What regimen can be followed for pulmonary tuberculosis (P.Tb) treatment in a patient intolerant to isoniazid (INH) and rifampicin (RIF) according to Indian guidelines?

From the Guidelines

For patients intolerant to both isoniazid (INH) and rifampicin (RIF), the recommended regimen for pulmonary tuberculosis treatment according to Indian guidelines is a combination of ethambutol, pyrazinamide, levofloxacin, and bedaquiline for 6-9 months, as per the latest World Health Organization (WHO) recommendations 1.

Key Considerations

• The intensive phase typically lasts for 2-3 months with all four drugs, followed by a continuation phase of 4-6 months with ethambutol, pyrazinamide, and levofloxacin.
• Dosing should be weight-based, with ethambutol at 15-20 mg/kg/day, pyrazinamide at 20-30 mg/kg/day, levofloxacin at 750-1000 mg/day, and bedaquiline at 400 mg/day for the first 2 weeks, then 200 mg three times a week 1.
• Regular monitoring is essential, including monthly sputum cultures, liver function tests, renal function tests, and electrocardiograms for patients on bedaquiline.

Rationale

• The absence of INH and RIF requires substitution with second-line medications, and the use of bedaquiline, a potent bactericidal agent, is recommended for patients aged ≥18 years 1.
• The fluoroquinolone (levofloxacin) provides bactericidal activity, while bedaquiline adds potency during the intensive phase.
• Treatment duration may need extension based on clinical and microbiological response.

Important Notes

• Kanamycin and capreomycin are not recommended for use in longer MDR-TB regimens 1.
• Linezolid should be included in the treatment of MDR/RR-TB patients on longer regimens, but its use is not recommended as a first-line agent in this scenario 1.
• Ethambutol may be included in the treatment of MDR/RR-TB patients on longer regimens, but its use should be based on individual patient needs and susceptibility patterns 1.

From the Research

Treatment Regimen for Pulmonary Tuberculosis (P.Tb) in Patients Intolerant to Isoniazid and Rifampicin

According to Indian guidelines, the treatment regimen for P.Tb in patients intolerant to isoniazid (INH) and rifampicin (RIF) is not explicitly stated in the provided studies. However, some studies suggest alternative treatment options:

• A study published in 2022 2 investigated the clinical relevance of rifampicin-moxifloxacin interaction in isoniazid-resistant/intolerant tuberculosis patients. The study found that moxifloxacin exposure was decreased when co-administered with rifampicin, but increasing the dose of moxifloxacin may compensate for this interaction.
• Another study published in 2025 3 compared the effects of rifampicin plus levofloxacin or isoniazid on immune function in patients with pulmonary tuberculosis. The study found that rifampicin plus levofloxacin had a better clinical effect and could effectively regulate patients' immune functions and inhibit inflammatory reactions.

Alternative Treatment Options

Some possible alternative treatment options for P.Tb in patients intolerant to INH and RIF include:

• Moxifloxacin-based regimens, as suggested by the study published in 2022 2
• Levofloxacin-based regimens, as suggested by the study published in 2025 3
• Other fluoroquinolone-based regimens, as mentioned in the study published in 2018 4

Key Considerations

When selecting an alternative treatment regimen, key considerations include:

• The patient's specific intolerance or resistance pattern to INH and RIF
• The potential for drug-drug interactions, such as the interaction between rifampicin and moxifloxacin
• The patient's overall health status and potential comorbidities
• The availability and accessibility of alternative treatment options in the patient's region.