Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706-110, USA.
J Antimicrob Chemother. 2009 Nov;64(5):1018-23. doi: 10.1093/jac/dkp339. Epub 2009 Sep 16.
Mycobacterium avium subspecies paratuberculosis (MAP) has been targeted for treatment with clarithromycin and rifamycin derivatives in numerous cases of Crohn's disease (CD). 6-Mercaptopurine and its pro-drug azathioprine are widely used as immunomodulators in the treatment of CD and have recently been shown to have anti-MAP activity in vitro. The objectives of the study were to evaluate the in vitro effects on MAP of (i) 6-mercaptopurine when combined with each of eight conventional antibacterial agents with in vitro anti-MAP activity and (ii) antibacterial combinations consisting of two drugs (clarithromycin combined with amikacin, rifampicin, ciprofloxacin or ethambutol) and three drugs (clarithromycin, rifabutin and clofazimine).
The drug interaction effects on nine human isolates of MAP were determined by the chequerboard method adapted for the BACTECMGIT960 culture system and by calculation of the fractional inhibitory concentration index (FICI) for drug combinations.
Synergism (FICI < or = 0.5) was observed between 6-mercaptopurine and azithromycin (seven isolates), clarithromycin, rifampicin, rifabutin (four isolates each) and ethambutol (two isolates). 6-Mercaptopurine was not antagonistic with any of the antibacterial agents tested. Among the combinations of two and three antibacterials tested, the clarithromycin/rifampicin combination was synergistic against four isolates, while all other combinations showed no interaction.
This in vitro study suggests that 6-mercaptopurine may be synergistic with macrolides and rifamycin derivatives against MAP. The activity of clarithromycin against MAP seems to be enhanced by rifampicin.
分枝杆菌亚种副结核分枝杆菌（MAP）已成为治疗许多克罗恩病（CD）的目标。6-巯基嘌呤及其前药硫唑嘌呤作为 CD 的免疫调节剂被广泛使用，最近已证明其在体外具有抗 MAP 活性。该研究的目的是评估（i）6-巯基嘌呤与具有体外抗 MAP 活性的八种常规抗菌药物中的每一种联合使用时对 MAP 的体外影响，以及（ii）由两种药物（克拉霉素联合阿米卡星、利福平、环丙沙星或乙胺丁醇）和三种药物（克拉霉素、利福布汀和氯法齐明）组成的抗菌联合用药对 MAP 的影响。
通过适用于 BACTECMGIT960 培养系统的棋盘法和药物联合的部分抑菌浓度指数（FICI）计算来确定九个人源 MAP 分离株的药物相互作用效应。
6-巯基嘌呤与阿奇霉素（7 个分离株）、克拉霉素、利福平、利福布汀（各 4 个分离株）和乙胺丁醇（2 个分离株）之间观察到协同作用（FICI≤0.5）。6-巯基嘌呤与测试的任何抗菌药物均无拮抗作用。在所测试的两种和三种抗菌药物组合中，克拉霉素/利福平组合对四个分离株具有协同作用，而其他所有组合均无相互作用。
这项体外研究表明，6-巯基嘌呤可能与大环内酯类和利福霉素衍生物对 MAP 具有协同作用。克拉霉素对 MAP 的活性似乎被利福平增强。
