What antibiotics are recommended for individuals exposed to tuberculosis (TB)?

Treatment of Latent Tuberculosis Infection (TB Exposure)

For individuals exposed to tuberculosis, isoniazid 300 mg daily for 9 months is the preferred antibiotic regimen for treatment of latent TB infection (LTBI), with alternative regimens including rifampin plus pyrazinamide for 2 months or rifampin alone for 4 months. 1

Primary Regimen: Isoniazid Monotherapy

• Isoniazid 300 mg (5 mg/kg, maximum 300 mg) daily for 9 months is the preferred treatment for LTBI in adults, providing maximal benefit with proven efficacy in preventing progression to active disease 1
• A 6-month isoniazid regimen is an acceptable alternative that provides substantial protection and may be preferred from a cost-effectiveness standpoint in certain situations 1
• For HIV-infected persons or those with radiographic evidence of prior TB, the 9-month duration is strongly recommended over 6 months 1
• Intermittent dosing (isoniazid 900 mg twice weekly) may be used but must be administered as directly observed therapy (DOT) 1

Alternative Regimens

Rifampin-Based Options

• Rifampin 600 mg daily for 4 months is recommended for patients who cannot tolerate isoniazid or pyrazinamide, based on efficacy in tuberculin-positive persons with silicosis and those exposed to isoniazid-resistant TB 1
• Rifampin 600 mg plus pyrazinamide daily for 2 months was previously recommended based on trials showing similar safety and efficacy to 12-month isoniazid in HIV-infected persons 1
• When rifampin cannot be used (e.g., HIV-infected persons on protease inhibitors), rifabutin may be substituted 1

Special Population Considerations

Children and Adolescents

• Isoniazid 10-15 mg/kg (maximum 300 mg) daily for 9 months is the recommended regimen 1
• Recent evidence supports 1 month of daily rifapentine plus isoniazid (1HP) as a safe and feasible alternative, with 94% completion rates in children aged 2-19 years 2

Pregnant Women

• Isoniazid 300 mg daily or twice weekly for 9 or 6 months is recommended for HIV-negative pregnant women 1
• For women at high risk for progression (HIV-infected or recently infected), therapy should not be delayed based on pregnancy alone, even during the first trimester 1
• For lower-risk women, some experts recommend waiting until after delivery 1
• Prophylactic pyridoxine 10 mg/day should be given with isoniazid during pregnancy 3

HIV-Infected Persons

• 9-month isoniazid regimen is strongly preferred over 6 months for HIV-infected individuals 1
• For those on protease inhibitors or NNRTIs where rifampin cannot be used, rifabutin with appropriate dose adjustments should be substituted 1

Drug-Resistant TB Exposure

Isoniazid-Resistant, Rifampin-Susceptible TB

• Rifampin 600 mg plus pyrazinamide daily for 2 months is recommended 1
• For patients with pyrazinamide intolerance: rifampin 600 mg daily for 4 months 1

Multidrug-Resistant (MDR) TB Exposure

• Pyrazinamide plus ethambutol OR pyrazinamide plus a fluoroquinolone (levofloxacin or ofloxacin) for 6-12 months 1
• Immunocompetent contacts may be observed or treated for at least 6 months 1
• Immunocompromised contacts (e.g., HIV-infected) should be treated for 12 months 1

Critical Pre-Treatment Requirements

Before initiating LTBI treatment, active TB disease must be ruled out through:

• History and physical examination 1
• Chest radiography 1
• Bacteriologic studies when indicated 1

This is essential because treating active TB with LTBI regimens (monotherapy or two-drug regimens) will lead to drug resistance.

Monitoring Requirements

Clinical Monitoring

• Monthly follow-up evaluations for patients receiving isoniazid alone or rifampin alone 1
• Evaluations at 2,4, and 8 weeks for patients receiving rifampin plus pyrazinamide 1
• Each visit should include questioning about side effects and physical assessment for signs of hepatitis 1

Laboratory Monitoring

• Baseline liver function tests are NOT routinely indicated for all patients 1
• Baseline testing IS indicated for: HIV-infected patients, pregnant women, women in immediate postpartum period (within 3 months of delivery), persons with chronic liver disease history, regular alcohol users, and those at risk for chronic liver disease 1
• Routine laboratory monitoring during treatment is indicated for those with abnormal baseline tests or at risk for hepatic disease 1

Common Pitfalls and Caveats

• Active hepatitis and end-stage liver disease are relative contraindications to isoniazid or pyrazinamide for LTBI treatment 1
• Patients must be educated about side effects and advised to stop treatment immediately and seek medical evaluation if symptoms of hepatitis develop (nausea, vomiting, abdominal pain, jaundice, dark urine) 1
• The 2-month rifampin-pyrazinamide regimen should ideally be given as DOT, which can consist of five observed and two self-administered doses weekly 1
• Rifampin has significant drug interactions including with oral contraceptives, anticoagulants, and antiretroviral drugs, requiring careful medication review 1