Meropenem population pharmacokinetics in patients with decompensated cirrhosis and severe infections

美罗培南 医学 药代动力学 群体药代动力学 肝硬化 重症监护医学 人口 抗生素 内科学 微生物学 抗生素耐药性 生物 环境卫生
作者
Carla Bastida,María Hernández‐Tejero,Fátima Aziz,Cristina Espinosa,Miquel Sanz,Merçè Brunet,Ester López,Javier Fernández,Dolors Soy
出处
期刊:Journal of Antimicrobial Chemotherapy [Oxford University Press]
卷期号:75 (12): 3619-3624 被引量:12
标识
DOI:10.1093/jac/dkaa362
摘要

Meropenem pharmacokinetics (PK) may be altered in patients with cirrhosis, hampering target attainment. We aimed to describe meropenem PK in patients with decompensated cirrhosis and severe bacterial infections, identify the sources of PK variability and assess the performance of different dosing regimens to optimize the PK/pharmacodynamic (PD) target.Serum concentrations and covariates were obtained from patients with severe infections under meropenem treatment. A population PK analysis was performed using non-linear mixed-effects modelling and the final model was used to simulate meropenem exposure to assess the PTA.Fifty-four patients were enrolled in the study. Data were best described by a one-compartment linear model. The estimated typical mean value for clearance (CL) was 8.35 L/h and the estimated volume of distribution (V) was 28.2 L. Creatinine clearance (CLCR) and MELD score significantly influenced meropenem CL, and acute-on-chronic liver failure (ACLF) significantly affected V. Monte Carlo simulations showed that a lower meropenem dose would be needed as CLCR decreases and as the MELD score increases. Patients with ACLF would have lower peak meropenem concentrations but similar steady-state concentrations compared with patients with no ACLF.Our study identified two new covariates that influence meropenem PK in patients with decompensated cirrhosis in addition to CLCR: MELD score and ACLF. Dosing regimens are recommended to reach several PK/PD targets considering these clinical variables and any MIC within the susceptibility range.

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