抗菌药物合理应用浙一-培训课件.pptVIP

Contaminated surfaces increase cross-transmission X represents multi-drugs resistant pathogens culture positive sites 无处不在！ Highly refractory to both vigorouscleaning and to disinfectants! alcohol-based handrubs may make matters worse rather than better!! Bernard Dixon. The Lancet Infectious Disease. 2008,8 alcohol or an alcohol-based handrub provided the organism with an additional source of carbon Europe clone II ACICU:AbaR2 Michele I, et al. AAC. 2008, 52:2616-25 CRAB meningitis cefoperazone/sulbactam 35d Polymyxin E Methods to Increase % Time MIC - More frequent dosing - Higher doses Strategies to Improve Efficacy and Limit Resistance for ?-Lactams TMIC Concentration Time (hours) MIC MIC Strategies to Improve Efficacy: Dose Escalation 0.1 10 100 1000 1 Concentration (μg/mL) 0 12 24 20 4 8 16 Time (hours) Dose (g) 2 x Dose (g) Nicolau DP. Critical Care 2008;12(Suppl 4):1-5. Treatment of Multidrug Resistant Burkholderia cepacia With Prolonged Infusion Time (h) Concentration (mcg/mL) 0 8 16 24 32 40 0.1 1 10 100 MIC = 16 mcg/mL TMIC exposure was 40% and 52% of the dosing interval at MICs of16 and 8 mcg/mL, respectively. Kuti JL, et al. Pharmacotherapy 2004;24:1641-5. MIC = 8 mcg/mL Dandekar PK et al. Pharmacotherapy. 2003;23:988-991. Extended Infusions Overcome the Instability of Carbapenems While Still Increasing %TMIC MIC 0 2 4 6 8 0.1 1.0 10.0 100.0 Concentration(mcg/mL) Time (h) Rapid Infusion (30 min) Extended Infusion (3 h) 0.5-Hour or 3-Hour Infusion MIC MIC MIC Methods to Increase % Time MIC - Higher doses - More frequent dosing - Most potent (In Vitro) Improved Potency (In Vivo Exposure) TMIC Concentration Time (hours) MIC Strategies to Improve Efficacy and Limit Resistance for ?-Lactams 谢谢！ IVZ 2008-W-1259216-SS MS* 和其它的β内酰胺类抗生素一样，对于特定致病菌，碳青霉烯类和临床效果相关性较好的重要药代动力学参数是给药间隔内药物浓度超过MIC的时间比值。如要抑制细菌， 则碳青霉烯类浓度在给药间隔内超过MIC的时间比值约占30%(如, 厄他培南大约是8小时).1 一项药代动力学研究纳入68名健康成人受试者，在静脉滴注（30分钟）1g厄他培南后测定了血浆总浓度和游离（未结合）浓度.2 如幻灯所示，给药后，肠杆菌属MIC90低于厄他培南 (红色方格) 总浓度平均值达24小时，