Division of Clinical Microbiology, Royal University Hospital and Saskatchewan Health Authority, Saskatoon, Saskatchewan, Canada.
Departments of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
J Chemother. 2024 Sep;36(5):389-397. doi: 10.1080/1120009X.2024.2313908. Epub 2024 Feb 10.
Nosocomial infections with drug resistant bacteria impact morbidity and mortality, length of therapy and stay and the overall cost of treatment. Key pathogens with ventilator associated pneumonia may be drug-susceptible or multi-drug resistant and inhaled amikacin has been investigated as an adjunctive therapy option. High pulmonary drug concentrations (epithelial lining fluid [ELF]) along with minimal systemic toxicity is seen as an advantage to inhaled formulations. killing of bacteria using clinically relevant drug concentrations provide insight on bug-drug interactions. The aim of this study was to measure killing of clinical isolates of , , , , methicillin-resistant and methicillin-susceptible using the minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and median (976 µg/ml) ELF drug concentration for amikacin. Overall killing took longer at the MIC drug concentration and was inconsistent amongst the pathogens tested with the percentage of bacteria killed following 180 min of drug exposure ranging from growth in the presence of the drug to 95% kill. At the MPC drug concentrations, killing ranged from 55-88% for all pathogens following 30 min of drug exposure and increased to 99-100% following 180 min of drug exposure. At the ELF amikacin tested, killing was 81-100% following 20 min and 94-100% by 30 min of drug exposure. Rapid killing against MDR respiratory pathogens by amikacin ELF drug concentrations is encouraging.
医院获得性耐药菌感染会影响发病率和死亡率、治疗时间和住院时间以及整体治疗成本。呼吸机相关性肺炎的主要病原体可能对药物敏感或具有多药耐药性，吸入性阿米卡星已被研究作为辅助治疗选择。高肺部药物浓度（上皮衬里液[ELF]）和最小的全身毒性被认为是吸入制剂的优势。使用临床相关药物浓度杀死细菌可以深入了解细菌-药物相互作用。本研究的目的是测量最低抑菌浓度（MIC）、突变预防浓度（MPC）和阿米卡星 976μg/ml 中位 ELF 药物浓度对临床分离株、、、、耐甲氧西林金黄色葡萄球菌和甲氧西林敏感金黄色葡萄球菌的杀菌作用。在 MIC 药物浓度下，总体杀菌作用需要更长的时间，并且在测试的病原体之间不一致，在药物暴露 180 分钟后，细菌被杀灭的百分比从药物存在下的生长到 95%不等。在 MPC 药物浓度下，所有病原体在药物暴露 30 分钟后的杀菌率为 55-88%，而在药物暴露 180 分钟后增加到 99-100%。在 ELF 测试的阿米卡星中，药物暴露 20 分钟后的杀菌率为 81-100%，药物暴露 30 分钟后的杀菌率为 94-100%。阿米卡星 ELF 药物浓度对 MDR 呼吸道病原体的快速杀菌作用令人鼓舞。
