What is the recommended treatment for a patient with a positive Purified Protein Derivative (PPD) test and a negative chest x-ray?

Treatment for Positive PPD and Negative Chest X-Ray

A patient with a positive PPD test and negative chest x-ray has latent tuberculosis infection (LTBI) and should be treated with isoniazid 300 mg daily for 9 months, which is the preferred regimen for preventing progression to active disease. 1

Initial Evaluation

Before initiating treatment, you must:

• Exclude active tuberculosis through clinical evaluation, chest radiograph, and symptom assessment (cough, fever, night sweats, weight loss) 1, 2
• Obtain baseline liver function tests, particularly in patients over 35 years old or those with risk factors for hepatic disease 1
• Assess for contraindications to isoniazid therapy 1

Recommended Treatment Regimens

First-Line Option: Isoniazid Monotherapy

• Isoniazid 300 mg daily for 9 months is the preferred regimen (Rating A-II for both HIV-positive and HIV-negative patients) 1
• This duration provides maximal benefit, as studies show 9 months is superior to 6 months in preventing progression to active TB 1
• Twice-weekly directly observed therapy is an acceptable alternative (Rating B-II) 1

Alternative Regimens

If isoniazid cannot be used or adherence is a concern:

• Rifampin 600 mg daily for 4 months (Rating B-II for HIV-negative, B-III for HIV-positive) 1
• This option is particularly useful when isoniazid toxicity is a concern 1

Important caveat: The 2-month rifampin-pyrazinamide regimen, while previously recommended, should now be reserved only for patients unlikely to complete longer therapy who can be monitored closely, due to increased hepatotoxicity risk 1

Special Populations Requiring Extended Therapy

Certain high-risk groups require 12 months of isoniazid instead of 9 months 3:

• HIV-infected individuals 1, 3
• Patients with fibrotic lesions on chest x-ray consistent with old healed TB 1, 3
• Patients with pulmonary silicosis 3

For these patients, an alternative is 4 months of combined isoniazid and rifampin 3

Monitoring During Treatment

Clinical Monitoring

• Monthly clinical assessments to evaluate for symptoms of hepatotoxicity (nausea, vomiting, jaundice, abdominal pain) 1
• Educate patients to stop medication and seek immediate care if these symptoms develop 1

Laboratory Monitoring

Routine laboratory monitoring is indicated for 1:

• Patients with abnormal baseline liver function tests
• Persons over 35 years of age
• Those with chronic liver disease, HIV infection, or alcohol use
• Pregnant or postpartum women (within 3 months of delivery)

Withhold isoniazid if: 1

• Transaminases exceed 3 times the upper limit of normal with symptoms
• Transaminases exceed 5 times the upper limit of normal without symptoms

Common Pitfalls to Avoid

1. Do not treat with isoniazid alone if active TB is suspected - this creates drug resistance 3. Always use multi-drug therapy for active disease 1

2. Do not automatically exclude patients over 35 from treatment - age alone is not a contraindication if they have risk factors for progression to active TB 1

3. Do not use the 2-month rifampin-pyrazinamide regimen as first-line - hepatotoxicity concerns have relegated this to a last-resort option 1

4. Do not forget to assess for drug-resistant TB exposure - if the source case has multidrug-resistant TB, standard LTBI regimens are inadequate and consultation with TB specialists is required 4

HIV-Infected Patients

For HIV-positive individuals with positive PPD 1, 5:

• Minimum 12 months of isoniazid therapy is required 1, 3
• Three-month rifampin-containing regimens (rifampin plus isoniazid or rifampin plus pyrazinamide) provide sustained protection for up to 3 years 5
• Six months of isoniazid provides only short-term protection in this population 5