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Background: Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia. Previously, we established a population pharmacokinetics (PPK) model for meropenem in pediatric severe infection and simulated the control rate of the time during which the free plasma concentration of meropenem exceeds the minimum inhibitory concentration (MIC) is 70% of the dosing interval (70% fT > MIC). Therefore, we plan to conduct a multicenter randomized controlled trial (RCT) to compare the efficacy and safety between conventional regimen and model regimen for meropenem in pediatric severe pneumonia.Methods: One hundred patients (aged 3 months to 15 years) will be recruited in this RCT. They will be assigned randomly (at a 1:1 ratio) to a conventional treatment group (20 mg/kg, q8h, with 0.5–1 h infusion) and a model treatment group (20 mg/kg, q8 h, with 4 h infusion). The primary outcome will be 70% fT > MIC. Secondary outcomes will be the prevalence of meropenem therapy failure, duration of antibiotic therapy, changes in levels of inflammatory indicators, changes in imaging examination results, and prevalence of adverse events. Ethical approval of our clinical trial has been granted by the ethics committee of Beijing Children’s Hospital ([2022]-E-133-Y). This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200061207).Discussion: Based on our previous PPK data, we have designed this RCT. It is hoped that it will promote rational use of antibacterial drugs in children suffering from severe pneumonia.Clinical Trial Registration: http://www.chictr.org.cn identifier, ChiCTR2200061207.

Objective Cefepime is used to treat severe infections in neonates. Pharmacokinetic data have only been evaluated among preterm neonates and population pharmacokinetic model lacked external validation. Hence, our aim is to obtain the population pharmacokinetic parameters of cefepime with large sampling and optimize the cefepime dosage regimen for neonatal infection based on developmental pharmacokinetics-pharmacodynamics. Methods Blood samples from neonates and young infants treated with cefepime were collected using the opportunistic sampling design. The concentration of cefepime was determined using high performance liquid chromatography with ultraviolet detection. The population pharmacokinetic model was established using NONMEM software. Results One hundred blood samples from eighty-five neonates were analyzed. The population pharmacokinetics of cefepime were described by a one-compartment model with first-order elimination. Covariate analysis indicated that serum creatinine concentration, postmenstrual age and current weight had significant impact on the pharmacokinetic parameters of cefepime. Monte Carlo simulation results showed that the current dosage regimen (30 mg/kg, q12 h) had a high risk of insufficient dose. For 70% of neonates to obtain a higher free drug concentration than the minimum inhibitory concentration during 70% of the dosing interval, 50 mg/kg q12 h was needed with a susceptibility breakpoint of 4 mg/l. For a minimum inhibitory concentration of 8 mg/l, 40 mg/kg q8 h was recommended for all neonates. Conclusion A population pharmacokinetic model of cefepime in neonates and young infants was established. According to simulation results based on the developmental pharmacokinetics-pharmacodynamics, different dosage regimens should be given depending on pathogens and the postmenstrual age.