Indian Guidelines for Treatment of Tuberculosis
Standard Treatment Regimen for New TB Cases
For new cases of drug-susceptible tuberculosis in India, the recommended treatment is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) given daily for 2 months, followed by isoniazid and rifampin (HR) given daily or three times weekly for 4 months under directly observed therapy (DOTS). 1
Initial Intensive Phase (2 Months)
The intensive phase must include all four first-line drugs administered together to maximize effectiveness and prevent drug resistance 2:
- Isoniazid: 5 mg/kg daily (maximum 300 mg/day) 1
- Rifampin: 10 mg/kg daily (maximum 600 mg/day) 1
- Pyrazinamide: 35 mg/kg daily for patients <50 kg; 2.0 g daily for patients ≥50 kg 1
- Ethambutol: 15 mg/kg daily 1
The four-drug regimen is mandatory because it prevents emergence of drug resistance, particularly in areas where isoniazid resistance exceeds 4% 3. Higher dose intermittent therapy given three times weekly (2E3H3R3Z3) has been advocated by WHO and implemented by the Revised National TB Control Programme in India 1.
Continuation Phase (4 Months)
After completing the 2-month intensive phase, continue with 1:
- Isoniazid: 5 mg/kg daily (maximum 300 mg/day)
- Rifampin: 10 mg/kg daily (maximum 600 mg/day)
The continuation phase can be administered daily or three times weekly (4H3R3) under DOTS 1. Daily dosing is preferred for better outcomes, though intermittent therapy is acceptable when directly observed 2.
Directly Observed Treatment Short-Course (DOTS)
All TB patients in India should receive treatment under DOTS, where drug ingestion is directly observed by a health worker to ensure regularity and prevent drug resistance 1. This is particularly critical because most multidrug-resistant TB in India (14% prevalence in Delhi) is acquired due to poor chemotherapy adherence, with primary resistance being only 1.4% 1.
Fixed-dose combinations (FDCs) consisting of two or three antituberculosis medications provide a realistic alternative to direct observation that minimizes the opportunity for selective medication intake 1.
Special Populations
Pregnancy and Lactation
All first-line drugs (rifampin, isoniazid, ethambutol, pyrazinamide) can be used during pregnancy 1. However, streptomycin is contraindicated due to fetal ototoxicity 1. Prophylactic pyridoxine 10 mg/day should be given along with antituberculosis therapy 1.
Diabetes Mellitus
The drug regimen remains the same as in non-diabetics 1. Strict blood glucose control is mandatory, and doses of oral hypoglycemic agents may need to be increased due to interaction with rifampin 1. Prophylactic pyridoxine is indicated 1.
HIV Co-infection
The usual short-course chemotherapy (2HRZE/4HR) is indicated in HIV-positive patients, with good initial response but frequent relapse 1. In early HIV stages, TB presentation is similar to HIV-negative patients, but in late stages extrapulmonary and disseminated disease are common 1.
Antiretroviral therapy containing protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) cannot be used concurrently with rifampin, as rifampin induces metabolism of PI and reduces efficacy 1. Options include: postponing antiretroviral therapy, using regimens without PI or NNRTI, using efavirenz or saquinavir with ritonavir without dose adjustment, or using non-rifampin regimens (2SHEZ + 10HE) 1.
Renal Failure
Dosages must be adjusted according to creatinine clearance, especially for streptomycin, ethambutol, and isoniazid 1. In acute renal failure, ethambutol should be given 8 hours before hemodialysis 1.
Pre-existing Liver Disease
In stable disease with normal liver enzymes, all antituberculosis drugs may be used, but frequent monitoring of liver function tests is required 1.
Children
Infants and children younger than 4 years should begin treatment immediately when TB is suspected due to high risk of disseminated disease 2. The same regimen as adults is used with weight-adjusted dosing 2. Ethambutol is not routinely used in young children who cannot be monitored for visual acuity 3.
Site-Specific Treatment Duration
Standard Pulmonary TB
6 months total (2HRZE/4HR) 1
Extended Duration Required
- TB meningitis: 12 months (2HRZE followed by 10 months HR) 4
- Spinal TB with neurological involvement: 9 months 4
- Miliary TB in children: 12 months 3
- Bone/joint TB in children: 12 months 3
Treatment Monitoring
Sputum smear examination of 3 deeply coughed samples (spot sample day 1, overnight sample, morning spot sample day 2) is the preferred screening test 1. Sputum smear positivity exceeds 90% when >5 ml of sputum is used 1.
Drug susceptibility testing should be performed on all initial isolates from new patients 1, 4. Culture is the gold standard, detecting 10-100 viable mycobacteria per ml with 81% sensitivity and 98.5% specificity 1.
Patients with positive sputum smears at 3 months should be evaluated for nonadherence or drug-resistant disease 5. Positive cultures after 3 months warrant investigation for treatment failure 2.
Common Pitfalls to Avoid
- Never use fewer than four drugs in the initial phase, even if local isoniazid resistance is <4%, as this is a critical error that promotes resistance 3
- Do not discontinue ethambutol before drug susceptibility results are available unless there is documented full susceptibility to isoniazid and rifampin 6
- Avoid using rifampin-containing regimens in post-renal transplant patients as rifampin increases cyclosporin clearance 1
- Never use streptomycin in pregnant women due to fetal ototoxicity 1
- Do not use three-drug regimens without rifamycin, aminoglycoside, or capreomycin for HIV-related TB; if used, minimum duration should be 18 months 5
Multidrug-Resistant TB (MDR-TB)
MDR-TB treatment should be referred to specialized units with quality-controlled drug susceptibility testing 1. When initiating therapy for MDR-TB, drug selection must rely on prior treatment history, susceptibility testing results, and patient adherence evaluation 1. The regimen should include 5-7 drugs selected based on patient characteristics while awaiting susceptibility results 7.
Public Health Reporting
All suspected TB cases must be reported promptly to local public health authorities before culture confirmation 2. This allows contact tracing, monitoring of treatment adherence, identification and treatment of infected contacts, and surveillance to assess TB control efforts 2.