A 28-year-old woman with newly diagnosed drug-susceptible pulmonary tuberculosis is intolerant to pyrazinamide due to severe hyperuricemia and acute gouty arthritis. What is the drug of choice to replace pyrazinamide in her intensive phase regimen?

Explanation

## Management of Pyrazinamide Intolerance in TB **Key Point:** When pyrazinamide cannot be tolerated, streptomycin is the preferred replacement in the intensive phase regimen for drug-susceptible TB. The modified regimen becomes HRSE (isoniazid, rifampicin, streptomycin, ethambutol) for 2 months, followed by HR for 4 months (total 6 months). **High-Yield:** Streptomycin is the only first-line agent that can reliably substitute for pyrazinamide in drug-susceptible TB because: - It is bactericidal and has rapid early bactericidal activity - It is well-established in WHO-endorsed alternative regimens - The HRSE regimen has proven efficacy equivalent to HRZE when given for the standard 2-month intensive phase - It has minimal cross-resistance with other first-line drugs **Clinical Pearl:** Pyrazinamide intolerance (hyperuricemia, gout, hepatotoxicity) is not uncommon. The HRSE regimen is officially recognized by WHO and Indian TB guidelines as a standard alternative for pyrazinamide-intolerant patients with drug-susceptible TB. ## Comparison of Alternatives | Drug | Role in TB | Reason for Use/Non-Use | |------|-----------|------------------------| | **Streptomycin** | First-line alternative | Bactericidal, proven efficacy in HRSE regimen | | Fluoroquinolone | Second-line (MDR-TB) | Not recommended for drug-susceptible TB; reserved for resistant strains | | Ethionamide | Second-line (MDR-TB) | Hepatotoxic, used only for drug-resistant TB | | PAS | Second-line (MDR-TB) | Gastrointestinal side effects, used only for resistant TB | **Mnemonic:** HRSE = **H**isoniazid, **R**ifampicin, **S**treptomycin, **E**thambutol (alternative intensive phase when pyrazinamide contraindicated) [cite:Park 26e Ch 6]