Discontinue inciting antibiotic agent(s) — An important initial step in the treatment of CDI is the discontinuation of the inciting antibiotic agent(s) as soon as possible
Supportive care with attention to the correction of fluid losses and electrolyte imbalances is important.
Patients may have a regular, low-residue diet as tolerated (to reduce stool frequency and volume). If abdominal distention and diarrhea decrease, toxic megacolon may be the cause.
Early surgical consultation is warranted for patients with CDI who meet one or more of the following clinical indicators that have been associated with poor prognosis(hypotension, lactate>2,2, wbc> 15,000)
If a patient worsens, earlier surgical consultation allows for prompt operational care. Timely surgery for C. difficile colitis improves outcomes. Society recommendations recommend early surgical consultation for severe or complicated CDI.
If Ileus is present, additional considerations include:
Subtotal colectomy can be lifesaving, but the optimal timing is difficult to establish. Early surgical consultation when the fulminant or refractory disease is suspected is highly recommended.
References:
1- Boutros M, Al-Shaibi M, Chan G, Cantarovich M, Rahme E, Paraskevas S, et al. Clostridium difficile colitis. Transplantation. 2012;93(10):1051–7
Similar to your sensible approach, I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment that may include surgical option in subset of patients.
Could it be a C. def-induced pseudomembranous colitis?
If yes, is it diagnosed by stool culture?
NO, to confirm diagnosis we need to send CD toxin in the stool or multiplex PCR,
What is the differential diagnosis?
Toxic megacolon secondary to Pseudomembranous colitis (Clostridium difficile).
Inflammatory Causes such as Ulcerative colitis or Crohn disease.
Infectious Causes (Clostridium difficile, Salmonella, Shigella, Campylobacter colitis, Enter hemorrhagic or enter aggregative Escherichia coli O157 (can lead to hemolytic-uremic syndrome), Cytomegalovirus and Entamoeba).
Ischemia .
How would you confirm the diagnosis?
The most commonly used diagnostic criteria for toxic megacolon (by Jalan et al.) :
Radiographic evidence of the dilation of the colon greater than 6 cm AND🙁 here in our case 8.7 cm).
At least three of the following:
Fever over 38 degrees C (patient in shocked status).
Heart rate greater than 120 beats/min (patient in shocked status).
Neutrophilic leukocytosis exceeding 10500/micro/L(in our case WBC was 53.9 109 /L).
Anemia
At least one of the following:
Dehydration
Altered sensorium
Electrolyte disturbances
Hypotension ((in our case blood pressure was 65/41 mmHg).).
Colonoscopy is not necessary for diagnosis. Therefore, colonoscopy is discouraged due to the high risk of perforation.
Who would manage this patient?
Our patient status is critical and need urgent surgical intervention to avoid colonic perforation because some studies conclude favorable outcomes in patients where surgical intervention is done soon after making the diagnosis of toxic megacolon.
The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
It is important to start with initial treatment involves supportive therapy and medical management.
Should be started on IV fluid.
The most commonly used antibiotics are metronidazole or vancomycin for C,difficle.
If cytomegalovirus is the suspected cause, then ganciclovir should be given.
TTT of the associated IBD.
Patients must be on bowel rest and a nasogastric tube can be inserted to help decompress the stomach, but it will not decompress the colon.
References:
1- Skomorochow E, Pico J. Toxic Megacolon. [Updated 2022 Jul 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547679/.
2- Mukhopadhya A, Samal SC, Patra S, et al. Toxic megacolon in a renal allograft recipient with cytomegalovirus colitis. Indian J Gastroenterol. 2001;20(3):114-115.
Similar to your sensible approach, I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment that may include surgical option in subset of patients.
complicated pseudomembranous colitis with life-threatening toxic megacolon in an old kidney transplant patient recently treated with ciprofloxacin and on intense triple immunosuppression she is in septic shock with lower BP despite inotrope support, dilated bowel > 6cm, indication for urgent surgical intervention and get MDT approach, surgery, transplant physician and infectious disease team in board with stopping all current immunosuppression and continue on stress dose of hydrocortisone along with broad-spectrum antibiotics to cover gram-positive, negative and anaerobic bacteria, parenteral feeding and hemicolectomy based on the gross appearance upon surgery
I wonder in such cases of toxic megacolon is it reasonable to go with colonoscopy as it carries a high risk of perforation and preferred to send for clostridia toxin and CT imaging
I appreciate your concerns in contemplating colonoscopy!
What is the differential diagnosis?-Unforfortnately this monther had features of C.difficile infections and her risk factors are;
-She is critically ill, in florid sepsis, haemodynamically unstable, worsening toxic mega colon and pan colitis
-Allograft dysfunction
-Metabolic derangement
-Not responding to the initial treatment due to the toxic mega colon which is purely a surgical problem
-She had poor prognostic features including raising WCC
-Risk of mortality is high
-The differential diagnosis of diarrhea in posttransplant is wide and may include:
A. Infection
B. Non-infection
-How would you confirm the diagnosis?
-How would manage this patient?
Source
I like you problem-oriented clinical step-wise approach.
Thnxs, prof
pseudomembranous colitis induced Toxic megacolon
1– is a life-threatening condition characterized by
2– nonobstructive
3– segmental or pancolonic
4– dilatation of at least 6 cm
5– with systemic toxicity
Although (IBD) is a common reason for toxic megacolon, other etiologies including infections (CMV) , inflammation, bowel ischemia, radiation, and certain medications can lead to the development of this condition
Some antibiotics are more commonly linked to pseudomembranous colitis than others,
including: Fluoroquinolones, such as ciprofloxacin (Cipro) and levofloxacin
diagnosis is clinically and with imagine
■Clinical manifestations
■Laboratory:
elevated WBC , elevated neutrophils, ESR, CRP. Imbalence of electrolytes…
■Ct
revealed segmental or pancolonic
dilatation of at least 6 cm
■The colonoscopy
above shows characteristic yellowish plaque in pseudomembranous colitis (Toxic Megacolon).
Colonoscopy may be not necessary for diagnosis. Therefore, colonoscopy is discouraged due to the high risk of perforation.
management
in our patient , the case wasn’t improved after supportive treatment. Therefore surgical management is considered
Surgical Management
●A surgeon should be involved in the patient’s care from day 1
●The current surgical treatment of choice in acute toxic megacolon is subtotal colectomy with ileostomy and either a Hartmann pouch, sigmoidostomy, or rectostomy.
●Previously there were two additional surgical methods used: total proctocolectomy and the Turnbull method.
●The exact time of surgery in toxic megacolon patients is still unclear.
●If there is perforation, bleeding, or clinical deterioration of a patient, surgical intervention is unavoidable.
Indications for surgical consultation in the management of CDI
Medical Management
○This approach is usually successful in about half of the patients. But not in our patient.
○ admission to the ICU
CBC Electrolytes
AXR
○the medications which can aggravate the megacolon, should be stopped.
○IV fluids to provide adequate hydration.
○The most commonly used antibiotics are metronidazole or vancomycin
○If CMV is the suspected cause, then gancyclovir should be given. And perform PCR (CMV)
○ bowel rest. NGT
REFERENCES
1– Clostridioides difficile infection in adults: Treatment and prevention(UpToDate)
2– Toxic Megacolon. Skomorochow E, Pico J.
3– Diarrhea in a Patient With Combined Kidney-Pancreas Transplant. Krunal Amin.
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment that may include surgical option in subset of patients.
What is the differential diagnosis?
-Toxic megacolon can be suspected in patients with abdominal distension and diarrhea. The diagnosis is made based on clinical signs of systemic toxicity combined with imaging evidence of colonic dilatation (colonic diameter >6 cm).
The toxic megacolon is most commonly considered a complication of inflammatory bowel disease, especially ulcerative colitis but can be a complication of almost any inflammatory or infectious condition of the colon can lead to toxic dilatation, in our transplant patient it can be secondary to:
-Clostridioides difficile pseudomembranous colitis (patient had UTI post transplantation and received wide spectrum antibiotic for 14 days.
-CMV colitis.
–Cryptosporidium.
-Other chronic nontoxic processes leading to colonic dilatation by its inflammatory trigger like:
Congenital megacolon (Hirschsprung’s disease).
Acquired megacolon (eg, due to chronic constipation).
Chagas megacolon.
Colonic pseudo-obstruction.
Diffuse gastrointestinal dysmotility.
How would you confirm the diagnosis?
The diagnosis is made based on clinical signs combined with imaging evidence of colonic dilatation (diameter >6 cm). The used criteria are:
-Radiographic evidence of colonic dilation (diameter >6 cm)
PLUS at least three of the following:Fever >38ºC,Heart rate >120 beats/min,Neutrophilic leukocytosis >10,500/microL and Anemia
-PLUS at least one of the following:
Dehydration
Altered sensorium.
Electrolyte disturbances
Hypotension
Who would manage this patient?
Patient not responding to extensive medical treatment, Surgery is indicated in view of deterioration and signs of end-organ failure (eg, vasopressor requirement, intubation and mechanical ventilation, or acute renal failure). In addition, WBCs count >50,000 cell/mL and serum lactate level of >5 mmol/L. Early colectomy before the onset of septic shock was associated with a reduction of 30 day mortality from 45 to 21 percent.
References:
Ausch C, Madoff RD, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis 2006; 8:195.
Autenrieth DM, Baumgart DC. Toxic megacolon. Inflamm Bowel Dis 2012; 18:584.
Ahmed N, Kuo YH. Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection. South Med J 2020; 113:345.
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment.
I appreciate surgery in small subset of patients such as, as I quote you, “Early colectomy before the onset of septic shock was associated with a reduction of 30 day mortality from 45 to 21 percent.”
What is the differential diagnosis?
Toxic megacolon:
C.difficle colitis
Other infectious colitis: Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella spp.
Non- infectious: Inflammatory bowel syndrome, microscopic colilitis, and celiac disease.
How would you confirm the diagnosis?
Who would manage this patient?
1- Admission to ICU, with close monitoring, Vigorous iv fluid management, with electrolytes correction magnesium sulfate and potassium.
2- Iv antibiotics covering the highly suspected CDI.
3- Stop antimetabolites MMF, reduce the tacrolimus level to 5-8 ng/dl, but keep on steroid in a stress dose.
4- Immediate surgical consultation- evaluation and surgery if needed: indications for surgical intervention are:
· Hypotension
· Fever ≥38.5°C
· Ileus or significant abdominal distention
· Peritonitis or significant abdominal tenderness
· Altered mental status
· White blood cell count ≥20,000 cells/mL
· Serum lactate levels >2.2 mmol/L
· Admission to intensive care unit
· End organ failure (eg, requiring mechanical ventilation, renal failure)
· Failure to improve after three to five days of maximal medical therapy
Impression:
Fulminant colitis (previously referred to as severe, complicated CDI) – Hypotension or shock, ileus, or megacolon
Patients with ileus may benefit from using a rectal swab for a toxin assay or anaerobic culture as a diagnostic technique.
Treatment of C.diff. (patients with typical manifestations of CDI (acute diarrhea [≥3 loose stools in 24 hours] with no obvious alternative explanation) and a positive diagnostic laboratory assay):
Systemic vancomycin or fidaxomicin for 14 days
combination metronidazole, vancomycin and rifampicin, can be used
Metronidazole can be used but has a high resistance rate.
In the indexed case surgical intervention is the best treatment option.
Fecal transplant cane be implemented with data in good response rate and decreased mortality in severe disease.
References:
(1) Killeen S, Martin ST, Hyland J, O’ Connell PR, Winter DC. Clostridium difficile enteritis: a new role for an old foe. Surgeon. 2014 Oct;12(5):256-62. doi: 10.1016/j.surge.2014.01.008. Epub 2014 Mar 4. PMID: 24618362.
(2) UpToDate – clostridium difficle treatment and prevention, and outcome.
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment.
Thank you Prof. Ajay.
sorry i could not understand what you mean by principles of CCRISP or ACCC, would you please define them to me
What is the differential diagnosis?
The differential diagnoses include:
=========================
How would you confirm the diagnosis?
Histopathological examination:
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Who would manage this patient?
Substantiate your answer!
Reference
How do you think a colo-rectal surgeon can contribute to management of this patient?
If non-invasive treatments fail to reduce the size of the toxic megacolon within 2 to 3 days, surgery may be needed to remove part or all of the colon.
Can we diagnose c def colitis by stool culture?
Yes, it can be cultured from stool, though cultures are not widely used by most laboratories.
However, it might be needed in certain situations, for example some patients with disease do not have detectable levels of toxin in their stool.
Toxic mega colon with impending perforation complicated by septic shock, metabolic acidosis and peritonitis, underlying colitis might be resultant from acute exacerbation of chronic inflammatory bowel disease Ulcerative colitis vs Crohn’s disease. infective process mediated by bacterial infection such as clostridium difficile or HIV infection might be the culprit as well. However, Cultures were negative.
Urgent management must be implemented with surgical team taking over, as there is an impending perforation with complicated peritonitis,
surgical management with colectomy must be first line of management.
Antibiotic cover.
correction of volume status.
electrolytes correction.
diagnosis of underlying IBD.
plan for long term management.
Short and sweet.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Could it be a C. def-induced pseudomembranous colitis?
If yes, is it diagnosed by stool culture?
Yes , it can be C.def-induced pseudomembranous colitis complicated by toxic megacolon, its rarely occuring.
Stool culture is the most sensitive tool, but time consuming. EIA is the mostly used test for detection of C.def. toxins.