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In a 2012 meta-analysis, probiotic use was associated with 42% lower risk for antibiotic-associated diarrhea (AAD; JAMA 2012; 307:1959). However, the 63 trials varied widely in settings, participants, and regimens, and many were small or poorly documented, which yielded unclear clinical implications. To address some of these flaws, researchers in the U.K. identified 2941 older patients (age, >65) who were about to start or recently were exposed to systemic antibiotics in five hospitals; patients were randomized to receive single capsules that contained either a multistrain preparation of Lactobacilli and Bifidobacteria or placebo once daily for 21 days. AAD was defined as diarrhea without an identified pathogen and without an alternative explanation.
During an 8-week follow-up, incidence of AAD (including Clostridium difficile–associated diarrhea) was similar in the probiotic and placebo groups (10.8% and 10.4%) as was incidence of C. difficile–associated diarrhea specifically (0.8% and 1.2%). Rates of adverse events also were similar in the two groups.
Allen SJ et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013 Aug 8; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(13)61218-0)
Comment
The authors of the 2012 meta-analysis called for large, randomized clinical trials to address the limitations of the analysis; now, the first such trial has come to a contradictory conclusion. The pathophysiology of antibiotic-associated diarrhea is understood poorly, which complicates efforts to identify specific microbes and microbial strains that might lower risk for AAD in defined populations. For now, other methods, from handwashing to antimicrobial stewardship, might be more effective in preventing AAD, including C. difficile–associated diarrhea.