Abstract
Pretomanid (PA-824), a novel anti-tuberculosis nitroimidazoxazine, has been approved for multidrug-resistant tuberculosis treatment for a few years. Pretomanid has been demonstrated to be highly active against Mycobacterium tuberculosis when combined with other anti-tuberculosis drugs. This review provides an update of the current knowledge on the modes of action, resistance mechanisms, emergence of drug resistance, status of antimicrobial susceptibility testing for pretomanid and their relevance for clinical practice. Pretomanid resistance has been reported in in vitro and animal models but not yet in clinical trials. Pretomanid resistance-associated mutations have been reported in fbiA, fbiB, fbiC, fbiD, ddn and fgd1 genes. However, understanding of in vivo molecular resistance mechanisms remains limited and complicates the development of accurate antimicrobial susceptibility testing methods for pretomanid. Hence, no reference method for antimicrobial susceptibility testing of pretomanid has been established to guide clinical use. Further studies linking specific mutations, in vitro susceptibility, drug exposure and resistance mechanisms to treatment failure with pretomanid should be prioritized.
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