Min Yu-Hong, Kim Yong-Ung, Park Min Chul
College of K-Bio Health, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Microorganisms. 2024 Dec 6;12(12):2515. doi: 10.3390/microorganisms12122515.
The widespread resistance of enterococci to many commonly used antimicrobial agents is a growing concern. Given that the current treatment options for enterococcal infections are limited, the discovery of new therapies, including combination therapies, is necessary. We evaluated double-drug combinations of lefamulin with doxycycline, rifampin, and quinupristin/dalfopristin for in vitro synergy against strains of () and () by using checkerboard and time-kill assays. In the checkerboard assay, the synergistic effect of lefamulin with doxycycline and rifampin was observed in 29 (85.3%) and 33 (97.1%) of the 34 different strains tested, respectively. These combinations also showed synergistic effects against 17 (94.4%) of the 18 different vancomycin-resistant strains. Among the 33 different strains, the combination of lefamulin with doxycycline, quinupristin/dalfopristin, and rifampin displayed synergistic effects in 31 (93.9%), 26 (78.8%), and 20 (60.6%) strains, respectively. No antagonism was observed in any of the combinations. The time-kill assay confirmed the synergistic effects of all these combinations. These synergistic combinations exhibited bacteriostatic activity. Although lefamulin is not currently used to treat enterococcal infections, we suggest that these combinations may serve as alternative drug regimens.
肠球菌对许多常用抗菌药物的广泛耐药性日益受到关注。鉴于目前针对肠球菌感染的治疗选择有限，发现新的治疗方法，包括联合治疗，是必要的。我们通过棋盘法和时间杀菌试验评估了乐伐莫林与多西环素、利福平以及奎奴普丁/达福普汀的双药联合对粪肠球菌和屎肠球菌菌株的体外协同作用。在棋盘法试验中，分别在34株不同粪肠球菌菌株中的29株（85.3%）和33株（97.1%）中观察到乐伐莫林与多西环素和利福平的协同作用。这些联合用药对18株不同的耐万古霉素屎肠球菌菌株中的17株（94.4%）也显示出协同作用。在33株不同屎肠球菌菌株中，乐伐莫林与多西环素、奎奴普丁/达福普汀和利福平的联合用药分别在31株（93.9%）、26株（78.8%）和20株（60.6%）菌株中显示出协同作用。在任何联合用药中均未观察到拮抗作用。时间杀菌试验证实了所有这些联合用药的协同作用。这些协同联合用药表现出抑菌活性。尽管乐伐莫林目前未用于治疗肠球菌感染，但我们认为这些联合用药方案可能成为替代治疗方案。
