What is the recommended treatment for latent tuberculosis infection (LTBI) in individuals with a positive Purified Protein Derivative (PPD) test and a negative chest X-ray?

Treatment of Latent Tuberculosis Infection (Positive PPD, Negative Chest X-Ray)

For individuals with a positive PPD test and a normal chest X-ray, treatment of latent tuberculosis infection (LTBI) should be initiated with 9 months of daily isoniazid (300 mg/day), which reduces the risk of progression to active TB by up to 90% when completed. 1

Initial Evaluation Requirements

Before initiating LTBI treatment, the following must be completed:

• Chest radiograph is mandatory to exclude active pulmonary tuberculosis—if normal and no TB symptoms are present, the patient is a candidate for LTBI treatment 2
• Clinical assessment for TB symptoms including productive cough, fever, night sweats, weight loss, and hemoptysis must be performed 1
• Sputum examination is NOT routinely indicated for most persons with normal chest radiographs being considered for LTBI treatment 2
• Baseline liver function tests should be obtained for HIV-infected persons, pregnant women, those with history of liver disease, regular alcohol users, and those at risk for chronic liver disease 1

Recommended Treatment Regimens

First-Line Option: Isoniazid Monotherapy

• 9 months of daily isoniazid (300 mg/day) is the preferred regimen, providing up to 90% reduction in TB risk when completed 1
• This regimen is rated as the standard of care by the American Thoracic Society/CDC/IDSA 2
• Pyridoxine (vitamin B6, 10-25 mg/day) should be co-administered to prevent peripheral neuropathy and CNS effects 2

Alternative Regimens with Higher Completion Rates

• 4 months of daily rifampin is as effective as 9-month isoniazid with superior completion rates (70.3% vs 56.3%), lower cost, and better safety profile 3, 4
• 3 months of weekly rifapentine plus isoniazid (directly observed therapy) is non-inferior to 9-month isoniazid with better adherence (69.6% completion rate) 3, 4, 5
• 3 months of daily rifampin plus isoniazid is equivalent in efficacy to isoniazid monotherapy with similar toxicity rates 6, 5

Special Populations Requiring Priority Treatment

High-priority candidates for LTBI treatment include: 2, 1

• HIV-infected persons (regardless of CD4 count)
• Recent contacts of infectious TB cases (especially within 2 years)
• Children younger than 5 years
• Persons with radiographic evidence of prior healed TB (fibrotic lesions)
• Recent immigrants from high TB-incidence countries
• Persons with medical conditions increasing TB risk (diabetes, chronic renal failure, immunosuppressive therapy)

Monitoring During Treatment

Clinical Monitoring

• Monthly clinical assessment for symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice, dark urine) is required for all patients 1
• Repeat liver function tests are indicated if baseline abnormalities exist or if symptoms develop 2, 1

Criteria for Discontinuation

• Discontinue isoniazid immediately if aminotransferases exceed 5 times the upper limit of normal in asymptomatic patients, or 3 times the upper limit of normal with symptoms 1
• Hepatitis risk increases with age and alcohol consumption 2

Common Pitfalls to Avoid

• Do not delay treatment in high-risk populations—LTBI treatment is highly effective at preventing progression to active disease, which carries significant morbidity and mortality 1, 7
• Do not use rifampin plus pyrazinamide for 2 months—this regimen is contraindicated due to unacceptably high rates of severe hepatotoxicity and death 1
• Do not assume treatment completion—only 18.5% of patients prescribed LTBI treatment actually complete it in real-world settings, requiring adherence support strategies 4
• Do not forget pyridoxine supplementation with isoniazid, especially in patients at risk for neuropathy (diabetes, HIV, pregnancy, malnutrition, alcoholism) 2
• Do not initiate single-drug LTBI treatment if there is any suspicion of active TB—multidrug therapy should be started pending culture results 2

Treatment Selection Algorithm

For most patients: Start with 9-month isoniazid as the evidence-based standard 1

Consider 4-month rifampin if:

• Patient preference for shorter duration
• Concerns about adherence to 9-month regimen
• Contraindications to isoniazid (liver disease, previous hepatotoxicity)
• Higher completion rates are prioritized 3, 4

Consider 3-month rifapentine/isoniazid if:

• Directly observed therapy is feasible
• Patient preference for shortest regimen
• Adherence concerns with longer regimens 3, 5

Avoid rifamycin-based regimens if:

• Significant drug-drug interactions exist (rifampin induces cytochrome P450 enzymes)
• Patient is on medications with critical interactions (antiretrovirals, anticoagulants, immunosuppressants) 8