Mycobacteria susceptibility to epetraborole: how far can it go?

<sec><title>BACKGROUND</title>New chemotherapeutic agents are needed for the treatment of drug-resistant <i>Mycobacterium tuberculosis</i> (MTB), <i>M. avium</i> complex (MAC), <i>M. abscessus</i> (MAB), and <i>M. kansasii</i> (MKN) lung diseases. We tested epetraborole, a novel leucyl-tRNA synthetase (LeuRS) inhibitor, against four pathogenic mycobacteria.</sec><sec><title>METHODS</title>Reference and clinical strains were used in static concentration-response and minimum inhibitory concentration (MIC) studies. Data were used to calculate cumulative MIC for 50% of isolates (MIC₅₀), MIC₉₀, and concentration mediating 50% of maximal effect (EC₅₀).</sec><sec><title>RESULTS</title>Epetraborole microbial kill (log₁₀ CFU/ml) below day 0 bacterial burden was 0.37 ± 0.33 for MAB, 2.59 ± 0.06 for MAC, 1.49 ± 0.02 for MKN, and 0.51 ± 0.0 for MTB. Epetraborole EC₅₀, in mg/L, was 0.19 ± 0.03 for MAB, 0.28 ± 0.02 for MAC, 0.54 ± 0.06 for MKN, and 0.43 ± 0.86 for MTB. Epetraborole MIC₅₀ and MIC₉₀ were 0.25 and 0.5 mg/L for MAB (n = 59), respectively. For MAC, epetraborole MIC₅₀ and MIC₉₀ were 2 and 16 mg/L for <i>M. avium</i> (n = 17) and were 4 and 8 mg/L for <i>M. intracellulare</i> (n = 26), respectively. For MKN (n = 20), epetraborole MIC₅₀ and MIC₉₀ were 16 mg/L. For MTB (n = 21), MIC₅₀ and MIC₉₀ were 2 and 8 mg/L respectively.</sec><sec><title>CONCLUSION</title>Epetraborole MICs and EC₅₀s were lowest for MAB while the best kill was with MAC. Systematic pharmacokinetic/pharmacodynamic studies are warranted for non-tuberculous mycobacteria and MTB.</sec>.