Treatment of Latent Tuberculosis Infection

Preferred Treatment Options

The Centers for Disease Control and Prevention (CDC) strongly recommends a 4-month daily regimen of rifampin for patients with latent tuberculosis infection taking hydroxychloroquine after stopping Orencia, with moderate quality evidence 1, 2
A 3-month once-weekly isoniazid plus rifapentine regimen is strongly recommended with moderate quality evidence, and may be considered if daily medication is challenging 1, 2
The CDC conditionally recommends a 3-month daily isoniazid plus rifampin regimen with very low quality evidence in HIV-negative patients 2

A 6-month daily isoniazid regimen is strongly recommended with moderate quality evidence in HIV-negative patients, and is less effective than longer courses but may be better tolerated 1, 2

Before starting treatment, the CDC recommends ruling out active TB through history, physical examination, chest radiography, and when indicated, bacteriologic studies, and obtaining baseline liver function tests, especially with hydroxychloroquine use 3
During treatment, monthly clinical evaluations for patients receiving rifampin, monitoring for drug interactions between rifampin and other medications, and assessing for side effects with brief physical examinations checking for signs of hepatitis are recommended 1, 3, 2

Rifamycin-based regimens have potential drug interactions with many medications, but hydroxychloroquine does not have significant interactions with rifampin 1, 3, 2
After stopping Orencia, rifampin can be safely used as the immunosuppressive effect diminishes 3

The CDC recommends initiating treatment of latent TB infection as soon as clinically appropriate after discontinuation of Orencia, and rifampin-based regimens are particularly beneficial due to shorter duration and better completion rates 1, 3

The Infectious Diseases Society of America (IDSA) advises against confusing treatment regimens for latent TB infection with those for active TB disease, and against adding a single drug to a failing regimen as this may lead to drug resistance 4, 5, 6
Ensuring that active TB has been ruled out before starting treatment for latent TB infection, and monitoring liver function more closely in patients taking hydroxychloroquine due to potential additive hepatotoxicity are recommended 3

The American Thoracic Society recommends 9 months of daily isoniazid for the treatment of LTBI, which provides better efficacy than the 6-month regimen but has lower completion rates 7, 8

For contacts of MDR-TB patients, treatment for LTBI is suggested versus observation alone, with a conditional recommendation to use 6-12 months of a later-generation fluoroquinolone alone or with a second drug based on source-case susceptibility 9
Pyrazinamide should not be routinely used as the second drug due to increased toxicity and discontinuation rates 9
Rifampin-based regimens can be used in pregnant women, though careful monitoring is essential 8
Rifampin-based approaches appear safe and effective in children, but studies are needed to establish optimal regimens 8

The American Thoracic Society suggests that directly observed therapy (DOT) should be considered for all LTBI patients to ensure completion, particularly with the once-weekly rifapentine/isoniazid regimen 10
Combination preparations or blister packs may facilitate adherence when available 7, 8

The Centers for Disease Control and Prevention (CDC) recommends 9 months of daily isoniazid for latent TB treatment, with >90% efficacy if completed 11

Baseline liver function tests, including AST/ALT and bilirubin, are required before initiating isoniazid treatment, as recommended by the American Thoracic Society 12
The CDC recommends ruling out active TB through history, physical examination, and chest radiography before starting treatment 13
Monthly clinical monitoring is essential for preventing severe hepatotoxicity in patients taking isoniazid, according to the American Journal of Respiratory and Critical Care Medicine 12
The CDC advises withholding isoniazid if transaminase levels exceed 3 times the upper limit of normal with symptoms, or 5 times the upper limit if asymptomatic 13, 14

The American College of Chest Physicians recommends considering rifampin-based regimens as alternatives to isoniazid if concerns about dual hepatotoxicity arise 11
Active hepatitis and end-stage liver disease are relative contraindications to isoniazid treatment, as stated by the CDC 12, 13, 14