When and how to treat latent tuberculosis (TB) infection?

Treatment of Latent Tuberculosis Infection

Before initiating any LTBI treatment, active TB disease must be definitively excluded through history, physical examination, chest radiography, and when indicated, bacteriologic studies (sputum AFB smear and culture). 1, 2

When to Treat: High-Risk Populations Requiring LTBI Treatment

Treat the following groups who have positive tuberculin skin test (TST ≥5mm) or positive IGRA:

Highest Priority (Treat Immediately)

• HIV-infected persons (5-10% annual reactivation risk; TST ≥5mm is positive) 2, 3
• Recent contacts of infectious pulmonary TB cases 2
• Patients initiating anti-TNF therapy or other biologics 2
• Patients preparing for organ or hematological transplantation 2
• Children <5 years old with positive testing 2
• Radiographic evidence of prior untreated TB (old fibronodular lesions) 2

High Priority (Strongly Consider Treatment)

• Patients receiving dialysis for chronic renal failure 2
• Patients with silicosis 2
• Pregnant women at high risk for progression (HIV-infected or recent infection) 1
• Patients with diabetes, being underweight, smoking history, or gastrectomy (when 2+ risk factors present) 4

How to Treat: Recommended Regimens

First-Line Regimens (Choose Based on Patient Factors)

1. Rifapentine + Isoniazid for 12 weeks (once weekly, directly observed)

• Most convenient short-course option with proven efficacy 2, 5
• Efficacy: OR 0.36 vs. no treatment 5
• Cannot be used with protease inhibitors; substitute rifabutin if needed 1

2. Rifampin monotherapy for 4 months (daily)

• Best option for patients who cannot tolerate isoniazid or pyrazinamide 1, 2
• Less hepatotoxicity and better compliance than isoniazid 6
• Efficacy: OR 0.41 vs. placebo 5

3. Rifampin + Isoniazid for 3-4 months (daily)

• Equivalent efficacy to 6-9 months isoniazid with better completion rates 6, 5
• Efficacy: OR 0.53 vs. placebo 5
• Requires monitoring at weeks 2,4, and 8 1

4. Isoniazid for 9 months (daily or twice weekly)

• Traditional regimen with most abundant evidence (60-90% protective effect) 6, 2
• For HIV-infected persons or those with radiographic evidence of prior TB, use 9 months rather than 6 months 1
• Efficacy: OR 0.50 for 12-72 months vs. placebo 5
• When given intermittently (twice weekly), must be directly observed 1

Special Population Regimens

Children and Adolescents:

• Isoniazid for 9 months is the only recommended regimen (daily or twice weekly) 1, 7
• Dose: 10-15 mg/kg up to 300 mg daily, or 20-40 mg/kg up to 900 mg twice weekly 7

Pregnant Women:

• Isoniazid for 6-9 months (daily or twice weekly) 1
• Do not delay treatment during first trimester for high-risk women (HIV-infected or recent infection) 1
• For lower-risk women, some experts recommend waiting until after delivery 1

Drug-Resistant Source Cases:

• Isoniazid-resistant, rifampin-susceptible: Rifampin + pyrazinamide for 2 months, or rifampin alone for 4 months 1
• Multidrug-resistant (isoniazid + rifampin resistant): Pyrazinamide + ethambutol OR pyrazinamide + quinolone (levofloxacin/ofloxacin) for 6-12 months 1
  • Immunocompetent: treat or observe for ≥6 months 1
  • Immunocompromised (HIV-infected): treat for 12 months 1

Clinical and Laboratory Monitoring

Baseline Assessment

Obtain baseline liver function tests (AST/ALT, bilirubin) for: 1, 3

• HIV-infected patients
• Pregnant women and women within 3 months postpartum
• History of chronic liver disease (hepatitis B/C, alcoholic hepatitis, cirrhosis)
• Regular alcohol use
• Patients on other hepatotoxic medications

Baseline testing is NOT routinely indicated for all patients 1, 3

Ongoing Monitoring Schedule

• Monthly clinical evaluations for isoniazid alone or rifampin alone regimens 1, 3
• Evaluations at weeks 2,4, and 8 for rifampin + pyrazinamide regimens 1
• At each visit: assess adherence, review symptoms of adverse reactions, check for hepatotoxicity signs 3

Patient Education on Hepatotoxicity Warning Signs

Instruct patients to immediately stop treatment and seek medical evaluation if they develop: 3

• Unexplained anorexia, nausea, or vomiting
• Dark urine or jaundice
• Persistent fatigue or abdominal tenderness
• Easy bruising or bleeding
• Persistent paresthesias or rash

Laboratory Monitoring Thresholds

Withhold isoniazid if: 1

• Transaminases >3× upper limit of normal WITH symptoms
• Transaminases >5× upper limit of normal WITHOUT symptoms

Critical Pitfalls to Avoid

1. Never treat LTBI without first excluding active TB disease - obtain chest X-ray and assess for TB symptoms in all patients 1, 2

2. Do not use rifampin-pyrazinamide regimen routinely - this 2-month regimen was previously recommended but has fallen out of favor due to hepatotoxicity concerns, though it remains in older guidelines 1

3. Avoid ethambutol in young children whose visual acuity cannot be monitored 7

4. Check drug interactions - rifampin significantly interacts with protease inhibitors and many other medications; consider rifabutin substitution 1, 2

5. Do not use intermittent dosing without directly observed therapy - twice or thrice weekly regimens must always be directly observed 1

6. Pregnant women should avoid pyrazinamide due to inadequate teratogenicity data, and never use streptomycin (causes congenital deafness) 7