Pyrazinamide (PZA) is uniquely active against tubercle bacilli in which microenvironment, explaining its irreplaceable role in the intensive phase of TB therapy?
- A Alkaline pH of macrophage phagolysosomes, where PZA is maximally active
- B Neutral pH of extracellular fluid surrounding granulomas
- C Acidic pH of caseous necrotic lesions and within macrophage phagolysosomes, where PZA is converted to pyrazinoic acid and is bactericidal ✓
- D Aerobic environment of rapidly dividing bacilli in cavitary lesions
Correct answer: C. Acidic pH of caseous necrotic lesions and within macrophage phagolysosomes, where PZA is converted to pyrazinoic acid and is bactericidal
Explanation
PZA is a prodrug hydrolysed by mycobacterial pyrazinamidase to pyrazinoic acid (POA), which is bactericidal specifically at acidic pH (5.0–5.5)—conditions found in macrophage phagolysosomes and caseous necrotic granulomas. This activity against 'persisters' in these acidic microenvironments is unique to PZA and explains why its inclusion in the intensive phase allows treatment shortening from 9–12 months to 6 months. At neutral or alkaline pH, PZA is inactive.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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