Clostridium difficile

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• Major (? only) important infectious cause of diarrhoea that develops in patients after hospitalization in developed countries
• Clostridium difficile infection may present in a variety of ways: uncomplicated diarrhoea, moderate to severe colitis ± pseudomembranes, fulminant colitis (uncm).
• Toxic megacolon is most serious complication. May present in the absence of diarrhoea.

Clostridium difficile related disease occurs in 5-21% of hospitalized patients, especially in ICU. ? accounts for approximately half of the cases of diarrhoea in ICU patients receiving antibiotics

• Unclear. Probably result of disruption of normal gut flora by antibiotics and subsequent colonization/infection by oro-faecal route. Host’s normal flora is a less likely route. Some additional factor(s) also involved: determines whether patient becomes an asymptomatic carrier or develops symptomatic disease
• Clindamycin, ampicillin and cephalosporins most frequently associated with pseudomembranous colitis. Parenteral aminoglycosides, vancomycin and metronidazole infrequently implicated.
• Currently 3^rd generation cephalosporins most frequently implicated. Appear more prone to cause Clostridium difficile associated diarrhoea than other broad spectrum agents eg ticarcillin/clavulanate
• Pathogenic strains produce toxins that result in colitis and diarrhoea. Toxin A and possibly toxin B appear to be responsible for disease.
• Asymptomatic carriage does not appear to predispose patient to disease.

• sensitivity of EIA for detecting C. difficile is 72% for the first sample and 84% for the second while the sensitivity for the tissue culture toxin assay is 81% for the first sample and 91% for the second sample.
• repeat cultures are not worthwhile once therapy is commenced
• faecal leukocyte test is non-specific on its own (40%); use of the lacroferrin latex agglutination test increases sensitivity to 75%.
• culture of the organism is technically demanding, requiring 2-3 days for growth, and is not useful for distinguishing between the presence of toxin positive strains or toxin negative strains. May be useful in the setting of nosocomial outbreaks for epidemiological purposes.
• direct visualisation of pseudomembranes is highly specific for the diagnosis of C. difficile colitis. Sensitivity in one study was around 71%. Not a first line investigation, however a role for direct visualisation may exist in cases requiring rapid diagnosis if laboratory results will be delayed or if false negative assays are suspected. Many clinicians would treat such patients empirically rather than do sigmoidoscopy or colonoscopy.

• Vancomycin PO 125 mg qds or metronidazole PO 250 mg qds or metronidazole IV for those unable to tolerate oral medication.
• Oral vancomycin and metronidazole are equally effective but the latter is cheaper and there are concerns regarding the emergence of vancomycin resistant enterococci. Faecal metronidazole concentrations are markedly reduced in the absence of diarrhoea. This may be because metronidazole is secreted across inflammed mucosa or because absorption is decreased due to decreased transit time in patients with diarrhoea.
• Relapse rates are 7-34% due to the persistence of spores which proliferate after treatment stopped. Relapses should be treated with repeat courses. After the course has been repeated twice it should be followed by either tapering doses of vancomycin or rifampicin ± vancomycin, cholestyramine or lactobacilli
• Fulminant colitis may require surgical intervention

• Limit use of antimicrobials
• Handwashing between all patients, their body substances or environmental surfaces
• Enteric (stool) isolation precautions. Isolation room if possible.
• Wear gloves when in contact with patients who have Clostridium difficile-associated diarrhoea or with their environmental surfaces
• Disinfect objects contaminated with C. difficile with sodium hypochlorite, akaline glutaraldehyde or ethylene oxide

©Charles Gomersall, August, 2008 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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