Jitaree Kamonchanok, Sathirakul Korbtham, Houngsaitong Jantana, Asuphon Orarik, Saelim Weerayuth, Thamlikitkul Visanu, Montakantikul Preecha
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
Antibiotics (Basel). 2019 Aug 22;8(3):125. doi: 10.3390/antibiotics8030125.
The purpose was to explore the optimal dosage regimen of colistin using Monte Carlo simulations, for the treatment of carbapenem-resistant and carbapenem-resistant based on PK/PD targets in critically ill patients. A total of 116 carbapenem-resistant and were obtained from various clinical specimens at Siriraj Hospital in Bangkok, Thailand. Minimum inhibitory concentrations (MICs) of colistin were determined by broth microdilution method. Monte Carlo simulation was used to calculate the cumulative fraction of response (CFR) for European Medicine Agency (EMA), US-Food and Drug Administration (FDA), Nation et al., Siriraj Hospital and our study regimens. The targeted CFR was 90%. For colistin-susceptible , all of the dosage regimens achieved ≥90% CFR in patients with creatinine clearance <80 mL/min except the FDA-approved regimens for patients with creatinine clearance 51-79 and 11-29 mL/min, respectively. While, patients with creatinine clearance ≥80 mL/min, CFR ≥90% was observed in Siriraj Hospital and our study regimen. For colistin-susceptible , all of the dosage regimens achieved ≥90% CFR regardless of renal function. In contrast, the currently approved regimens achieved CFR target in only 10-50% for colistin-resistant isolates subgroup. These results suggest that currently approved regimens still recommended for colistin-susceptible CRE. For colistin-resistant CRE, alternative approaches such as high dose or combination therapy should be considered.
目的是基于重症患者的药代动力学/药效学(PK/PD)靶点,通过蒙特卡洛模拟探索多黏菌素的最佳给药方案,用于治疗耐碳青霉烯类肠杆菌科细菌(CRE)。从泰国曼谷诗里拉吉医院的各种临床标本中总共获取了116株耐碳青霉烯类肠杆菌科细菌。采用肉汤微量稀释法测定多黏菌素的最低抑菌浓度(MIC)。使用蒙特卡洛模拟计算欧洲药品管理局(EMA)、美国食品药品监督管理局(FDA)、Nation等人、诗里拉吉医院以及我们研究方案的累积反应分数(CFR)。目标CFR为90%。对于对多黏菌素敏感的CRE,除了FDA批准的分别用于肌酐清除率为51 - 79 mL/min和11 - 29 mL/min患者的给药方案外,所有给药方案在肌酐清除率<80 mL/min的患者中均达到≥90%的CFR。而对于肌酐清除率≥80 mL/min的患者,在诗里拉吉医院和我们的研究方案中观察到CFR≥90%。对于对多黏菌素敏感的肺炎克雷伯菌,所有给药方案无论肾功能如何均达到≥90%的CFR。相比之下,对于耐多黏菌素的分离株亚组,目前批准的方案仅在10% - 50%的患者中达到CFR目标。这些结果表明,目前批准的方案仍推荐用于对多黏菌素敏感的CRE。对于耐多黏菌素的CRE,应考虑高剂量或联合治疗等替代方法。