Probiotics May Prevent Antibiotic Diarrhea
Probiotic administration was associated with a 42% reduced relative risk of antibiotic-associated diarrhea (P<0.001), Susanne Hempel, PhD, of RAND Health in Santa Monica, Calif., and colleagues found.
The number needed to treat to prevent one case of diarrhea from antibiotic use was just 13, they reported in the May 9 issue of the Journal of the American Medical Association.
Antibiotics lead to diarrhea in as many as 30% of patients, which is an important cause of nonadherence to the drugs.
"Potentially, probiotics maintain or restore gut microecology during or after antibiotic treatment through receptor competition, competition for nutrients, inhibition of epithelial and mucosal adherence of pathogens, introduction of lower colonic pH favoring the growth of nonpathogenic species, stimulation of immunity, or production of antimicrobial substances," the group suggested.
In children, probiotics have proven effective in preventing antibiotic-induced diarrhea and treating acute infectious diarrhea.
Most of the evidence, though, has accrued in adult trials almost universally underpowered to show the kind of impact seen in Hempel's analysis.
The meta-analysis included 82 randomized controlled trials, 57 of which used Lactobacillus-based interventions alone or in combination with other genera of probiotics (32 with Bifidobacterium). All but two trials used probiotics to prevent rather than treat existing antibiotic-associated diarrhea.
The effect on diarrhea risk could be pooled from 63 of the trials, with a total of 11,811 participants, and remained significant at P<0.001 when excluding any individual trial.
The trials where Lactobacillus probiotics was used exclusively were associated with reduced risk of antibiotic-associated diarrhea, similar to that in the overall analysis (pooled RR 0.64, P=0.004), with a number needed to treat of 14.
The 16 trials using only yeast as the probiotic, such as Saccharomyces boulardii [cerevisiae] or Hansen CBS 5926, also showed significantly reduced risk of antibiotic-associated diarrhea with a pooled relative risk of 0.48 (P<0.001) and number needed to treat of 10.
The researchers also looked for Streptococcus, Enterococcus, and Bacillus probiotic studies but found few.
Pooled results from three older trials using Enterococcus [Streptococcus] faecium SF68 showed a relative risk of 0.51 (P<0.001) and a number needed to treat of 12.
The difference between the different probiotic types wasn't significant (P=0.45) and didn't appear to explain away heterogeneity. Nor did the head-to-head comparison trials point to a clear winner.
The exact strains of the probiotic bugs used, though, were poorly documented, Hempel's group cautioned.
The analysis turned up no evidence of publication bias; no difference in probiotic treatment effect by conflict of interest status of the trials; and similar findings looking only at double-blind trials, or only at those with placebo control.
Nor did results vary for adults versus children, outpatient versus inpatient care, or by duration of antibiotic treatment.
In addition to unexplained heterogeneity among included trials and poorly documented probiotics, limitations of the study included lack of information from experts about published or unpublished studies.
"Determining which populations would benefit most from adjunct probiotics therapy is an ongoing challenge; it must be considered that antibiotic-associated diarrhea does not occur in the majority of patients and when it occurs, it is usually self-limiting," Hempel's group wrote.
Little data was available on probiotic-specific adverse events. In rare cases reported decades ago, serious adverse effects like fungemia and bacterial sepsis were reported with probiotics, the researchers noted.
The RAND Corporation internally funded the review, building on the literature database established for a contracted evidence report on the safety of probiotics commissioned by the Agency for Healthcare Research and Quality, and funded jointly by the National Institutes of Health and the FDA Center for Food Safety and Applied Nutrition.
The researchers reported having no conflicts of interest.
The researchers reported having no conflicts of interest.
Primary source: Journal of the American Medical Association
Source reference:
Hempel S, et al "Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis" JAMA 2012; 307: 1959-1969; DOI: 10.1001/jama.2012.3507.
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