Treatment for TB Disease

NewThe 4-month TB treatment regimen consists of

• high-dose daily rifapentine (RPT) with
• moxifloxacin (MOX),
• isoniazid (INH), and
• pyrazinamide (PZA).

The 4-month rifapentine-moxifloxacin regimen has an intensive phase of 2 months, followed by a continuation phase of 2 months and 1 week (total 17 weeks for treatment).

The 6- to 9-month RIPE TB treatment regimens consist of

• Rifampin (RIF),
• Isoniazid (INH),
• Pyrazinamide (PZA), and
• Ethambutol (EMB)

RIPE regimens for treating TB disease have an intensive phase of 2 months, followed by a continuation phase of either 4 or 7 months (total of 6 to 9 months for treatment).

Table 2. 6- to 9-month RIPE TB treatment regimen

Intensive Phase				Continuation Phase
Drugsa	Duration	Frequencyb		Drugs	Duration	Frequencyb,c		Total Doses	Commentsc,d,e,f	Regimen Effectiveness
INH RIF PZA EMB	8 weeks	7 days/week for 56 doses	5 days/week for 40 doses	INH RIF	18 weeks	7 days/week for 126 doses	5 days/week for 90 doses	182 to 130	This is the preferred regimen for patients with newly diagnosed pulmonary TB.
INH RIF PZA EMB	8 weeks	7 days/week for 56 doses	5 days/week for 40 doses	INH RIF	18 weeks	3 times weekly for 54 doses		110 to 94	Preferred alternative regimen in situations in which more frequent DOT during continuation phase is difficult to achieve.
INH RIF PZA EMB	8 weeks	3 times weekly for 24 doses		INH RIF	18 weeks	3 times weekly for 54 doses		78	Use regimen with caution in patients with HIV and/or cavitary disease. Missed doses can lead to treatment failure, relapse, and acquired drug resistance.
INH RIF PZA EMB	8 weeks	7 days/week for 14 doses then twice weekly for 12 dosesg		INH RIF	18 weeks	2 times weekly for 36 doses		62	Do not use twice-weekly regimens in HIV-infected patients or patients with smear positive and/or cavitary disease. If doses are missed then therapy is equivalent to once weekly, which is inferior.

Abbreviations: INH = isoniazid; RIF = rifampin; PZA = pyrazinamide; EMB = ethambutol; HIV = human immunodeficiency virus

^aOther combinations may be appropriate in certain circumstances; additional details are provided in the Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.
^bWhen directly observed therapy (DOT) is used, drugs may be given 5 days per week and the necessary number of doses adjusted accordingly. Although there are no studies that compare 5 with 7 daily doses, extensive experience indicates this would be an effective practice. DOT should be used when drugs are administered less than 7 days per week.
^cBased on expert opinion, patients with cavitation on initial chest radiograph and positive cultures at completion of 2 months of therapy should receive a 7-month (31-week) continuation phase.
^dPyridoxine (vitamin B6), 25–50 mg/day, is given with INH to all persons at risk of neuropathy (e.g., pregnant women; breastfeeding infants; persons with HIV; patients with diabetes, alcoholism, malnutrition, or chronic renal failure; or patients with advanced age). For patients with peripheral neuropathy, experts recommend increasing pyridoxine dose to 100 mg/day.
^eThe recommended time frame for regimen, in tuberculosis control programs in the United States and in several European countries, is to administer all of the specified number of doses for the intensive phase within 3 months and those for the 4-month continuation phase within 6 months, so that the 6-month regimen is completed within 9 months.
^fIn general, TB drugs are administered together, at one dosing so as to achieve maximal peak serum concentrations and to facilitate DOT. Bioavailability of all of the drugs (except for RPT) is greatest when taken on an empty stomach.
^gAlternatively, some U.S. TB control programs have administered intensive-phase regimens 5 days per week for 15 doses (3 weeks), then twice weekly for 12 doses.

Note: Use of once-weekly therapy with INH 900 mg and rifapentine 600 mg in the continuation phase is not generally recommended. In uncommon situations where more than once-weekly DOT is difficult to achieve, once-weekly continuation phase therapy with INH 900 mg plus rifapentine 600 mg may be considered for use only in persons without HIV and without cavitation on chest radiography.

When using the 4-month rifapentine-moxifloxacin regimen as an option to treat people with drug-susceptible pulmonary TB disease, healthcare providers can consider the following information:

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

Considerations for the 4-month Rifapentine-moxifloxacin Regimen [PDF - 233 KB]

• 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 listed below

Note: A 4-month regimen for smear-negative, culture-negative, noncavitary pulmonary TB disease exists in the 2016 Treatment of Drug-Susceptible Tuberculosis Guidelines for the treatment of drug-susceptible TB disease and may also be used.

CDC recommends that clinical consultation be obtained to determine if the 4-month rifapentine-moxifloxacin regimen is an acceptable treatment option for

• People at increased risk of Mycobacterium tuberculosis (M. tuberculosis) resistance to any drug in the 4-month regimen
• People who received more than 5 doses of TB treatment in the prior 6 months
• People who received more than 5 doses of latent TB infection treatment in the prior 6 months
• People who received more than 5 doses of treatment with any one or more of the following drugs for any reason (e.g., urinary tract infection, pneumonia) in the prior 30 days:
  • Isoniazid (INH), rifampin (RIF), rifabutin, rifapentine (RPT), pyrazinamide (PZA), or any fluoroquinolone
• People who have serum or plasma alanine aminotransferase or aspartate aminotransferase more than 3 times the upper limit of normal or total bilirubin more than 2.5 times the upper limit of normal, or with preexisting advanced liver disease

• People who have renal insufficiency or end-stage renal disease, or
  • Serum or plasma creatinine level more than 2 times the upper limit of normal, or
  • Plasma potassium level less than 3.5 milliequivalents per liter (mEq/L)
• People who have types of extrapulmonary TB that are likely to be paucibacillary, not pose a substantial risk of death or disability, and not require prolonged treatment (i.e., pleural or lymph node TB)
• People with a sputum specimen that is unable to be submitted for any M. tuberculosis resistance testing prior to initiating the 4-month treatment regimen

CDC does not recommend the 4-month rifapentine-moxifloxacin regimen for

• People who are younger than 12 years old
• People with a body weight below 40 kilograms (kg)
• People who are pregnant or breastfeeding
• People who have most types of suspected or documented extrapulmonary TB
• People who have a history of prolonged QT syndrome or concurrent use of one or more QT-prolonging medications (in addition to moxifloxacin (MOX))
• People who are receiving medications with known clinically relevant drug-drug interactions with INH, RPT, PZA, or MOX
• People with a baseline M. tuberculosis isolate known or suspected to be resistant to RIF, INH, PZA, or any fluoroquinolone

For additional questions and answers about the 4-month rifapentine-moxifloxacin regimen, visit the Frequently Asked Questions (FAQs) webpage.

The State TB Control Offices and TB Centers of Excellence for Training, Education, and Medical Consultation can provide additional assistance and support in treating people with TB disease.

The 6-month regimen for the treatment of drug-susceptible pulmonary TB can be used in most patients. It consists of four anti-TB drugs and is sometimes called the RIPE regimen because of the medications

• Rifampin
• Isoniazid
• Pyrazinamide
• Ethambutol

CDC recommends the 9-month regimen for the treatment of drug-susceptible pulmonary TB for the following groups:

• People with cavitary pulmonary TB caused by drug-susceptible organisms and whose sputum culture obtained at the time of completion of 2 months of treatment is positive
• People whose intensive phase of treatment did not include pyrazinamide
• People with HIV who are not receiving antiretroviral treatment (ART) during TB treatment
• People being treated with once weekly isoniazid (INH) and rifapentine and whose sputum culture obtained at the time of completion of the intensive phase is positive
  (Note: Use of once-weekly therapy with INH 900 mg and rifapentine 600 mg in the continuation phase is not generally recommended. In uncommon situations where more than once-weekly directly observed therapy is difficult to achieve, once-weekly continuation phase therapy with INH 900 mg plus rifapentine 600 mg may be considered for use, but only in persons without HIV and without cavitation on chest radiography.) 

Learn more about considerations for

• Treatment of LTBI and TB for Persons with HIV
• Treatment for TB Disease & Pregnancy
• TB Treatment for Children
• Drug-Resistant TB