Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Centre for Tuberculosis Research, University of British Columbia, Vancouver, British Columbia, Canada.
Antimicrob Agents Chemother. 2018 Jul 27;62(8). doi: 10.1128/AAC.00283-18. Print 2018 Aug.
is a rapidly emerging mycobacterial pathogen causing dangerous pulmonary infections. Because these bacteria are intrinsically multidrug resistant, treatment options are limited and have questionable efficacy. The current treatment regimen relies on a combination of antibiotics, including clarithromycin paired with amikacin and either imipenem or cefoxitin. Tigecycline may be added when triple therapy is ineffective. We initially screened a library containing the majority of clinically available antibiotics for anti- activity. The screen identified rifabutin, which was then investigated for its interactions with antibiotics used in drug regimens. Combination of rifabutin with either clarithromycin or tigecycline generated synergistic anti- activity, dropping the rifabutin MIC below concentrations found in the lung. Importantly, these combinations generated bactericidal activity. The triple combination of clarithromycin, tigecycline, and rifabutin was also synergistic, and clinically relevant concentrations had a sterilizing effect on cultures. We suggest that combinations including rifabutin should be further investigated for treatment of pulmonary infections.
是一种迅速出现的分枝杆菌病原体，可导致严重的肺部感染。由于这些细菌本身具有多重耐药性，因此治疗选择有限，疗效也存在疑问。目前的治疗方案依赖于抗生素的联合使用，包括克拉霉素与阿米卡星联合使用，以及亚胺培南或头孢西丁。当三联疗法无效时，可能会添加替加环素。我们最初筛选了一个包含大多数临床可用抗生素的文库，以寻找抗活性。该筛选确定了利福布汀，然后研究了它与药物方案中使用的抗生素的相互作用。利福布汀与克拉霉素或替加环素联合使用产生协同抗活性，使利福布汀的 MIC 降至肺部中发现的浓度以下。重要的是，这些组合具有杀菌活性。克拉霉素、替加环素和利福布汀的三联组合也具有协同作用，临床相关浓度对培养物具有杀菌作用。我们建议进一步研究包括利福布汀在内的组合，以治疗肺部感染。
