In vitro susceptibility of 147 international clinical Mycobacterium abscessus isolates to epetraborole and comparators by broth microdilution.

BACKGROUND

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.

OBJECTIVES

To determine epetraborole MIC distribution for 147 recent M. abscessus isolates via broth microdilution.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.