Rifabutin Acts in Synergy and Is Bactericidal with Frontline Mycobacterium abscessus Antibiotics Clarithromycin and Tigecycline, Suggesting a Potent Treatment Combination

Abstract

<i>Mycobacterium abscessus</i> 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-<i>M. abscessus</i> activity. The screen identified rifabutin, which was then investigated for its interactions with <i>M. abscessus</i> antibiotics used in drug regimens. Combination of rifabutin with either clarithromycin or tigecycline generated synergistic anti-<i>M. abscessus</i> 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 <i>M. abscessus</i> cultures. We suggest that combinations including rifabutin should be further investigated for treatment of <i>M. abscessus</i> pulmonary infections.