A 32-year-old man from rural India presents with a 3-week history of productive cough, fever, and night sweats. Chest X-ray shows cavitary lesions in the right upper lobe. Sputum smear microscopy is positive for acid-fast bacilli. Which is the drug of choice for initiating treatment of drug-susceptible pulmonary tuberculosis?

Explanation

## Drug of Choice for Drug-Susceptible Pulmonary Tuberculosis **Key Point:** Isoniazid (INH) is the cornerstone and drug of choice for drug-susceptible pulmonary tuberculosis. It is the most potent bactericidal agent against actively dividing *Mycobacterium tuberculosis* and is included in **all phases** of the standard 6-month regimen. ### Role of Each First-Line Agent | Drug | Bactericidal/Static | Primary Role | Key Feature | |------|-------------------|--------------|-------------| | **Isoniazid** | Bactericidal | **Drug of choice; cornerstone of all regimens** | Highest early bactericidal activity (EBA); active against rapidly dividing bacilli | | Rifampicin | Bactericidal | Backbone; sterilizing agent | Shortens treatment duration; penetrates caseous lesions | | Pyrazinamide | Bactericidal | Intensive phase only (2 months) | Active in acidic pH of macrophages | | Ethambutol | Bacteriostatic | Companion drug | Prevents resistance development | ### Standard Regimen Structure (WHO / RNTCP) **Intensive Phase (2 months):** **Isoniazid** + Rifampicin + Pyrazinamide + Ethambutol **Continuation Phase (4 months):** **Isoniazid** + Rifampicin **High-Yield:** Isoniazid has the **highest early bactericidal activity (EBA)** among all anti-TB drugs. It inhibits mycolic acid synthesis (InhA enzyme), which is unique to mycobacteria, making it highly selective and potent. It is the only drug present in **both** the intensive and continuation phases as the primary bactericidal agent. **Clinical Pearl:** Isoniazid is used as **monotherapy for latent TB infection (LTBI)** — a 6–9 month course — precisely because it is the drug of choice for TB. No other first-line agent is used as monotherapy for LTBI prophylaxis in this manner (KD Tripathi, *Essentials of Medical Pharmacology*, 8th ed.; Harrison's *Principles of Internal Medicine*, 21st ed.). **Mnemonic:** **RIPE** = Rifampicin, Isoniazid, Pyrazinamide, Ethambutol — but **Isoniazid** is the anchor drug present throughout all 6 months. ### Why Isoniazid Is Preferred Over Others - **Rifampicin:** Excellent sterilizing activity and shortens treatment duration, but Isoniazid has superior early bactericidal activity and is the drug used for LTBI monotherapy. - **Pyrazinamide:** Only used in the intensive phase (first 2 months); not continued thereafter. - **Ethambutol:** Bacteriostatic; used to prevent resistance, not as the primary bactericidal agent. **Warning:** Isoniazid can cause peripheral neuropathy (prevented by pyridoxine/Vitamin B6 supplementation) and hepatotoxicity. Pyridoxine 10–25 mg/day is co-administered routinely.