What is the recommended treatment regimen for Mycobacterium tuberculosis (M. tuberculosis) Acid-Fast Bacilli (AFB) infection?

Treatment of Mycobacterium tuberculosis (Drug-Sensitive)

For drug-sensitive pulmonary tuberculosis, treat with 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE), followed by 4 months of isoniazid and rifampin (4HR), for a total of 6 months. 1, 2, 3

Initial Intensive Phase (First 2 Months)

All four first-line drugs must be given daily during the initial phase: 1, 2, 3

• Isoniazid: 5 mg/kg up to 300 mg daily 1, 2, 3
• Rifampin: 10 mg/kg up to 600 mg daily (450 mg if <50 kg, 600 mg if >50 kg) 1, 2
• Pyrazinamide: 35 mg/kg daily for patients <50 kg; 1.5-2.0 g daily for patients >50 kg 1, 2
• Ethambutol: 15 mg/kg daily 1, 2, 4

When Can Ethambutol Be Omitted?

Ethambutol can only be discontinued if: 1, 2

• The patient is previously untreated AND
• HIV-negative (or very low risk) AND
• Not a contact of known drug-resistant TB AND
• Local isoniazid resistance is documented to be <4% 1, 3

However, for disseminated TB, all four drugs are mandatory regardless of these factors because patients are seriously ill and may have unrecognized resistance. 2

Continuation Phase (Months 3-6)

Continue with isoniazid and rifampin only for 4 additional months: 1, 2, 3

• Isoniazid: 5 mg/kg up to 300 mg daily 1, 2
• Rifampin: 10 mg/kg up to 600 mg daily 1, 2

Daily dosing is strongly preferred over intermittent (twice or thrice weekly) therapy, especially for disseminated disease. 2, 3

Critical Management Principles

Drug Susceptibility Testing

Perform drug susceptibility testing on all initial M. tuberculosis isolates. 2, 3, 4 If the isolate shows resistance to isoniazid or rifampin after starting treatment, the regimen must be changed immediately based on susceptibility patterns. 3

Directly Observed Therapy (DOT)

All TB patients should receive directly observed therapy to ensure treatment completion and prevent emergence of drug resistance. 2, 3 This is particularly critical because patient noncompliance is a major cause of drug-resistant tuberculosis. 3

If Pyrazinamide Cannot Be Used

If pyrazinamide is not prescribed or cannot be tolerated, extend total treatment duration to 9 months: 2 months of isoniazid, rifampin, and ethambutol, followed by 7 months of isoniazid and rifampin. 1

Site-Specific Treatment Modifications

CNS Tuberculosis (Meningitis)

Extend total treatment duration to 12 months: 2 months of HRZE followed by 10 months of HR. 1, 2 Add corticosteroids (prednisolone 60 mg/day initially, tapering over several weeks) for stages II and III disease to prevent neurologic sequelae. 2

Other Extrapulmonary Sites

• Bone/joint TB: Standard 6-month regimen is effective 2
• Tuberculous pericarditis: Standard 6-month regimen plus corticosteroids to prevent cardiac constriction 2
• Peripheral lymph node TB: Standard 6-month regimen 2
• Miliary TB in infants/children: Consider extending to 12 months 3

Special Populations

Pregnant Women

Use isoniazid, rifampin, and ethambutol for the initial phase. 3 Avoid streptomycin (causes congenital deafness). 3 Pyrazinamide is not routinely recommended in pregnancy due to inadequate teratogenicity data, though some experts now consider it acceptable. 3

HIV Co-infection

Use the same 6-month regimen (2HRZE/4HR) for HIV-infected patients. 2, 3 Be aware of drug interactions between rifampin and antiretroviral agents, particularly protease inhibitors and NNRTIs. 2 HIV-infected patients may have malabsorption issues requiring therapeutic drug monitoring. 3

Children

Dosing for children: 1, 3

• Isoniazid: 10-15 mg/kg up to 300 mg daily
• Rifampin: 10 mg/kg daily
• Pyrazinamide: 35 mg/kg daily
• Ethambutol: 15 mg/kg daily (avoid in children whose visual acuity cannot be monitored) 1, 3

Isoniazid-Resistant Tuberculosis

If isoniazid resistance is confirmed, add a later-generation fluoroquinolone (levofloxacin or moxifloxacin) to a 6-month regimen of rifampin, ethambutol, and pyrazinamide. 1 This represents a critical modification because treatment of isoniazid-resistant TB with standard first-line drugs alone results in failure/relapse rates of 15% and acquired multidrug resistance in 8% of cases. 5

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

Common Pitfalls to Avoid

• Never use fewer than four drugs in the initial phase for disseminated TB or when isoniazid resistance is ≥4%. 1, 2, 3
• Do not discontinue ethambutol before drug susceptibility results confirm full susceptibility to isoniazid and rifampin. 1, 2
• Avoid intermittent dosing unless directly observed therapy is guaranteed. 2, 3
• Do not use ciprofloxacin as a substitute agent—it results in higher relapse rates and longer time to sputum conversion. 6
• Never treat isoniazid-resistant TB with the standard four-drug regimen without adding a fluoroquinolone—this contributes substantially to the MDR-TB epidemic. 5