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大剂量延长输注美罗培南在成年囊性纤维化患者肺部加重期的药代动力学:病例系列研究

Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: a case series.

作者信息

Delfino Emanuele, Fucile Carmen, Del Bono Valerio, Marchese Anna, Marini Valeria, Coppo Erika, Casciaro Rosaria, Minicucci Laura, Giacobbe Daniele Roberto, Martelli Antonietta, Viscoli Claudio, Mattioli Francesca

机构信息

Infectious Diseases Division, University of Genoa (DISSAL) and San Martino Hospital, Genoa, Italy.

Clinical Pharmacology and Toxicology Unit, University of Genoa (DIMI), Genoa, Italy.

出版信息

New Microbiol. 2018 Jan;41(1):47-51. Epub 2018 Jan 9.

Abstract

This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] ±34.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated.

摘要

本病例系列研究了美罗培南(MEM)在因肺部加重而住院的成年囊性纤维化(CF)患者中的药代动力学/药效学(PK/PD)特征。2015年1月至2016年6月,纳入所有患有囊性纤维化(CF)且因对美罗培南(MEM)敏感/中介的铜绿假单胞菌导致慢性肺部感染、接受至少48小时MEM持续3小时输注以治疗肺部加重的成年患者。通过高效液相色谱法测定MEM血浆浓度。该研究纳入了6名中位年龄为47岁的成年CF患者。MEM表现出高分布容积(平均45.98 L,标准差[SD]±34.45)。在5/6例患者(83%)中,相对于在病情加重期间从痰液中分离出的铜绿假单胞菌菌株的MEM最低抑菌浓度(MIC),实现了40% T>MIC的最低PK/PD目标。仅1例患者未达到该目标,其菌株在我们的队列中显示出最高的MEM MIC(8 mg/L)。所有患者对MEM耐受性良好,未报告不良事件。总之,在肺部加重期间,高剂量、延长输注的MEM在6名中位年龄较高的成年CF患者中显示出高分布容积,且耐受性良好。

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