Guidelines for Drug-Resistant Tuberculosis Treatment in India
For drug-resistant tuberculosis in India, treatment should follow a standardized regimen of at least five effective drugs in the intensive phase and four drugs in the continuation phase, with bedaquiline and a later-generation fluoroquinolone as core components. 1, 2
Core Treatment Principles
- The intensive phase should last 5-7 months after culture conversion 1
- The total treatment duration should be 15-21 months after culture conversion for MDR-TB 1
- For pre-XDR and XDR-TB, treatment should be extended to 15-24 months after culture conversion 1, 3
Essential Drugs for MDR-TB Regimen
First-line (strongly recommended) drugs:
Second-line (conditionally recommended) drugs:
Drug Dosing Considerations
- Pyrazinamide: 15-30 mg/kg once daily (maximum 2g/day) 4
- Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg three times weekly 5, 6
- Linezolid: Initial dose of 600 mg daily with potential reduction to 300 mg daily after 9-13 weeks to reduce toxicity while maintaining efficacy 7
- Delamanid: 100 mg twice daily 8, 9
- Clofazimine: 100 mg once daily 5, 9
Drugs to Avoid in Drug-Resistant TB Treatment
- Kanamycin or capreomycin are not recommended due to poor outcomes 1, 3
- Macrolides (azithromycin and clarithromycin) are not recommended due to lack of efficacy 1, 3
- Amoxicillin-clavulanate alone should not be used (only use with carbapenems) 1
- Ethionamide/prothionamide should be avoided if more effective drugs are available 1, 3
- p-aminosalicylic acid should be avoided if more effective drugs are available 1, 3
Treatment Monitoring
- Monitor for sputum culture conversion - a key indicator of treatment efficacy 9, 6
- QTc interval monitoring is essential when using bedaquiline and delamanid, though combined use appears safe with proper monitoring 8, 6
- Watch for myelosuppression with linezolid (occurs in approximately 52% of patients) 9, 7
- Monitor for peripheral neuropathy with linezolid (occurs in approximately 42% of patients) 9, 7
Special Considerations for XDR-TB
- For XDR-TB, the regimen should include bedaquiline, a later-generation fluoroquinolone (if susceptible), linezolid, and clofazimine as core components 3, 5
- Treatment duration should be extended to 15-24 months after culture conversion 3, 2
- Consider surgical intervention (elective partial lung resection) in selected cases where medical therapy alone may be insufficient 3
Common Pitfalls to Avoid
- Using fewer than five effective drugs in the intensive phase leads to poorer outcomes 1, 3
- Treating for less than 15 months after culture conversion for MDR/XDR-TB is associated with higher relapse rates 1, 3
- Failing to adjust linezolid dosing can lead to unnecessary toxicity while structured dose reduction maintains efficacy 7
- Neglecting to monitor for QTc prolongation when using bedaquiline and/or delamanid 8, 6