What are the RNTCP (Revised National Tuberculosis Control Programme) guidelines for treating tuberculosis?

RNTCP (Revised National Tuberculosis Control Programme) Guidelines for Tuberculosis Treatment

Drug-Susceptible Pulmonary Tuberculosis

The standard treatment for drug-susceptible TB under RNTCP is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 2 months, followed by isoniazid and rifampin (HR) for 4 months, administered daily. 1, 2

Initial Phase (First 2 Months)

• Four-drug regimen: Isoniazid, rifampin, pyrazinamide, and ethambutol given daily 3, 1
• Dosing for adults: Rifampin 450 mg daily for patients <50 kg, 600 mg daily for patients ≥50 kg 2, 4
• Dosing for children: Isoniazid 10-15 mg/kg (max 300 mg), rifampin 10-20 mg/kg (max 600 mg) daily 4, 5
• Ethambutol can be discontinued once drug susceptibility testing confirms susceptibility to isoniazid and rifampin, particularly in low-risk patients 1, 2

Continuation Phase (Months 3-6)

• Two-drug regimen: Isoniazid and rifampin given daily for 4 months 3, 1
• Total treatment duration is 6 months for most pulmonary TB cases 3

Critical Implementation Points

• Directly Observed Therapy (DOT) is strongly recommended for all TB patients to prevent treatment failure and drug resistance 3, 1
• Administer rifampin 1 hour before or 2 hours after meals with a full glass of water 4
• HIV testing should be offered to all newly diagnosed TB patients 3, 1
• Immediate reporting of all TB cases to local public health departments is mandatory 3, 1

Special Populations

HIV-Infected Patients

• Use the same 6-month standard regimen (2 months HRZE, 4 months HR) 1, 2
• Add pyridoxine (vitamin B6) 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent neurologic side effects 1, 2
• Be aware of significant drug interactions between rifampin and antiretroviral therapy 3, 2

Pregnant Women

• Standard regimen can be used, but streptomycin is absolutely contraindicated as it causes congenital deafness 2
• For drug-resistant TB in pregnancy, avoid ethionamide and use linezolid-based regimens 2

Drug-Resistant Tuberculosis

Multidrug-Resistant TB (MDR-TB)

For MDR/RR-TB without fluoroquinolone resistance, the WHO now recommends a 6-month all-oral BPaLM regimen (bedaquiline, pretomanid, linezolid 600 mg, and moxifloxacin) as the preferred treatment. 3, 2

BPaLM Regimen (First-Line for Eligible MDR-TB)

• Duration: 6 months (26 weeks) 3, 2
• Composition: Bedaquiline + pretomanid + linezolid + moxifloxacin 3, 2
• Eligibility criteria: MDR/RR-TB or pre-XDR-TB confirmed, no fluoroquinolone resistance, excludes CNS TB, miliary TB, and osteoarticular TB 3, 2

Alternative 9-Month Regimen

• For patients with MDR/RR-TB who cannot take BPaLM due to intolerance, drug interactions, or exclusion criteria 3
• Use bedaquiline-containing all-oral regimen for 9 months 3, 2

Longer 18-Month Regimens

• At least 5 effective drugs in the intensive phase and 4 drugs in the continuation phase 3, 6
• Core drugs: Bedaquiline, later-generation fluoroquinolone (levofloxacin or moxifloxacin), linezolid, and clofazimine 3, 6
• Additional drugs may include cycloserine, ethambutol, pyrazinamide, ethionamide, or carbapenems 6
• Intensive phase lasts 5-7 months after culture conversion 6
• Total duration: 15-21 months after culture conversion 6

Isoniazid-Resistant TB

• 6-month regimen: Rifampin, ethambutol, pyrazinamide, plus a later-generation fluoroquinolone 6
• Pyrazinamide can be shortened to 2 months in noncavitary, lower-burden disease 6

Monitoring and Safety

Hepatotoxicity Monitoring

• Monitor liver function tests monthly, especially during the first 2 months, as hepatotoxicity is the most common serious adverse event 1, 2
• Baseline and periodic monitoring of liver enzymes is essential 3, 2

Additional Monitoring for Drug-Resistant TB

• QTc monitoring for patients receiving bedaquiline, delamanid, or fluoroquinolones 2
• Monthly assessments of weight, adherence, symptom improvement, and side effects 1
• Consider rifampin blood level monitoring if poor response suggests under-dosing or malabsorption 2

Treatment Interruptions

• Interruption <14 days: Continue treatment to complete the planned total dose 1
• Interruption ≥14 days: Restart treatment from the beginning 1
• Patients should complete 90% of doses within the first 6 months, though all should receive evaluation if this target is not met 3

Common Pitfalls and Caveats

Critical Errors to Avoid

• Never use fewer than 5 effective drugs in MDR-TB intensive phase—this leads to treatment failure and further resistance 6
• Do not use 2 months of rifampin plus pyrazinamide for latent TB due to severe hepatotoxicity risk 3
• Avoid ethambutol in young children whose visual acuity cannot be monitored 5
• Do not ignore drug interactions between rifampin and oral contraceptives, anticoagulants, and antiretroviral drugs 2

Post-Treatment Follow-Up

• RNTCP historically has not systematically followed patients after treatment completion 7
• Studies show 10% relapse rate in previously treated patients, highlighting the need for post-treatment surveillance 7
• Consider follow-up sputum examination in high-risk patients even after successful treatment completion 7

Adherence Challenges

• Nonadherence is the main reason for treatment failure and drug resistance development 3
• DOT significantly reduces drug-resistant TB rates and relapse 3
• High-risk groups (injection drug users, alcoholics, homeless persons) require intensive DOT efforts 3