What is the typical treatment regimen for pulmonary tuberculosis?

Treatment of Pulmonary Tuberculosis

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

Initial Phase (First 2 Months)

Four-drug therapy is essential during the intensive phase:

• Administer isoniazid, rifampin, pyrazinamide, and ethambutol together daily for 8 weeks 1, 2
• Ethambutol can be omitted only if drug susceptibility testing confirms isoniazid resistance is less than 4% in your community AND the patient has no risk factors for drug resistance 1, 2
• This intensive phase rapidly kills tubercle bacilli and renders patients non-infectious within weeks 1

Dosing for adults:

• Isoniazid: 5 mg/kg (maximum 300 mg) daily 2
• Rifampin: 10 mg/kg daily 1
• Pyrazinamide: 25 mg/kg daily 1
• Ethambutol: 15 mg/kg daily 1

Continuation Phase (Months 3-6)

Two-drug therapy for most patients:

• Isoniazid and rifampin daily for 4 additional months (total treatment duration: 6 months) 1
• This applies to patients with non-cavitary disease who have negative sputum cultures at 2 months 1

Extended continuation phase (7 months total, for 9 months treatment) is required for:

• Cavitary pulmonary tuberculosis on initial chest radiograph with positive sputum culture at 2 months 1
• Patients whose initial phase did not include pyrazinamide 1

Alternative Dosing Schedules

Intermittent therapy options (all require directly observed therapy):

• Option 1: Daily therapy for 2 weeks, then twice-weekly for 6 weeks in intensive phase, followed by twice-weekly for 16 weeks in continuation phase 1, 2
• Option 2: Three times weekly throughout entire 6-month treatment 1, 2
• When using intermittent dosing, increase doses: isoniazid to 15 mg/kg (twice weekly) or 10 mg/kg (three times weekly), pyrazinamide to 50 mg/kg (twice weekly) or 35 mg/kg (three times weekly) 1

Critical Monitoring Requirements

Obtain baseline testing before treatment:

• Medical history, physical examination, chest x-ray, tuberculin skin test 1
• At least three sputum specimens for acid-fast bacilli smear, culture, and drug susceptibility testing 1
• HIV antibody testing and counseling 1
• Baseline liver function tests if patient has risk factors for hepatotoxicity 1

During treatment:

• Monthly sputum cultures until two consecutive negatives are documented 3
• Expect sputum conversion within 2-3 months; if not achieved, evaluate for non-adherence and drug resistance 3
• Monitor for adverse effects, particularly hepatotoxicity with rifampin, isoniazid, and pyrazinamide 1

Special Populations

HIV-Positive Patients

• Use the same 6-month regimen as HIV-negative patients 1, 2
• Never use once-weekly isoniazid-rifapentine in the continuation phase 1
• Avoid twice-weekly dosing if CD4+ count is less than 100 cells/mm³ 1
• Consider extending treatment to 9 months due to potentially impaired immune response 2
• Screen for drug malabsorption, especially in advanced HIV disease 1

Pregnant Women

• Initiate standard treatment whenever tuberculosis is suspected due to risk to the fetus 1, 2
• Use isoniazid, rifampin, pyrazinamide, and ethambutol safely 1
• Avoid streptomycin—it is ototoxic to the fetus 1
• Breastfeeding is safe while on first-line antituberculosis medications 1
• Counsel about reduced oral contraceptive effectiveness with rifampin 1

Children

• Use the same 6-month regimen as adults: rifampin and isoniazid for 6 months, supplemented by pyrazinamide for first 2 months 1
• Dosing: isoniazid 10-15 mg/kg (maximum 300 mg) daily, rifampin 10 mg/kg daily 1, 2
• Ethambutol can be used in children age 5 years or older at 15 mg/kg/day; use cautiously in younger children only if visual acuity can be monitored 1
• Pyridoxine supplementation only needed for breastfed infants and malnourished children 1

Renal Disease

• Rifampin, isoniazid, and pyrazinamide can be given in standard doses 1
• For patients on hemodialysis, administer all medications after dialysis to avoid premature drug removal 1

Liver Disease

• Standard regimen can still be used despite potential hepatotoxicity of rifampin, isoniazid, and pyrazinamide 1
• Perform weekly liver function tests for first 2 weeks, then every 2 weeks during initial phase 1
• Monitor closely for drug-induced liver damage 1

Recurrent or Previously Treated Tuberculosis

Assume drug resistance until proven otherwise:

• Start with at least 4-5 drugs that the patient has NOT received previously, including a fluoroquinolone if available 3
• Obtain drug susceptibility testing immediately for isoniazid, rifampin, pyrazinamide, and fluoroquinolones 3
• Never add a single drug to a failing regimen—this creates further resistance 3
• Implement directly observed therapy for all recurrent cases 3

Common Pitfalls to Avoid

Treatment interruptions:

• Continuous treatment is more critical in the initial phase than continuation phase 1
• If interruption occurs early or is prolonged, consider restarting therapy from the beginning 1

Shortened regimens:

• Do not use 4-month fluoroquinolone-containing regimens—they substantially increase relapse rates compared to standard 6-month treatment 4
• Four-month regimens replacing ethambutol with moxifloxacin or gatifloxacin increase relapse by 2-3 fold 4

Isoniazid-resistant tuberculosis:

• Can still use isoniazid in a 6-month four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) with successful outcomes 5
• This approach produced no treatment failures and minimal relapse in clinical practice 5

Directly observed therapy (DOT):

• Implement DOT for all intermittent regimens, HIV-positive patients, and recurrent cases 1, 3
• DOT improves adherence and treatment success, particularly in high-risk populations 1