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U.S. Department of Health and Human Services


Core Curriculum on Tuberculosis, 2000

Chapter 7
Treatment of TB Disease


Drug-Resistant TB
(See table 3)

A 6-month regimen of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin has been demonstrated to be effective for the treatment of TB resistant only to isoniazid. 18 When resistance to isoniazid is documented during the recommended initial four-drug therapy, the regimen should be adjusted by discontinuing isoniazid and continuing the other three drugs for the entire 6 months of therapy. TB resistant only to isoniazid may also be treated with rifampin and ethambutol for 12 months. 19

When isoniazid resistance is documented in the 9-month regimen without pyrazinamide, isoniazid should be discontinued. If ethambutol was included in the initial regimen, treatment with rifampin and ethambutol should be continued for a minimum of 12 months. If ethambutol was not included initially, susceptibility tests should be repeated, isoniazid should be discontinued, and two other drugs, to which the isolate is susceptible (e.g., ethambutol and streptomycin), should be added. The regimen can be adjusted when the results of the susceptibility tests become available.

Multidrug-resistant TB (i.e., TB resistant to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on the patientís medication history and susceptibility studies.

Unfortunately, adequate data are not available on the effectiveness of various regimens and the necessary duration of treatment for patients with organisms resistant to both isoniazid and rifampin. Moreover, many of these patients also have resistance to other first-line drugs (e.g., ethambutol and streptomycin) when drug resistance is discovered. Because of the poor outcome in such cases, it is preferable to give at least three new drugs to which the organism is susceptible. This regimen should be continued until culture conversion is documented, followed by at least 12 months of two-drug therapy. Often, a total of 24 months of therapy is given empirically. Some experts recommend that at least 18-24 months of three-drug therapy be given after culture conversion. 20 MDR TB should be treated using a daily regimen under direct observation (DOT). Intermittent administration of medications is not possible in treatment of MDR TB.

Clinicians who are unfamiliar with the treatment of drug-resistant TB should seek expert consultation. Because second-line drugs can cause serious adverse reactions, patients taking these drugs should be monitored closely throughout the course of treatment. The role of agents such as the quinolone derivatives and amikacin in the treatment of multidrug-resistant disease is not well characterized, although these drugs are commonly being used in such cases. Surgery may offer considerable benefit and a significantly improved cure rate for patients who have multidrug-resistant TB if the bulk of disease can be resected. 21 However, drug therapy is usually required to sterilize the remaining disease.

TB Treatment for HIV-Positive Patients with Drug-Resistant TB

TB disease resistant to isoniazid only. The treatment regimen should generally consist of a rifamycin (rifampin or rifabutin), pyrazinamide, and ethambutol for the duration of treatment. Because the development of acquired rifamycin resistance would result in MDR TB, clinicians should carefully supervise and manage TB treatment for these patients.

TB disease resistant to rifampin only. The 9-month treatment regimen should generally consist of an initial 2-month phase of isoniazid, streptomycin, pyrazinamide, and ethambutol. The second phase of treatment should consist of isoniazid, streptomycin, and pyrazinamide administered for 7 months. Because the development of acquired isoniazid resistance would result in MDR TB, clinicians should carefully supervise and manage TB treatment for these patients.

Multidrug-resistant TB (resistant to both isoniazid and rifampin). These patients should be managed by or in consultation with physicians experienced in the management of MDR TB. Most drug regimens currently used to treat MDR TB include an aminoglycoside (e.g., streptomycin, kanamycin, amikacin) or capreomycin, and a fluoroquinolone, along with other agents to which the organism is sensitive. The recommended duration of treatment for MDR TB in HIV-positive patients is 24 months after culture conversion, and posttreatment follow-up visits to monitor for TB relapse should be conducted every 4 months for 24 months. Because of the serious personal and public health concerns associated with MDR TB, health departments should always use DOT for these patients and take whatever steps are needed to ensure their adherence to the treatment regimen.


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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