New Option for Prevention of TB: Recommendations From the CDC

Primary Care Update
Brief Summaries for Clinical Practice 


Although the number of persons with tuberculosis (TB) disease in the United States is at an all-time low (11,182 total cases in 2010), about 4% of the US population, or 11 million people, have Mycobacterium tuberculosis infection. Persons of color and recent immigrants are disproportionately affected.1

Treatment of latent Mycobacterium tuberculosis infection (LTBI) to prevent progression to active TB represents the foundation of US public health efforts to combat the disease. However, a drawback of the standard 9-month isoniazid (INH) regimen has been that many patients fail to complete the course of therapy.

Recently, the CDC announced that a new 12-dose combination regimen of INH and rifapentine (RPT) administered weekly as directly observed therapy (DOT) is as effective as longer regimens for the prevention of TB and is more likely to be completed.1 The CDC’s recommendations are based on the results of three randomized controlled trials,2-4 as well as expert opinion. Highlights of the recommendations are presented here.


INH is the only drug approved by the FDA for the prevention of TB. INH monotherapy has been shown to prevent TB in diverse patient populations; however, self-supervised daily INH regimens have completion rates of 60% or less, largely because the duration of therapy is 6 months or longer. A rare adverse effect of these regimens is severe liver injury.5-7

RPT is a rifamycin-class antibiotic with an FDA-approved indication for TB disease. Its use for the treatment of LTBI is off label. RPT is microbicidal for susceptible M tuberculosis. Its long plasma half-life allows infrequent dosing, which can increase adherence.


The new 12-dose regimen is recommended as an alternative to the 9-month INH regimen for otherwise healthy patients aged 12 years and older who have LTBI and risk factors for the development of TB. Persons with HIV infection who are otherwise healthy and not taking antiretrovirals may also use this regimen if TB preventive treatment is indicated.

The preferred regimen for children aged 2 to 11 years is 9 months of daily INH.5 However, the INH-RPT regimen can be considered for patients at high risk for TB who are unlikely to complete a 9-month daily INH regimen.

The INH-RPT regimen is not recommended for the following patients:

•Children younger than 2 years.

•HIV-infected patients who are
receiving antiretroviral therapy.

•Pregnant women or women expecting to become pregnant during treatment.

•Patients who have LTBI with presumed INH or rifampin resistance.


Before the regimen is started, TB disease needs to be ruled out. Treatment of LTBI when TB is active could result in drug resistance.

Neutropenia and increased se-rum concentrations of liver enzymes are uncommon adverse effects of RPT. For other rifamycins, rare hypersensitivity reactions have been reported, with symptoms such as fever, headache, dizziness, musculoskeletal pain, petechiae, purpura, and pruritus.8 RPT induces increased metabolism of many drugs, particularly those metabolized by cytochrome P450 isoenzyme 3A. RPT should not be used with medications that have narrow therapeutic ranges (eg, methadone or warfarin), except with careful monitoring. Women who use any form of hormonal birth control should be advised to add, or switch to, a barrier method.

DOT is recommended in order to ensure completion of doses and to allow for monitoring of patient safety. DOT workers should use a symptom checklist for adverse effects and should report problems to a clinician. In addition, patients should be instructed to seek medical attention immediately if they have fever, yellow eyes, dizziness, rash, or aches or more than 1 day of nausea, vomiting, weakness, abdominal pain, or loss of appetite. A monthly clinical assessment is also recommended for patients who are receiving this regimen. 



1. Jereb JA, Goldberg SV, Powell K, et al. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Myco-bacterium tuberculosis infection. MMWR. 2011;60:

2. Schechter M, Zajdenverg R, Falco G, et al. Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. 
Am J Respir Crit Care Med. 2006;173:922-926.

3. Martinson NA, Barnes GL, Moulton LH, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011;365:11-20.

4. Sterling TR, Villarino ME, Borisov AS, et al. Three months of once-weekly rifapentine and isoniazid for M. tuberculosis infection. N Engl J Med. 2011;365:2155-2166.

5. CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR. 2000;49
(No. RR-6).

6. Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;

7. CDC. Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection—United States, 2004–2008. MMWR. 2010;59:224-229.

8. Girling DJ. Adverse effects of antituberculosis drugs. Drugs. 1982;23:56-74.