Making the change to area under the curve–based vancomycin dosing

Abstract

Vancomycin, a glycopeptide antimicrobial, is commonly employed for empirical and definitive treatment of infections due to resistant gram-positive pathogens, notably methicillin-resistant Staphylococcus aureus (MRSA). Given wide interpatient and intrapatient pharmacokinetic variability coupled with exposure-dependent nephrotoxicity, vancomycin therapeutic drug monitoring has long been a focus for clinical pharmacy services. However, over time, the therapeutic targets for vancomycin have evolved. Results from experimental murine infection models initially demonstrated that the ratio of the 24-hour area under the concentration–time curve (AUC24) to the minimum inhibitory concentration (MIC) (the AUC24:MIC ratio) is the parameter that best characterizes the effectiveness of vancomycin.1 Due to the lack of clearly defined AUC:MIC pharmacodynamic targets for optimal vancomycin dosing coupled with practical issues related to the need for multiple postdose serum levels for monitoring, a trough-targeted dosing approach has been the standard long employed for vancomycin monitoring, with the last decade bringing aggressive targets (15–20 mg/L) recommended by current published guidelines for severe, life-threatening infections.2–4