title: Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication.
abstract: BACKGROUND
  When 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.
  
  
  METHODS
  For 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.
  
  
  RESULTS
  Of 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).
  
  
  CONCLUSIONS
  Diarrhea 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.
authors.affiliation: 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.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Gillies
authors.affiliation: 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.
authors.forename: Anggi
authors.initials: A
authors.lastname: Ranakusuma
authors.affiliation: 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.
authors.forename: Tammy
authors.initials: T
authors.lastname: Hoffmann
authors.affiliation: 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.
authors.forename: Sarah
authors.initials: S
authors.lastname: Thorning
authors.affiliation: 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.
authors.forename: Treasure
authors.initials: T
authors.lastname: McGuire
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
authors.affiliation: 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. cdelmar@bond.edu.au.
authors.forename: Christopher
authors.initials: C
authors.lastname: Del Mar
mesh_terms: D000658:Amoxicillin / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced* / Q000453:epidemiology; D014943:Global Health; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin