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 Clostridium Difficile

C. difficile is a ubiquitous, Gram-positive, anaerobic, motile, spore-forming bacillus that colonizes the intestines of nursing homes or long-stay hospital patients. The acquisition is estimated to occur in ~13% of patients with a hospital stay of up to 2 weeks, and in ~50% of those with hospital stays longer than 4 weeks. It is resistant to most antibiotics and forms heat and disinfectant resistant spores. Consequently, C. difficile survives for long periods in hospital environments. Fortunately, bleach-containing disinfectants destroy the organism.

   C. difficile induced diarrhoea has been linked to the use of certain broad-spectrum antibiotics, including cephalosporins, clindamycin, and especially quinolones (e.g. ciprofloxacin).

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Clinical Features of Clostridium Difficile

Spores are transmitted by the faecal-oral route. Following ingestion, they pass through the stomach because they are acid-resistant, and then change to their active form and multiply in the colon. In small numbers, C. difficile does not cause significant disease, but, after disruption of normal intestinal flora by broad-spectrum antibiotic therapy (especially quinolones, cephalosporins), overgrowth may cause a spectrum of symptoms. These range from asymptomatic colonization to severe, life-threatening diarrhoea with pseudomembranous colitis and, occasionally, bowel perforation. Pathogenic C. difficile produces toxins responsible for diarrhoea and inflammation. The best characterized of these are enterotoxins (toxin A) and cytotoxin (toxin B).

Diagnosis of Clostridium Difficile

Diagnosis is based on clinical features (e.g. odorous diarrhoea, antibiotic exposure), detection of toxins A + B, and characteristic CT scan features (e.g. colonic wall thickening >4 mm, pericolonic stranding, ascites, and colon wall nodularity). Toxin assessment is by enzyme-linked immunoabsorbent assay (ELISA). It is important to test for both toxins, as some hospital strains only express toxin B. Delayed diagnosis risks bowel perforation and increases mortality.

Treatment of Clostridium Difficile

In symptomatic patients, the initial choice of drugs to eliminate C. difficile is oral metronidazole (500 mg three times daily). Oral vancomycin (125 mg four times daily) is second line therapy and can be used in severe disease if metronidazole is ineffective or the organism is resistant to metronidazole, and in pregnant patients. There is a theoretical risk of converting intestinal flora into vancomycin-resistant organisms. Linezolid may also be used. In relapse, the addition of rifampicin to vancomycin may be effective. Asymptomatic patients may not require antibiotic therapy.

Obstetrics and Gynaecology Lecture Notes PDF Download Link

Antidiarrhoeal drugs (e.g. loperamide) are contraindicated, as they prolong toxin-induced colonic damage. Probiotics (i.e. ‘good’ intestinal flora) may be beneficial and help prevent relapse. Colestyramine (4 g daily) binds toxins and slows bowel motility, which may reduce dehydration. Intravenous immunoglobulin is a last resort treatment in immunocompromised patients. Colectomy may be required in patients who develop systemic symptoms of C. difficile.

Prevention of Clostridium Difficile

Prevention includes avoiding inappropriate antibiotic therapy (especially in the elderly), the use of gloves, and appropriate infection control measures to reduce transmission. The value of prophylactic probiotics has not been established.