Source: Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, Guyatt GH. Probiotics for the Prevention of Clostridium difficile-Associated Diarrhea: A Systematic Review and Meta-analysis. Annals of Internal Medicine. Published Online First: 13 November 2012.
Efficacy Endpoints: Clostridium difficile-associated diarrhea, and adverse effects associated with antibiotic use (abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance)
Harm Endpoints: Adverse events potentially caused by propbiotics (allergic reactions, abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance)
Narrative: Taking antibiotics commonly causes diarrhea. One of the most dreaded forms of antibiotic-associated diarrhea is from a pathogen normally found in the gastrointestinal tract called Clostridium difficile. Clostridium difficile-associated diarrhea (CDAD) can range from mild to severe and life-threatening disease. Currently, in developed countries, CDAD is the most common cause of hospital acquired infectious diarrhea, with the majority of cases attributable to antibiotic use. CDAD arises when antibiotics deplete the normal gastrointestinal flora, which allows Clostridium difficile to multiply and produce toxins. As such, replenishing the flora of the gastrointestinal tract with probiotics could reduce the risk of CDAD.
The authors included 20 trials, 18 of them placebo-controlled, with 3818 subjects randomized to probiotics or control as co-administration with antibiotics. Overall, they found a decrease in the incidence of CDAD with the use of probiotics (ARR of 4%, NNT of 25). The authors also analyzed adverse event (symptom side effect) rates and found an arguable, borderline significant decrease in symptoms among patients taking probiotics (ARR 3%, NNT of 30). These event rates were analyzed in aggregate, including the rates of abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance.
In other words, among patients receiving antibiotics, we would need to treat 25 with probiotics to prevent one case of CDAD, and, presuming significance for symptom reduction, 30 to prevent adverse events in 1 patient.
Caveats: First, this meta-analysis included a heterogeneous population of patients. Both children and adults were included, with an event rate in the control group ranging from 0% to 40%. Second, in 13 of the 20 trials, up to 45% of the data on CDAD was missing in some of the included studies. Third, the authors assumed that the use of one type of probiotic is clinically equivalent to another (e.g. L acidophilus and L plantarum), an unproved assumption. Fourth, the dosage and duration of treatment varied, with some some studies using probiotics only during their antibiotic course while others extended probiotics up to 14 days beyond completion of the antibiotic course.
Author: Jarone Lee, MD, MPH
Published/Updated: February 11, 2013
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