What is the recommended therapy for tuberculosis (TB) prevention?

Tuberculosis Prevention Therapy

Recommended Regimens for Latent TB Infection

For HIV-negative adults and children, the preferred regimen is 9 months of daily isoniazid (300 mg for adults, 10 mg/kg/day for children), which provides over 90% efficacy when completed properly. 1

Standard Regimen Options

Isoniazid-Based Regimens:

• 9 months of daily isoniazid is the standard regimen for most patients with latent TB infection 1
• Alternatively, 9 months of twice-weekly isoniazid (76 doses minimum) can be administered 1
• For HIV-infected persons, 12 months of isoniazid is recommended 1
• For children, 9-12 months of isoniazid is recommended 1

Short-Course Rifamycin-Based Regimens:

• 2 months of daily rifampin and pyrazinamide can be used for HIV-infected adults not receiving protease inhibitors or NNRTIs (60 doses minimum) 1
• 4 months of rifampin alone has shown better completion rates and less hepatotoxicity than 9 months of isoniazid 2
• 4 months of isoniazid plus rifampin is an acceptable alternative for persons with silicosis or inactive fibrotic lesions 1

Special Populations

HIV-Infected Patients:

• 9-month isoniazid regimen (daily or twice-weekly) is preferred 1
• 2-month rifabutin and pyrazinamide can be used daily when not on protease inhibitors or NNRTIs 1
• Rifabutin is contraindicated with ritonavir, hard-gel saquinavir, and delavirdine 1
• When rifabutin is used with indinavir, nelfinavir, or amprenavir, reduce daily dose from 300 mg to 150 mg 1

Pregnant Women:

• For HIV-infected pregnant women, initiate 9-month isoniazid regimen (daily or twice-weekly) without delay, even during first trimester 1
• For other pregnant women recently infected or with high-risk conditions (especially HIV), begin isoniazid when infection is documented 1
• For pregnant women without these risk factors, preventive therapy can be delayed until after delivery 1

Drug-Resistant Exposure:

• For contacts of isoniazid-resistant, rifamycin-susceptible TB: 2 months of rifamycin (rifampin or rifabutin) plus pyrazinamide 1
• For pyrazinamide intolerance: 4-6 months of rifamycin alone 1
• For multidrug-resistant TB exposure: use at least two drugs the strain is susceptible to (e.g., ethambutol and pyrazinamide, or levofloxacin and ethambutol) based on source patient's susceptibility pattern 1

Monitoring and Safety

Monthly Clinical Evaluation Required:

• All persons on preventive therapy must receive monthly assessment of adherence and medication side effects 1
• Educate patients about signs of liver damage and other adverse reactions 1

Hepatotoxicity Monitoring:

• For persons >35 years old: obtain baseline transaminase measurement, then monthly until completion 1
• Higher risk groups requiring closer monitoring: daily alcohol users, chronic liver disease, injection drug users, postpubertal Black and Hispanic women 1
• Discontinue isoniazid if transaminases exceed 3-5 times upper limit of normal 1

Pyridoxine Supplementation:

• Administer vitamin B6 (25-50 mg daily or 50-100 mg twice weekly) to all HIV-infected patients receiving isoniazid to reduce central and peripheral nervous system side effects 1

Directly Observed Preventive Therapy (DOPT)

DOPT should always be used with intermittent dosing regimens and is recommended when operationally feasible, especially for: 1

• 2-month preventive therapy regimens
• Institutional settings
• Community outreach programs
• Household contacts of TB patients receiving home-based DOT

Treatment Completion Criteria

Completion is based on total doses administered, not calendar duration: 1

• Daily isoniazid: minimum 270 doses over 9 months (up to 12 months if interruptions occur)
• Twice-weekly isoniazid: minimum 76 doses over 9 months (up to 12 months if interruptions occur)
• Daily rifamycin plus pyrazinamide: minimum 60 doses over 2 months (up to 3 months if interruptions occur)

For interruptions ≥2 months: perform medical examination to rule out TB disease before restarting therapy 1

Common Pitfalls to Avoid

• Do not use rifapentine in HIV-infected patients, as safety and effectiveness have not been established 1
• Avoid three-drug regimens (isoniazid, ethambutol, pyrazinamide) without rifamycin for HIV-related TB; if used, minimum duration is 18 months 1
• Do not delay preventive therapy in HIV-infected pregnant women based on pregnancy alone 1
• Do not rely solely on liver function tests for monitoring; monthly clinical evaluations are essential 1
• Rifampin-pyrazinamide for 2 months should not be used in non-HIV-infected adults due to unacceptably high rates of severe hepatotoxicity 2