Chai Dong, Liu Xu, Wang Rui, Bai Yan, Cai Yun
Department of Pharmaceutical Care, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
Department of Clinical Pharmacology, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
Biomed Res Int. 2016;2016:6413982. doi: 10.1155/2016/6413982. Epub 2016 Jun 5.
As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA) infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI) and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P < 0.05). In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development.
作为长期存在的临床问题,导管相关感染和其他慢性生物膜感染由于生物膜具有高抗生素耐药性而更难治疗。因此,需要新的治疗方法来更有效地清除细菌。在本研究中,我们评估了几种常见抗生素单独使用及其组合对生物膜包裹的耐甲氧西林金黄色葡萄球菌(MRSA)感染的抗菌活性,包括体外和体内实验。简而言之,在三种MRSA菌株中,分别测试了磷霉素、左氧氟沙星和利福平单独使用或与利奈唑胺联合使用对浮游和生物膜包裹的MRSA感染的体外抗菌活性。通过部分抑菌浓度指数(FICI)和时间杀菌曲线评估利奈唑胺与其他三种抗生素之间的协同作用,结果显示利奈唑胺加磷霉素的组合在所有菌株中均表现出最佳的协同效应。为了进行进一步的体内评估,我们在导管相关生物膜大鼠模型中应用了利奈唑胺和磷霉素的组合,发现治疗后生物膜中的活菌数显著减少(P < 0.05)。总之,我们在此表明,利奈唑胺和磷霉素联合治疗对生物膜包裹的MRSA感染在体外和体内均具有改善的治疗效果,这为新的临床治疗开发提供了重要依据。