Suya Sujareenoot, Nasomsong Worapong, Santimaleeworagun Wichai, Juntanawiwat Piraporn, Chatreewonanakul Tassananwan, Saelim Weerayuth
The College of Pharmacotherapy of Thailand, Nonthaburi, Thailand.
Department of Internal Medicine, Division of Infectious Diseases, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
J Glob Antimicrob Resist. 2024 Dec;39:257-265. doi: 10.1016/j.jgar.2024.10.263. Epub 2024 Nov 14.
We aimed to use Monte Carlo simulation, based on pharmacokinetic/pharmacodynamic targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients.
We collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction. Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target attainment (PTA) and cumulative fraction of response.
The 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was bla (42.6%), followed by bla (29.6%) and coexistence of bla and bla (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline-colistin (67.9%), tigecycline-gentamicin (62.2%), and tigecycline-amikacin (51.4%).
Tigecycline-colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance of <90 mL/min can raise the cumulative fraction of response target and less nephrotoxicity.
我们旨在基于药代动力学/药效学靶点，运用蒙特卡洛模拟，研究并确定针对重症患者耐碳青霉烯类肺炎克雷伯菌（CRKP）的现有联合治疗方案的最佳剂量。
我们收集了2020年10月至2022年6月期间孔敬皇家海军医院的CRKP临床分离株。使用聚合酶链反应对抗性基因进行分子研究。采用肉汤微量稀释棋盘法评估单一和协同抗生素活性。基于目标达成概率（PTA）和反应累积分数，运用蒙特卡洛模拟确定最佳抗生素治疗方案。
54株CRKP分离株对替加环素（100%）、黏菌素（75.9%）、阿米卡星（70.4%）和庆大霉素（63.0%）耐药。最常见的碳青霉烯酶基因型是bla（42.6%），其次是bla（29.6%）以及bla和bla共存（22.2%）。基于PTA，使用适当剂量的替加环素 - 黏菌素（67.9%）、替加环素 - 庆大霉素（62.2%）和替加环素 - 阿米卡星（51.4%）时，观察到对CRKP分离株的协同和相加活性。
替加环素 - 黏菌素是治疗CRKP重症患者的最佳现有联合治疗方案，尤其是针对新德里金属β - 内酰胺酶（NDM）。当与替加环素联合使用时，黏菌素肌酐清除率<90 mL/min可提高反应累积分数目标且肾毒性较小。
