Common harms from amoxicillin: A systematic review and meta-analysis of randomized placebo-controlled trials for any indication

Malcolm Gillies, Anggi Ranakusuma, Tammy Hoffmann, Sarah Thorning, Treasure McGuire, Paul Glasziou, Christopher Del Mar

Research output: Contribution to journalArticleResearchpeer-review

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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).

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.

Original languageEnglish
Pages (from-to)E21-E31
JournalCMAJ
Volume187
Issue number1
DOIs
Publication statusPublished - 6 Jan 2015

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Amoxicillin
Amoxicillin-Potassium Clavulanate Combination
Meta-Analysis
Randomized Controlled Trials
Placebos
Candidiasis
Confidence Intervals
Anti-Bacterial Agents
Diarrhea
Odds Ratio
Publication Bias
Clavulanic Acid
Liver Function Tests
Pruritus
Exanthema
MEDLINE
Nausea
Vomiting
Observational Studies
Language

Cite this

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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).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.",
author = "Malcolm Gillies and Anggi Ranakusuma and Tammy Hoffmann and Sarah Thorning and Treasure McGuire and Paul Glasziou and {Del Mar}, Christopher",
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Common harms from amoxicillin : A systematic review and meta-analysis of randomized placebo-controlled trials for any indication. / Gillies, Malcolm; Ranakusuma, Anggi; Hoffmann, Tammy; Thorning, Sarah; McGuire, Treasure; Glasziou, Paul; Del Mar, Christopher.

In: CMAJ, Vol. 187, No. 1, 06.01.2015, p. E21-E31.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gillies, Malcolm

AU - Ranakusuma, Anggi

AU - Hoffmann, Tammy

AU - Thorning, Sarah

AU - McGuire, Treasure

AU - Glasziou, Paul

AU - Del Mar, Christopher

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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.

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