What is the typical treatment schedule for pulmonary tuberculosis (PTB)?

Treatment Schedule for Pulmonary Tuberculosis

For drug-susceptible pulmonary tuberculosis, treat with a 2-month intensive phase of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) given daily, followed by a 4-month continuation phase of isoniazid and rifampin (HR) given daily or intermittently under directly observed therapy, for a total treatment duration of 6 months. 1, 2

Initial Intensive Phase (First 2 Months)

Four-drug regimen:

• Isoniazid, rifampin, pyrazinamide, and ethambutol should be administered for the first 2 months 1, 2
• Ethambutol can be discontinued once drug susceptibility testing confirms the organism is susceptible to both isoniazid and rifampin 1
• This is particularly relevant when the community prevalence of isoniazid resistance is ≤4% 1, 3

Dosing frequency options for the intensive phase:

• Daily administration for 8 weeks (Regimen 1) - this is the preferred approach and rated as "A" evidence 1, 2
• Daily for 2 weeks, then twice weekly for 6 weeks (Regimen 2) - rated as "A" evidence 1
• Three times weekly throughout (Regimen 3) - rated as "B" evidence 1

Continuation Phase (Next 4 Months)

Two-drug regimen:

• Isoniazid and rifampin for 4 months (18 weeks) 1, 2

Dosing frequency options for the continuation phase:

• Daily administration (Regimen 1a) - preferred approach, rated as "A" evidence 1, 2
• Twice weekly under directly observed therapy (Regimen 1b) - rated as "A" evidence 1, 2
• Three times weekly under directly observed therapy (Regimen 3a) - rated as "B" evidence 1, 2

When to Extend Treatment to 9 Months

The continuation phase must be extended to 7 months (total 9 months of treatment) in three specific situations: 1

1. Cavitary pulmonary TB with positive sputum culture at 2 months: Patients with cavitary disease on chest radiograph who remain culture-positive after completing the 2-month intensive phase 1

2. Initial phase without pyrazinamide: Patients whose initial treatment regimen did not include pyrazinamide (Regimen 4) - this applies when pyrazinamide is contraindicated due to severe liver disease, gout, or possibly pregnancy 1

3. Once-weekly continuation phase with positive culture at 2 months: Patients receiving once-weekly isoniazid and rifapentine who have positive sputum culture at completion of the intensive phase 1

Special Populations

HIV-Positive Patients on Antiretroviral Therapy

• Use the standard 6-month daily regimen (2 months HRZE, then 4 months HR) when receiving ART 1
• Avoid intermittent (twice-weekly or once-weekly) regimens - these are associated with high relapse rates and rifamycin resistance, especially in patients with CD4 counts <100 cells/μL 1, 2

HIV-Positive Patients NOT on Antiretroviral Therapy

• Extend the continuation phase to 7 months (total 9 months of treatment) 1
• Minimum treatment duration should be 9 months with at least 6 months beyond documented culture conversion 2

Pregnant Women

• Use the standard regimen of isoniazid, rifampin, pyrazinamide, and ethambutol 3
• Avoid streptomycin - causes congenital deafness due to in utero ear development interference 3
• Add prophylactic pyridoxine 10 mg daily 4

Directly Observed Therapy (DOT)

DOT is the standard of practice and should be used: 2

• For all intermittent regimens (twice-weekly or three times weekly) 1, 2
• When medications are administered less than 7 days per week 2
• Drugs may be given 5 days per week with appropriate dose adjustments when using DOT 1, 2

Monitoring Requirements

During treatment, patients require: 2

• Medical assessment at least twice monthly until asymptomatic and smear-negative 2
• Monthly sputum cultures until negative 2
• Sputum conversion should occur within 3 months - if not, evaluate for non-adherence and drug resistance 2

Critical Pitfalls to Avoid

Never add a single drug to a failing regimen - this leads to further drug resistance 2, 4

Do not use shortened 4-month regimens - recent high-quality evidence from multiple randomized trials demonstrates that fluoroquinolone-containing 4-month regimens (whether using moxifloxacin or gatifloxacin) substantially increase relapse rates compared to standard 6-month treatment (RR 3.56 for moxifloxacin, RR 2.11 for gatifloxacin) 5

Avoid once-weekly continuation phase therapy - this is strongly recommended against except in very limited circumstances (HIV-negative, non-cavitary disease, negative cultures at 2 months) 1

For patients on methadone receiving rifampin - increase methadone dosage to prevent withdrawal symptoms due to drug interactions 2

Treatment interruptions require specific management: 1

• If interruption during intensive phase is <14 days: continue to complete planned doses within 3 months 1
• If interruption during intensive phase is ≥14 days: restart treatment from the beginning 1
• If interruption during continuation phase with <80% of doses received and lapse ≥3 months: restart entire treatment from the beginning 1