RESUMO
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.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Resistência a Vancomicina/efeitos dos fármacos , Vancomicina/farmacologia , Vancomicina/farmacocinética , Animais , Antibacterianos/administração & dosagem , Área Sob a Curva , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Mutação , Coelhos , Infecções Estafilocócicas/microbiologia , Vancomicina/administração & dosagemRESUMO
By using emergy analysis method, a trend analysis was made on the total emergy, its input-output structure, and emergy indices of the agro-ecosystem in Hunan Province of South-central China from 1999 to 2008. In the study period, the available total emergy input of the ecosystem was basically maintained at a stable level, but the input structure changed with the input of non-renewable industrial auxiliary emergy increased from 4.00E+22 sej in 1999 to 5.53E+22 sej in 2008, while that of renewable organic emergy decreased from 1.32E+23 sej to 1.20E+23 sej. Both the total emergy output and the output efficiency of the ecosystem had a great increase, with the total output reached 1.69E+23 sej in 2008, which was 23.8% higher than that in 1999, and the net output ratio increased from 0.79 to 0.96. Owing to the ever-increasing trend of the environmental loading ratio which was from 1.12 to 1.79, the sustainable development index of the ecosystem presented a decreasing trend, from 0.71 to 0.54, indicating that the agriculture in Hunan Province was overall belonged to the type of ecosystem driven by high consumption, and had relatively apparent extensive development characteristics.