Evaluation of Linezolid Pharmacokinetics in Critically Ill Obese Patients with Severe Skin and Soft Tissue Infections

Linezolid standard dosing is fixed at 600mg 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/m(2) 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/m(2), and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses, and four received 600mg 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 4mg/liter, respectively. In conclusion, target attainment of >= 90% is not achieved with standard linezolid doses for noncirrhotic patients >= 140 kg with MICs of >= 2mg/liter. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.

Automated summary

This study demonstrates that standard linezolid doses may not be adequate for all patients, especially for noncirrhotic patients weighing over 140 kg with minimum inhibitory concentrations of >= 2mg/liter, as target attainment of >= 90% is not achieved in this population.