Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic.
Drift-Food Research Centre, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic.
Molecules. 2024 Aug 2;29(15):3665. doi: 10.3390/molecules29153665.
Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases due to antibiotic resistance. This has encouraged the development of innovative strategies, such as combination therapy, to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory drugs and the combined antimicrobial effect of celecoxib and oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs against standard strains and clinical isolates of , including methicillin-resistant strains (MRSAs), were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated using checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all tested strains (MICs ranging from 32 to 64 mg/L), followed by that of diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/L). Several synergistic effects were observed against the tested strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/L, with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/L). This is the first report on the combined antistaphylococcal effect of celecoxib and oxacillin. These findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by This study further indicates that celecoxib could resensitize certain MRSA strains, in some cases, to be susceptible to β-lactams (e.g., oxacillin) that were not previously tested. It is essential to mention that the in vitro concentrations of anti-inflammatory drugs are higher than those typically obtained in patients. Therefore, an alternative option for its administration could be the use of a drug delivery system for the controlled slow release from an implant at the infection site.
肌肉骨骼感染 (MIs) 是最难治疗的葡萄球菌病之一，因为存在抗生素耐药性。这促使人们开发了创新策略，如联合治疗，以对抗 MI。本研究旨在研究抗炎药物的体外抗葡萄球菌活性以及塞来昔布和苯唑西林的联合抗菌作用。使用肉汤微量稀释法测定 17 种抗炎药物对标准株和临床分离株 的最低抑菌浓度 (MIC)，包括耐甲氧西林金黄色葡萄球菌 (MRSA)。使用棋盘试验评估部分抑菌浓度指数 (FICI)。塞来昔布对所有测试菌株（MIC 范围为 32 至 64mg/L）表现出最强的抗葡萄球菌作用，其次是二氯乙酸对 MRSA3 和 MRSA ATCC 33592（MIC 64mg/L）。对测试菌株观察到几种协同作用，包括 MRSA（FICI 范围为 0.087 至 0.471）。对 MRSA ATCC 33592，在塞来昔布浓度为 2mg/L 时，观察到最强的协同相互作用（FICI 0.087），使苯唑西林 MIC 降低 19 倍（从 512 至 26.888mg/L）。这是关于塞来昔布和苯唑西林联合抗葡萄球菌作用的首次报道。这些发现表明塞来昔布及其与苯唑西林的联合使用可能成为研究开发针对 引起的 MI 新型疗法的有前景的药物。本研究进一步表明，塞来昔布可以使某些 MRSA 菌株重新对以前未测试的β-内酰胺（如苯唑西林）敏感。需要指出的是，抗炎药物的体外浓度高于患者通常获得的浓度。因此，其给药的替代方案可能是在感染部位使用药物输送系统，以从植入物中控制缓慢释放药物。
