Rates of adverse effects of treatment for otitis media varies by antibiotic and dose

Référence

Hum SW, Shaikh KJ, Musa SS, Shaikh N. Adverse events of antibiotics used to treat acute otitis media in children: a systematic meta-analysis. J Pediatr 2019;215:139-143.e7.

Sommaire

These authors searched MEDLINE for published studies that reported the frequency of common adverse events (diarrhea, generalized rash, diaper rash, and candida diaper dermatitis) associated with the use of amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir, and placebo in children treated for acute otitis media (AOM). The authors included English-language randomized trials, cohort studies, and cross-sectional studies in which treatment lasted at least 7 days (or 5 days in the case of azithromycin). The authors only included studies of amoxicillin/clavulanate that used a high dose (90/6.4 mg/kg/day) and studies of azithromycin that used a low dose (< 10 mg/kg/day) because these are the only formulations "currently available for AOM." (Of course, in the real world, we know there is much greater variation in what clinicians actually use.) The authors used very narrow definitions of adverse effects; for example, they only included studies that used the word "diarrhea" and excluded those that used terms such as "loose stools," "stool changes," or "gastrointestinal effects." Therefore, the rates they report are likely to be underestimates. Ultimately, they included 82 studies, most at high risk of bias. The number of children in the studies varied from 40 to 810. The authors correctly point out the inconsistent reporting of adverse events across studies, resulting in heterogeneity. Generally, diarrhea was the most common adverse event, but it ranged from 2.2% (azithromycin) to 18.9% (amoxicillin/clavulanate). The placebo caused diarrhea in approximately 7% of children, perhaps a reflection of underlying viral infections. In the 3 studies that used diaries, the rate of diarrhea was higher (range = 14.6% - 21.1%). The rate of generalized rash varied from 1.4% (azithromycin) to 6.5% (high-dose amoxicillin; ie, at least 80 mg/kg/day). Diaper rash occurred in 4.6% of children and varied up to 14.8% in children treated with amoxicillin/clavulanate. The rate of candida diaper rash was only reported for 2 antibiotics: 3.3% for amoxicillin/clavulanate and 5.8% for low-dose amoxicillin (< 80 mg/kg/day). This latter outcome is likely to be influenced by underreporting and by the authors' very narrow definition.