Role of Lactobacillus in the Prevention of Antibiotic-Associated Diarrhea: A Meta-analysis

Study Objective. To evaluate the efficacy of a Lactobacillus probiotic single-agent regimen in preventing antibiotic-associated diarrhea (AAD). Design. Meta-analysis of 10 randomized, blinded, placebo-controlled trials. Patients. A total of 1862 pediatric and adult patients who received a Lactobacillus single-agent regimen or placebo for the prevention of AAD. Measurements and Main Results. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception through May 2008 by two investigators independently using the following key words: probiotic, Lactobacillus, antibiotic-associated diarrhea. Full reports published in English were included if the studies were randomized, blinded, and placebo-con trolled trials that evaluated the efficacy of Lactobacillus single-agent regimens versus placebo in the prevention of AAD. Bibliographies of recent review articles and systematic reviews were hand searched. Quality of the studies was assessed by using the Jadad scoring system. Number of subjects, age, Lactobacillus regimen, follow-up period, and occurrence of AAD were extracted into a standardized data collection form. Overall impact of Lactobacillus on AAD was compared with placebo by using a random-effects model. Ten studies with a total of 1862 patients (50.4% male) met all criteria. Six studies included patients aged 18 years or older, whereas four included patients younger than 18 years (range 2 wks-14 yrs). Jadad scores ranged from 2-5 (out of 5). The total daily dose of Lactobacillus ranged from 2 x 10(9)-4 x 10(10) colony-forming units and was administered throughout the entire antibiotic treatment (5-14 days) for all patients. The follow-up period varied from 2 days-3 months after the end of the probiotic regimen. The combined risk ratio (RR) of developing AAD was significantly lower with Lactobacillus compared with placebo (RR 0.35, 95% confidence interval [CI] 0.19-0.67). In a subgroup analysis, this held true for adults but not pediatric patients (RR 0.24, 95% CI 0.08-0.75 and RR 0.44, 95% CI 0.18-1.08, respectively). Conclusion. Administration of a Lactobacillus single-agent regimen as a prophylactic agent during antibiotic treatment reduced the risk of developing AAD compared with placebo in adults but not pediatric patients.