Safety of Quinolones in Children: A Systematic Review and Meta-Analysis

BackgroundThe results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial.ObjectiveThe aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making.Data SourcesThe MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021.Study SelectionAll types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies.Data ExtractionData extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form.ResultsThe overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82–2.26; p < 0.001; I2 = 18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2–6 months: RR 2.56, 95% CI 2.26–2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98–1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37–3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00–1.77; low-quality evidence).ConclusionsAlthough the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.