What are the prophylactic antibiotics for Tuberculosis (TB)?

Prophylactic Antibiotics for Tuberculosis

Isoniazid for 9 months is the primary prophylactic regimen for latent TB infection, with rifampin-based alternatives available for specific situations such as isoniazid resistance or intolerance. 1

Standard Prophylaxis Regimens

First-Line Option: Isoniazid Monotherapy

• 9 months of daily isoniazid is the preferred regimen for treatment of latent TB infection (LTBI) in most patients 1, 2
• Dosing consists of at least 270 doses administered over 9 months, or up to 12 months if interruptions occur 1
• Twice-weekly isoniazid regimens should consist of at least 76 doses over 9 months 1
• For HIV-infected children, a 12-month regimen of daily isoniazid is recommended 1, 2

Alternative Regimen: Rifampin Plus Pyrazinamide

• 2 months of daily rifampin and pyrazinamide is an effective alternative for patients not receiving protease inhibitors or NNRTIs 1, 2
• This regimen should consist of at least 60 doses administered over 2 months, or up to 3 months if interruptions occur 1
• Important caveat: This regimen has shown unacceptably high rates of severe hepatotoxicity in non-HIV-infected adults and should be used cautiously 3
• Directly observed preventive therapy (DOPT) should always be used with this 2-month regimen 1, 2

Alternative Regimen: Rifampin Monotherapy

• 4 months of daily rifampin alone is recommended for patients with isoniazid intolerance or resistance 1
• This regimen has shown significantly better completion rates and less hepatotoxicity compared to isoniazid 3

Special Situations Requiring Modified Prophylaxis

Isoniazid-Resistant TB Contacts

• For contacts of patients with isoniazid-resistant, rifamycin-susceptible TB: 2 months of rifampin and pyrazinamide is recommended 1
• If pyrazinamide cannot be used: 4-6 months of rifampin alone 1

Multidrug-Resistant TB Contacts

• For contacts likely infected with isoniazid and rifampin-resistant TB: use a combination of at least two drugs to which the strain is susceptible (e.g., ethambutol and pyrazinamide, or levofloxacin and ethambutol) 1
• Treatment duration should be 6-12 months for immunocompetent contacts and 12 months for immunocompromised contacts 1
• Review the drug-susceptibility pattern of the source patient's isolate before selecting the regimen 1
• 6-12 months of a later-generation fluoroquinolone alone or with a second drug is suggested, avoiding pyrazinamide as the second drug due to increased toxicity 1

Pregnancy

• For HIV-infected pregnant women: do not delay initiation of prophylaxis based on pregnancy alone, even during the first trimester 1
• 9 months of daily or twice-weekly isoniazid is the only recommended option during pregnancy 1
• For HIV-negative pregnant women with lower risk: some experts recommend waiting until after delivery, though this should be individualized based on risk of progression 1

HIV Co-infection

• 9 months of daily isoniazid is recommended for HIV-infected adults 1, 2
• HIV-infected contacts should receive prophylaxis regardless of tuberculin skin test results 2
• For patients receiving protease inhibitors or NNRTIs: use the 9-month isoniazid regimen, as rifampin-based regimens have significant drug interactions 1
• Rifabutin may be substituted for rifampin with appropriate dose adjustments in HIV-infected patients on antiretroviral therapy 1

Monitoring During Prophylactic Treatment

Clinical Monitoring

• Monthly clinical evaluation is required for all persons undergoing preventive treatment to assess adherence and medication side effects 1, 2
• Patients should be educated about symptoms of active TB (cough, fever, night sweats, weight loss) and advised to seek immediate medical attention if these develop 1

Laboratory Monitoring

• Baseline hepatic measurements (AST/ALT and bilirubin) are indicated for: HIV-infected patients, pregnant women, women in the immediate postpartum period (within 3 months of delivery), persons with history of chronic liver disease, and persons who use alcohol regularly 1
• Baseline testing is not routinely indicated for all patients or based solely on age 1

Critical Implementation Points

Directly Observed Preventive Therapy (DOPT)

• DOPT should always be used with intermittent dosing regimens 1, 2
• DOPT should also be used when operationally feasible, especially with 2-month regimens and in institutional settings 1

Completion of Therapy

• Completion is based on total number of medication doses administered, not duration alone 1
• When therapy is interrupted for ≥2 months, a medical examination to rule out active TB disease is indicated before reinstituting treatment 1

Common Pitfalls to Avoid

• Drug interactions: Rifampin induces metabolism of many medications including oral contraceptives, anticoagulants, and antiretroviral drugs, requiring careful medication review 1
• Hepatotoxicity risk: Monitor especially during the first 2 months; the 2-month rifampin-pyrazinamide regimen carries higher hepatotoxicity risk in non-HIV-infected adults 3
• Pyridoxine supplementation: Administer 10-25 mg daily to all HIV-infected patients and those at risk for peripheral neuropathy receiving isoniazid 1

Follow-up After Completion

• Follow-up care including chest x-rays and medical evaluations is not necessary for patients who complete prophylaxis, unless they develop symptoms of active TB or are subsequently reexposed to infectious TB 1