Probiotics reduced incidence of antibiotic-associated diarrhea

James P. Nataro, MD, PhD, MBA

Diarrhea is the most frequent adverse effect of antibiotic administration. Although it is rarely a serious threat to the child, it does compromise adherence to therapy and will occasionally lead to full-blown colitis. Many pediatricians recommend probiotics or probiotic-containing interventions to prevent or treat antibiotic-associated diarrhea (AAD), although the data to support this practice have heretofore been limited.

This study by Hempel and coauthors presents a comprehensive review and meta-analysis of studies that utilize probiotics in the prevention and treatment of AAD. In this thorough and well-presented analysis, the authors conclude that probiotics are associated with a significant reduction in AAD. Their conclusion comes as no surprise to pediatricians long accustomed to the use of probiotics for AAD, but there are some messages which warrant consideration.

It is widely believed that antibiotics cause diarrhea via perturbation of the commensal intestinal microbiota. Accordingly, the administration of abundant constituents of the microbiota carries the weight of biological plausibility. In fact, it is tempting to move beyond the assignment of “probiotic” species, defined as microorganisms that produce health effect when consumed, toward a broader appreciation that our microbiota are in general good for us, and that they should be preserved, protected, characterized, and, yes, reconstituted when and where possible. In keeping with this idea, Hempel and colleagues have found consistent benefit to probiotic administration, regardless of the product consumed, including but not limited to members of the genera Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus and Bacillus. Certainly these species are marketed as probiotic preparations based on pre-clinical and often clinical evidence, but we should not assume that only these species will provide therapeutic or prophylactic benefit. 

Although Hempel and colleagues have confirmed the benefit of probiotics against AAD, the paper does not allow the reader to infer which probiotic formulations to recommend for our patients, or whether it is better to prescribe them prior to the onset of diarrhea. It is intuitive, of course, that probiotic formulations delivering higher titers of live bacteria are more efficacious, but this effect cannot be discerned from the data. Importantly, the meta-analysis approach was required to confirm the benefit of probiotics in AAD because the effect size is modest: the number-needed-to-treat to benefit one patient was 13 for diarrhea, and colitis was not an endpoint of this study. It is therefore left to the practitioner and the family to select their preferred product, and to decide whether the benefits of probiotics warrant the cost and inconvenience of another medication administration. The report by Hempel may stimulate further studies that compare formulations or drive the development of more efficacious preparations.