Rifabutin Is Active against Mycobacterium abscessus Complex

May 28, 2017 at 4:54 pm

Antimicrob. Agents Chemother. June 2017 V.61 N.6

Dinah Binte Aziz, Jian Liang Low, Mu-Lu Wu, Martin Gengenbacher, Jeanette W. P. Teo, Véronique Dartois, and Thomas Dick

aDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

bDepartment of Laboratory Medicine, National University Hospital, Singapore

cPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA

Lung infections caused by Mycobacterium abscessus 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. M. abscessus 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 M. abscessus lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an M. abscessus 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 M. abscessus 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 M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii CCUG 50184-T, and M. abscessus subsp. massiliense 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 Mycobacterium abscessus complex bacteria in vitro and may be considered for treatment of M. abscessus lung disease.




Entry filed under: Antimicrobianos, Biología Molecular, Infecciones respiratorias, Metodos diagnosticos, Micobacterias, Resistencia bacteriana, Sepsis, Update.

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