Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis. The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy. MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial". Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death. Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView. Of eleven studies identified, two were subsequently excluded because patients were stool positive for C. difficile, but did not have diarrhea or because the study was not a randomized controlled trial. All of the remaining nine studies involved patients with diarrhea who recently received antibiotics for an infection other than C. difficile. The definition of diarrhea ranged from at least two loose stools per day with an associated symptom such as rectal temperature > 38(o)C, to at least six loose stools in 36 hours. In terms of symptomatic cure, metronidazole, bacitracin and fusidic acid were not shown to be less effective than vancomycin. Teicoplanin may be slightly more effective than vancomycin with a relative risk of 1.