What is the recommended treatment regimen for tuberculosis (TB) according to the latest guidelines?

Latest TB Treatment Guidelines

The recommended standard treatment regimen for drug-susceptible tuberculosis (TB) is a 4-month regimen consisting of rifapentine, isoniazid, pyrazinamide, and moxifloxacin, as conditionally recommended by the WHO in 2022 for eligible persons aged 12 years and older with pulmonary TB. 1

Drug-Susceptible TB Treatment

First-Line Regimens

1. 4-month regimen (newest recommendation):

   • Rifapentine + isoniazid + pyrazinamide + moxifloxacin
   • For eligible persons aged ≥12 years with pulmonary TB 1

2. Standard 6-month regimen:

   • Intensive phase (2 months): Isoniazid + rifampin + pyrazinamide + ethambutol
   • Continuation phase (4 months): Isoniazid + rifampin
   • This remains the standard for most patients 2

Dosing for Adults (Standard 6-month regimen)

• Isoniazid: 5 mg/kg (up to 300 mg) daily
• Rifampin: 10 mg/kg (up to 600 mg) daily
• Pyrazinamide: 15-30 mg/kg (up to 2 g) daily
• Ethambutol: 15 mg/kg daily 3

Important Considerations

• Pyridoxine (25 mg/day) should be given with isoniazid to prevent peripheral neuropathy 3
• Daily therapy is strongly preferred over intermittent dosing for optimal outcomes 3
• Fixed-dose combinations should be used when possible to improve adherence 3
• Directly observed therapy (DOT) is strongly recommended to ensure adherence 3

Drug-Resistant TB Treatment

Isoniazid-Resistant TB

• Recommended regimen: 6 months of daily rifampin, ethambutol, pyrazinamide, plus a later-generation fluoroquinolone (levofloxacin or moxifloxacin) 1
• In selected situations (noncavitary disease, low bacterial burden, or pyrazinamide toxicity), pyrazinamide may be shortened to 2 months 1

Multidrug-Resistant TB (MDR-TB)

Shorter MDR-TB Regimen (9-11 months)

For patients who:

• Have no previous exposure to second-line TB drugs >1 month
• No fluoroquinolone resistance
• No extensive pulmonary disease or severe extrapulmonary TB
• Not pregnant
• Age appropriate 1

Regimen structure:

• Intensive phase (4-6 months): Bedaquiline (6 months) + levofloxacin/moxifloxacin + clofazimine + pyrazinamide + ethambutol + high-dose isoniazid + ethionamide
• Continuation phase (5 months): Levofloxacin/moxifloxacin + clofazimine + pyrazinamide + ethambutol 1

Longer MDR-TB Regimen (18 months)

For patients with:

• Extensive pulmonary disease
• Severe extrapulmonary TB
• Additional resistance to fluoroquinolones
• Previous exposure to second-line medicines >1 month 1

Drug prioritization for building a regimen:

• Group A (include all three): Levofloxacin/moxifloxacin, bedaquiline, linezolid
• Group B (add at least one): Clofazimine, cycloserine/terizidone
• Group C (add when needed): Ethambutol, delamanid, pyrazinamide, imipenem-cilastatin/meropenem, amikacin/streptomycin, ethionamide/prothionamide, p-aminosalicylic acid 1

Important recommendations:

• Do NOT include amoxicillin-clavulanate (except with carbapenems) 1
• Do NOT include macrolides (azithromycin, clarithromycin) 1
• Do NOT include ethionamide/prothionamide or p-aminosalicylic acid if more effective drugs are available 1
• Do NOT include kanamycin or capreomycin 1

Special Populations

HIV Co-infection

• Same basic regimens as for HIV-negative patients
• Avoid once-weekly isoniazid-rifapentine in continuation phase
• Avoid twice-weekly isoniazid-rifampin/rifabutin in patients with CD4+ counts <100 cells/mm³ 1
• Consider drug interactions between rifamycins and antiretroviral agents 1

Children

• Same regimens as adults with appropriate dose adjustments
• Ethambutol should be used with caution in children whose visual acuity cannot be monitored (typically under 6 years) 3
• For disseminated TB and TB meningitis, treat for 9-12 months 1

Extrapulmonary TB

• Most forms can be treated with the same 6-month regimen as pulmonary TB
• Extended treatment (9-12 months) recommended for TB meningitis, bone/joint TB, and miliary TB 1, 3
• Consider adding corticosteroids for tuberculous pericarditis or meningitis 1

Common Pitfalls and Caveats

1. Inadequate initial regimen: Always include at least 4 effective drugs for drug-susceptible TB and more for drug-resistant TB

2. Poor adherence monitoring: Use directly observed therapy whenever possible to ensure compliance

3. Premature discontinuation: Complete the full recommended course even if symptoms improve quickly

4. Treatment interruptions: More serious if they occur early in treatment or are longer in duration; may require restarting therapy from the beginning 1

5. Drug resistance development: Regular monitoring of treatment response is essential; consider drug susceptibility testing if treatment is failing

6. Overlooking drug interactions: Particularly important with rifamycins and HIV medications

7. Inadequate monitoring: Regular clinical and laboratory monitoring is essential, including monthly clinical evaluations and appropriate liver function tests 3