TB Treatment Guidelines in India
For drug-sensitive pulmonary tuberculosis in India, the standard treatment is a 2-month intensive phase with isoniazid, rifampicin, pyrazinamide, and ethambutol (2HRZE), followed by a 4-month continuation phase with isoniazid and rifampicin (4HR), administered daily or thrice weekly under directly observed therapy (DOTS). 1
Drug-Sensitive Tuberculosis
Standard Regimen Structure
The treatment follows a two-phase approach with an intensive phase to rapidly reduce bacterial load and a continuation phase to eliminate remaining organisms 2:
Intensive Phase (2 months):
- Isoniazid (H): 5 mg/kg up to 300 mg daily or 10-15 mg/kg in children 3
- Rifampicin (R): Standard adult dosing 4
- Pyrazinamide (Z): Included in all phases 1
- Ethambutol (E): Added as fourth drug when isoniazid resistance exceeds 4% in the community 2, 1
Continuation Phase (4 months):
Dosing Schedules
India has adopted WHO-recommended higher-dose intermittent therapy administered thrice weekly (2E₃H₃R₃Z₃, 4H₃R₃) under the Revised National TB Control Programme 1. This approach improves adherence through directly observed therapy where patients take medications under direct observation of a health worker 1.
Fixed-dose combinations (FDCs) containing two or three anti-tuberculosis medications are recommended as they minimize the opportunity for selective drug intake and improve compliance 1.
Extended Treatment Indications
Seven-month continuation phase (total 9 months) is required for:
- Cavitary pulmonary TB with positive sputum culture at 2 months 2
- Patients whose initial phase did not include pyrazinamide 2
- Patients receiving once-weekly isoniazid and rifapentine with positive culture at 2 months 2
Twelve-month treatment is indicated for:
Special Populations
Pregnancy and Lactation
All first-line drugs (rifampicin, isoniazid, ethambutol, pyrazinamide) can be used during pregnancy 1. Streptomycin must be avoided due to fetal ototoxicity 1. Prophylactic pyridoxine 10 mg/day should be given with isoniazid 1.
Diabetes Mellitus
The standard regimen is used, but strict glucose control is mandatory 1. Oral hypoglycemic doses may need to be increased due to rifampicin-induced metabolism 1. Prophylactic pyridoxine is indicated 1.
HIV Co-infection
Standard short-course chemotherapy is indicated, though relapse rates are higher 1. Rifampicin-containing regimens interact with protease inhibitors and NNRTIs 1. Options include:
- Postponing antiretroviral therapy until TB treatment completion 1
- Using efavirenz or saquinavir with ritonavir without dose adjustment 1
- Using non-rifampicin regimens (2SHEZ + 10HE) 1
Treatment should be for at least 9 months as directly observed therapy wherever possible 6.
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 drugs may be used but frequent monitoring of liver function tests is required 1.
Multidrug-Resistant TB (MDR-TB)
MDR-TB should be referred to specialized units with quality-controlled drug susceptibility testing 1. India reported 14% MDR-TB incidence in Delhi, with primary resistance of only 1.4%, indicating most cases result from poor chemotherapy adherence 1.
Treatment Principles
Drug selection must rely on prior treatment history, susceptibility testing results, and adherence evaluation 1. At least five effective drugs should be used in the intensive phase and four in the continuation phase 2.
Newer Regimens (Based on International Guidelines)
BPaLM Regimen (6 months):
- Bedaquiline, pretomanid, linezolid, moxifloxacin 2
- Not recommended for children under 14 years due to lack of pretomanid safety data 2
9-Month All-Oral Regimen:
- Intensive phase (4-6 months): Bedaquiline (6 months), fluoroquinolone, clofazimine, pyrazinamide, ethambutol, high-dose isoniazid, ethionamide or linezolid (2 months maximum) 2
- Continuation phase (5 months): Fluoroquinolone, clofazimine, pyrazinamide, ethambutol 2
- Preferred for patients without previous second-line drug exposure 2
Longer Regimens (18-20 months):
- Reserved for severe extrapulmonary TB, additional resistance to key medicines, lack of response to shorter regimens, or drug intolerance 2
Drug Recommendations for MDR-TB
Strongly recommended:
Conditionally recommended:
NOT recommended:
- Kanamycin or capreomycin 2
- Macrolides (azithromycin, clarithromycin) 2
- Amoxicillin-clavulanate (except with carbapenems) 2
Monitoring and Adherence
Diagnostic Requirements
At least three sputum samples should be examined (spot sample day 1, overnight sample, morning spot sample day 2) 1. Sputum smear positivity exceeds 90% when greater than 5 ml of sputum is used 1.
Culture is the gold standard, detecting 10-100 viable mycobacteria per ml with 81% sensitivity and 98.5% specificity 1. Drug susceptibility testing should be performed on all initial isolates from newly diagnosed patients 5.
Treatment Supervision
Directly Observed Therapy (DOTS) is essential to prevent drug resistance from non-compliance 3, 1. A major cause of drug-resistant tuberculosis is patient non-compliance 3.
Common Pitfalls
Arthralgia occurs in 45-70% of patients on pyrazinamide-containing regimens, but chemotherapy modification is needed in only 5-12% 7. Jaundice occurs in 7% of rifampicin-containing regimens versus 1% without rifampicin 7.
Never add a single drug to a failing regimen - this is unacceptable practice and promotes resistance 2. When resistance emerges, therapy must be changed to agents to which bacilli are susceptible 3.
Rifampicin causes discoloration (yellow, orange, red, brown) of teeth, urine, sweat, sputum, and tears 4. Soft contact lenses may be permanently stained 4.