Nguyen Minh-Vu H, Calado Nogueira de Moura Vinicius, Keepers Tiffany R, van Ingen Jakko, Daley Charles L
Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, CO, USA.
Department of Clinical Microbiology, AN2 Therapeutics, Inc, Menlo Park, CA, USA.
J Antimicrob Chemother. 2025 Mar 3;80(3):713-716. doi: 10.1093/jac/dkae461.
Mycobacterium abscessus is a highly drug-resistant non-tuberculous mycobacterium (NTM) for which treatment is limited by the lack of active oral antimycobacterials and frequent adverse reactions. Epetraborole is a novel oral, boron-containing antimicrobial that inhibits bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis, and has been shown to have anti-M. abscessus activity in preclinical studies.
To determine epetraborole MIC distribution for 147 recent M. abscessus isolates via broth microdilution.
M. abscessus isolates collected in 2021 from the USA (n = 122) from pulmonary sources and during 2019-22 predominantly from Europe (n = 25) from pulmonary and extrapulmonary sources had MICs determined by broth microdilution according to CLSI guidelines for epetraborole and a panel of 12 other antimycobacterials. Descriptive analyses were done on the MIC values.
Of the 147 M. abscessus isolates, 101 were subspecies abscessus, 6 were bolletii and 40 were massiliense. Epetraborole MICs ranged from 0.03 to 0.25 mg/L and were consistent across subspecies. Epetraborole MIC50/MIC90 for all isolates were 0.06/0.12 mg/L. When stratified by subspecies, amikacin resistance, clarithromycin resistance and morphotype, the MIC50/MIC90 values remained 0.06/0.12 mg/L.
Epetraborole demonstrated potent in vitro activity against M. abscessus with MICs from 0.03 to 0.25 mg/L and consistent activity against all subspecies, resistance phenotypes and morphotypes. These data support clinical evaluation of epetraborole as a therapeutic option for M. abscessus disease.
脓肿分枝杆菌是一种高度耐药的非结核分枝杆菌（NTM），由于缺乏有效的口服抗分枝杆菌药物以及频繁的不良反应，其治疗受到限制。依匹硼罗是一种新型的含硼口服抗菌药物，可抑制细菌亮氨酰 - tRNA合成酶（蛋白质合成中的一种必需酶），并且在临床前研究中已显示出对脓肿分枝杆菌有活性。
通过肉汤微量稀释法确定147株近期脓肿分枝杆菌分离株的依匹硼罗最低抑菌浓度（MIC）分布。
2021年从美国收集的122株来自肺部的脓肿分枝杆菌分离株以及2019 - 2022年主要从欧洲收集的25株来自肺部和肺外部位的脓肿分枝杆菌分离株，根据美国临床和实验室标准协会（CLSI）指南，通过肉汤微量稀释法测定依匹硼罗和一组其他12种抗分枝杆菌药物的MIC。对MIC值进行描述性分析。
147株脓肿分枝杆菌分离株中，101株为脓肿亚种，6株为博勒亚种，40株为马西利亚亚种。依匹硼罗的MIC范围为0.03至0.25mg/L，各亚种间一致。所有分离株的依匹硼罗MIC50/MIC90为0.06/0.12mg/L。按亚种、阿米卡星耐药性、克拉霉素耐药性和形态型分层时，MIC50/MIC90值仍为0.06/0.12mg/L。
依匹硼罗对脓肿分枝杆菌显示出强大的体外活性，MIC为0.03至0.25mg/L，对所有亚种、耐药表型和形态型均具有一致活性。这些数据支持对依匹硼罗作为脓肿分枝杆菌病治疗选择进行临床评估。
