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Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e02071-18. doi: 10.1128/AAC.02071-18. Print 2019 Apr.

Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model.

Author information

1
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA gregory.robertson@colostate.edu.
2
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
3
TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA.
4
Anacor Pharmaceuticals, Palo Alto, California, USA.

Abstract

AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline antituberculosis agent isoniazid.

KEYWORDS:

C3HeB/FeJ mice; antimicrobial resistance; caseum; drug development; isoniazid; necrotic lesions; tuberculosis

PMID:
30745397
DOI:
10.1128/AAC.02071-18
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