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U.S. Department of Health and Human Services


Core Curriculum on Tuberculosis, 2000

Chapter 7
Treatment of TB Disease


For most patients, the preferred regimen for treating TB disease consists of an initial 2-month phase of four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol followed by a 4-month continuation phase of isoniazid and rifampin. Streptomycin may be substituted for ethambutol, but must be given by injection. Ethambutol (or streptomycin) can be discontinued when drug susceptibility results show the infecting organism to be fully drug-susceptible. In areas where the rate of isoniazid resistance is documented to be less than 4% and the patient has had no previous treatment with TB drugs, is not from a country with a high prevalence of drug resistance, and has no known exposure to a patient with drug-resistant disease, three drugs (isoniazid, rifampin, and pyrazinamide) may be adequate for the initial regimen. TB treatment regimens may need to be altered for HIV-positive patients taking HIV protease inhibitors. Whenever possible, the care for HIV-related TB should be provided by or in consultation with experts in the management of both TB and HIV disease. The major determinant of the outcome of treatment is patient adherence to the drug regimen. Thus, careful attention should be paid to measures designed to foster adherence, and treating all patients with directly observed therapy (DOT) is strongly recommended. Multidrug-resistant TB (i.e., TB resistant to both isoniazid and rifampin) presents difficult treatment problems and requires expert consultation.


After working through this chapter, you will be able to

  • Describe the recommended regimen for the initial treatment of TB in HIV-negative persons;
  • Describe the recommended TB treatment regimens for HIV-positive persons;
  • Explain why case management and directly observed therapy are important;
  • List the common adverse reactions to the drugs used to treat TB;
  • Describe how patients should be evaluated for their response to treatment.

TB must be treated for a long time (at least 6 months for most patients) compared with many other infectious diseases. If treatment is not continued for a sufficient length of time, some tubercle bacilli may survive and the patient may become ill and infectious again. Regimens for the treatment of TB must contain multiple drugs to which the organisms are susceptible. Treatment with a single drug can lead to the development of a bacterial population resistant to that drug. Likewise, the addition of a single drug to a failing anti-TB regimen can lead to resistance to that drug. When two or more drugs to which there is susceptibility are used simultaneously, each helps prevent the emergence of tubercle bacilli resistant to the others.

The initial phase of treatment is crucial for preventing the emergence of drug resistance and determining the ultimate outcome of the regimen. Four drugs isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin should be included in the initial treatment regimen until the results of drug susceptibility tests are available. Each of the drugs in the initial regimen plays an important role. Isoniazid and rifampin allow for short-course regimens with high cure rates. Pyrazinamide has potent sterilizing activity which allows further shortening of the regimen from 9 to 6 months. Ethambutol (or streptomycin) is added to prevent the emergence of drug resistance when primary isoniazid resistance is possible. In the rare circumstance where the disease-causing strain is known to be drug-sensitive or where the likelihood of drug resistance is low (i.e., less than 4% primary resistance to isoniazid in the community and the patient has had no previous treatment with TB drugs, is not from a country with a high prevalence of drug resistance, and has no known exposure to a patient with drug-resistant disease), three drugs (isoniazid, rifampin, and pyrazinamide) may be adequate for the initial regimen.

There are several options for daily and intermittent therapy, but the aim of treatment should be to provide the safest and most effective therapy in the shortest period of time. Given adequate treatment, almost all patients will become bacteriologically negative, recover, and remain well.

For each patient with newly diagnosed TB, a specific treatment and monitoring plan should be developed in collaboration with the local health department within 1 week of the presumptive diagnosis. This plan should include a description of the treatment regimen, the methods of assessing and ensuring adherence to the anti-TB regimen, and the methods of monitoring for adverse reactions.


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination -

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