Evaluating linezolid dose regimens against methicillin-resistant Staphylococcus aureus based on renal function in populations with different body weight.

Abstract

Linezolid is an alternative first-line agent for MRSA pneumonia. This study assessed whether dose adjustments of linezolid against methicillin-resistant Staphylococcus aureus (MRSA) infections were needed based on renal function in populations with different body weight. Monte Carlo simulations were conducted to evaluate renal function in relation to the probability of target attainment (PTA) in three population groups with different body weight. Area under the concentration time curve (AUC)/ minimum inhibitory concentration (MIC) ratio and percentage of time above the MIC (%T > MIC) were regarded as pharmacokinetic/pharmacodynamic targets. The PTA and cumulative fractions of response (CFR) were calculated to assess the efficacy. Regarding safety, trough plasma concentration (Cmin ) > 8mg/L was used as target for toxicity. Using AUC/MIC >100 as the target pharmacodynamic (PD) index, the CFR of linezolid at the standard dose (600 mg every 12 h [q12h]) were 57.01%, 93.22%, and 99.93% in patients with normal renal function, patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. Using 100%T> MIC as the target PD index, all the CFR of three population groups were more than 90% at the standard dose. The percentages of Cmin > 8mg/L at the standard dose of linezolid were 24.16%, 53.24%, and 90.10% in three population groups on day 7. The risk of thrombocytopenia of linezolid was extremely higher in low body weight patients with renal impairment when receiving standard linezolid dose compared with patients with normal renal function. 450 mg q12h and 300 mg q12h might be effective and safe against MRSA infection in patients with renal dysfunction and low body weight patients with renal dysfunction, respectively.