What are the revised guidelines for tuberculosis (TB) treatment?

Revised TB Guidelines

Standard Treatment Regimen for Drug-Susceptible TB

The current standard treatment for drug-susceptible tuberculosis consists of a 6-month regimen: isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1, 2, 3

Intensive Phase (First 2 Months)

• Four-drug regimen: Isoniazid, rifampin, pyrazinamide, and ethambutol administered daily for 8 weeks 1, 2
• Alternative dosing: Daily for at least the first 2 weeks, followed by 2-3 times per week for 6 weeks to complete the 2-month induction phase 1
• Three-times-weekly option: All four drugs can be administered three times weekly for 6 months 1
• Fourth drug rationale: Ethambutol or streptomycin should be added until susceptibility to isoniazid and rifampin is demonstrated; the fourth drug is optional only if community isoniazid resistance is ≤4% 2

Continuation Phase (Months 3-6)

• Two-drug regimen: Isoniazid and rifampin administered daily or 2-3 times per week for 4 months 1, 2
• Minimum duration: At least 180 doses (one dose per day for 6 months) must be completed 1

Dosing Specifications

Adults: 2

• Isoniazid: 5 mg/kg up to 300 mg daily (or 15 mg/kg up to 900 mg twice or three times weekly)
• Rifampin: Standard dosing per protocol

Children: 2

• Isoniazid: 10-15 mg/kg up to 300 mg daily (or 20-40 mg/kg up to 900 mg twice or three times weekly)

Special Populations

HIV-Infected Patients

For HIV-infected patients receiving protease inhibitors or NNRTIs, rifabutin should replace rifampin in the standard 6-month regimen to avoid significant drug interactions. 1, 4

• Rifabutin-based regimen: Isoniazid, rifabutin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifabutin for 4 months 1, 4
• Rifabutin dose adjustments: 1
  • Decrease from 300 mg to 150 mg daily when used with indinavir, nelfinavir, or amprenavir
  • Increase from 300 mg to 450 mg when used with efavirenz
  • Twice-weekly dose remains 300 mg regardless of concurrent antiretroviral therapy
• Pyridoxine supplementation: 25-50 mg daily (or 50-100 mg twice weekly) must be administered to all HIV-infected patients on isoniazid to prevent peripheral neuropathy 1, 4
• ART timing: 4
  • CD4 <50 cells/mm³: Initiate ART within 2 weeks of starting TB treatment
  • CD4 >50 cells/mm³: Initiate ART within 8 weeks of starting TB treatment

Critical caveat: Rifampin's CYP450 induction effect persists for at least 2 weeks after discontinuation, requiring a 2-week washout period before starting protease inhibitors or NNRTIs 1

HIV-Infected Patients Without Antiretroviral Therapy

For HIV-infected patients not receiving antiretroviral therapy, the standard 6-month rifampin-based regimen remains the preferred option. 1

Pregnant Women

HIV-infected pregnant women with TB should be treated without delay using rifamycin-containing regimens. 1

• Treatment should not be delayed based on pregnancy alone, even during the first trimester 1

Drug-Resistant TB

Isoniazid-Resistant TB

The regimen should consist of rifamycin (rifampin or rifabutin), pyrazinamide, and ethambutol for 6-9 months or 4 months after culture conversion. 1

• Intermittent therapy (twice weekly) can be used after at least 2 weeks (14 doses) of daily therapy 1
• Isoniazid is generally stopped when resistance is confirmed, except in cases of low-level resistance where some experts continue isoniazid 1

Rifampin-Resistant TB

A 9-month regimen consisting of isoniazid, streptomycin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid, streptomycin, and pyrazinamide for 7 months. 1

Multidrug-Resistant TB (MDR-TB)

Patients with MDR-TB (resistant to both isoniazid and rifampin) must be managed by or in consultation with physicians experienced in MDR-TB treatment. 1

• Regimen components: Most regimens include an aminoglycoside (streptomycin, kanamycin, amikacin) or capreomycin, plus a fluoroquinolone 1
• Duration: 24 months after culture conversion 1
• Follow-up: Monitor every 4 months for 24 months post-treatment 1

Extrapulmonary TB

Standard Extrapulmonary TB

A 6-9 month short-course regimen is effective for most extrapulmonary TB. 2

Special Extrapulmonary Sites

Miliary TB, bone/joint TB, and tuberculous meningitis in infants and children require 12 months of therapy. 2

For tuberculous meningitis with headache or neurological symptoms: 5

• Four-drug regimen (rifampin, isoniazid, pyrazinamide, ethambutol/streptomycin) for at least 2 months
• Continue rifampin and isoniazid for a total of 12 months
• Corticosteroids are recommended for patients with cerebral TB, especially with increased intracranial pressure or neurological deficits 5
• If pyrazinamide is omitted, extend treatment to 18 months 5

Critical Implementation Principles

Directly Observed Therapy (DOT)

DOT should be used for all patients with HIV-related TB and is the standard of care for pulmonary TB. 1, 6

• All intermittent dosing regimens (twice or three times weekly) must be administered via DOT 2
• Virtual treatment monitoring using digital technologies is increasingly used as a patient-centered alternative 6

Drug Susceptibility Testing

Drug susceptibility testing must be performed on organisms initially isolated from all patients with newly diagnosed TB. 2

• If bacilli become resistant, therapy must be changed to agents to which the bacilli are susceptible 2

Monitoring Requirements

• HIV-infected patients: Assess CD4 counts and HIV viral load at least every 3 months 4
• Liver function: Regular monitoring is essential due to hepatotoxicity risk, particularly in HIV/hepatitis C co-infected patients (14-fold increased risk) 4
• TB response: Follow-up sputum microscopy and culture 4

Regimens to Avoid

Three-drug regimens without a rifamycin, aminoglycoside, or capreomycin should generally not be used for HIV-related TB; if used, minimum duration is 18 months (or 12 months after culture conversion). 1