Treatment for Drug-Susceptible Tuberculosis Disease

Overview

Treating TB disease benefits the patient and the community by:

• Curing the patient,
• Minimizing risk for death and disability,
• Reducing transmission of TB bacteria to other people, and
• Preventing acquisition of drug resistance during treatment.

Given full treatment with an appropriate regimen, almost all patients will recover and be cured.

Selecting a treatment regimen

There are recommended for use in the United States. Treatment for drug-susceptible TB disease typically takes 4, 6, or 9 months depending on the regimen. Directly observed therapy (DOT) is the standard of care.

The goal of treatment for TB disease should be to provide the safest, most tolerable and most effective therapy for the shortest period of time. Health care providers should choose the appropriate TB treatment regimen based on:

• Drug-susceptibility results,
• Coexisting medical conditions, and
• Potential for drug-drug interactions.

Guidelines

Phases of treatment

Treatment regimens for drug-susceptible TB disease consist of an intensive treatment phase followed by a continuation phase.

If treatment is not continued for a long enough time, the surviving bacilli may cause TB disease in the patient later. The possibility of drug resistance increases if too many doses are missed during the period of treatment, especially if the patient is taking only some of the prescribed medicines instead of all of them.

• During the intensive phase, the TB drugs kill actively growing TB bacilli. This phase of treatment is crucial for determining the ultimate clinical outcome and preventing emergence of drug resistance. For most patients, it brings relief from the disabling symptoms of TB disease.
• During the continuation phase, the TB drugs eliminate any remaining TB bacilli. This helps to reduce treatment failure and relapse.

4-month (2HPZM/2HPM) treatment regimen

The 4-month 2HPZM/2HPM TB treatment regimen consists of:

• Isoniazid (H),
• Rifapentine (P),
• Pyrazinamide (Z), and
• Moxifloxacin (M)
  

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

Recommendations

The 4-month rifapentine-moxifloxacin regimen is an option for treating pulmonary TB disease caused by organisms that are not known or suspected to be drug-resistant for:

• 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 an antiretroviral therapy (ART) regimen that does not have known drug-drug interactions with the 2HPZM/2HPM regimen, and
• People who have no contraindications to this regimen.

6- to 9-month (2HRZE/4HR or 2HRZE/7HR) treatment regimens

The 6- to 9-month 2HRZE/4HR or 2HRZE/7HR TB treatment regimens consist of:

• Isoniazid (H),
• Rifampin (R)
• Pyrazinamide (Z), and
• Ethambutol (E).

These regimens for treating TB disease have an intensive phase of 2 months of isonaizid, rifampin, pyrazinamide, and ethambutol (2HRZE), followed by a continuation phase of either 4 or 7 months of isonaizid and rifampin (4HR or 7HR) for total of 6 to 9 months for treatment.

Recommendations

6-month 2HRZE/4HR regimen

CDC recommends the 6-month 2HRZE/4HR regimen as an option for treating drug-susceptible pulmonary TB disease for adults and adolescents.

9-month 2HRZE/7HR regimen

CDC recommends the 9-month 2HRZE/7HR regimen for the treatment of drug-susceptible pulmonary TB disease for:

• People with cavitary pulmonary TB disease caused by drug-susceptible organisms and whose sputum culture obtained at the time of completion of 2 months of treatment persists positive with drug-susceptible organism,
• People whose intensive phase of treatment did not include pyrazinamide or whose organism was identified as resistant to pyrazinamide,
• People with HIV who did not or are unable to receive antiretroviral therapy (ART) during TB treatment.
  

Summary table

This table describes 6-month treatment regimens for drug-susceptible TB disease.

This table describes 6-month treatment regimens for drug-susceptible TB disease.

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.

^aOther combinations may be appropriate in certain circumstances; additional details are provided in the .
^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.

Other treatment regimens

Health care providers may consider using other treatment regimens in certain cases. TB treatment guidelines, TB programs, and the TB Centers of Excellence for Training, Education, and Medical Consultation can provide additional information.

A 4-month regimen of isonaizid, rifampin, pyrazinamide, and ethambutol may be used for smear-negative, culture-negative, noncavitary pulmonary TB disease. Consult the for more information.

For information on TB disease treatment regimens for specific populations, refer to clinical guidelines or:

Evaluation and testing considerations

Healthcare providers should evaluate a patient’s response to treatment to determine the efficacy of the treatment and to identify any adverse reactions through:

1. Clinical evaluation (including symptom and medication review and physical examination),
2. Laboratory evaluation including bacteriologic examination, and
3. Chest radiograph and other relevant imaging (depending on the site of the disease).

Consult CDC guidelines, clinical resources, drug package inserts, and other medical sources for information about side effects or drug-drug interactions. Adverse reactions to anti-TB drugs are relatively rare, but for certain patients, they can be severe.

Clinical evaluation

Patients should have clinical evaluations at least monthly to:

• Identify possible adverse reactions to medications,
• Assess adherence, and
• Determine treatment efficacy.

Although each patient responds to treatment at a different pace, all TB signs and symptoms should gradually improve and eventually resolve. If a patient’s symptoms do not improve during the first 2 months of treatment, or if symptoms worsen after initial improvement, the patient should be evaluated for nonadherence to, or malabsorption of, the treatment regimen; development of drug resistance; or symptoms consistent with immune reconstitution.

Laboratory evaluation

Testing recommendations and frequency vary depending on the treatment regimen. Consult CDC guidelines for more information on recommended tests.

Laboratory evaluation may include rapid molecular testing, acid-fast bacilli smear microscopy and culture, phenotypic drug susceptibility testing, and other tests as recommended.

Crucial treatment decisions concerning the continuation phase regimen are based on the patient's bacteriologic status at the end of the intensive treatment phase. For patients with extrapulmonary TB disease, the frequency and kinds of evaluations will depend on the sites involved and the ease with which specimens can be obtained.

Additional monitoring may be recommended, depending on the prescribed regimen. Patients taking other medications or with underlying comorbidities with higher risk for adverse events may also require additional considerations.

Chest radiograph

All patients should have a chest radiograph prior to treatment and also after 2 months of treatment if baseline cultures are negative. For patients with pulmonary TB disease who had an abnormal chest imaging at treatment initiation, repeat chest radiograph can be useful after 2 months of treatment and at treatment completion to evaluate for treatment response.

Other imaging might be used for monitoring of extrapulmonary disease.

Adherence strategies

It is critically important for people with TB disease to complete recommended treatment. Health care providers should consult their health department's TB program to ensure that TB patients can adhere to a prescribed treatment regimen. TB programs can provide information on strategies and programs that can assist the patients with completing treatment for TB disease.

Directly observed therapy

CDC recommends directly observed therapy (DOT) as the standard of care for TB disease treatment. During DOT, a health care worker observes (in-person or virtually) a patient ingest the medications, monitors for adverse events, and provides social support.

Video DOT (vDOT) is a type of electronic DOT (eDOT). It uses a video-enabled device (e.g., smart phone, tablet, computer) for TB treatment observation. CDC recommends vDOT as an equivalent alternative to in-person DOT during TB treatment.

However, in-person DOT may be a better option for patients who:

• Receive injectable medications,
• Would benefit from additional monitoring, or
• Are unable to use vDOT technology.

Patient education

Educating patients about TB disease helps ensure successful therapy completion. Health care providers should cover topics such as:

• Expected clinical outcomes and duration of therapy;
• General principles about infectiousness before and during therapy;
• What medications to take, how much, how often, and when;
• Possible adverse reactions to the medications;
• When it is necessary to seek medical attention;
• Consequences of not taking medications as prescribed;
• TB infection control measures and potential need for isolation;
• Treatment reminders;
• Availability of TB program staff support;
• Patient support groups; and
• Directly observed therapy.

Side effects

Inform patients that rifampin and rifapentine may cause urine or other body fluids to turn orange. This side effect is harmless. Contact lens wearers may wish to choose disposable lenses during treatment since rifamycins can permanently stain lenses.

Instruct patients at the start of treatment to stop taking their medication and seek medical attention immediately if they experience any of the following medication side effects:

• Unexplained anorexia, nausea or vomiting, dark urine, or icterus (jaundice);
• Persistent numbness, pain, tingling, or hot or cold sensations in the hands or feet;
• Persistent weakness, fatigue, fever, or unexplained or persistent abdominal pain;
• Easy bruising or bleeding;
• Blurred vision or changed vision; or
• Rash.

Patient education resources

Patient education materials are available in multiple languages and formats from:

Support for patients with TB disease

Contact your state or local TB program or organizations like for information on support groups for people with TB disease. CDC's TB personal stories video series highlights the personal experiences of people who were diagnosed and treated for TB disease.

Post-treatment considerations

People who have had a satisfactory response to a TB disease treatment regimen do not require routine follow up after treatment completion.

People should receive documentation of their diagnosis and treatment to have available if future TB testing is required. This should include:

• TB blood test or TB skin test results,
• Chest radiograph results,
• Names and dosages of medication, and
• Duration of treatment.

Remind patients about the signs and symptoms of TB disease and advise them to seek medical care if they develop any of these signs or symptoms in the future.

Most people who have a positive TB test result will continue to have a positive test result. Additional TB blood tests or TB skin tests will probably not contribute to medical care, regardless of the result.

Resources