AUTHOR=Zheng Luyao , Qi Xueting , Zhang Weiyan , Wang Hong , Fu Lei , Wang Bin , Chen Xi , Chen Xiaoyou , Lu Yu 

TITLE=Efficacy of PBTZ169 and pretomanid against Mycobacterium avium, Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum in BALB/c mice models

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1115530

DOI=10.3389/fcimb.2023.1115530

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) <italic>in vitro</italic> and <italic>in vivo</italic>.</p></sec><sec><title>Methods</title><p>The minimum inhibitory concentrations (MICs) of 11 antibiotics, against slow-growing mycobacteria (SGMs) and rapid-growing mycobacteria (RGMs) were tested using the microplate alamarBlue assay. The <italic>in vivo</italic> activities of bedaquiline, clofazimine, moxifloxacin, rifabutin, PBTZ169 and pretomanid against four common NTMs were assessed in murine models.</p></sec><sec><title>Results</title><p>PBTZ169 and pretomanid had MICs of &gt;32 μg/mL against most NTM reference and clinical strains. However, PBTZ169 was bactericidal against <italic>Mycobacterium abscessus</italic> (3.33 and 1.49 log10 CFU reductions in the lungs and spleen, respectively) and <italic>Mycobacterium chelonae</italic> (2.29 and 2.24 CFU reductions in the lungs and spleen, respectively) in mice, and bacteriostatic against Mycobacterium avium and <italic>Mycobacterium fortuitum</italic>. Pretomanid dramatically decreased the CFU counts of <italic>M. abscessus</italic> (3.12 and 2.30 log10 CFU reductions in the lungs and spleen, respectively), whereas it showed moderate inhibition of <italic>M. chelonae</italic> and <italic>M. fortuitum</italic>. Bedaquiline, clofazimine, and moxifloxacin showed good activities against four NTMs <italic>in vitro</italic> and <italic>in vivo</italic>. Rifabutin did not inhibit <italic>M. avium</italic> and <italic>M. abscessus</italic> in mice.</p></sec><sec><title>Conclusion</title><p>PBTZ169 appears to be a candidate for treating four common NTM infections. Pretomanid was more active against <italic>M. abscessus</italic>, <italic>M. chelonae</italic> and <italic>M. fortuitum</italic> than against <italic>M. avium</italic>.</p></sec>