Zheng Lily, Alshaer Mohammad H, Peloquin Charles, Venugopalan Veena, Alnuaimat Hassan M, Converse Maureen
Department of Pharmacy Services, University of Florida Health Jacksonville North, 15255 Max Leggett Pkwy, Jacksonville, FL, USA.
Pharmacotherapy & Translational Research, University of Florida College of Pharmacy, Medical Science Bldg Rm P4 05, 1600 SW Archer Rd., Gainesville, FL, USA.
Pulm Pharmacol Ther. 2024 Mar;84:102271. doi: 10.1016/j.pupt.2023.102271. Epub 2023 Nov 25.
The impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/dynamics (PK/PD) of beta-lactam antibiotics have not been well studied in general, but cefepime specifically has the least amount of data. We aimed to investigate whether ECMO alters the PK of cefepime in adult intensive care unit (ICU) patients.
This single-center, retrospective case-control study evaluated cefepime therapeutic drug monitoring (TDM) results from ECMO patients that were matched 1:1 with TDM results in non-ECMO patients for drug regimen and renal function. The primary outcome was the difference in PK/PD of cefepime in ECMO compared with non-ECMO ICU patients. Secondary outcomes included hospital length of stay, treatment failure, superinfection, bacterial resistance, and survival to discharge.
Eighty-two patients were included with 44 matched cefepime concentrations in each group. ECMO patients had higher free maximum concentrations (fCmax) (p = 0.003), lower free minimum concentration (fCmin)/1x minimum inhibitory concentration (MIC) ratios (p = 0.040), and lower attainment of free Cmin/4x MIC (p = 0.010). There were no differences between the groups for free Cmin, time above 1xMIC or 4x MIC, and pharmacokinetic parameters (ke, half-life, and Vd). Of those who survived to discharge, hospital length of stay was longer in the ECMO group (p < 0.001). Patients on ECMO were more likely to experience treatment failure (p = 0.036). The incidence of bacterial resistance, superinfection, or survival were similar among the groups.
These data suggest that more aggressive empiric dosing may be warranted in patients on ECMO. Therapeutic drug monitoring and future prospective studies would provide more evidence to guide decision making regarding dose adjustments.
一般而言，体外膜肺氧合（ECMO）对β-内酰胺类抗生素的药代动力学/药效学（PK/PD）的影响尚未得到充分研究，而头孢吡肟的相关数据尤其少。我们旨在调查ECMO是否会改变成年重症监护病房（ICU）患者中头孢吡肟的药代动力学。
这项单中心回顾性病例对照研究评估了ECMO患者的头孢吡肟治疗药物监测（TDM）结果，并将其与非ECMO患者的TDM结果按1:1进行匹配，以确保药物治疗方案和肾功能相似。主要结局是ECMO患者与非ECMO ICU患者相比，头孢吡肟PK/PD的差异。次要结局包括住院时间、治疗失败、二重感染、细菌耐药性和出院生存率。
共纳入82例患者，每组有44对匹配的头孢吡肟浓度。ECMO患者的游离最大浓度（fCmax）较高（p = 0.003），游离最小浓度（fCmin）/1倍最低抑菌浓度（MIC）比值较低（p = 0.040），游离Cmin/4倍MIC的达标率较低（p = 0.010）。两组在游离Cmin、高于1倍MIC或4倍MIC的时间以及药代动力学参数（消除速率常数、半衰期和分布容积）方面没有差异。在存活至出院的患者中，ECMO组的住院时间更长（p < 0.001）。接受ECMO治疗的患者更有可能出现治疗失败（p = 0.036）。各组之间细菌耐药性、二重感染或生存率的发生率相似。
这些数据表明，对于接受ECMO治疗的患者，可能需要更积极的经验性给药。治疗药物监测和未来的前瞻性研究将提供更多证据，以指导剂量调整的决策。
