title: Rifabutin Is Active against Mycobacterium abscessus Complex.
abstract: Lung infections caused byMycobacterium abscessusare 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.M. abscessusis 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 ofM. abscessuslung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against anM. abscessusclinical 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 threeM. abscessussubspecies 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 strainsM. abscessussubsp.abscessusATCC 19977,M. abscessussubsp.bolletiiCCUG 50184-T, andM. abscessussubsp.massilienseCCUG 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 theMycobacterium abscessuscomplex bacteriain vitroand may be considered for treatment ofM. abscessuslung disease.
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Dinah Binte
authors.initials: DB
authors.lastname: Aziz
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Jian Liang
authors.initials: JL
authors.lastname: Low
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Mu-Lu
authors.initials: ML
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Martin
authors.initials: M
authors.lastname: Gengenbacher
authors.affiliation: Department of Laboratory Medicine, National University Hospital, Singapore.
authors.forename: Jeanette W P
authors.identifier: 0000-0002-9321-3341
authors.initials: JWP
authors.lastname: Teo
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dartois
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore td367@njms.rutgers.edu.|Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Thomas
authors.identifier: 0000-0002-9604-9452
authors.initials: T
authors.lastname: Dick
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000382:microbiology; D000073358:Mycobacterium abscessus / Q000187:drug effects* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D017828:Rifabutin / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin; D017291:Clarithromycin
keywords: Mycobacterium abscessus; NTM; repurposing; rifabutin