Pyrazinamide is a first-line anti-TB drug that is particularly active against which mycobacterial population and under which condition?
- A Rapidly dividing extracellular bacilli in well-aerated cavities at neutral pH
- B Semi-dormant bacilli in open cavities exposed to high oxygen tension
- C Dormant intracellular bacilli within macrophage phagolysosomes at acidic pH ✓
- D All populations equivalently, making it the most broadly active first-line drug
Explanation
Pyrazinamide is a prodrug converted by pyrazinamidase (pncA gene product) to pyrazinoic acid, which is the active form. This conversion occurs optimally at acidic pH (pH 5.0–5.5), the environment inside macrophage phagolysosomes where intracellular 'dormant' or 'persistor' bacilli reside. Pyrazinoic acid disrupts membrane potential and inhibits fatty acid synthesis (FAS-I). Its unique activity against this intracellular population explains why pyrazinamide allows shortening of TB treatment from 9–12 months to 6 months. Rifampicin is active against rapidly dividing extracellular populations.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.