We report a case of severe pseudomembranous colitis in a 55 year old lady living in suburban area and discuss the implications for diagnostic testing and treatment for Clostridium difficile-associated diarrhoea.
Case Report
A 55 year old lady from Than-lyan Township presented with two-week history of watery diarrhoea 5-6 times/day. It did not contain blood and mucus. In last 5 days, she had high fever and cramping abdominal pain and noticed that urine output was reduced and abdomen became more distended.
Actually, she had history of self-prescription with tetracycline as she had acute diarrhorea 3 weeks ago. She was OK in 2 days, so she stopped the drug. And after 5 days, she had another diarrhea. So she took tetracycline again for 5 days. But it did not work, diarrhea continued and she became ill and toxic.
So she consulted a general practioner and Ultrasound abdomen was requested. It revealed ?rectal mass, moderate ascites and right pleural effusion.
She denied other medications and herbal medicine. She had no diabetes, no history suggestive of connective tissue disease nor no malignancy and chemotherapy.
On examination, patient looked toxic, febrile and tachypnoeic . Faint pulse was 136/min and blood pressure was 110/80. There was right pleural effusion upto mid-zone. Abdomen was markedly distended. Mild tenderness over the whole abdomen and shifting dullness were noted. There was no abnormality in DRE and proctoscopic examination.
Regarding investigations, CBC showed marked neutrophil leucocytosis. Apart from mild hypokalaemia, her renal function was normal and there was no proteinuria. She had marked hypoalbuminaemia. Thyroid function test, infection screen and ANA were normal. Chest X’ray revealed old Koch’s lung and bilateral pleural effusion. Toxic megacolon was roughly excluded by Plain X ‘ray abdomen.
At that time, (1) antibiotic associated severe diarrhea (2) TB intestine and (3) colorectal cancers were suspected. So stool for Clostridium difficile toxin A and B were sent and PO metronidazole 400 mg TDS was started since admission. Colonoscopy was performed cautiously with minimal air insufflations. Multiple area of raised exudative plaques 2-10 mm in size, coalescence of which gives rise to yellowish pseudomembranes, were noted throughout the colon mainly at caecum and ascending colon as follow.
Biopsy was taken and revealed focal ulceration of the mucosa which is covered with fibrinosuppurative pseudomembrane ; and no granuloma, no caseation and no Langhan’s giant cells were noted.
As the patient did not response well to PO metronidazole upto 72 hours, IV vancomycin 500 mg 6 Hourly was added (because PO vancomycin was not available). Health education about proper hand washing was delivered. Patients’ rooms and beds were sterilized with appropriate disinfectants. Although patient should be kept in isolation with dedicated toilet facilities, it was impossible in our ward. So, the patient was moved to corner-most bed of common room.
After 72 hours from starting IV Vancomycin (continuing PO metronidazole), the general condition of patient became OK. Temp touched down to normal completely. Abdominal distension and ascites were significantly reduced. CECT abdomen revealed no abnormal finding in abdomen, right minimal pleural effusion and atelectasis in right lower zone, no bowel wall thickening, no bowel dilatation nor ascites. The patient was discharged after 10-day course of IV vancomycin and 2-week course of PO metronidazole. No recurrence was noted upto now.
Discussion
Clostridium difficile infection (CDI) is a unique colonic disease and one of the hottest topics in the field of nosocomial infectious diseases. It is acquired almost exclusively in association with antimicrobial use and the consequent disruption of the normal colonic flora. Pseudomembranous colitis is one of presentations of severe Clostridium difficile infection. Risk factors include antibiotic exposure, proton pump inhibitor, antidepressants, elderly (>60 year) and immunocompromised person.
The diagnosis of C. difficile infection should be suspected in any patient with diarrhea who has received antibiotics within the previous 3 months, has been hospitalized, and/or has an occurrence of diarrhea 48 hours or more after hospitalization.
Regarding diagnostic testing, stool assays for C. difficile, from the most to least sensitive, include stool culture, Glutamate dehydrogenase enzyme immunoassay, PCR assay, Stool cytotoxin test and EIA for detecting toxins A and B. Detecting stool toxin A and B is used in most laboratories (Specific but not sensitive). But none of these tests is imperfect. If the patient is sick and C. difficile infection is suspected, empiric treatment should be started.
None of the scoring system for severity of disease is very good. Four criteria (abdominal distension, fever, elevated white cells count > 15000 cells/mm3 and hypoalbuminaemia < 30 g/L) are correlated with poor outcomes.
All current guidelines strongly recommend the use of soap and water after being in contact with CDI patients. The duration of contact precautions until at least 48 h after diarrhea resolution is emphasized. Chlorine-containing disinfection agents are preferred for the cleaning of patient rooms and the equipment used in CDI cases. Withdrawal of unnecessary antibiotics is recommended.
Regarding initiation of pharmacological therapy, the ESCMID guidelines advocate a 48-h “wait-and-see” policy after stopping all systemic antibiotics for the initial management of a first non-severe episode of CDI (recommendation C-II). In contrast, the IDSA/SHEA guidelines and the WSES guidelines recommend initiating empiric antibiotic treatment in all cases of strong suspicion of CDI even before microbiological confirmation is available (recommendation C-III and 1B, respectively). The ACG guidelines recommend full treatment in this scenario even in cases of negative microbiological results (strong recommendation, moderate-quality evidence). This last document also suggests the prompt initiation of empiric therapy in the particular case of severe colitis in a patient with inflammatory bowel disease (conditional recommendation, low-quality evidence).
All guidelines agree on recommending oral metronidazole as the first choice of antibiotic in case of mild-moderate CDI; and oral vancomycin in the presence of severe CDI. The ACG, WSES and ASID documents also recommend changing metronidazole to vancomycin when no improvement is observed after 3–7 days of treatment (ACG: strong recommendation and moderate-quality evidenc
Some patients with mild C. difficile colitis may recover without specific therapy; however, persistent diarrhea may be debilitation and can last for several weeks; therefore treatment is recommended even in mild disease. Mortality rate for fulminant C. difficle colitis is 34.7% and it increases with age. Toxic megacolon and colonic perforation are also severe complications. The use of oral metronidazole or oral vancomycin produces response rates of greater than 95%.
Approximately 20-27% of patients treated for first episode relapse after successful completing therapy, typically 3 days to 3 weeks. CDI recurrence is defined as a reappearance of documented CDI either within 8 weeks of completion of anticlostridial treatment. Fidaxomicin or vancomycin is recommended for recurrent disease. Intestinal microbiota transplantation is also considered as equally valid as a treatment option for multiple recurrences as fidaxomicin or vancomycin.
References
McDonald LC, Coignard B, Dubberbe E, et al., Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol. 2017 Feb. 28(2): 140-5.
Aberra FN, Curry JA. Clostridium difficile colitis. Medscape. Updated on Apr 6, 2017
Feher C, Mensa J. A Comparison of Current Guidelines of Five International Societies on Clostridium difficile Infection Management. Infect Dis Ther (2016) 5:207–230
- 2010 guidelines of the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA)
- 2013 guidelines of the American College of Gastroenterology (ACG)
- 2014 guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
- 2015 guidelines of the World Society of Emergency Surgery (WSES)
- the most recent 2016 update of the 2011 guidelines of the Australasian Society for Infectious Diseases (ASID)
- Professor and Head, Department of Gastroenterology, Yangon General Hospital
- Professor, Department of Gastroenterology, Yangon General Hospital
- Associate Professor, Department of Gastroenterology, Yangon General Hospital
- Consultant Gastroenterologist, Department of Gastroenterology, Yangon General Hospital
- Doctorate student, Department of Gastroenterology, University of Medicine 1, Yangon
