OBJECTIVE To investigate the risk factors associated with neutropenia in pediatric patients receiving levofloxacin(LVX).

METHODS Clinical data were retrospectively collected from hospitalized children who received LVX therapy at the Children’s Hospital of Chongqing Medical University between September 2015 and September 2025. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for LVX-associated neutropenia. Restricted cubic spline models were used to evaluate the dose-response relationships between continuous risk factors and neutropenia. Sensitivity analyses were conducted to assess the robustness of the findings.

RESULTS A total of 2 891 pediatric patients were included, of whom 405(14.0%) developed LVX-associated neutropenia. The median age was 3.44(0.72, 6.87) years, and the median duration of LVX treatment was 7.04(5.55, 10.89) d. Multivariable Logistic regression analysis showed that concomitant use of imipenem/cilastatin sodium(OR=4.996, P<0.001), lower baseline absolute neutrophil count(OR=0.874, P<0.001), concomitant use of voriconazole(OR=3.470, P<0.001), oral administration(OR=0.360, P<0.001), longer treatment duration(OR=1.028, P<0.001), lower estimated glomerular filtration rate(eGFR)(OR=0.997, P=0.002), younger age(OR=0.944, P=0.002), and concomitant use of meropenem(OR=1.849, P=0.003) were the risk factors for LVX-associated neutropenia. Baseline absolute neutrophil count and eGFR showed significant nonlinear dose-response relationships with the risk of LVX-associated neutropenia, whereas no significant nonlinear relationships were observed for LVX treatment duration or age. Sensitivity analyses results supported the robustness of the main findings.

CONCLUSION In pediatric patients receiving LVX therapy, attention should be paid to concomitant use of imipenem/cilastatin sodium, voriconazole, and meropenem, as well as risk factors including baseline absolute neutrophil count, route of administration, treatment duration, age, and renal function. A comprehensive assessment of these risk factors in the context of anti-infective treatment needs may help prevent the occurrence of neutropenia.