In vitro activity of bedaquiline against rapidly growing nontuberculous mycobacteria.

Diana A Aguilar-Ayala,Margo Cnockaert,Koen Andries,Emmanuel André,Anandi Martin,Jorge A Gonzalez-Y-Merchand,Peter Vandamme,Juan Carlos Palomino

doi:10.1099/jmm.0.000537

Abstract

Bedaquiline (BDQ) has been proven to be effective in the treatment of multidrug-resistant tuberculosis. We hypothesized that BDQ could be a potential agent to treat nontuberculous mycobacterial (NTM) infection. The objective of this study was to evaluate the in vitro activity of BDQ against rapidly growing mycobacteria by assessing the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against 18 NTM strains. For MIC determination we performed the resazurin microtitre assay broth dilution, and for the MBC the c.f.u. was determined. BDQ exhibited a strong inhibitory effect against most NTM tested; however, for some NTM strains the MBC was significantly higher than the MIC. A new finding is that Mycobacterium flavescens has a mutation in the gene atpE associated with natural resistance to BDQ. These preliminary promising results demonstrate that BDQ could be potentially useful for the treatment of NTM.

Highlights

The genus Mycobacterium comprises more than 150 different species of mycobacteria with the capacity to cause pathogenicity in humans [1]
For infections caused by nontuberculous mycobacteria (NTM), combination antimicrobial chemotherapy is the treatment of choice in most cases [10, 11]
Mycobacterium smegmatis CCUG 28063 was used for quality control since its minimum inhibitory concentration (MIC) for BDQ of 0.015 μg mlÀ1 is well known [9]

Summary

Introduction

The genus Mycobacterium comprises more than 150 different species of mycobacteria with the capacity to cause pathogenicity in humans [1]. In order to shed light on the conditions and parameters guiding the potential use of BDQ for NTM infections, we evaluated its in vitro activity against a panel of rapidly growing NTM reference strains and clinical isolates, and explored the possible correlation of single nucleotide polymorphisms in the target gene and natural resistance to the drug.

Objectives

Results

Conclusion