Meta-analysis: Probiotics in Antibiotic-Associated Diarrhoea

E. J. Videlock; F. Cremonini


Aliment Pharmacol Ther. 2012;35(12):1355-1369. 

In This Article

Abstract and Introduction


Background Diarrhoea is a common occurrence in association with antibiotic administration. Earlier studies and meta-analyses have suggested that probiotic administration reduces the incidence of antibiotic-associated diarrhoea (AAD).
Aim To estimate the reduction in risk of AAD with administration of probiotics in randomised placebo-controlled trials and to identify factors associated with such reduction.
Methods Meta-analysis of randomised, double-blinded, placebo-controlled trials including patients treated with antibiotics and administered a probiotic for at least the duration of the antibiotic treatment. The outcome was incidence of diarrhoea irrespective of the presence of Clostridium difficile or the development of pseudomembranous colitis. Meta-analysis and meta-regression methods were used to synthesise data and to assess influence of: mean age, duration of antibiotics, risk of bias and incidence of diarrhoea in the placebo group on outcomes. Subgroup analyses explored effects of different probiotic species, patient populations and treatment indications.
Results A total of 34 studies were included with 4138 patients. The pooled relative risk (RR) for AAD in the probiotic group vs. placebo was 0.53 (95% CI 0.44–0.63), corresponding to a number needed to treat (NNT) of 8 (95% CI 7–11). The preventive effect of probiotics remained significant when grouped by probiotic species, population age group, relative duration of antibiotics and probiotics, study risk of bias and probiotic administered. The pooled RR for AAD during treatment for Helicobacter pylori (H. pylori) was 0.37 (95% CI 0.20–0.69), corresponding to a NNT of 5 (95% CI 4–10).
Conclusions This updated meta-analysis confirms earlier results supporting the preventive effects of probiotics in AAD.


Antibiotic-associated diarrhoea (AAD) remains a prevalent condition in both in-patient and out-patient settings. The prevalence of AAD is estimated at 5–39% and is associated with increased costs and hospital length of stay.[1] AAD is a separate clinical entity from Clostridium difficile (C. difficile)-induced diarrhoea and from C. difficile-associated pseudomembranous colitis. The occurrence of AAD can be a limiting factor to adherence to antibiotic regimens and to successful completion of treatment.

Probiotics are 'live microorganisms, which, when consumed in adequate amounts, confer a health benefit on the host'.[2] Probiotic administration has been linked to modulation of gut mucosal immunity, barrier function, metabolism and direct interaction with pathogenic bacteria.[3] These effects have been the rationale for the use of probiotics in a variety of conditions affecting the gastrointestinal tract, including travellers' diarrhoea, inflammatory bowel disease, irritable bowel syndrome, bacterial overgrowth and C. difficile infection.[4]

Probiotics have been used empirically for the treatment and prevention of AAD. Previous meta-analyses of adult and paediatric randomised trials of various probiotics in AAD have estimated an average relative risk (RR) of development of AAD while on probiotics of approximately 0.4.[5,6] Furthermore, probiotic supplementation during multiple antibiotic regimens for Helicobacter pylori (H. pylori) eradication regimens has been proposed as a potential option in guidelines based on results for clinical trials.[7]

The research of probiotics continues to expand and clinical trials continue to proliferate, and a number of high-quality, randomised, placebo-controlled trials have been published since the previous systematic reviews and meta-analyses on this topic.


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