National TB Guidelines in India (2023 NTEP)
Drug-Sensitive TB Treatment
India's National TB Elimination Programme (NTEP) follows WHO-recommended first-line therapy: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (intensive phase), followed by 4 months of isoniazid and rifampin (continuation phase), for a total of 6 months. 1
Key Diagnostic Approach
- CBNAAT (GeneXpert) is the mandatory first-line diagnostic test for all suspected TB cases in India, simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance 2
- When rifampicin is sensitive, classify as drug-sensitive TB and initiate standard HRZE; when resistant, classify as RR-TB and never start standard HRZE 2
- Standard CBNAAT does not detect isoniazid resistance—this requires line-probe assay or culture-based drug susceptibility testing (DST) 2
Treatment Monitoring
- Sputum smear and culture monitoring at months 2,4, and 6 is essential to assess treatment response 2
- Approximately 85% of drug-sensitive TB cases can be successfully treated with the 6-month regimen 3
Drug-Resistant TB Management
For MDR/RR-TB, the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid 600 mg daily, and moxifloxacin) is now the preferred first-line treatment, replacing older 9-month or 18-month regimens. 4, 2
Regimen Hierarchy (Most to Least Preferred)
- BPaLM (6 months) – for fluoroquinolone-susceptible MDR/RR-TB 4, 2
- BPaL (6 months, without moxifloxacin) – for pre-XDR TB (fluoroquinolone-resistant) 4, 2
- 9-month all-oral regimen – when BPaLM/BPaL are unsuitable 2
- Individualized 18-20 month regimen – when shorter regimens cannot be used 2
BPaLM Eligibility Criteria
Eligible patients:
- Adults ≥14 years with MDR/RR-TB 4
- Fluoroquinolone-susceptible disease 4
- No prior exposure >30 days to bedaquiline, pretomanid, or linezolid 4
- People living with HIV are eligible 4
- Extensive pulmonary TB (cavities) is no longer a contraindication 2
Absolute contraindications:
- Age <14 years (no pretomanid safety data in children) 4
- Pregnancy or breastfeeding (no pretomanid safety data) 4
- Known resistance to bedaquiline, pretomanid, or linezolid 4
- Central nervous system TB, osteoarticular TB, or disseminated (miliary) TB 4, 2
Critical Management Principles
Do not delay BPaLM waiting for fluoroquinolone DST results—start empirically and switch to BPaL (9 months total) if resistance is documented later 4, 2
If fluoroquinolone resistance is detected after starting BPaLM, immediately stop moxifloxacin and continue as BPaL for 9 months total 4, 2
Never add a single drug to a failing regimen—this creates de facto monotherapy and amplifies resistance; always add ≥2 drugs to which the organism is susceptible 5
Baseline Evaluation Before MDR/RR-TB Therapy
Mandatory baseline assessments: 2
- Complete blood count (CBC)
- Liver function tests (AST, ALT, bilirubin, alkaline phosphatase)
- Renal function tests
- ECG with QTc measurement
- Electrolytes (potassium, magnesium, calcium)
- HIV status
- Pregnancy status
- Weight and BMI
- Visual acuity testing
- Peripheral neuropathy assessment
- Detailed history of prior TB drug exposure
Drug Susceptibility Testing Requirements
Comprehensive DST for fluoroquinolones and all second-line drugs is required to inform regimen selection 2
Fluoroquinolone DST is pivotal for deciding between BPaLM, BPaL, the 9-month regimen, or longer individualized regimens, but should not delay treatment initiation 4, 2
BPaLM Monitoring Protocol
Cardiac Monitoring
- Baseline ECG and repeat at weeks 2,4,8,12, then monthly to detect QTc prolongation from bedaquiline and moxifloxacin 4, 2
- Discontinue if QTcF >500 ms or clinically significant ventricular arrhythmia develops 4
- Correct hypokalemia, hypomagnesemia, and hypocalcemia before and during treatment 6
Hematologic Monitoring
- Monthly CBC to identify linezolid-induced myelosuppression (anemia, thrombocytopenia) 4, 2
- If toxicity develops, linezolid dose reduction to 300 mg daily is acceptable to mitigate toxicity while maintaining efficacy 5, 4
Neurologic Monitoring
- Monthly assessment for peripheral neuropathy (numbness, tingling, pain in extremities) from linezolid 4, 6
- Monthly visual acuity and color vision screening for optic neuropathy from linezolid 6
- Refer to ophthalmology if any visual symptoms develop 6
Hepatotoxicity Monitoring
- Monitor AST, ALT, bilirubin, and alkaline phosphatase at baseline, monthly, and if symptomatic 4
- More frequent monitoring needed with other hepatotoxic medications or underlying liver disease 4
9-Month All-Oral Regimen (Alternative)
When BPaLM/BPaL cannot be used, the 9-month all-oral regimen is suggested for fluoroquinolone-susceptible MDR/RR-TB 2
Typical Composition
Intensive phase (4-6 months): bedaquiline + linezolid or ethionamide + fluoroquinolone + clofazimine + pyrazinamide + ethambutol + high-dose isoniazid 2
Continuation phase (~5 months): fluoroquinolone + clofazimine + pyrazinamide + ethambutol 2
Mandatory fluoroquinolone DST; susceptibility to all other regimen drugs should be confirmed 2
Long Individualized Regimen (18-20 Months)
Used when BPaLM, BPaL, or the 9-month regimen cannot be applied due to drug intolerance, drug-drug interactions, extensively drug-resistant TB, or previous treatment failure 2
WHO Drug Grouping for Regimen Construction
Group A (preferred—include all three if possible): 5, 2
- Levofloxacin or moxifloxacin
- Bedaquiline
- Linezolid
Group B (add at least one): 5, 2
- Clofazimine
- Cycloserine or terizidone
Group C (add to reach ≥4 effective drugs): 5, 2
- Ethambutol
- Delamanid
- Pyrazinamide
- Imipenem-cilastatin or meropenem
- Amikacin (only if no oral alternatives available)
- Ethionamide or prothionamide
- p-aminosalicylic acid
Core Requirements
- ≥4 effective drugs in the intensive phase and ≥3 in the continuation phase 2, 6
- Total duration: 18-20 months or 15-17 months after culture conversion 6
Injectable Agents (Discouraged)
WHO no longer recommends routine use of injectable agents (amikacin, kanamycin, capreomycin) 2
Amikacin or streptomycin may be included only when an adequate number of effective oral drugs cannot be assembled and susceptibility is confirmed 5, 2
Kanamycin and capreomycin are strongly discouraged due to poor outcomes and high toxicity 5, 2
TB Preventive Therapy (TPT)
India's NTEP prioritizes TPT for high-risk groups, though implementation remains a challenge 7
Preferred Regimens
- Isoniazid + rifapentine for 3 months (3HP) 1
- Isoniazid + rifampin for 3 months (3HR) 1
- Rifampin alone for 4 months (4R) 1
- Isoniazid for 9 months (9H) is the only recommended regimen for children 5
High-Risk Groups Requiring TPT
- HIV-infected persons 5, 1
- Recent contacts of pulmonary TB cases 5, 1
- Persons with injection drug use history 5
- Homeless persons 5
- Incarcerated individuals 5
Tuberculin Skin Test Interpretation
- ≥5 mm: positive for HIV-infected persons, recent TB contacts, immunosuppressed persons, or those with chest X-ray suggesting old TB 5
- ≥10 mm: positive for recent arrivals from high-prevalence countries, injection drug users, children <4 years, or persons at increased risk 5
- ≥15 mm: positive for persons with no known TB risk factors 5
Common Pitfalls to Avoid
Never accept a three-drug MDR-TB regimen as adequate—this violates WHO guidelines and markedly raises the risk of treatment failure and acquired resistance 6
Never use standard HRZE for rifampicin-resistant TB—CBNAAT detection of rifampicin resistance mandates immediate MDR-TB regimen 2
Never prolong BPaLM beyond 6 months—if poor response is suspected, switch to an 18-20 month individualized regimen rather than extending BPaLM 5
Do not discontinue therapy early even after culture conversion—complete the full prescribed duration (6,9, or 18-20 months) 2
Do not give BPaLM to children <14 years—pretomanid has not been studied in this age group; opt for the 9-month regimen instead 2
Do not use ethionamide in pregnancy—substitute with a linezolid-based variation of the 9-month regimen 2
NTEP Program Strengthening Measures
India's path to TB elimination by 2025 requires: 8
- Strengthening health systems and mainstreaming private sector participation
- Enhancing diagnostic facilities and including latest techniques (CBNAAT expansion)
- Addressing social stigma and under-reporting
- Advocacy for higher budget allocation
- Improving treatment success rates and reducing dropout rates
- Swift performance in identification, notification, and treatment of TB cases