Adverse events in people taking macrolide antibiotics versus placebo for any indication

• Published in: Cochrane database of systematic reviews 2019-01, Vol.1 (1), p.CD011825
• Main Authors: Hansen, Malene Plejdrup, Scott, Anna M, McCullough, Amanda, Thorning, Sarah, Aronson, Jeffrey K, Beller, Elaine M, Glasziou, Paul P, Hoffmann, Tammy C, Clark, Justin, Del Mar, Chris B
• Format: Article
• Language: English
• Subjects: Abdominal Pain - chemically induced; Adverse events; Anti-Bacterial Agents - adverse effects; Bile Duct Diseases - chemically induced; Child health; Diarrhea - chemically induced; Hearing Loss - chemically induced; Heart Diseases - chemically induced; Humans; Infectious disease; Macrolides - adverse effects; Macrolides - therapeutic use; Nausea - chemically induced; Numbers Needed To Treat; Placebos; Randomized Controlled Trials as Topic; Taste Disorders - chemically induced; Vomiting - chemically induced
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.CD011825.pub2

Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the trea