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

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Abstract

Background

The 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.

Objective

The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making.

Data Sources

The 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 Selection

All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies.

Data Extraction

Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form.

Results

The 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).

Conclusions

Although 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.

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Authors and Affiliations

  1. Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

    Siyu Li, Zhe Chen, Liang Huang, Zheng Liu, Yuqing Shi, Miao Zhang, Hailong Li, Linan Zeng, Jiaqi Ni, Zhi-Jun Jia & Lingli Zhang

  2. Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

    Siyu Li, Zhe Chen, Liang Huang, Zheng Liu, Yuqing Shi, Miao Zhang, Hailong Li, Linan Zeng, Jiaqi Ni, Zhi-Jun Jia & Lingli Zhang

  3. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China

    Siyu Li, Zhe Chen, Liang Huang, Zheng Liu, Yuqing Shi, Miao Zhang, Hailong Li, Linan Zeng, Zhi-Jun Jia, Guo Cheng & Lingli Zhang

  4. West China School of Medicine, Sichuan University, Chengdu, 610041, China

    Siyu Li & Zheng Liu

  5. West China School of Pharmacy, Sichuan University, Chengdu, 610041, China

    Yuqing Shi, Miao Zhang, Jiaqi Ni & Zhi-Jun Jia

  6. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

    Yu Zhu & Guo Cheng

  7. Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Sichuan University, Chengdu, 610041, China

    Guo Cheng

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  1. Siyu Li
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Author Contributions

Siyu Li conceptualized and designed the study, conducted the systematic review, analyzed the data, drafted the initial manuscript, and reviewed and revised the manuscript. Zhe Chen conceptualized and designed the study and reviewed and revised the manuscript. Lingli Zhang conceptualized the study and reviewed and revised the manuscript. Zheng Liu, Yuqing Shi, Miao Zhang and Jiaqi Ni conducted the systematic review, including screening of abstracts and full text, extracting data and assessing study quality. As pediatric clinical experts, Liang Huang and Yu Zhu gave their clinical opinions in the study process and manuscript writing. Hailong Li, who specializes in statistics, participated in data processing and analysis. All authors critically revised the manuscript for important intellectual content, approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Li, S., Chen, Z., Huang, L. et al. Safety of Quinolones in Children: A Systematic Review and Meta-Analysis. Pediatr Drugs 24, 447–464 (2022). https://doi.org/10.1007/s40272-022-00513-2

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  • DOI: https://doi.org/10.1007/s40272-022-00513-2

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