Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany.
Department of Internal Medicine V - Pneumology, Allergology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany.
Crit Care. 2020 Nov 25;24(1):664. doi: 10.1186/s13054-020-03397-1.
Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO.
Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints.
The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem.
ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.
有效的抗菌治疗是降低重症监护病房（ICU）中细菌败血症相关死亡率的关键。为了考虑生理病理变化或肾脏替代治疗，通常需要进行剂量调整。体外膜肺氧合（ECMO）越来越多地用于治疗呼吸和/或心脏衰竭。然而，对于接受 ECMO 支持的败血症患者，是否需要进行剂量调整以避免药物治疗水平不足，目前仍不清楚。在这里，我们旨在评估并比较评估在接受和不接受 ECMO 治疗的重症监护患者中连续应用抗生素的血清浓度。
在 2018 年 10 月至 2019 年 12 月期间，我们前瞻性地招募了德国西南部一家呼吸科 ICU 的接受抗生素治疗的患者，他们接受了哌拉西林/他唑巴坦、头孢他啶、美罗培南或利奈唑胺治疗。所有抗生素均采用持续输注，使用高效液相色谱法测定血清浓度（以 mg/L 表示）进行治疗药物监测。根据 EUCAST 折点，目标浓度定义为敏感细菌分离株最小抑菌浓度（MIC）的四倍以上。
最终纳入了 105 例 ICU 患者，其中 30 例接受 ECMO 治疗。ECMO 患者的年龄明显更小（平均年龄：47.7 岁 vs. 61.2 岁；p<0.001），更频繁地需要肾脏替代治疗（53.3% vs. 32.0%；p=0.048），ICU 死亡率更高（60.0% vs. 22.7%；p<0.001）。在 ECMO 患者的 112 次测量和非 ECMO 患者的 186 次测量中，来自 112 次测量的抗生素血清浓度数据显示，哌拉西林（32.3 与 52.9；p=0.029）和标准剂量美罗培南（15.0 与 17.8；p=0.020）的中位数血清浓度明显较低。在 ECMO 组中，我们发现抗生素血清浓度低于规定 MIC 目标的情况发生率很高（哌拉西林：48% vs. 非 ECMO 组的 13%；利奈唑胺：35% vs. 非 ECMO 组的 15%），而头孢他啶和美罗培南则没有这种差异。
ECMO 治疗与特定抗生素的血清浓度显著降低有关。未来需要评估 ICU 患者接受 ECMO 支持时抗生素的药代动力学特征。
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