DeRyke C Andrew, Kuti Joseph L, Nicolau David P
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102, USA.
Pharmacotherapy. 2007 Mar;27(3):333-42. doi: 10.1592/phco.27.3.333.
To determine the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures against common nosocomial pathogens.
Pharmacodynamic Monte Carlo simulation model.
Microbiologic data generated from isolates from the 14 centers in the United States in the 2004 Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance study.
Five thousand simulated patients with infection.
Pharmacokinetic profiles of the patients were simulated to determine the bactericidal cumulative fraction of response (CFR) for commonly used intravenous regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam against Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella species. Ciprofloxacin and levofloxacin had CFRs among the lowest of all drugs against all pathogens, especially P. aeruginosa (40.4-65.5%) and A. baumannii (43.6-48.2%). The low CFR of about 78% against E. coli with these two agents was of particular concern. Among the beta-lactams, only high-dose cefepime and ceftazidime regimens achieved CFRs of greater than 90% against P. aeruginosa, followed by cefepime 2 g every 12 hours and the carbapenems (86.3-89.7%). No regimen achieved an optimum CFR for A. baumannii. All beta-lactam regimens achieved a greater-than-90% likelihood of having bactericidal CFRs against Enterobacteriaceae.
Because of the continual evolution of resistance among gram-negative bacteria in the United States, reevaluation of optimum dosing strategies for beta-lactam and fluoroquinolone antibiotics is necessary.
确定抗生素治疗方案对常见医院病原体达到杀菌药效学暴露的可能性。
药效学蒙特卡洛模拟模型。
2004年美罗培南年度药敏试验信息收集（MYSTIC）监测研究中美国14个中心分离株产生的微生物学数据。
5000名模拟感染患者。
模拟患者的药代动力学特征，以确定常用静脉注射用头孢吡肟、头孢他啶、头孢曲松、环丙沙星、亚胺培南、左氧氟沙星、美罗培南和哌拉西林-他唑巴坦对铜绿假单胞菌、鲍曼不动杆菌、大肠杆菌和克雷伯菌属的杀菌累积反应分数（CFR）。环丙沙星和左氧氟沙星对所有病原体的CFR在所有药物中最低，尤其是对铜绿假单胞菌（40.4 - 65.5%）和鲍曼不动杆菌（43.6 - 48.2%）。这两种药物对大肠杆菌的CFR约为78%，特别令人担忧。在β-内酰胺类药物中，只有高剂量头孢吡肟和头孢他啶方案对铜绿假单胞菌的CFR大于90%，其次是每12小时2g头孢吡肟和碳青霉烯类药物（86.3 - 89.7%）。没有方案对鲍曼不动杆菌达到最佳CFR。所有β-内酰胺类方案对肠杆菌科细菌的杀菌CFR可能性均大于90%。
由于美国革兰阴性菌耐药性不断演变，有必要重新评估β-内酰胺类和氟喹诺酮类抗生素的最佳给药策略。
