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  • Title: Use of Monte Carlo simulation to evaluate the development of vancomycin resistance in meticillin-resistant Staphylococcus aureus.
    Author: Mei Q, Ye Y, Zhu YL, Cheng J, Yang HF, Liu YY, Li HR, Li JB.
    Journal: Int J Antimicrob Agents; 2015 Jun; 45(6):652-6. PubMed ID: 25813394.
    Abstract:
    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 1mg/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 2mg/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.
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