What are the treatment guidelines for pulmonary tuberculosis (TB)?

Treatment Guidelines for Pulmonary Tuberculosis

For drug-susceptible pulmonary TB, the standard treatment is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1

Initial Treatment Regimen for Drug-Susceptible TB

Intensive Phase (First 2 Months)

• Four-drug regimen is mandatory: Isoniazid, rifampin, pyrazinamide, and ethambutol should be given daily 1, 2, 3, 4
• Ethambutol can be omitted only if: Primary isoniazid resistance is documented to be less than 4% in the community AND the patient has no previous TB treatment AND is not from a high-prevalence drug-resistance country AND has no known exposure to drug-resistant cases 1, 2
• This four-drug regimen remains effective even when the organism is resistant to isoniazid 5

Continuation Phase (Months 3-6)

• Two-drug regimen: Isoniazid and rifampin for 4 months 1
• Daily or intermittent dosing: May be given daily, or after initial 2 weeks of daily therapy, can transition to thrice-weekly or twice-weekly directly observed therapy (DOT) in selected low-risk patients (HIV-negative, noncavitary, smear-negative disease) 1

Dosing Specifics

Adults: 2, 4

• Isoniazid: 5 mg/kg up to 300 mg daily (or 15 mg/kg up to 900 mg twice or thrice weekly)
• Rifampin: 10 mg/kg up to 600 mg daily
• Pyrazinamide: Per standard dosing guidelines
• Ethambutol: Per standard dosing guidelines

Children: 2, 4

• Isoniazid: 10-15 mg/kg up to 300 mg daily (or 20-40 mg/kg up to 900 mg twice or thrice weekly)
• Rifampin: 10-20 mg/kg up to 600 mg daily

Alternative Regimens

When Pyrazinamide Cannot Be Used

• 9-month regimen: Isoniazid and rifampin for 9 months, with ethambutol included until drug susceptibility results are available 5
• If isoniazid resistance is demonstrated: Continue rifampin and ethambutol for minimum 12 months 5

Directly Observed Therapy (DOT)

DOT should be considered for all TB patients to ensure treatment completion, prevent drug resistance, and improve cure rates 1, 6

• A healthcare provider or designated person directly observes medication ingestion 7
• Critical importance: Patient noncompliance is a major cause of drug-resistant TB 2

Monitoring Requirements

Baseline Evaluation 1

• Sputum: Obtain for smear and culture; at least one specimen tested with rapid molecular test
• Drug susceptibility testing: For isoniazid, rifampin, ethambutol, and pyrazinamide
• Chest radiograph: All patients
• HIV testing: All patients
• Hepatitis B/C screening: For patients with risk factors
• Baseline visual acuity and color discrimination: For patients receiving ethambutol

Follow-up Monitoring 1

• Monthly sputum cultures: Until 2 consecutive specimens are negative
• Repeat drug susceptibility testing: If patient remains culture-positive after 3 months of treatment
• Monthly assessments: Weight, adherence, symptom improvement (cough, fever, night sweats), adverse effects
• Liver function tests: Only at baseline unless abnormalities present, symptoms of hepatotoxicity develop, or patient has risk factors (chronic alcohol use, viral hepatitis, HIV, other hepatotoxic medications) 1
• Visual monitoring: Monthly inquiry about visual disturbance and color discrimination tests for patients on ethambutol 1

Special Populations

HIV Co-infection

• Same 6-month regimen applies but critically important to assess clinical and bacteriologic response 5
• If slow or suboptimal response: Prolong therapy on case-by-case basis 5
• Consider extending treatment: To at least 9 months and for at least 6 months beyond documented culture conversion 8

Pregnant Women

• Initial regimen: Isoniazid, rifampin, and ethambutol 2
• Avoid streptomycin: Due to ototoxicity risk 7
• Pyrazinamide: Not routinely recommended due to inadequate teratogenicity data 2

Children

• Managed essentially the same as adults with appropriately adjusted doses 5
• Ethambutol use: Should not be used in children whose visual acuity cannot be monitored 1
• Extended duration for specific conditions: Miliary TB, bone/joint TB, or tuberculous meningitis require minimum 12 months of therapy 5

Drug-Resistant Tuberculosis

Isoniazid-Resistant TB

Add a later-generation fluoroquinolone (levofloxacin, moxifloxacin, or gatifloxacin) to a 6-month regimen of rifampin, ethambutol, and pyrazinamide 1

• Pyrazinamide duration can be shortened to 2 months in selected situations (noncavitary, lower burden disease, or pyrazinamide toxicity) 1

Multidrug-Resistant TB (MDR-TB)

• Consultation with TB expert is mandatory 1, 9
• Treatment must be individualized based on drug susceptibility testing 2, 5
• Newer regimens: For MDR/RR-TB with extrapulmonary involvement, a 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) is recommended 8
• Avoid older fluoroquinolones: Especially ciprofloxacin, which shows higher relapse rates 10
• Surgery may be considered: Elective partial lung resection (lobectomy or wedge resection) for patients at high risk of treatment failure or relapse based on clinical judgment, bacteriological and radiographic data 1

Management of Treatment Interruptions 1

During Intensive Phase

• Lapse <14 days: Continue treatment to complete planned total doses (within 3 months)
• Lapse ≥14 days: Restart treatment from the beginning

During Continuation Phase

• Received ≥80% of doses and initially smear-negative: Continue until all doses completed
• Received ≥80% of doses and initially smear-positive: Continue until all doses completed unless consecutive lapse >2 months
• Received <80% of doses and lapse <3 months: Restart from beginning if cannot complete within recommended timeframe
• Received <80% of doses and lapse ≥3 months: Restart entire treatment (new intensive and continuation phases)

Common Pitfalls to Avoid

• Never use fewer than 4 drugs initially unless isoniazid resistance is documented to be <4% in the community and patient meets all low-risk criteria 1, 2
• Do not confuse rifampin and rifapentine: They are not interchangeable 1
• Avoid twice-weekly dosing from the start: Initial 2 weeks of daily therapy required; missed doses in twice-weekly regimens result in once-weekly dosing, which is inferior 1
• Do not use ciprofloxacin as substitute agent: Associated with higher relapse rates and longer time to sputum conversion 10
• Never rely on patient self-administration alone: DOT significantly improves outcomes 1, 6