Do you treat a patient with a positive Purified Protein Derivative (PPD) skin test and a negative chest X-ray (CXR) for latent tuberculosis (TB) infection?

Treatment of Latent TB with Positive PPD and Negative Chest X-Ray

Yes, treat for latent tuberculosis infection with isoniazid for 9 months after excluding active disease. 1, 2

Confirming Latent TB vs Active Disease

A positive PPD with a negative chest radiograph and absence of symptoms effectively confirms latent TB infection rather than active disease. 3 The key steps are:

• Obtain chest radiograph to exclude active pulmonary tuberculosis, looking specifically for infiltrates, cavitation, or Ghon complex 1
• Assess for symptoms of active TB including fever, night sweats, weight loss, cough, or hemoptysis 1
• Consider sputum examination only if symptoms are present or chest radiograph is abnormal 1

A normal chest radiograph and negative sputum culture effectively rule out active pulmonary tuberculosis. 3

Treatment Regimen for Latent TB

The preferred regimen is isoniazid 300 mg daily for 9 months. 1, 2 This is the standard recommendation from the CDC and FDA for latent TB infection. 3, 2

Alternative regimens include:

• Rifampin for 4 months as an acceptable alternative 1
• Rifampin plus isoniazid for 3 months (though not included in older CDC recommendations, this has equivalent efficacy) 4

Risk Stratification Determines Treatment Threshold

The PPD positivity threshold varies by risk category: 1, 2

• ≥5 mm induration is positive for:

  • HIV-infected persons 1, 3, 2
  • Recent close TB contacts 1, 2
  • Persons with chest radiograph findings consistent with old TB 1, 2
  • Immunosuppressed patients (including those on biologics or corticosteroids) 1, 2

• ≥10 mm induration is positive for:

  • Recent immigrants from high-prevalence countries 1, 2
  • Injection drug users 1, 2
  • Healthcare workers with TB exposure 1
  • Persons with diabetes, renal failure, silicosis, or other high-risk medical conditions 1, 2

• ≥15 mm induration is positive for:

  • Low-risk persons without other risk factors 1, 2

Critical Monitoring During Treatment

Baseline liver function tests are mandatory before initiating isoniazid. 1, 3 Follow-up includes:

• Monitor liver enzymes every 2-4 weeks during treatment 1
• Assess clinically for hepatotoxicity symptoms including nausea, vomiting, jaundice, or abdominal pain 1
• Monthly clinical monitoring is essential to assess adherence and adverse effects 3

Special Considerations and Common Pitfalls

Do not withhold treatment based solely on BCG vaccination history. 1 The PPD should be interpreted the same way regardless of prior BCG vaccination in persons with risk factors. 1

Anergy testing is controversial and generally not recommended. 1 Even if a patient is anergic, the risk of TB in the presence of a negative PPD is low (0-10% in immunocompromised patients). 1

For patients from areas with >10% drug resistance, consider two-drug therapy even for latent infection. 1

HIV-infected patients require special attention:

• All HIV-positive patients with ≥5 mm induration should receive treatment 3, 2
• Treatment duration should be at least 12 months in HIV-infected persons 3, 2
• CD4 count influences tuberculin sensitivity; patients with advanced immunosuppression may have false-negative results 3, 5

Age considerations for hepatotoxicity risk:

• The risk of isoniazid hepatitis increases with age, particularly over 35 years 2
• However, treatment is still recommended when additional risk factors are present (HIV, recent conversion, close contact, abnormal chest radiograph, immunosuppression) 2
• Weigh hepatitis risk against TB progression risk on an individual basis for those over 35 without additional risk factors 2

When Treatment is Mandatory

Treatment is particularly critical for: 2

• Recent converters (≥10 mm increase within 2 years for age <35; ≥15 mm increase for age ≥35) 2
• All children <4 years old with ≥10 mm induration 2
• Close contacts of infectious TB cases, even if initially tuberculin-negative; retest at 12 weeks and treat if positive 2