Regimens for treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV^*

Regimen	Dosing	Clinical considerations
Rifamycin-based regimens^¶ (preferred)
Rifampin (daily for 4 months; 4R)	Rifampin 10 mg/kg (600 mg maximum) orally daily for 4 months	Better completion rates and less toxicity (relative to isoniazid monotherapy)
Isoniazid^Δ and rifampin (daily for 3 months; 3HR)	Isoniazid 5 mg/kg (300 mg maximum) orally daily for 3 months Rifampin 10 mg/kg (600 mg maximum) orally daily for 3 months	Better completion rates and less toxicity (relative to isoniazid monotherapy)
Isoniazid^Δ and rifapentine (weekly for 3 months; 3HP)	Isoniazid (orally once weekly for 3 months; direct observation is preferred): 15 mg/kg, rounded up to the nearest 50 or 100 mg; 900 mg maximum Rifapentine (orally once weekly for 3 months; direct observation is preferred): 10 to 14 kg: 300 mg 14.1 to 25.0 kg: 450 mg 25.1 to 32.0 kg: 600 mg 32.1 to 49.9 kg: 750 mg ≥50 kg: 900 mg maximum	Better completion rates (relative to isoniazid monotherapy) Important side effects of 3HP include hypersensitivity or flu-like symptoms (eg, light headedness, dizziness, headache, nausea or vomiting, syncope, rash, or angioedema). For this reason, 3HP usually is administered via directly observed therapy, to facilitate side effect review and treatment withholding if needed. Self-administration of 3HP may be acceptable for patients who can reliably take their medications on schedule and inform their providers promptly of side effects (while withholding the next dose pending provider review).
Isoniazid monotherapy regimens (alternative)
Isoniazid^Δ	Isoniazid 5 mg/kg (300 mg maximum) orally daily for 9 months^◊ Isoniazid 5 mg/kg (300 mg maximum) orally daily for 6 months^◊ Isoniazid 15 mg/kg (900 mg maximum) orally twice weekly^§ for 9 or 6 months	Fewer drug interactions (relative to rifamycin-based regimens)

The efficacy and toxicity of these regimens differ, and some are appropriate only for certain patient populations. For a discussion of the clinical approach to selecting a regimen for the treatment of tuberculosis infection, refer to the UpToDate topics on treatment of TB infection in adults without HIV. Dosing assumes normal renal and hepatic function. For nonobese individuals, dosing for isoniazid and rifampin is based on actual body weight; optimal dosing for obese individuals has not been established.

* The regimens summarized in the table are for treatment of TB infection due to Mycobacterium tuberculosis presumed to be susceptible to isoniazid and rifamycins. For details regarding treatment of drug-resistant TB infection, refer to UpToDate topic on treatment of TB infection.

¶ In August 2020, the US Food and Drug Administration (FDA) announced detection of nitrosamine impurities in samples of rifampin and rifapentine. Refer to UpToDate topic on treatment of drug-susceptible pulmonary TB for further discussion.

Δ Peripheral neuropathy can occur among patients on TB infection regimens containing isoniazid due to interference with metabolism of pyridoxine and can be prevented with pyridoxine supplementation (25 to 50 mg daily). This is especially important for patients with conditions that can predispose to neuropathy (including diabetes, uremia, alcoholism, malnutrition, and HIV infection) as well as in the setting of pregnancy and seizure disorders. Pyridoxine should also be administered to infants of breastfeeding mothers receiving isoniazid.

◊ If isoniazid is used, we favor daily administration for 9 months given its established efficacy; daily treatment achieves greater adherence than intermittent therapy (ie, 3 times per week or 2 times per week). Isoniazid daily for 6 months (6H) provides some protection; in the setting of difficulty with adherence, providers may prefer to concentrate efforts in ensuring 6 months of therapy. This approach is favored by the World Health Organization. However, regimens shorter than 9 months should not be used for patients with fibrotic lesions on chest radiograph.

§ Twice-weekly regimens of isoniazid must be administered with directly observed therapy.

Adapted from:

Blumberg HM, Leonard MK Jr, Jasmer RM. Update on treatment of tuberculosis and latent tuberculosis infection. JAMA 2005; 293:2776.
Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR 2011; 60:1650.
World Health Organization. Latent TB infection: Updated and consolidated guidelines for programmatic management. Available at: http://www.who.int/tb/publications/2018/latent-tuberculosis-infection/en/ (Accessed on May 24, 2018).
Sterling T, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations From the National Tuberculosis Controllers Association and CDC, 2020. MMWR 2020; 69:1.

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Regimens for treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV*

Regimens for treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV^*