To find a therapeutic alternative for the treatment of skin and soft tissue infections, we evaluated the effects of combinations of retapamulin with macrolide, lincosamide, and streptogramin (MLS) antibiotics against Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecium, and Enterococcus faecalis. Using both the disk diffusion test and checkerboard assay, we initially examined the effects of combinations of retapamulin with MLS antibiotics against standard strains of these species. Combinations of retapamulin with erythromycin, quinupristin/dalfopristin and quinupristin showed synergistic activity against E. faecalis only. Synergy of retapamulin with clindamycin and dalfopristin was not observed. Then, a checkerboard assay was performed to evaluate the effects of the combinations against 15 clinical strains of E. faecalis. Retapamulin and quinupristin, the most synergistic combination, showed activity against all erythromycin-susceptible, -intermediate, and -resistant strains tested. Among the eight strains with high-level erythromycin resistance, five strains were synergistically inhibited in the presence of only 1 μg of retapamulin per ml. Time-kill assay revealed that combinations of retapamulin with erythromycin and quinupristin were bacteriostatic. These results suggest that combinations of retapamulin with erythromycin and quinupristin have in vitro synergistic activity against E. faecalis, including strains with high-level erythromycin resistance.

中文翻译：

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retapamulin与红霉素和quinupristin对粪肠球菌的体外协同作用。

为了找到治疗皮肤和软组织感染的替代疗法，我们评估了雷帕莫林与大环内酯，林可酰胺和链霉菌素（MLS）抗生素联合使用对金黄色葡萄球菌，化脓性链球菌，粪肠球菌和粪肠球菌的影响。我们同时使用了纸片扩散测试和棋盘检测，我们初步研究了瑞他莫林与MLS抗生素联合使用对这些物种的标准菌株的影响。retapamulin与红霉素，quinupristin / dalfopristin和quinupristin的组合显示仅对粪肠球菌具有协同活性。没有观察到瑞他莫林与克林霉素和达福普汀的协同作用。然后，进行棋盘分析以评估所述组合对15种粪肠球菌临床菌株的作用。瑞塔木林和奎奴普丁是最有效的组合，对所有受试验的红霉素敏感菌株，中间菌株和耐药菌株均具有活性。在八种具有高水平红霉素抗性的菌株中，在每毫升仅含1μgretapamulin的情况下，五种菌株被协同抑制。时间杀伤试验表明，瑞他莫林与红霉素和奎奴普丁的组合具有抑菌作用。这些结果表明，retapamulin与红霉素和quinupristin的组合对粪便大肠杆菌，包括具有高水平红霉素抗性的菌株，具有体外协同活性。在八种具有高水平红霉素抗性的菌株中，在每毫升仅含1μgretapamulin的情况下，五种菌株被协同抑制。时间杀伤试验表明，瑞他莫林与红霉素和奎奴普丁的组合具有抑菌作用。这些结果表明，retapamulin与红霉素和quinupristin的组合具有体外抗屎肠球菌的协同活性，包括具有高水平红霉素抗性的菌株。在八种具有高水平红霉素抗性的菌株中，在每毫升仅含1μgretapamulin的情况下，五种菌株被协同抑制。时间杀伤试验表明，瑞他莫林与红霉素和奎奴普丁的组合具有抑菌作用。这些结果表明，retapamulin与红霉素和quinupristin的组合具有体外抗屎肠球菌的协同活性，包括具有高水平红霉素抗性的菌株。