• Malcolm Gillies, Anggi Ranakusuma, Tammy Hoffmann, Sarah Thorning, Treasure McGuire, Paul Glasziou, and Christopher Del Mar.
• NPS MedicineWise Ltd. (Gillies), Sydney, New South Wales, Australia; Center for Clinical Epidemiology and Evidence-Based Medicine (Ranakusuma), Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Centre for Research in Evidence-Based Practice (Hoffmann, Thorning, Glasziou, Del Mar) and Faculty of Health Sciences and Medicine (McGuire), Bond University, Gold Coast, Queensland, Australia.
• CMAJ. 2015 Jan 6; 187 (1): E21E31E21-E31.

BackgroundWhen prescribing antibiotics for common indications, clinicians need information about both harms and benefits, information that is currently available only from observational studies. We quantified the common harms of the most frequently prescribed antibiotic, amoxicillin, from randomized placebo-controlled trials.MethodsFor this systematic review, we searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, without language restriction, for any randomized, participant-blinded, placebo-controlled trials of amoxicillin or amoxicillin-clavulanic acid for any indication, in any setting. Our main outcome was any reported adverse event.ResultsOf 730 studies identified, we included 45 trials: 27 involving amoxicillin, 17 involving amoxicillin-clavulanic acid and 1 involving both. The indications for antibiotic therapy were variable. The risk of bias was low, although only 25 trials provided data suitable for assessment of harms, which suggested under-reporting. Diarrhea was attributed to amoxicillin only in the form of amoxicillin-clavulanic acid (Peto odds ratio [OR] 3.30, 95% confidence interval [CI] 2.23-4.87). The OR for candidiasis (3 trials) was significantly higher (OR 7.77, 95% CI 2.23-27.11). Rashes, nausea, itching, vomiting and abnormal results on liver function tests were not significantly increased. The results were not altered by sensitivity analyses, nor did funnel plots suggest publication bias. The number of courses of antibiotics needed to harm was 10 (95% CI 6-17) for diarrhea with amoxicillin-clavulanic acid and 27 (95% CI 24-42) for candidiasis with amoxicillin (with or without clavulanic acid).InterpretationDiarrhea was caused by use of amoxicillin-clavulanic acid, and candidiasis was caused by both amoxicillin and amoxicillin-clavulanic acid. Harms were poorly reported in most trials, and their true incidence may have been higher than reported. Nevertheless, these rates of common harms associated with amoxicillin therapy may inform decisions by helping clinicians to balance harms against benefits.© 2015 Canadian Medical Association or its licensors.

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