PK Laboratory, Department of Biology and Ecology, Faculty of Sciences, Trg Dositeja Obradovica 3, University of Novi Sad, 21000 Novi Sad, Serbia.
Viruses. 2022 Jul 14;14(7):1542. doi: 10.3390/v14071542.
Phage-antibiotic synergy is a promising therapeutic strategy, but there is no reliable method for synergism estimation. Although the time-kill curve assay is a gold standard, the method is not appropriate for fast and extensive screening of the synergy. The aim is to optimize the checkerboard method to determine phage-chemical agent interactions, to check its applicability by the time-kill curve method, and to examine whether the synergy can be obtained with both simultaneous and successive applications of these agents. In addition, the aim is to determine interactions of the Pseudomonas phage JG024 with ciprofloxacin, gentamicin, or ceftriaxone, as well as the Staphylococcus phage MSA6 and SES43300 with ciprofloxacin, gentamicin, and oxacillin. The results show that the optimized checkerboard method is reliable and that results correspond to those obtained by the time-kill curve. The synergy is detected with the phage JG024 and ciprofloxacin or ceftriaxone against , and the phage SES43300 with ciprofloxacin against MRSA. The synergy was obtained after simultaneous applications, and in the case of after application of the second agent with delay of one hour, indicating that simultaneous application is the best mode of synergy exploitation for therapy. The checkerboard method can be used for thorough clinical studies on synergy and in the future for personalized therapy when infections are caused by multiple resistant bacteria.
噬菌体-抗生素协同作用是一种很有前途的治疗策略，但目前还没有可靠的协同作用评估方法。虽然时间-杀菌曲线测定法是一种金标准，但该方法不适合快速广泛筛选协同作用。本研究旨在优化棋盘法来确定噬菌体-化学药剂相互作用，并通过时间-杀菌曲线法检查其适用性，以及检查这些药剂同时和先后应用是否能获得协同作用。此外，本研究还旨在确定假单胞菌噬菌体 JG024 与环丙沙星、庆大霉素或头孢曲松的相互作用，以及金黄色葡萄球菌噬菌体 MSA6 和 SES43300 与环丙沙星、庆大霉素和苯唑西林的相互作用。结果表明，优化后的棋盘法可靠，结果与时间-杀菌曲线法一致。噬菌体 JG024 与环丙沙星或头孢曲松对 ，噬菌体 SES43300 与环丙沙星对耐甲氧西林金黄色葡萄球菌（MRSA）有协同作用。协同作用可通过同时应用噬菌体 JG024 和环丙沙星或头孢曲松来实现，而在应用第二种药物一小时后延迟应用时，噬菌体 SES43300 对 MRSA 也能获得协同作用，这表明同时应用是协同作用治疗的最佳模式。棋盘法可用于深入研究协同作用，并在未来对由多种耐药菌引起的感染进行个性化治疗。
