Pyrazinamide exerts its sterilising effect primarily against which population of bacilli during antitubercular therapy?

• A Extracellular rapidly multiplying bacilli in the cavity wall
• B Persisters undergoing spontaneous metabolism-independent dormancy
• C Intracellular semidormant bacilli within macrophage phagolysosomes ✓
• D Bacilli in the caseous centre of closed lesions

Explanation

Pyrazinamide requires an acidic pH to be active. Inside macrophage phagolysosomes, where pH falls below about 6, the bacillus converts the prodrug to pyrazinoic acid via its pyrazinamidase (pncA gene). It therefore kills semidormant intracellular organisms and contributes sterilising activity in the first two months. Extracellular bacilli in cavities encounter neutral pH where pyrazinamide is inactive.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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