Pharmacodynamics of Meropenem Against Carbapenemase-producing Enterobacteriaceae

OBJECTIVE To evaluate the pharmacodynamics of meropenem against carbapenemase-producing Enterobacteriaceae(CPE) and provide reference for clinical treatment. METHODS The MIC of CPE was 0.5, 1, 2, 4, 8, 16, 32, and 64 mg·L^-1. Pharmacokinetic parameters of meropenem in healthy volunteers and elderly patients in ICU were obtained from the literature. Monte Carlo simulation was performed to analyze 30 min traditional infusion (TI) and 3 h prolonged infusion (PI) of meropenem. Dosing regimens of 1 000 mg q6h TI, 1 000 mg q6h PI, 2 000 mg q8h TI, 2 000 mg q8h PI, 1 500 mg q6h TI, and 1 500 mg q6h PI were used to compare probability of target attainment(PTA). RESULTS When the pharmacodynamic target was 40%T> MIC, if the MIC of meropenem for CPE did not exceed 4 mg·L^-1, the PTA obtained by six regimens in healthy people was 100%, and the PTA obtained by six regimens in elderly ICU patients was more than 97%. If the MIC of meropenem for CPE was 8 mg·L^-1, the PTA obtained by three regimens of 2 000 mg q8h PI, 1 500 mg q6h TI and 1 500 mg q6h PI in healthy people were 100%, 99.48%, and 100% respectively, while the PTA obtained by the six regimens in elderly ICU patients was more than 90%. If the MIC of meropenem for CPE was 16 mg·L^-1, the PTA obtained by the six regimens in healthy people was less than 16%, and the PTA obtained by the six regimens in elderly ICU patients was less than 90%. When the pharmacodynamic target was 100%T>MIC, if the MIC of meropenem for CPE was 8 mg·L^-1, the highest PTA was obtained in the elderly ICU patients with 1500 mg q6h PI (61.62%), followed by 2 000 mg q8h PI(46.95%). CONCLUSION When the MIC of meropenem for CPE does not exceed 8 mg·L^-1, meropenem is suitable for treatment. High-dose regimen of PI can achieve optimum PTA. Meropenem regimen of 1 500 mg q6h PI may be the most ideal drug regimen and can be recommended as an empirical treatment regimen for CPE.