Rifabutin Is Active against Mycobacterium abscessus Complex

Abstract

Lung infections caused by <i>Mycobacterium abscessus</i> are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation. <i>M. abscessus</i> is an intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of <i>M. abscessus</i> lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an <i>M. abscessus</i> clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three <i>M. abscessus</i> subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains <i>M. abscessus</i> subsp. <i>abscessus</i> ATCC 19977, <i>M. abscessus</i> subsp. <i>bolletii</i> CCUG 50184-T, and <i>M. abscessus</i> subsp. <i>massiliense</i> CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the <i>Mycobacterium abscessus</i> complex bacteria <i>in vitro</i> and may be considered for treatment of <i>M. abscessus</i> lung disease.