Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication
Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication
复制标题
DOI：
10.1503/cmaj.140848
复制
发表时间：
2015-01-06
影响因子：
14.6
通讯作者：
Del Mar, Christopher
中科院分区：
文献类型：
--
作者：
Gillies, Malcolm;Ranakusuma, Anggi;Del Mar, Christopher
背景：当为常见的适应症开抗生素时，临床医生需要关于危害和益处的信息，这些信息目前只能从观察性研究中获得。我们从随机的安慰剂对照试验中量化了最常用的抗生素阿莫西林的常见危害。方法：在这项系统性综述中，我们搜索MEDLINE、Embase和Cochrane中央对照试验登记处，没有语言限制，在任何环境下，任何随机的、参与者盲的、安慰剂对照的阿莫西林或阿莫西林-克拉维酸试验。结果：在确认的730项研究中，我们包括45项试验：27项涉及阿莫西林，17项涉及阿莫西林-克拉维酸，1项涉及两者。抗生素治疗的适应症多种多样。偏倚的风险很低，尽管只有25项试验提供了适合评估危害的数据，这表明报告不足。腹泻仅归因于阿莫西林-克拉维酸形式的阿莫西林(Peto优势比[OR]3.30，95%可信区间[CI]2.23-4.87)。念珠菌病的OR值(3次试验)显著高于对照组(OR7.77，95%CI 2.23~27.11)。皮疹、恶心、瘙痒、呕吐和肝功能检查异常均未见明显增加。敏感性分析没有改变结果，漏斗图也没有表明发表存在偏见。阿莫西林-克拉维酸引起的腹泻所需的抗生素疗程数为10(95%CI 6~17)，阿莫西林-克拉维酸所致的念珠菌病所需的抗生素疗程数为27(95%CI 24~42)。在大多数试验中，危害的报告很少，而且它们的真实发生率可能比报告的要高。然而，这些与阿莫西林治疗相关的常见伤害的比率可能会帮助临床医生平衡伤害和好处，从而为决策提供参考。
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.