体外膜肺氧合患者中头孢比普的药代动力学/药效学

Pharmacokinetics/pharmacodynamics of ceftobiprole in patients on extracorporeal membrane oxygenation.

作者信息

Coppens Alexandre, Zahr Noël, Chommeloux Juliette, Bleibtreu Alexandre, Hekimian Guillaume, Pineton de Chambrun Marc, LeFevre Lucie, Schmidt Matthieu, Robert Jérôme, Junot Helga, Combes Alain, Luyt Charles-Edouard

机构信息

Médecine Intensive Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne-Université, Hôpital Pitié-Salpêtrière, Paris, France.

AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1901, Pharmacokinetics and Therapeutic Drug Monitoring Unit, UMR-S 1166, F-75013 Paris, France.

出版信息

Int J Antimicrob Agents. 2023 Apr;61(4):106765. doi: 10.1016/j.ijantimicag.2023.106765. Epub 2023 Feb 18.

DOI:10.1016/j.ijantimicag.2023.106765

PMID:36804372

Abstract

INTRODUCTION

Due to its bacteriological spectrum and efficacy in skin and soft tissue infections, ceftobiprole may be of interest for extracorporeal membrane oxygenation (ECMO) cannula-related infection. It is unknown whether ceftobiprole pharmacokinetics (PK) are changed by ECMO.

METHODS

A retrospective monocentric cohort study was performed of 35 patients with suspected ECMO-related cannula infections (28 on ECMO, seven after ECMO removal), who received ceftobiprole as empiric treatment and had ceftobiprole blood levels measured at trough, peak and CT50 (50% of the dosing interval). Ceftobiprole blood levels of the 28 patients on ECMO were compared with those of the seven patients without ECMO. Factors associated with low ceftobiprole trough levels were also explored.

RESULTS

Among the 35 patients included, 29 had a confirmed cannula-related infection and 48 pathogens were isolated. Ceftobiprole MIC was determined in 29 of these 48, and 23 (79%) were susceptible to ceftobiprole. Ceftobiprole blood levels (at trough, peak and CT50) were similar in ECMO and non-ECMO patients. Moreover, in patients whose pathogens responsible for infection were susceptible to ceftobiprole, 94% had a ceftobiprole trough level above the MIC. Ceftobiprole blood levels were decreased in patients with acute renal failure requiring renal replacement therapy (RRT) and in those with increased renal clearance (defined as creatinine clearance > 130 mL/min), independent of ECMO. No other factor was associated with modification of ceftobiprole PK/pharmacodynamics (PK/PD).

CONCLUSIONS

The ceftobiprole PK/PD was no different in patients during ECMO or after its withdrawal. Factors associated with decreased ceftobiprole blood levels were patients requiring RRT and those with increased renal clearance.

摘要

引言

由于头孢托罗的抗菌谱及其在皮肤和软组织感染中的疗效，其可能对体外膜肺氧合（ECMO）插管相关感染有治疗价值。目前尚不清楚ECMO是否会改变头孢托罗的药代动力学（PK）。

方法

对35例疑似ECMO相关插管感染患者进行了一项回顾性单中心队列研究（28例在ECMO治疗期间，7例在拔除ECMO后），这些患者接受头孢托罗作为经验性治疗，并在谷值、峰值和CT50（给药间隔的50%）时测定了头孢托罗血药浓度。将28例接受ECMO治疗患者的头孢托罗血药浓度与7例未接受ECMO治疗患者的血药浓度进行比较。还探讨了与头孢托罗谷值水平低相关的因素。

结果

在纳入的35例患者中，29例确诊为插管相关感染，分离出48种病原体。在这48种病原体中的29种测定了头孢托罗的最低抑菌浓度（MIC），其中23种（79%）对头孢托罗敏感。ECMO患者和非ECMO患者的头孢托罗血药浓度（谷值、峰值和CT50）相似。此外，在感染病原体对头孢托罗敏感的患者中，94%的患者头孢托罗谷值水平高于MIC。需要肾脏替代治疗（RRT）的急性肾衰竭患者和肾清除率增加（定义为肌酐清除率>130 mL/min）的患者，其头孢托罗血药浓度降低，且与ECMO无关。没有其他因素与头孢托罗的药代动力学/药效学（PK/PD）改变相关。