土耳其针对耐碳青霉烯类铜绿假单胞菌分离株的哌拉西林/他唑巴坦、头孢吡肟和头孢他啶剂量优化研究
Dose optimization of piperacillin/tazobactam, cefepime, and ceftazidime for carbapenem-resistant Pseudomonas aeruginosa isolates in Türkiye.
作者信息
Buyukyanbolu Ecem, Gill Christian M, Genc Leyla, Karakus Mehmet, Comert Fusun, Otlu Baris, Aktas Elif, Nicolau David P
机构信息
Department of Medical Microbiology, University of Health Sciences Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
Center for Anti-Infective Research & Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA.
出版信息
Eur J Clin Microbiol Infect Dis. 2025 Jan;44(1):159-165. doi: 10.1007/s10096-024-04990-w. Epub 2024 Nov 15.
INTRODUCTION
Although CRPA may test susceptible to other β-lactams such as ceftazidime (CAZ), cefepime (FEP), and piperacillin/tazobactam (TZP), reduced potency has been observed. We assessed the adequacy of EUCAST Susceptible (S) or Susceptible Increased Exposure (SIE)/(I) doses for CAZ, FEP, and TZP against CRPA clinical isolates.
METHODS
CRPA isolates were collected from patients at three Turkish hospitals. CAZ, FEP, and TZP MICs were determined using broth microdilution. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for a free time above the MIC (fT > MIC) targets for various doses of each agent against isolates defined as susceptible. fT > MIC targets were 70% for CAZ or FEP and 50% for TZP. Cumulative fraction of response (CFR) was calculated. Optimal PTA and CFR was 90% target achievement.
RESULTS
The percentages of isolates SIE/I to CAZ, FEP, and TZP were 49,8%, 47%, and 31,8% respectively. Reduced potency was noted with 54,1% of CAZ-S isolates having MICs of 4 or 8 mg/L. Of the FEP and TZP-S isolates, MICs at the breakpoint (8 and 16 mg/L, respectively) were the mode with 45,2 and 53,9% of isolates for each, respectively. At an MIC of 8 mg/L for CAZ, the EUCAST standard dose was insufficient (CFR of 85%). 3 h infusions of EUCAST SIE doses were required for 90% PTA at MIC of 8 mg/L and an optimized CFR of 100%. For FEP, the SIE dose of 2 g q8h 0.5 h infusion of was effective (CFR 96%), utilization of an extended 3 h infusion further optimized the PTA at 8 mg/L (CFR 99%). For TZP, the standard dose of 4.5 q6h administered as a 0.5 h infusion was inadequate (CFR 86%). A standard TZP dose with an extended infusion (4.5 g q8h over 4 h) and the SIE dose 4.5 g q6h 3 h infusion resulted in CFRs > 95%.
CONCLUSION
These data support the EUCAST SIE breakpoints for FEP and TZP. To optimize PTA at the SIE breakpoint for CAZ, prolonged infusion is required.
引言
虽然耐碳青霉烯类肺炎克雷伯菌（CRPA）可能对其他β-内酰胺类药物如头孢他啶（CAZ）、头孢吡肟（FEP）和哌拉西林/他唑巴坦（TZP）检测显示敏感，但已观察到其效力降低。我们评估了欧洲抗菌药物敏感性试验委员会（EUCAST）针对CRPA临床分离株的CAZ、FEP和TZP敏感（S）或敏感增加暴露（SIE）/（I）剂量的充足性。
方法
从土耳其三家医院的患者中收集CRPA分离株。采用肉汤微量稀释法测定CAZ、FEP和TZP的最低抑菌浓度（MIC）。进行蒙特卡洛模拟，以确定针对定义为敏感的分离株，各种剂量的每种药物达到游离时间高于MIC（fT > MIC）目标的达标概率（PTA）。CAZ或FEP的fT > MIC目标为70%，TZP为50%。计算累积反应分数（CFR）。最佳PTA和CFR为目标达成率90%。
结果
对CAZ、FEP和TZP的SIE/I分离株百分比分别为49.8%、47%和31.8%。注意到效力降低，54.1%的CAZ-S分离株MIC为4或8mg/L。在FEP和TZP-S分离株中，断点处的MIC（分别为8和16mg/L）是模式值，每种分离株分别占45.2%和53.9%。对于CAZ，当MIC为8mg/L时，EUCAST标准剂量不足（CFR为85%）。在MIC为8mg/L时，需要输注3小时的EUCAST SIE剂量才能达到90%的PTA和优化的CFR为100%。对于FEP，2g每8小时0.5小时输注的SIE剂量有效（CFR为96%），延长至3小时输注进一步优化了8mg/L时的PTA（CFR为99%）。对于TZP，每6小时0.5小时输注4.5g的标准剂量不足（CFR为86%）。延长输注的标准TZP剂量（4.5g每8小时4小时输注）和SIE剂量4.5g每6小时3小时输注导致CFRs＞95%。
结论
这些数据支持EUCAST针对FEP和TZP的SIE断点。为了在CAZ的SIE断点处优化PTA，需要延长输注时间。
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