What is the recommended treatment regimen for pulmonary tuberculosis?

Treatment of Pulmonary Tuberculosis

For drug-susceptible pulmonary tuberculosis, treat with a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1, 2, 3

Standard First-Line Regimen

Intensive Phase (First 2 Months)

• Four drugs daily: Isoniazid, rifampin, pyrazinamide, and ethambutol 1, 2, 3
• Ethambutol (or streptomycin in young children) must be included until drug susceptibility results confirm susceptibility to isoniazid and rifampin 1, 3
• The fourth drug can be omitted only if primary isoniazid resistance is less than 4% in your community AND the patient has no prior TB treatment, no exposure to drug-resistant cases, and is not from a high-prevalence drug-resistance country 3

Continuation Phase (Months 3-6)

• Two drugs: Isoniazid and rifampin daily for 4 additional months 1, 2, 3
• Extend to 7 months (total 9 months) if cavitary disease is present on initial chest radiograph OR if sputum cultures remain positive at 2 months 4, 3

Dosing

Adults: 2

• Isoniazid: 5 mg/kg (maximum 300 mg) daily
• Rifampin: 10 mg/kg (maximum 600 mg) daily
• Pyrazinamide: Per weight-based dosing 5
• Ethambutol: 15 mg/kg daily 1

Children: 2

• Isoniazid: 10-15 mg/kg (maximum 300 mg) daily
• Rifampin: Weight-based dosing
• Pyrazinamide: Per weight-based dosing 5
• Avoid ethambutol in children whose visual acuity cannot be monitored 2

Alternative Dosing Schedules

Intermittent Therapy Options

All intermittent regimens require directly observed therapy (DOT) 1, 6

Option 1: Daily therapy for 2 weeks, then twice-weekly for 6 weeks (same four drugs), followed by twice-weekly isoniazid and rifampin for 16 weeks 1

Option 2: Three times weekly throughout entire 6 months with isoniazid, rifampin, pyrazinamide, and ethambutol 1, 7

Note: When drugs are given twice or three times weekly, doses must be increased (isoniazid 15 mg/kg up to 900 mg; rifampin remains the same) 1, 2

Critical Monitoring Requirements

Bacteriologic Response

• Obtain sputum smears and cultures monthly until two consecutive negatives are documented 4
• Sputum should convert to negative by 3 months 1, 4
• If smear-positive at 3 months: Immediately evaluate for non-adherence or drug resistance 1, 4

Drug Susceptibility Testing

• Obtain at baseline on all initial isolates for isoniazid, rifampin, pyrazinamide, and ethambutol 1
• Adjust regimen based on susceptibility results 1, 3

Special Situations

Isoniazid-Resistant TB

• Use rifampin, ethambutol, and pyrazinamide for 6 months if only isoniazid resistance is present 1
• Add a fluoroquinolone to this regimen for enhanced efficacy 1

Rifampin-Resistant or Multidrug-Resistant TB

• Requires at least 18-24 months of therapy with individualized regimens based on susceptibility 1
• Consult a TB expert immediately 1, 4
• Consider newer regimens including bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM regimen) for eligible MDR-TB patients 4

Recurrent TB

• Assume drug resistance until proven otherwise 4
• Start at least 4-5 drugs the patient has NOT received previously, including a fluoroquinolone 4
• Never add a single drug to a failing regimen—this creates further resistance 4
• Obtain immediate drug susceptibility testing including molecular testing for resistance 4

HIV Co-infection

• Use the same 6-month regimen as for HIV-negative patients 3
• Monitor response closely—if slow or suboptimal response, extend therapy on a case-by-case basis 3
• Screen for malabsorption and consider drug level monitoring in advanced HIV disease 6

Pregnancy

• Use isoniazid, rifampin, and ethambutol 2
• Avoid pyrazinamide due to inadequate teratogenicity data 2
• Never use streptomycin—causes congenital deafness 2

Directly Observed Therapy (DOT)

All patients with TB should receive DOT 1, 4, 6, 3

• DOT means a healthcare provider or responsible person directly watches the patient swallow medications 1
• Non-adherence is the primary cause of treatment failure and drug resistance 1, 6
• Physicians cannot reliably predict which patients will adhere 1
• Virtual DOT using digital technologies is increasingly acceptable for patient-centered care 6

Common Pitfalls to Avoid

• Never treat with fewer than 4 drugs initially when drug resistance prevalence exceeds 4% or risk factors are present 1, 3
• Never shorten therapy to less than 6 months for drug-susceptible disease—recent trials show fluoroquinolone-containing 4-month regimens increase relapse rates substantially (RR 3.56) 8
• Never continue a failing regimen—if cultures remain positive at 3 months, reassess immediately 1, 4
• Never add a single drug to a failing regimen—always add at least two drugs to which the organism has not been exposed 4
• Never assume completion of 6 months of calendar time equals adequate therapy—gaps in treatment require extension of the regimen 1