Center for Infectious Disease and Biodefense Research, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
J Antimicrob Chemother. 2011 Jul;66(7):1533-6. doi: 10.1093/jac/dkr154. Epub 2011 Apr 11.
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.
In this study, we screened 1040 FDA-approved drugs against M. abscessus and M. chelonae.
Of the drugs screened, 32 compounds exhibited significant antimicrobial activity, with an MIC ≤ 8 mg/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.
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.
快速生长的分枝杆菌在药物发现工作中一直被忽视，这种忽视反映在针对这些感染的治疗方法有限。本研究的目的是通过测试美国食品和药物管理局批准的药物对脓肿分枝杆菌和溃疡分枝杆菌的抗菌活性，为治疗非结核分枝杆菌（NTM）寻找新的候选药物。脓肿分枝杆菌和溃疡分枝杆菌是两种新兴的 NTM 耐药病原体。
在这项研究中，我们对 1040 种美国食品和药物管理局批准的药物进行了筛选，以对抗脓肿分枝杆菌和溃疡分枝杆菌。
在所筛选的药物中，有 32 种化合物对溃疡分枝杆菌表现出显著的抗菌活性，MIC≤8mg/L，而只有 7 种化合物对脓肿分枝杆菌表现出这种活性。值得注意的是，溴新斯的明和肉桂嗪对溃疡分枝杆菌表现出高度显著的抗菌活性，但对脓肿分枝杆菌的效力较小。甲硝唑和嘌呤霉素是仅有的两种对两种菌株均具有同等效力的药物，其效力依次递减。
鉴定出的对脓肿分枝杆菌有活性的化合物很少，这说明了它抵抗药物的能力以及快速生长的 NTM 的弹性。重新利用已批准的药物是一种替代从头药物发现和开发的可行方法。
