450. Evaluation of Linezolid Pharmacokinetics in Obese Patients with Severe Skin and Soft-Tissue Infections

Abstract

BackgroundLinezolid is an oxazolidinone antibiotic with broad activity against Gram-positive bacteria and serves as an option for treating severe skin and soft-tissue infections (SSTIs). Adult FDA-labeled dosing is fixed at 600 mg IV/PO twice daily. Although conflicting, current literature is suggestive that critically ill, obese patients require increased doses. Based on this literature, our institutional guidelines recommend linezolid 600 mg every 8 hours for patients ≥150 kg. This study aimed to determine whether obese patients receiving linezolid for severe SSTI attain pharmacokinetic/pharmacodynamic (PK/PD) targets.MethodsAdult patients with a body mass index (BMI) ≥30 who were hospitalized and receiving IV linezolid were eligible for consent in this prospective cohort study. A severe SSTI was defined by one of the following: necrotizing fasciitis, myonecrosis, or SSTI with sepsis based on qSOFA score or SIRs criteria. Four blood samples were collected at steady state, after at least 3 linezolid doses, at 2, 4, and 6 hours after the dose and as a trough before the next dose. Linezolid serum concentrations were determined by HPLC. Non-compartmental methods in Phoenix-WinNonlin (Version 6.4) were used to estimate individual PK parameters. The PK parameters were used to determine the concentration-time profile assuming one-compartment kinetics. Target attainment was defined as achieving a 24-hour area under the curve (AUC0–24)/minimum inhibitory concentration (MIC) ≥100 or time above the MIC ≥ 85%.ResultsEleven patients were included in the study. The median BMI was 45.7 (34.6–72.7) and median total body weight was 141.3 kg (99.9–188). Necrotizing fasciitis was the most common SSTI type at 45.5%. Four patients received linezolid 600 mg every 8 hours, 3 patients of which were ≥150 kg. Two patients received renal replacement therapy at the time levels were drawn. Based on non-compartmental analysis, the mean AUC0–24 was 208.1 hr*mg/L (± 85.3). All but one patient, who grew E. faecalis with a MIC of 2, met PK/PD targets based on AUC/MIC ≥100. All patients achieved concentrations above MIC for 100% of the dosing interval.ConclusionAll patients met defined PK/PD targets with linezolid doses received. This study validates current institutional dosing guidelines for patients with severe SSTIs. Disclosures All authors: No reported disclosures.