In a patient with pulmonary TB, the sputum smear converts to negative after 2 months of HRZE therapy. This early bactericidal activity (EBA) is primarily attributable to which drug's activity against the rapidly dividing bacilli population?

• A Rifampicin — most bactericidal drug overall, responsible for early smear conversion
• B Pyrazinamide — active primarily against persisters in acidic intracellular environment, not rapidly dividing extracellular bacilli
• C Isoniazid — highest EBA among all TB drugs due to rapid cidal activity against actively metabolising bacilli via InhA inhibition of mycolic acid synthesis ✓
• D Ethambutol — primary bactericidal drug killing rapidly dividing bacilli by arabinosyl transferase inhibition

Explanation

Early bactericidal activity (EBA) measures the rate of fall in viable bacilli in sputum during the first 2-14 days of treatment. Isoniazid has the highest EBA of all anti-TB drugs due to its potent inhibition of InhA (enoyl-ACP reductase) and KasA — essential for de novo mycolic acid synthesis — in rapidly dividing, actively metabolising bacilli. Rifampicin has less EBA but superb sterilising activity against semi-dormant populations during continuation phase. Pyrazinamide targets intracellular acid-environment persisters and shows minimal EBA. Ethambutol is primarily bacteriostatic, preventing acquired resistance rather than contributing to early killing.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.