What is the recommended post-exposure prophylaxis (PEP) regimen for individuals exposed to tuberculosis (TB)?

Tuberculosis Post-Exposure Prophylaxis

For individuals exposed to tuberculosis, a 9-month regimen of isoniazid is the recommended post-exposure prophylaxis, with alternative regimens including a 2-month course of rifampin plus pyrazinamide for those exposed to isoniazid-resistant TB. 1

Candidates for TB Post-Exposure Prophylaxis

Post-exposure prophylaxis should be provided to:

• Persons who have had recent contact with an infectious TB patient, regardless of age, tuberculin skin test (TST) results, or history of previous TB preventive treatment 1
• Persons with a TST reaction size of ≥5 mm who have not previously received treatment for M. tuberculosis infection 1
• Persons with a history of prior untreated or inadequately treated TB that healed 1
• HIV-infected persons with ongoing high risk of exposure to M. tuberculosis (e.g., residents of prisons, jails, or homeless shelters with high TB prevalence) 1

Recommended Prophylaxis Regimens

For Standard Drug-Susceptible TB Exposure

For patients not receiving protease inhibitors or NNRTIs:

• 9-month daily isoniazid regimen (270 doses total, can be extended to 12 months if interruptions occur) 1
• 9-month twice-weekly isoniazid regimen (76 doses total, directly observed preventive therapy [DOPT] required) 1
• 2-month daily rifampin and pyrazinamide regimen (60 doses total) 1

For patients receiving protease inhibitors or NNRTIs:

• 9-month daily isoniazid regimen (drug interactions with rifampin must be avoided) 1
• 9-month twice-weekly isoniazid regimen with DOPT 1
• 2-month daily rifabutin and pyrazinamide regimen (note: rifabutin is contraindicated with ritonavir, hard-gel saquinavir, and delavirdine) 1

For Drug-Resistant TB Exposure

For contacts of isoniazid-resistant, rifampin-susceptible TB:

• 2-month regimen of rifampin and pyrazinamide 1
• 4-month regimen of rifampin alone (for patients with intolerance to pyrazinamide) 1

For contacts of multidrug-resistant TB (resistant to at least isoniazid and rifampin):

• 6-12 month regimen of pyrazinamide and ethambutol or pyrazinamide and a fluoroquinolone (levofloxacin or ofloxacin), if the organisms are susceptible to these agents 1
• Immunocompetent contacts may be observed or treated for at least 6 months; immunocompromised contacts (e.g., HIV-infected) should be treated for 12 months 1
• Expert consultation should be sought for treatment of persons exposed to MDR TB 1

Special Populations

HIV-Infected Individuals

• HIV-infected contacts should receive TB preventive treatment regardless of TST results 1
• For HIV-infected adults, a 9-month regimen of isoniazid is recommended 1
• If exposed to MDR TB, HIV-infected individuals should be treated for 12 months with appropriate regimens based on susceptibility patterns 1

Children and Adolescents

• For HIV-infected children, a 12-month regimen of daily isoniazid is recommended 1
• For children exposed to MDR TB, a 9-12 month combination of pyrazinamide and ethambutol is recommended if the isolate is susceptible to both drugs 1
• Long-term use of fluoroquinolones in children should be avoided due to potential effects on growing cartilage 1

Monitoring and Follow-up

• Monthly clinical evaluation for adherence to treatment and medication side effects is recommended for all persons undergoing preventive treatment 1
• DOPT should be used with all intermittent dosing regimens and is recommended when feasible for 2-month preventive therapy regimens 1
• Follow-up care including chest x-rays and medical evaluations is not necessary for patients who complete preventive therapy unless they develop symptoms of active TB or are subsequently re-exposed 1

Recent Developments

• A 3-month weekly regimen of rifapentine plus isoniazid (3HP) has shown similar preventive effect to isoniazid monotherapy with fewer adverse events and higher completion rates, though this was not included in the older guidelines provided 2, 3
• Recent research suggests that isoniazid preventive therapy may have some benefit even for contacts of MDR TB patients, contrary to theoretical expectations 4

Common Pitfalls and Caveats

• Drug interactions must be carefully considered, particularly for HIV-infected individuals on antiretroviral therapy 1
• The administration of TB preventive therapy regimens containing rifampin is contraindicated for patients taking protease inhibitors or NNRTIs 1
• When therapy is interrupted for ≥2 months, a medical examination to rule out active TB disease is required before restarting preventive therapy 1
• Completion of therapy is based on total number of medication doses administered, not duration alone 1