Use of Monte Carlo simulation to evaluate the development of vancomycin resistance in meticillin-resistant Staphylococcus aureus

摘要

Monte Carlo simulations were performed for various vancomycin dosage regimens to evaluate the potential for development of vancomycin resistance in meticillin-resistant Staphylococcus aureus (MRSA). When the target of free AUC(24)/MIC >= 200 was considered (where AUC(24) is the area under the drug concentration-time curve in a 24-h interval and MIC is the minimum inhibitory concentration), a standard dose regimen (1000 mg every 12 h) yielded unacceptable simulated outcomes in patients with normal renal function; in particular, the probability of target attainment (PTA) was only 30.5% at an MIC of 1 mg/L. For the same dosage regimens and the mutant prevention concentration (MPC)-based pharmacokinetic target (total AUC(24)/MPC > 15), the cumulative fraction of response exceeded 80% for all renal function strata; low values of PTA (< 80%) were obtained only for isolates with MPCs of >= 22.4 mg/L, which consisted of all 21 strains of heterogeneous vancomycin-intermediate S. aureus (hVISA) and a handful of non-hVISA strains with MICs of 2 mg/L (32%; 16/50). Based on the current status of vancomycin resistance, we conclude that total AUC(24)/MPC > 15, derived from in vivo experiments, is more suitable to predict the development of vancomycin resistance. In clinical practice, individualised vancomycin therapy should be considered to minimise selection of resistance mutations. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.