Exposure to ciprofloxacin and risk of musculoskeletal adverse events in children: a systematic review and meta-analysis of randomized controlled trials

Summary Ciprofloxacin use in pediatric patients has raised concerns about musculoskeletal adverse events. We assessed the safety of ciprofloxacin in children aged 0–17 years in a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library on 11 June 2021. We included randomized controlled trials of pediatric patients treated with oral or intravenous ciprofloxacin and compared with a comparator. We included all ciprofloxacin regimens except those involving concomitant drug use. Two authors independently selected studies, extracted data, and assessed risk of bias. The main outcomes were risk ratios (RRs) for musculoskeletal adverse events and adverse events. Eight studies met the inclusion criteria, including 1176 ciprofloxacin-exposed patients, and six studies contributed to the meta-analysis. The RR for musculoskeletal adverse events was 1.13 [95% confidence interval (CI) 0.85–1.51], and the RR for adverse events was 1.12 (95% CI 0.93–1.35). We graded the quality of evidence for both outcomes as very low. Based on this very low-certainty evidence, we found no significant increase in musculoskeletal adverse events in pediatric patients exposed to ciprofloxacin. Ciprofloxacin should therefore be considered when the benefits outweigh the risks, such as in severe infections or when bacterial resistance limits other treatment options. However, high-quality studies are needed before firm conclusions can be drawn.