Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae

Abstract

Objectives: Rapidly growing mycobacteria have long been neglected in drug discovery efforts and this neglect is reflected in the paucity of therapeutic options available for diseases resulting from these infections. The purpose of this work is to identify new candidate drugs for treating non-tuberculous mycobacteria (NTM) by testing FDA-approved drugs for antimicrobial activity against Mycobacterium abscessus and Mycobacterium chelonae, two emerging NTM drug-resistant pathogens. Methods: In this study, we screened 1040 FDA-approved drugs against M. abscessus and M. chelonae. Results: Of the drugs screened, 32 compounds exhibited significant antimicrobial activity, with an MIC ≤8mg/L, against M. chelonae, while only 7 compounds showed such activity against M. abscessus. Notably, neostigmine bromide and cinnarizine exhibited highly significant antimicrobial activity against M. chelonae, but had little potency against M. abscessus. Metronidazole and puromycin were the only drugs that acted equipotently against both strains, in decreasing order of effectiveness. Conclusions: The dearth of identified compounds active against M. abscessus exemplifies its ability to resist drugs as well as the resilience of rapidly growing NTM. Repurposing of approved drugs is a viable alternative to de novo drug discovery and development. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.