St Brieuc Hospital, Réanimation Polyvalente, F-22000 St Brieuc, France.
Univ Rennes, Rennes University Hospital, Inserm, EHESP, Irset (Institut de Recherche en santé, Environnement et Travail) - UMR_S 1085, F-35000 Rennes, France.
J Antimicrob Chemother. 2021 Apr 13;76(5):1242-1249. doi: 10.1093/jac/dkab031.
To describe the impact of extracorporeal membrane oxygenation (ECMO) devices on piperacillin exposure in ICU patients.
This observational, prospective, multicentre, case-control study was performed in the ICUs of two tertiary care hospitals in France. ECMO patients with sepsis treated with piperacillin/tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin were described based on a population pharmacokinetic model, calculating the proportion of time the piperacillin plasma concentration was above 64 mg/L (i.e. 4× MIC breakpoint for Pseudomonas aeruginosa).
Forty-two patients were included. Median (IQR) age was 60 years (49-66), SOFA score was 11 (9-14) and creatinine clearance was 47 mL/min (5-95). There was no significant difference in the proportion of time piperacillin concentrations were ≥64 mg/L in patients treated with ECMO and controls during the first administration (P = 0.184) or at steady state (P = 0.309). Following the first administration, 36/42 (86%) patients had trough piperacillin concentrations <64 mg/L. Trough concentrations at steady state were similar in patients with ECMO and controls (P = 0.535). Creatinine clearance ≥40 mL/min was independently associated with piperacillin trough concentration <64 mg/L at steady state [OR = 4.3 (95% CI 1.1-17.7), P = 0.043], while ECMO support was not [OR = 0.5 (95% CI 0.1-2.1), P = 0.378].
ECMO support has no impact on piperacillin exposure. ICU patients with sepsis are frequently underexposed to piperacillin, which suggests that therapeutic drug monitoring should be strongly recommended for severe infections.
描述体外膜肺氧合（ECMO）设备对 ICU 患者哌拉西林暴露的影响。
这是一项在法国两家三级医院 ICU 进行的观察性、前瞻性、多中心病例对照研究。纳入了接受哌拉西林/他唑巴坦治疗脓毒症并接受 ECMO 治疗的患者。根据 SOFA 评分和肌酐清除率匹配对照患者。基于群体药代动力学模型描述哌拉西林的药代动力学，计算哌拉西林血浆浓度超过 64mg/L（即铜绿假单胞菌 4×MIC 折点）的时间比例。
共纳入 42 例患者。中位（IQR）年龄为 60 岁（49-66），SOFA 评分为 11（9-14），肌酐清除率为 47mL/min（5-95）。在首次给药期间（P=0.184）或在稳态时（P=0.309），接受 ECMO 治疗和对照组患者的哌拉西林浓度≥64mg/L 的时间比例无显著差异。首次给药后，36/42（86%）例患者的哌拉西林谷浓度<64mg/L。ECMO 组和对照组患者的稳态时哌拉西林谷浓度相似（P=0.535）。肌酐清除率≥40mL/min 与稳态时哌拉西林谷浓度<64mg/L 独立相关[比值比（OR）=4.3（95%可信区间 1.1-17.7），P=0.043]，而 ECMO 支持则无相关性[OR=0.5（95%可信区间 0.1-2.1），P=0.378]。
ECMO 支持对哌拉西林暴露无影响。脓毒症 ICU 患者常暴露不足，提示严重感染时应强烈推荐进行治疗药物监测。
