5 Things to Know About the New 4-Month TB Treatment Regimen

Wendy Carr, PhD; Ekaterina Kurbatova, MD, PhD, MPH; Bria Marlow, MPH, CHES; Meredith Moore, MPH


July 08, 2022

Editorial Collaboration

Medscape &

On February 24, 2022, the Centers for Disease Control and Prevention (CDC) published new interim guidance in Morbidity and Mortality Weekly Report on a 4-month treatment regimen as an option for US patients with drug-susceptible pulmonary tuberculosis (TB).[1] The 4-month treatment regimen consists of high-dose daily rifapentine with moxifloxacin, isoniazid, and pyrazinamide. Shorter regimens help patients complete treatment faster.

Here are five things to know about treating people with drug-susceptible pulmonary TB disease with the 4-month rifapentine-moxifloxacin treatment regimen:

1. The 4-month TB treatment regimen uses rifapentine, moxifloxacin, isoniazid, and pyrazinamide.

The 4-month rifapentine-moxifloxacin regimen for drug-susceptible TB disease consists of an intensive phase composed of 8 weeks of daily treatment with rifapentine (RPT), isoniazid (INH), pyrazinamide (PZA), and moxifloxacin (MOX), followed by a continuation phase of 9 weeks of daily treatment with RPT, INH, and MOX.

Anti-TB drugs should be administered once daily with food, 7 days per week for a total of 119 treatment doses. Similar to the standard 6-month regimen, at least 5 of 7 weekly doses should be administered under direct observation.[2]

2. The 4-month rifapentine-moxifloxacin regimen is one of several regimens recommended in the United States to treat people with drug-susceptible TB disease.

TB treatment can take 4, 6, or 9 months depending on the regimen.[1,2] Healthcare providers can choose the appropriate TB treatment regimen based on drug-susceptibility results, coexisting medical conditions (eg, HIV, diabetes), and potential for drug-drug interactions.

Healthcare providers can work with patients to determine the best TB disease treatment regimen and provide support and resources to help patients complete treatment successfully.

3. CDC recommends the use of the 4-month rifapentine-moxifloxacin regimen in certain patient groups.

CDC recommends the 4-month rifapentine-moxifloxacin regimen as an option for treating pulmonary TB disease caused by organisms that are not known or suspected to be drug-resistant for the following patient groups in the United States:

  • People who are 12 years and older

  • People with a body weight at or above 40 kg

  • People with HIV with CD4 counts at or above 100 cells/microliter (μL), who are receiving or planning to start efavirenz as part of their antiretroviral therapy (ART) regimen in the absence of any other known drug-drug interactions between antituberculosis and antiretroviral medications

  • People who have no contraindications to this regimen

  • People with a negative sputum culture who in the judgment of the clinician likely represent paucibacillary or low mycobacterial burden TB disease unless the person is included in one of the non-recommended groups.

CDC does not recommend the 4-month rifapentine-moxifloxacin regimen for the following patient groups:

  • People with a body weight below 40 kg

  • People who are less than 12 years old

  • People who are pregnant or breastfeeding

  • People who have drug-drug interactions with isoniazid, rifapentine, pyrazinamide, or moxifloxacin

  • People who have most types of suspected or documented extrapulmonary TB

  • People with a history of prolonged QT syndrome or concurrent use of one or more QT-prolonging medications (in addition to moxifloxacin),

  • People who have a baseline M tuberculosis isolate known or suspected to be resistant to rifampin (RIF), INH, PZA, or fluoroquinolones 

Although the 4-month rifapentine-moxifloxacin regimen may be an option for other patient groups (please refer to the guidance for a complete list), CDC recommends healthcare providers obtain clinician consultation first.[1] Healthcare providers can consult their State TB Control Offices and the TB Centers of Excellence for Training, Education, and Medical Consultation.

For more information, refer to Considerations for the 4-Month Rifapentine-Moxifloxacin Regimen.

4. Healthcare providers should be aware of the 4-month rifapentine-moxifloxacin regimen's evaluation and testing considerations.

CDC recommends the following microbiology, laboratory, and clinical assessments before starting and during treatment with the 4-month rifapentine-moxifloxacin regimen:[1]

  • As with the standard 6-month regimen, respiratory specimens for acid-fast bacilli smear microscopy and culture should be obtained at baseline and at monthly intervals during treatment until two consecutive specimens are negative on culture.

  • Before starting patients on the 4-month rifapentine-moxifloxacin regimen, baseline molecular drug susceptibility testing for rapid identification of mutations associated with resistance to at least INH, PZA, RIF, and fluoroquinolones is advisable.

  • At baseline for patients on the 4-month rifapentine-moxifloxacin regimen, phenotypic drug susceptibility testing should follow molecular drug susceptibility testing with a panel to include at least RIF (as surrogate for RPT), INH, PZA, and MOX as the preferred fluoroquinolone.

  • At baseline and every 4 weeks after initiating treatment, assess patients' weight, symptoms of TB disease, current medications, and any patient comorbidities and potential drug-drug interactions. During this timeframe, evaluate the patient's clinical history, social determinants of health, and adverse drug reactions to determine if the 4-month rifapentine-moxifloxacin regimen is right for them.

Refer to CDC's Healthcare Provider checklist and Frequently Asked Questions (FAQ) webpage for more information.

5. CDC, State TB Control Offices, and TB Centers of Excellence for Training, Education, and Medical Consultation have additional resources and information for healthcare providers.

Healthcare providers can contact their State TB Control Offices and the TB Centers of Excellence for Training, Education, and Medical Consultation for additional information about the treatment regimen and support in treating people with TB disease.

CDC resources on the 4-month rifapentine-moxifloxacin regimen include:


Interim Guidance: 4-Month Rifapentine-Moxifloxacin Regimen for the Treatment of Drug-Susceptible Pulmonary Tuberculosis — United States, 2022 | MMWR (

Frequently Asked Questions (FAQs) | Treatment | TB | CDC

Evaluations for patients treated with a 4-month rifapentine-moxifloxacin TB treatment regimen (

Four-month rifapentine-moxifloxacin tuberculosis (TB) treatment regimen: Considerations for specific groups of people with TB disease (

Treatment for TB Disease | Treatment | TB | CDC

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