Rifabutin Is Active against Mycobacterium abscessus Complex.

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

doi:10.1128/aac.00155-17

Abstract

ABSTRACTLung 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.

Highlights

Lung infections caused by Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and to other patient groups
To identify existing drugs that may be repurposed for the treatment of M. abscessus infections, we screened a collection of 2,720 approved drugs at 20 ␮M for their growth inhibition potential against the clinical isolate M. abscessus Bamboo
Due to its poor in vitro activity, the antituberculosis drug rifampin is not used in clinical practice for the treatment of lung disease caused by M. abscessus

Summary

Introduction

Lung infections caused by Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. 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. The already poorly performing treatments for M. abscessus infections are further complicated by the widespread occurrence of strains displaying inducible clarithromycin resistance [17, 18]. Erm[41] sequences appear to be present in all M. abscessus subspecies, inducible macrolide resistance appears to occur mainly in M. abscessus subsp. A subset of clinical isolates of this subspecies carrying a polymorphism within its erm[41] coding sequence does not express inducible clarithromycin resistance [21, 22]

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