Medical Management of Antimicrobial‐Associated Diarrhea and Colitis

Abstract

Gastrointestinal complications, including diarrhea, may occur with virtually all antimicrobial agents. Such diarrhea may represent either a common, nonspecific adverse effect, or it may be one of the manifestations of antimicrobial-associated colitis (AAC), a potentially fatal complication. Clostridium difficile and a cytotoxin neutralized by Clostridium sordellii antitoxin has been isolated from the stools of nearly all patients with antibiotic-associated pseudomembranous colitis, many patients with AAC, and approximately 20% of those with antimicrobial-induced diarrhea. Demonstration that C. difficile is responsible for cytotoxin production has allowed for specific therapy for these disorders. General treatment measures include discontinuation of the causative antimicrobial agent(s), bowel rest, and supportive care with fluids, electrolytes and colloids, if necessary. Antiperistaltic agents and corticosteroids are not recommended. Various antimicrobials demonstrate potential efficacy in treating AAC in humans. Oral vancomycin is the most widely tested and is currently the treatment of choice. It achieves high concentrations in the feces and is very active against C. difficile in doses of 125-500 mg by mouth every six hours. Other potentially useful but inadequately tested antimicrobials include metronidazole (500 mg by mouth every eight hours) and bacitracin (25,000 units by mouth every six hours). Tetracycline has been employed with some success in nonspecific antibiotic-associated diarrhea, although it is as yet untested in humans with AAC and may induce diarrhea itself. Both miconazole and rifampin are highly effective against C. difficile in vitro but have not been evaluated in AAC. Anion-exchange resins bind the cytotoxin found in stools of patients with AAC. Cholestyramine has been used with variable response in oral doses of 4 g every six to eight hours. Since these resins may also bind vancomycin, resulting in lowered vancomycin concentrations in the stool, combination therapy should be used cautiously. With specific therapy directed against the toxin and aggressive supportive therapy, surgical intervention is rarely necessary. More recently, investigations have been directed at using bacterial preparations to suppress C. difficile by restoring the normal flora. The development of immunological agents (i.e., vaccines, toxoids, antitoxins) for the prevention or treatment of AAC would be a significant advance in therapy.

Interindividual variability in biliary excretion of ceftriaxone: effects on biliary lipid metabolism and on intestinal microflora

“…It is reasonable to assume that a similar situation exists with many other antibiotics, which probably explains the difficulty correlating the incidence of diarrhoea with drug dosage [26]. It is reasonable to assume that a similar situation exists with many other antibiotics, which probably explains the difficulty correlating the incidence of diarrhoea with drug dosage [26].…”

“…From the present data, it is unlikely that ceftriaxone treatment would cause the formation of cholesterol gallstones, and chemical analysis of the precipitations of experimental animals has indeed demonstrated that they instead consist of calcium-ceftriaxone complexes Our detailed studies of ceftriaxone in healthy subjects clearly demonstrate the relationship that interindividual differences in excretion patterns of this anti- biotic lead to changes in intestinal microflora. It is reasonable to assume that a similar situation exists with many other antibiotics, which probably explains the difficulty correlating the incidence of diarrhoea with drug dosage [26]. Antibiotics such as clindamycin and cefoperazone, which are known to induce diarrhoea frequently [27,281, are excreted into the bile to a large extent [29,301.…”

Effect of a lactobacillus preparation on the absorption of oral ampicillin

“…Diarrhea may occur with virtually all antimicrobial agents (7). It may range from a commonly occurring mild, nonspecific annoyance to the rare, but potentially life-threatening, complication of antimicrobial agent-associated colitis (4).…”