TY - JOUR
T1 - Common harms from amoxicillin: A systematic review and meta-analysis of randomized placebo-controlled trials for any indication
AU - Gillies, Malcolm
AU - Ranakusuma, Anggi
AU - Hoffmann, Tammy
AU - Thorning, Sarah
AU - McGuire, Treasure
AU - Glasziou, Paul
AU - Del Mar, Christopher
N1 - Funding Information:
Funding: This study was conducted as a project of the Centre for Research Excellence in Minimising Antibiotic Resistance in Acute Respiratory Infections, with funding for the centre provided by the National Health and Medical Research Council (NHMRC) of Australia (grant 1044904). Paul Glasziou is supported by NHMRC Australia Fellowship 527500. Tammy Hoffmann is supported by NHMRC/Primary Health Care Research, Evaluation and Development Career Development Fellowship 1033038. NPS MedicineWise provides salary support for Malcolm Gillies.
Publisher Copyright:
© 2015 8872147 Canada Inc.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2015/1/6
Y1 - 2015/1/6
N2 - 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).INTERPRETATION: 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.
AB - 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).INTERPRETATION: 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.
UR - http://www.scopus.com/inward/record.url?scp=84920594254&partnerID=8YFLogxK
U2 - 10.1503/cmaj.140848
DO - 10.1503/cmaj.140848
M3 - Article
C2 - 25404399
SN - 0008-4409
VL - 187
SP - E21-E31
JO - CMAJ
JF - CMAJ
IS - 1
ER -