What is the standard treatment regimen for tuberculosis (TB)?

Standard Treatment Regimen for Tuberculosis

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

Initial Intensive Phase (First 2 Months)

All four drugs must be started simultaneously:

• Isoniazid 5 mg/kg up to 300 mg daily 2, 3
• Rifampin 10 mg/kg (450 mg if <50 kg, 600 mg if ≥50 kg) daily 2, 3
• Pyrazinamide 35 mg/kg (1.5 g if <50 kg, 2.0 g if ≥50 kg) daily 2, 3
• Ethambutol 15 mg/kg daily 2, 3

Ethambutol can be discontinued once drug susceptibility testing confirms full susceptibility to isoniazid and rifampin, particularly if the patient is from a low-risk population with <4% primary isoniazid resistance. 1, 2, 4

Continuation Phase (Months 3-6)

Continue only two drugs:

• Isoniazid 5 mg/kg up to 300 mg daily 2, 3
• Rifampin 10 mg/kg (450 mg if <50 kg, 600 mg if ≥50 kg) daily 2, 3

This continuation phase lasts 4 months for most patients. 1

When to Extend Treatment to 7-9 Months

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

• Cavitary pulmonary TB with positive sputum culture at 2 months of treatment 1
• Initial phase did not include pyrazinamide 1
• Patients receiving once-weekly isoniazid and rifapentine who had positive sputum culture at 2 months 1
• Bone/joint tuberculosis or tuberculous meningitis in children (extend to 12 months total) 5, 3, 4

Directly Observed Therapy (DOT)

All patients with tuberculosis should receive directly observed therapy, where medication ingestion is witnessed by a healthcare worker or trained observer. 1, 6 This is the standard of care because nonadherence is the primary cause of treatment failure and development of drug resistance. 1

If universal DOT is not feasible, prioritize these high-risk groups: patients with drug-resistant disease, injection drug users, alcoholics, homeless persons, and those with prior treatment failure. 1

Alternative Dosing Schedules

While daily dosing is preferred, twice-weekly or thrice-weekly DOT regimens are acceptable alternatives when daily supervision is not feasible. 1, 3 However, daily dosing during the intensive phase provides optimal efficacy. 5

Monitoring Response to Treatment

Assess treatment response at 2-3 months:

• Sputum smears and cultures should become negative by 3 months 1
• If sputum remains positive at 3 months, immediately evaluate for nonadherence or drug resistance 1
• Obtain drug susceptibility testing on all initial isolates 3, 4

Special Populations

HIV Co-infection

• Use the same 6-month regimen for HIV-positive patients 1, 5, 4
• Add pyridoxine (vitamin B6) 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent peripheral neuropathy 2, 5
• For patients on protease inhibitors or NNRTIs, substitute rifabutin for rifampin with appropriate dose adjustments due to drug interactions 2, 5
• Start antiretroviral therapy at least 14 days after initiating TB treatment to reduce immune reconstitution syndrome risk 1

Pediatric Patients

• Children receive the same four-drug regimen with weight-adjusted dosing: isoniazid 10-15 mg/kg (max 300 mg), rifampin 10-20 mg/kg, pyrazinamide 30-40 mg/kg, ethambutol 15-25 mg/kg 2, 3, 4
• Avoid ethambutol in young children who cannot be monitored for visual acuity 1, 3, 4

Extrapulmonary Tuberculosis

• Use the same 6-month regimen for most extrapulmonary TB 1, 3
• Extend to 9-12 months for miliary TB, bone/joint TB, and tuberculous meningitis, especially in children 5, 3, 4
• Consider adjunctive corticosteroids for tuberculous meningitis and pericarditis to reduce neurologic sequelae and prevent cardiac constriction 5, 3

Multidrug-Resistant TB (MDR-TB)

For MDR-TB (resistance to at least isoniazid and rifampin), use at least five effective drugs in the intensive phase, including a later-generation fluoroquinolone (levofloxacin or moxifloxacin) and bedaquiline unless contraindicated. 2

• Continue intensive phase for 5-7 months after culture conversion 2
• Total treatment duration is 15-21 months after culture conversion 2
• Consultation with a TB expert is mandatory for all MDR-TB cases 1, 4

Critical Monitoring and Safety

Monitor for hepatotoxicity, especially during the first 2 months of treatment: 2

• Baseline and periodic liver function tests
• Educate patients on symptoms of hepatitis (nausea, vomiting, jaundice, dark urine)

Monitor for drug-specific toxicities:

• Ethambutol: optic neuritis (monthly visual acuity and color vision testing) 2
• Rifampin: extensive drug interactions with oral contraceptives, anticoagulants, and antiretrovirals requiring dose adjustments 2
• Fluoroquinolones (if used): tendinopathy, peripheral neuropathy, QTc prolongation 2

Common Pitfalls to Avoid

• Never use fewer than four drugs in the initial phase when drug susceptibility is unknown 1, 4
• Do not discontinue pyrazinamide before completing 2 months, even if clinical improvement occurs 5
• Do not treat suspected TB with fluoroquinolones alone before confirming the diagnosis, as this can delay diagnosis and promote resistance 1
• Always report suspected and confirmed TB cases promptly to local public health authorities 1
• Fixed-dose combination tablets improve adherence and prevent selective medication taking 5

Recent Advances

A 4-month regimen using rifapentine (instead of rifampin) with isoniazid, pyrazinamide, and moxifloxacin has been conditionally recommended by WHO for eligible patients aged ≥12 years with pulmonary drug-susceptible TB. 1 However, the standard 6-month regimen remains the global standard of care.