Pretomanid is used in combination regimens for which TB category and what is its mechanism?

• A. MDR/XDR-TB; it inhibits mycolic acid synthesis under hypoxic conditions and generates reactive nitrogen species to kill TB.
• B. Drug-susceptible TB; inhibits ribosomal function
• C. Latent TB infection; inhibits DNA polymerase
• D. MDR/XDR-TB; inhibits ATP synthase

Answer: (A)

Pretomanid is used in combination regimens for drug-resistant TB, specifically MDR and XDR-TB. The key idea is that pretomanid must be activated inside the mycobacterium by nitroreductase enzymes, which leads to the production of reactive nitrogen species. These reactive species disrupt the bacterium’s energy production and other vital processes, and, importantly, pretomanid also inhibits the synthesis of mycolic acids, a critical component of the mycobacterial cell wall. This dual action is especially effective under the low-oxygen, hypoxic conditions found in granulomas, where dormant bacilli reside, allowing pretomanid to kill both actively growing and non-replicating bacteria. It’s not used for drug-susceptible TB, latent TB, or into mechanisms like ribosomal inhibition or DNA polymerase inhibition; and the ATP synthase inhibition used by bedaquiline is a different drug’s mechanism.