Contents
Introduction
Severe inflammation of the inner lining of the large intestine, manifests as an antibiotic-associated colonic inflammatory complication resulting in acute diarrhoea and characterised by colonic pseudomembranes.
- Clostridium difficile (M/C nosocomial pathogen of GI tract)
History:
The earliest description of PMC was in 1893 when a young woman died following gastric surgery. After surgery, she developed diarrhea, which became bloody, and she died shortly thereafter. Her postoperative care had included alcohol enemas. In this case, which clearly antedated the use of antibiotics, risk factors for altered colonic flora included the enemas as well as surgery of the gastrointestinal (GI) tract. In the pre-antibiotic era, PMC was associated with ischemic cardiovascular insufficiency, colonic obstructions, heavy metal intoxications, sepsis, shock and uremia. In the 1950s, the etiology of PMC was thought to be Staphylococcus aureus, but since 15–30% of normal healthy adults were also colonized, its role in PMC was disputed. Interest in PMC was reignited when clindamycin was introduced for anaerobic infections; one study found that 10% of patients treated with this antibiotic developed PMC. In the 1970s, the connection was made between the anaerobe, Clostridium difficile, a toxin produced in animals and PMC found in humans. Since that time, C. difficile has remained the major culprit attributable in 90–99% of PMC cases, but other etiologies may exist.
Aetiology
Recent antibiotic therapy:
Antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa.
- Most common with penicillin, ampicillin, clindamycin and cephalosporins and less frequent with trimethoprim-sulfamethoxazole and metronidazole
- Antibiotic-associated diarrhea is more common (10–30%) than PMC (1–5%)
Pathophysiology
- Disruption of normal intestinal microflora by inducing antibiotic/agent
- Toxins produced by pathogens lead to cellular distortion and subsequent diarrhea
- Excessive chemotaxic response to inflammatory cells
- Inflammatory cell effects on the enteric nervous system causing other symptoms like abdominal pain
Clinical features
Symptoms can occur within a day or two of starting antibiotics, suggesting that alteration in the colonic flora can develop rapidly.
- Diarrhoea: Watery >> gross/occult blood (99% cases)
- Fever (29% cases)
- Abdominal pain or cramping (33% cases)
- Leukocytosis (61% cases)
Complications
Early-onset complications:
- Hypokalemia (37%)
- Renal failure (27%)
- Hypoproteinemia (50%)
Late-onset complications:
- Acute oligoarthritis
- Hemolytic-uremic syndrome
Diagnosis
Enzyme immunoassay (EIA)
To screen for glutamate dehydrogenase antigen, present in most C. difficile isolates followed by EIA sampling for C. difficile toxin A and toxin B.
CT-abdomen:
GI endoscopy:
Colonoscopic or sigmoidoscopic visualization of pseudomembranes
Tissue culture assay for toxin B:
gold standard for C. difficile detection but this test is expensive, takes 24-48 h for results and is not available in all laboratories
Tissue biopsy:
- Epithelial necrosis, distended goblet cells, infiltration of the lamina propria with leukocytes, and plaques consisting of inflammatory cells, fibrin and mucin
Differential diagnosis:
Other causes of diarrhea which may mimic PMC
- Ischemic colitis, collagenous colitis, inflammatory bowel disease (IBD), CMV-induced colitis, vasculitis, bacterial and parasitic organisms, Behcet’s Disease, chemotherapeutic medications, and toxins, such as heavy metal poisoning
Management
Conservative management:
- Discontinuation of responsible drug
- Anti-clostridial antibiotic therapy: Oral vancomycin/metronidazole/bacitracin (10-day course)
- Biotherapy: Lactobacilli, Saccharomyces
Surgical management
Indications for surgery can include severe pain, development of organ failure, subserosal air in the colon wall, a worsening CT scan or signs of peritonitis