Probiotics could prevent C. difficile infections

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Systematic review and meta-analysis published in Gastroenterology

Administration of probiotics close to the time of the first dose of antibiotic therapy in hospitalized patients reduced the risk of Clostridium difficile infection by more than 50%, according to results of a systematic review and meta-analysis published in Gastroenterology.

The evidence supporting this finding was rated as high by the researchers via the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria; however, others view the evidence supporting this finding as low or very low because of limitations associated with the analysis. 

The incidence of C. difficile infections is rising and causing a substantial burden on the health care system. Researchers have estimated that more than 20% of patients with C. difficile infection fail initial treatment, with many patients having a recurrence. In addition, approximately 30,000 patients in the United States died from these infections in 2011.

Risk factors for infections caused by C. difficile include use of antibiotics, hospitalization, increasing age, and comorbidities. Because of the morbidity and mortality associated with these infections, measures that may prevent their occurrence are needed.    

Coadministration of probiotics with antibiotics has been proposed as one means to help prevent the occurrence of C. difficile. Unfortunately, published data have been conflicting regarding the efficacy of probiotics in this setting. Currently, guidelines from the American College of Gastroenterology and the Society for Healthcare Epidemiology of America do not recommend probiotics for primary prevention of C. difficile infections. 

Shen and colleagues conducted a systematic review and meta-analysis of 19 randomized controlled trials of hospitalized adult patients receiving antibiotic therapy where probiotics were used to prevent C. difficile infections.1 Among the 19 trials, 3,277 patients (weighted mean age 68 y) were randomized to the probiotic intervention, and 2,984 patients (weighted mean age 69 y) were randomized to placebo or a control group (i.e., no intervention).

Commonly excluded patients from the trials were women who were pregnant, those who were immunocompromised, those in the ICU, or those with a prosthetic heart valve or pre-existing gastrointestinal disorder. A variety of unique probiotic formulations were studied across the trials, with the four species being Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus. The dosing, timing, and duration of use for the probiotics also varied across the trials.   

The researchers reported that the incidence of C. difficile infections was 1.6% in the probiotic group compared with 3.9% in the control group (P < 0.001). This translated to a pooled relative risk of C. difficile infection of 0.42 (95% CI 0.30–0.57) in the probiotic group. In addition, the analysis showed that administration of probiotics closer to the time of initiation of antibiotics was significantly more effective compared to later administration. Specifically, probiotics given within 2 days of antibiotic initiation resulted in better outcomes compared with administration past 48 hours.

On the basis of the GRADE criteria, the researchers rated the overall quality of the evidence as high. In terms of safety, the incidence of adverse events across 15 of the studies was similar in the probiotic and control groups (14.2% vs. 15.9%). For adverse events, the overall quality of the evidence was rated as moderate.

For the full article, please visit for the upcoming March 2018 issue of Pharmacy Today.

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