Population pharmacokinetics and exposure-response analysis of levofloxacin in Chinese pediatric patients with severe refractory Mycoplasma pneumoniae pneumonia.

Levofloxacin is recommended as an optional treatment for pediatric patients with severe refractory Mycoplasma pneumoniae pneumonia (SRMPP), but its use remains off-label due to limited pharmacokinetic/pharmacodynamic (PK/PD) data in this population. This study aimed to characterize the PK/PD properties of levofloxacin in pediatric SRMPP patients and define optimal dosing regimens. Scavenged blood samples from patients aged ≤18 years were collected using opportunistic sampling strategy to develop a population pharmacokinetic (PopPK) model of levofloxacin. The Cox proportional hazards model was applied to identify the optimal AUCss,0-24h cutoff associated with improved efficacy (shorter levofloxacin treatment duration and shorter cough resolution). Monte Carlo simulations were then performed to evaluate target attainment for this efficacy cutoff under guideline regimens (8-10 mg/kg q12 h for ages 1-5 years; 8-10 mg/kg q24 h for ages 5-16 years). A total of 191 pediatric patients (0.16-16 years) with SRMPP receiving intravenous levofloxacin were included in the PK analysis, and 161 patients were included in the exposure-response analysis. A two-compartment PopPK model was developed, identifying body weight as a significant covariate on clearance and central volume of distribution, and serum creatinine as an additional covariate on clearance. Patients with AUCss,0-24h ≥ 30.74 mg·h/L achieved shorter levofloxacin treatment duration (P = 0.019). Guideline-recommended dosing regimens result in overexposure in children <5 years and underexposure in those ≥5 years. Our model-based analysis suggests that 11 mg/kg q24 h or 5.5 mg/kg q12 h may provide more appropriate dosing regimens for children aged 1-16 years for the treatment of SRMPP.