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Objective This study aimed to investigate the risk factors associated with quinolone-resistant Klebsiella pneumoniae (QRKP) infection in children hospitalized and to provide evidence for the prevention and management of this bacterial infection. Methods A retrospective analysis was conducted on the clinical data of 274 children with QRKP infection admitted to Anhui Provincial Children's Hospital between January 1, 2020, and November 22, 2022. These children were divided into two groups: the drug-resistant (120 cases) and -sensitive group (154 cases). Univariate analysis was performed to identify factors with statistically significant differences between the two groups, followed by logistic regression analysis to identify independent risk factors for quinolone resistance. Results Univariate analysis revealed that the drug-resistant group had a significantly higher proportion of children with a history of hospitalization, ICU admission, immunosuppressant use, antibiotic use, mechanical ventilation, and sputum suction compared to the sensitive group (all P < 0.05). Multivariate logistic regression analysis identified two independent risk factors for QRKP infection in children: a history of ICU admission within the past three months ( OR = 4.5361, P = 1.35e-06) and sputum suction during the current hospitalization ( OR = 2.3677, P = 0.0019). Conclusion A history of ICU admission in the past three months and sputum suction during hospitalization are major risk factors for QRKP infection in children. Clinicians should implement routine QRKP screening upon admission and strengthen infection control measures to reduce the incidence of this infection in pediatric patients.