罗粲PK-PD与抗菌药物的合理使用-全.pptVIP

* 1 * * * * * * * * Please consult your national prescribing information for currently recommended meropenem dose regimens. * 配置好的特治星室温24h稳定，2-8度48h稳定 ABT-773(Cethromycin,喹红霉素):酮内酯类 1 * Forrest et al. Antimicrob Agents Chemother 1993;37:1073–1081 Patients cured (%) 0 20 40 60 80 100 0–62.5 62.5–125 125–250 250–500 500 AUC/MIC Clinical Microbiological 氟喹诺酮: AUC/MIC 与CAP治疗反应 氟喹诺酮最佳AUIC（AUC/MIC） 30 125 G+ G- 0 5 10 15 20 0 20 40 60 80 100 提高AUIC可以减少耐药 敏感率（%） AUIC≥100 AUIC100 day 107例急性社区获得性呼吸道感染，使用5种方案（头孢甲肟、头孢他啶、环丙沙星、头孢他啶+妥布霉素，环丙沙星+哌拉西林） Thomas KL et al. Antimicrob Agents Chemother. 1998;42:521–527 Baquero Negri. BioEssays 1997; 19: 731-6 Drlica K. ASM News 2001; 67:27-33 Cantón et al. Inter J Antimicrob Chemother 2006 (in press) Concentration (μg/ml) Time post administration (h) Cmax MPC Tmax MIC Window of selection MIC MPC (MIC of mutants) Resistant mutant Susceptible bacteria Grant Nicolau. Antibiotics for Clinicians 1999;3(Suppl. 1):21–28 AUC/MIC 0 100 200 300 400 188–377 65–212 24–149 20–44 Ciprofloxacin750 mg Levofloxacin500 mg Gatifloxacin400 mg Moxifloxacin400 mg 不同氟喹诺酮对肺炎球菌 AUC/MIC 氟喹诺酮给药方案优化 提高疗效：推荐每日一次给药 Cmax/MIC ? 8-10 24-h AUC/MIC(AUIC) G-: AUIC 100-125 G+: AUIC 30-40 防止耐药 Cmax MPC 争取较高的 AUIC 三、Β-内酰胺类：TMIC 0 TMIC Concentration Time (hours) MIC Walker et al. ICAAC 1994 [Abstr. A-91] Change in log10 CFU/thigh over 24 h -3 -2 2 -1 0 1 Escherichia coli Pseudomonas aeruginosa 0 80 TMIC (% of 24-h period) 60 40 20 0 80 60 40 20 Carbapenem pharmacodynamics:relationship between TMIC and efficacy Required %TMIC for cidal: ~ 40% for carbapenems ~ 50% for penicillins ~70% for cephalosporins Drusano GL. Clin Infect Dis. 2003;36(suppl 1):S42-S50. Required %TMIC for static －20% for carbapenems －30% for penicillins －40% for cephalosporins ?-lactam:optimal TMIC? Kuti et al. Am J Health Syst Pharm 2002;59:2209–2215 Concentration (μg/mL) 0 0.1 1 10 100 4 8 6 2 Time (hours) MIC = 2 μg/mL; 60% TMIC MIC = 4 μg/mL; 46% TMIC 1