What is the recommended treatment regimen for drug-sensitive tuberculosis in India?

Treatment of Drug-Sensitive Tuberculosis in India

For drug-sensitive pulmonary tuberculosis in India, use the standard 6-month regimen: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE) followed by 4 months of isoniazid and rifampin (4HR), administered daily or thrice weekly under directly observed therapy. 1, 2, 3

Standard First-Line Regimen

Intensive Phase (First 2 Months)

• Four-drug combination: Isoniazid (H), Rifampin (R), Pyrazinamide (Z), and Ethambutol (E) 1, 2, 3
• Dosing for adults:
  • Isoniazid: 5 mg/kg (maximum 300 mg daily) 1, 2
  • Rifampin: 10 mg/kg (maximum 600 mg daily) 1
  • Pyrazinamide: 35 mg/kg daily for patients <50 kg or 2.0 g daily for patients ≥50 kg 1
  • Ethambutol: 15 mg/kg daily 1
• Ethambutol can be discontinued once drug susceptibility testing confirms susceptibility to both isoniazid and rifampin 1

Continuation Phase (Months 3-6)

• Two-drug combination: Isoniazid and Rifampin only 1, 2
• Continue same dosing as intensive phase 1

Dosing Frequency Options

• Daily administration is preferred 4
• Thrice-weekly intermittent therapy (2E₃H₃R₃Z₃, 4H₃R₃) is an acceptable alternative advocated by WHO and implemented by India's Revised National TB Control Programme 4
• All intermittent regimens must be given by directly observed therapy 2, 4

Critical Implementation Requirements

Directly Observed Therapy (DOT)

• DOT is mandatory for all TB patients to ensure treatment completion and prevent drug resistance 1, 4
• The patient must take medications under direct observation by a healthcare worker 4
• Fixed-dose combinations (FDCs) provide a realistic alternative that minimizes selective medication taking 4

Drug Susceptibility Testing

• Perform DST on all initial isolates before finalizing the regimen 1
• Modify the regimen appropriately once susceptibility results become available 1
• If primary isoniazid resistance is documented to be <4% in the region, ethambutol may be omitted initially 4

Pyridoxine Supplementation

• Add pyridoxine 25-50 mg daily (or 10 mg/day per Indian guidelines) for patients at risk of neuropathy 1, 4
• High-risk groups include: pregnant women, breastfeeding infants, HIV-positive patients, diabetics, and patients with chronic renal failure 1, 4

Special Populations

Pregnancy

• Use the standard four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) 1, 4
• Avoid streptomycin due to fetal ototoxicity 1, 4
• Mandatory pyridoxine supplementation at 10 mg/day 4

Diabetes Mellitus

• Same drug regimen as non-diabetics 4
• Strict blood glucose control is mandatory 4
• Increase doses of oral hypoglycemic agents due to rifampin interaction 4
• Prophylactic pyridoxine is indicated 4

Renal Failure

• Adjust dosages according to creatinine clearance, especially for streptomycin, ethambutol, and isoniazid 4
• In acute renal failure, give ethambutol 8 hours before hemodialysis 4

Pre-existing Liver Disease

• If liver enzymes are normal, all anti-tuberculous drugs may be used 4
• Frequent monitoring of liver function tests is required 4

HIV Co-infection

• Use the standard 6-month regimen 4, 5
• Treatment duration may need extension beyond 6 months in patients with concomitant HIV infection 2, 6
• Response is usually good but relapse is more frequent 4
• Watch for "paradoxical response" or "immune reconstitution phenomenon" after initiating therapy 4
• Avoid rifampin with protease inhibitors (PI) or NNRTIs due to drug interactions; consider efavirenz or saquinavir with ritonavir without dose adjustment 4

Common Pitfalls to Avoid

Inadequate Treatment Duration

• Never use 3-month regimens - they result in 20% relapse rates compared to 4% with 5-month continuation phases 7, 8
• The minimum total treatment duration is 6 months for drug-sensitive disease 1, 4

Streptomycin Misuse

• Streptomycin is NOT part of the standard first-line regimen for drug-sensitive TB in the modern era 1
• When used (in drug-resistant cases), maximum total dose should not exceed 120 g over the entire course 6
• Reduce dosage in patients >60 years due to increased toxicity risk 6

Monitoring Compliance

• Use urine testing (Potts-Cozart test or isoniazid test strips) to verify patient compliance 2
• Poor compliance is the major cause of drug-resistant tuberculosis 2, 4

Arthralgia Management

• Arthralgia complaints occur in 45-70% of patients on pyrazinamide-containing regimens 7
• However, chemotherapy modification is needed in only 5-12% of cases 7
• Do not prematurely discontinue pyrazinamide for mild arthralgia 7

Extrapulmonary Tuberculosis

• Use the same 6-month regimen as for pulmonary disease 1
• Exception: Consider 12-month therapy for miliary TB, bone/joint TB, and tuberculous meningitis in infants and children due to insufficient data 2
• Adjunctive corticosteroids are beneficial for tuberculous pericarditis and meningitis 2
• Surgery may be necessary for constrictive pericarditis and spinal cord compression 2