Pyrazinamide contributes mainly to the sterilizing phase of short-course antitubercular therapy. Its activity is restricted to a specific environment because the drug requires which condition to be effective?

• A Neutral pH inside caseating granulomas
• B Alkaline pH of the extracellular cavitary contents
• C Acidic pH, as found within macrophage phagolysosomes ✓
• D Oxygen-rich environment of actively dividing bacilli

Explanation

Pyrazinamide is a prodrug converted by bacterial pyrazinamidase (encoded by pncA) into pyrazinoic acid, which is active only at acidic pH. Such acidity exists inside macrophage phagolysosomes where semidormant bacilli reside, making the drug uniquely sterilizing against intracellular organisms. Isoniazid kills rapidly dividing extracellular bacilli, while rifampicin acts on both populations, so neither shares this pH dependence.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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