Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
Vet Microbiol. 2012 Nov 9;160(1-2):207-13. doi: 10.1016/j.vetmic.2012.05.031. Epub 2012 May 29.
There are no studies investigating interactions between clarithromycin or azithromycin and rifampin or other commonly used antimicrobial agents against virulent isolates of Rhodococcus equi. In addition, there is no published data on the postantibiotic effects (PAEs) and pharmacodynamics properties of antimicrobial agents against R. equi. The objectives were to assess in vitro interactions, pharmacodynamics, and PAEs of 11 antimicrobial agents belonging to various antimicrobial classes against R. equi. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, ceftiofur, and doxycycline) were selected based on in vitro activity against large numbers of isolates of R. equi and frequency of use in foals or humans infected with R. equi. Three virulent strains of R. equi were evaluated by time-kill curves and checkerboard assays, and the postantibiotic effect was measured at 5×MIC. Only amikacin, gentamicin, enrofloxacin, and vancomycin were bactericidal against R. equi. Combinations including a macrolide (erythromycin, clarithromycin, azithromycin) and either rifampin or doxycycline, and the combination doxycycline-rifampin were synergistic. Combinations containing amikacin and erythromycin, clarithromycin, azithromycin, or rifampin and the combination gentamicin-rifampin were antagonistic. The PAEs of rifampin, erythromycin, clarithromycin, vancomycin, and doxycycline were relatively long with median values ranging between 4.5 and 6.5h. Azithromycin, gentamicin, and imipenem had intermediate PAEs ranging between 3.3 and 3.5h. Amikacin, enrofloxacin, and ceftiofur had shorter PAEs ranging between 1.3 and 2.1h. Gentamicin, amikacin, enrofloxacin, and doxycycline exhibited concentration-dependent activity whereas erythromycin, clarithromycin, azithromycin, rifampin, ceftiofur, imipenem, and vancomycin exhibited time-dependent activity against R. equi.
目前尚无研究调查克拉霉素或阿奇霉素与利福平或其他常用抗微生物药物之间针对马红球菌毒力分离株的相互作用。此外，尚无关于抗微生物药物针对马红球菌的后抗生素效应（PAE）和药效学特性的已发表数据。本研究的目的是评估 11 种属于不同抗菌药物类别的抗菌药物对马红球菌的体外相互作用、药效学和 PAE。选择研究的抗菌药物（红霉素、克拉霉素、阿奇霉素、利福平、阿米卡星、庆大霉素、恩诺沙星、万古霉素、亚胺培南、头孢噻呋和多西环素）基于其对大量马红球菌分离株的体外活性以及在感染马红球菌的马驹或人中的使用频率。通过时间杀菌曲线和棋盘试验评估了 3 株马红球菌毒力株，并在 5×MIC 下测量后抗生素效应。只有阿米卡星、庆大霉素、恩诺沙星和万古霉素对马红球菌具有杀菌作用。包括大环内酯类（红霉素、克拉霉素、阿奇霉素）与利福平或多西环素的组合，以及多西环素-利福平的组合具有协同作用。包含阿米卡星和红霉素、克拉霉素、阿奇霉素或利福平的组合以及庆大霉素-利福平的组合具有拮抗作用。利福平、红霉素、克拉霉素、万古霉素和多西环素的 PAE 相对较长，中位数在 4.5 至 6.5 小时之间。阿奇霉素、庆大霉素和亚胺培南的 PAE 介于 3.3 至 3.5 小时之间。阿米卡星、恩诺沙星和头孢噻呋的 PAE 较短，在 1.3 至 2.1 小时之间。庆大霉素、阿米卡星、恩诺沙星和多西环素具有浓度依赖性活性，而红霉素、克拉霉素、阿奇霉素、利福平、头孢噻呋、亚胺培南和万古霉素对马红球菌具有时间依赖性活性。
