What is the recommended Anti-Tuberculosis Treatment (ATT) regimen according to newer guidelines?

Current Anti-Tuberculosis Treatment (ATT) Regimen Guidelines

According to the most recent guidelines, the recommended ATT regimen for drug-susceptible tuberculosis is a 4-month regimen consisting of rifapentine, isoniazid, pyrazinamide, and moxifloxacin for eligible persons aged 12 years and older with pulmonary TB, while a 6-month regimen of daily rifampin, ethambutol, pyrazinamide, plus a later-generation fluoroquinolone (levofloxacin or moxifloxacin) is recommended as an alternative. 1

Drug-Susceptible TB Treatment

Standard First-Line Regimen

• Initial Phase (2 months):

  • 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 2g daily)
  • Ethambutol (15 mg/kg daily) 1, 2

• Continuation Phase (4 months):

  • Isoniazid and Rifampin daily 1, 2

Key Administration Considerations

• Rifampin should be administered once daily, either 1 hour before or 2 hours after meals with a full glass of water 2
• Pyridoxine supplementation (25 mg/day) is recommended for all patients taking isoniazid to prevent peripheral neuropathy 1
• Daily therapy is preferred for optimal outcomes 1
• Fixed-dose combinations (FDCs) should be used whenever possible to improve adherence 1
• Directly observed therapy (DOT) is strongly recommended to ensure adherence 1

Drug-Resistant TB Treatment

Isoniazid-Resistant TB

• Add a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 3
• Pyrazinamide can be shortened to 2 months in selected situations (non-cavitary disease, lower burden disease, or toxicity) 3

MDR-TB Treatment

The World Health Organization recommends prioritizing drugs into three groups:

• Group A (include all three drugs):

  • Levofloxacin/Moxifloxacin
  • Bedaquiline
  • Linezolid 1

• Group B (add one or both drugs):

  • Clofazimine
  • Cycloserine/Terizidone 1

• Group C (add to complete regimen when drugs from Groups A and B cannot be used):

  • Ethambutol
  • Delamanid
  • Pyrazinamide
  • Imipenem-cilastatin/Meropenem
  • Amikacin/Streptomycin
  • Ethionamide/Prothionamide
  • p-aminosalicylic acid 1

Drugs to Avoid in MDR-TB Regimens

• Kanamycin or capreomycin 3
• Ethionamide/prothionamide if more effective drugs are available 3
• p-aminosalicylic acid if more effective drugs are available 3
• Macrolides (azithromycin, clarithromycin) 3, 1

Special Populations

HIV Co-infection

• Same basic regimens as for HIV-negative patients, with consideration of drug interactions between rifamycins and antiretroviral agents 1
• Regular monitoring of treatment response is critical; if there is evidence of a slow or suboptimal response, therapy should be prolonged on a case-by-case basis 1

Children

• Same regimens as adults with appropriate dose adjustments 1
• Ethambutol should be used with caution in children under 6 years old 1

Extrapulmonary TB

• The standard 6-month regimen is generally sufficient 1
• Extended treatment (9-12 months) is recommended for TB meningitis, bone/joint TB, and miliary TB 1
• Corticosteroids should be added for CNS tuberculomas to decrease neurological sequelae 1

Treatment Monitoring

• Monthly clinical evaluations to assess treatment response and adverse effects 1
• Baseline liver function tests before starting treatment 1
• Regular monitoring of liver function if baseline tests are abnormal or if symptoms develop 1

Pitfalls and Caveats

• Inadequate initial regimen, poor adherence, premature discontinuation, overlooking drug interactions, and inadequate monitoring can all lead to treatment failure 1
• If drug resistance is suspected or confirmed, at least two additional agents to which the organism is likely to be susceptible should be added to the treatment regimen 1
• Treatment interruptions require careful consideration; interruptions during the initial phase are more serious 1
• For MDR-TB, mortality may be reduced by including five likely effective drugs during the intensive phase of treatment 4
• If pyrazinamide is unlikely to be effective in an individual patient with MDR-TB, adding a different, likely effective drug is recommended 4

The evolution of TB treatment guidelines reflects ongoing efforts to optimize treatment duration, improve adherence, and address the growing challenge of drug resistance, with the ultimate goal of reducing morbidity and mortality while improving quality of life for patients with tuberculosis.