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Antibiotic-associated pseudomembranous colitis
Abstract:
C. difficile was originally described in 1935 but was of minimal clinical interest until recently, when studies showed it to be the cause of antibiotic-associated PMC. Intestinal complications caused by C. difficile appear almost exclusively in conjunction with exposure to antibiotics. Evidence that supports the etiologic role of this organism in antibiotic-associated PMC comes from both bacteriological studies and tissue culture assays. Tissue culture assays have been used to demonstrate that the stool supernate from nearly all patients with anatomically confirmed PMC contains a cytotoxin that is neutralized with Clostridium sordellii antitoxin. The cytotoxin has rarely been found in persons without gastro-intestinal complications related to antibiotic usage. Cultures of stool from patients with anti-biotic-associated PMC usually yield C. difficile, which is encountered only infrequently in the fecal flora of healthy persons. Strains of C. difficile have been shown to cause a similar disease in experimental animals administered antibiotics or intracecal injections of broth cultures of C. difficile. According to the antitoxin neutralization tests and biochemical purification studies done to date, C. difficile is the only organism that produces a cytotoxin similar or identical to the cytotoxin encountered in stools of patients with PMC. The toxin is a high-molecular-weight protein that appears to cause changes in the permeability of cells in tissue culture. However, the mechanism of its action on intestinal mucosa and the cause of its production with antibiotic exposure in clinical settings have not been well defined.
Insights
Clostridium difficile (C. difficile) causes antibiotic-associated pseudomembranous colitis (PMC). This bacterium produces a cytotoxin linked to PMC, but its exact action on the gut remains unclear.
Area of Science:
- Microbiology
- Gastroenterology
- Toxicology
Background:
- Clostridium difficile (C. difficile) was identified in 1935 but gained clinical significance due to its role in antibiotic-associated pseudomembranous colitis (PMC).
- The occurrence of intestinal complications linked to C. difficile is strongly associated with prior antibiotic exposure.
- C. difficile is rarely found in the gut flora of healthy individuals but is frequently isolated from patients with antibiotic-associated PMC.
Purpose of the Study:
- To investigate the etiological role of C. difficile in antibiotic-associated PMC.
- To characterize the cytotoxin produced by C. difficile and its association with PMC.
- To explore the mechanism of C. difficile toxin action and its production in relation to antibiotic use.
Main Methods:
- Bacteriological analysis of stool samples from patients with PMC and healthy individuals.
- Tissue culture assays to detect and neutralize cytotoxin in stool supernates using Clostridium sordellii antitoxin.
- Experimental animal models administered antibiotics or C. difficile cultures to induce disease.
- Antitoxin neutralization tests and biochemical purification studies to identify the toxin-producing organism.
Main Results:
- Stool supernates from nearly all patients with confirmed PMC contained a cytotoxin neutralized by C. sordellii antitoxin.
- This cytotoxin was rarely detected in individuals without gastrointestinal issues related to antibiotic use.
- C. difficile was consistently isolated from patients with antibiotic-associated PMC but infrequently from healthy controls.
- Experimental administration of antibiotics or C. difficile induced similar disease in animals.
- C. difficile was identified as the sole organism producing a cytotoxin identical or similar to that found in PMC patients' stools.
Conclusions:
- C. difficile is the causative agent of antibiotic-associated PMC, producing a high-molecular-weight protein cytotoxin.
- The cytotoxin appears to alter cell permeability in tissue culture.
- The precise mechanism of the toxin's action on intestinal mucosa and its induction by antibiotics require further investigation.