title: Use of Monte Carlo simulation to evaluate the development of vancomycin resistance in meticillin-resistant Staphylococcus aureus.
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.
authors: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
authors: Qing
authors: Q
authors: Mei
authors: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui 230022, China; Institute of Bacterium Resistance, Anhui Medical University, Hefei, Anhui 230022, China.
authors: Ying
authors: Y
authors: Ye
authors: Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
authors: Yu-lin
authors: YL
authors: Zhu
authors: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
authors: Jun
authors: J
authors: Cheng
authors: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
authors: Hai-fei
authors: HF
authors: Yang
authors: Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui 230022, China; Institute of Bacterium Resistance, Anhui Medical University, Hefei, Anhui 230022, China.
authors: Yan-yan
authors: YY
authors: Liu
authors: Class 7 Grade 2012, The Eight-year Program on Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, China.
authors: Hong-ru
authors: HR
authors: Li
authors: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui 230022, China; Institute of Bacterium Resistance, Anhui Medical University, Hefei, Anhui 230022, China; Department of Infectious Diseases, Chaohu Hospital Affiliated to Anhui Medical University, Chaohu, Anhui 238000, China. Electronic address: lijiabin948@vip.sohu.com.
authors: Jia-bin
authors: JB
authors: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D009154:Mutation; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Heteroresistance; Monte Carlo simulation; Mutant selection window; Pharmacokinetics/pharmacodynamics; Vancomycin resistance