Linezolid standard dosing is fixed at 600 mg every 12 h (q12h) for adults. Literature suggests critically ill, obese patients require higher doses. The study aim is 2-fold: (i) to describe linezolid pharmacokinetics (PK), and (ii) to evaluate if PK/pharmacodynamic (PD) target attainment is achieved with standard dosing in critically ill, obese patients with severe skin and soft tissue infections (SSTIs). Adult patients with a body mass index (BMI) of ≥30 kg/m² and receiving intravenous (i.v.) linezolid from August 2018 to April 2019 were eligible for consent in this prospective study. Severe SSTIs were defined as necrotizing fasciitis, myonecrosis, or SSTI with sepsis syndrome. Four blood samples were collected at steady state at 1, 3, 5 h postinfusion and as a trough. Target attainment was defined as achieving area under the concentration-time curve from 0 to 24 h to MIC (AUC_0–24h/MIC) of ≥100 h*mg/liter. Monte Carlo simulations were used to determine the probability of target attainment (PTA). Eleven patients were included in the study. The median BMI was 45.7 kg/m², and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses, and four received 600 mg q8h. A one-compartment model described linezolid PK. Based on AUC_0–24h/MIC targets, for noncirrhotic patients at 140 kg, the PTA with standard linezolid doses was 100%, 98.8%, 34.1%, and 0% for MICs of 0.5, 1, 2, and 4 mg/liter, respectively. In conclusion, target attainment of ≥90% is not achieved with standard linezolid doses for noncirrhotic patients ≥140 kg with MICs of ≥2 mg/liter. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.

中文翻译：

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严重皮肤和软组织感染的重症肥胖患者的利奈唑胺药代动力学评估

成人的利奈唑胺标准剂量定为每12 h（q12h）600 mg。文献表明，重症肥胖患者需要更高剂量。该研究的目标是2个方面：（i）描述利奈唑胺的药代动力学（PK），以及（ii）评价在重症，肥胖，皮肤和皮肤柔软的重症患者中，通过标准剂量是否达到PK /药效学（PD）目标组织感染（SSTI）。体重指数（BMI）≥30 kg / m ^2的成年患者并于2018年8月至2019年4月接受静脉（iv）利奈唑胺治疗的患者均同意接受此项前瞻性研究。严重的SSTI定义为坏死性筋膜炎，肌坏死或脓毒症综合征的SSTI。在输注后1、3、5 h并以槽的形式在稳态下收集了四个血样。目标达到率定义为浓度时间曲线下从0到24 h到MIC（AUC _0-24h / MIC）≥100 h * mg / l的达到面积。蒙特卡洛模拟用于确定目标达成的可能性（PTA）。该研究包括11名患者。BMI中位数为45.7 kg / m ²，中位总体重（TBW）为136.0公斤。7名患者接受标准利奈唑胺剂量，四名患者每8h服用600 mg。一室模型描述了利奈唑胺PK。基于AUC _0-24h / MIC目标，对于140 kg的非肝硬化患者，MIC为0.5、1、2和4 mg / L的标准利奈唑胺剂量的PTA为100％，98.8％，34.1％和0％ ， 分别。总之，对于标准剂量的利奈唑胺，对于≥140 kg且MIC≥2 mg / l的非肝硬化患者，不能达到≥90％的目标。这项研究增加了越来越多的证据表明标准利奈唑胺剂量可能并不适合所有患者。