What are the standard medications used to treat tuberculosis (TB)?

Standard Tuberculosis Medications

For drug-susceptible TB, treat with a four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 2 months, followed by isoniazid and rifampin for 4 months. 1, 2

Drug-Susceptible TB: Initial Phase (First 2 Months)

The standard initial phase consists of four medications given daily 1, 2:

• Isoniazid (INH): 5 mg/kg PO daily (max 300 mg) 3, 4
• Rifampin (RIF): 10 mg/kg PO daily; 450 mg if <50 kg, 600 mg if ≥50 kg 2, 3
• Pyrazinamide (PZA): 15-30 mg/kg PO daily (max 2 g daily) 4
• Ethambutol (EMB): 15-25 mg/kg PO daily 1, 4

Ethambutol can be discontinued once drug susceptibility confirms full susceptibility to isoniazid and rifampin, particularly if the patient has low risk for drug resistance (community INH resistance <4%, no prior TB treatment, no exposure to drug-resistant cases) 1, 2.

All medications should be taken once daily, either 1 hour before or 2 hours after meals with a full glass of water 3.

Drug-Susceptible TB: Continuation Phase (Next 4 Months)

After completing the initial 2-month phase, continue with two drugs 1, 2:

• Isoniazid: 5 mg/kg PO daily (max 300 mg) 1
• Rifampin: 10 mg/kg PO daily (max 600 mg) 2, 3

Total treatment duration is 6 months for most patients with drug-susceptible pulmonary TB 1, 5.

Extended Treatment Scenarios

Extend the continuation phase to 7 months (total 9 months) in these situations 2:

• Cavitary pulmonary TB with positive cultures after 2 months of treatment
• Inability to include pyrazinamide in the initial regimen

Extend total treatment to 12 months for 2:

• TB meningitis and CNS tuberculosis (2 months HRZE, then 10 months HR)

Multidrug-Resistant TB (MDR-TB): Intensive Phase

For MDR-TB, use at least five effective drugs in the intensive phase, prioritizing newer oral agents over injectable agents 1.

Strongly Recommended Core Drugs (Group A)

Include these drugs in every MDR-TB regimen unless contraindicated 1:

• Later-generation fluoroquinolone (levofloxacin or moxifloxacin) - strong recommendation 1
• Bedaquiline - strong recommendation 1

Additional Drugs to Reach Five-Drug Minimum

Add from these options to achieve at least five drugs 1:

• Linezolid - conditional recommendation 1
• Clofazimine - conditional recommendation 1
• Cycloserine - conditional recommendation 1
• Pyrazinamide - if susceptible, conditional recommendation 1
• Ethambutol - only when other more effective drugs cannot be assembled, conditional recommendation 1

Levofloxacin is preferred over moxifloxacin due to fewer adverse events and less QTc prolongation 6.

Duration of MDR-TB Intensive Phase

Continue the intensive phase for 5-7 months after culture conversion 1.

MDR-TB: Continuation Phase

Use at least four effective drugs in the continuation phase 1.

For the WHO shorter MDR/RR-TB regimen, the continuation phase includes levofloxacin, clofazimine, pyrazinamide, and ethambutol for a fixed duration of 5 months 6.

Total MDR-TB Treatment Duration

• Standard MDR-TB: 15-21 months after culture conversion 1
• Pre-XDR-TB and XDR-TB: 15-24 months after culture conversion 1

Drugs NOT Recommended for MDR-TB

Do not include these medications 1:

• Amoxicillin-clavulanate (except when used with a carbapenem) - strong recommendation against 1
• Macrolides (azithromycin, clarithromycin) - strong recommendation against 1

Pediatric Dosing Considerations

Children should receive appropriately adjusted doses 1, 7:

• Isoniazid: 10-20 mg/kg PO daily (max 300 mg) 4
• Rifampin: 10-20 mg/kg PO daily (max 600 mg) 4
• Pyrazinamide: 15-30 mg/kg PO daily 4
• Ethambutol: Usually not recommended in young children whose visual acuity cannot be monitored, except when increased likelihood of INH-resistant disease or "adult-type" TB 1

Critical Monitoring and Safety Considerations

Hepatotoxicity monitoring is essential, especially during the first 2 months 2.

For ethambutol: Monitor for optic neuritis 6.

For levofloxacin: Monitor for tendinopathy, peripheral neuropathy, and QTc prolongation 6.

For rifampin: Be aware of extensive drug interactions with oral contraceptives, anticoagulants, and antiretroviral drugs requiring dose adjustments 2.

Pyridoxine (vitamin B6) 25-50 mg daily should be administered to all HIV-infected patients receiving isoniazid to prevent neurological side effects 2.

HIV Co-infection Considerations

For HIV-positive patients receiving protease inhibitors or NNRTIs, substitute rifabutin for rifampin with appropriate dose adjustments 2.

HIV-infected patients may require longer treatment courses and more intensive monitoring for clinical and bacteriologic response 1, 7.

Treatment Adherence

Directly observed therapy (DOT) should be considered for all patients to maximize treatment completion 1, 7.

Fixed-dose combinations may improve adherence and provide more convenient administration 2.