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U.S. Department of Health and Human Services

  

Core Curriculum on Tuberculosis, 2000

Chapter 7
Treatment of TB Disease

Regimens
(See tables 3 - 7)

Pulmonary TB

The duration of therapy depends on the drugs used, the drug susceptibility test results, and the patient’s response to therapy. All TB drugs should be given once daily rather than in divided doses. Most patients with previously untreated pulmonary TB can be treated with either a 6-month or a 9-month regimen, although the 6-month regimen is preferred8. Both the 6-month and 9-month regimens are referred to as short-course regimens. All regimens of 9 months or less must contain isoniazid and rifampin; all 6-month regimens must contain isoniazid, rifampin, and, initially, pyrazinamide.

For adults with smear- or culture-positive pulmonary TB, the initial phase of a 6-month regimen should consist of a 2-month period of isoniazid, rifampin, and pyrazinamide. Ethambutol or streptomycin should also be included in the initial regimen until the results of drug susceptibility studies confirm isoniazid and rifampin susceptibility.

The initial use of a four-drug regimen is recommended to prevent the development of multidrug-resistant TB in areas where the prevalence of primary isoniazid resistance is 4% or higher. If susceptibility to isoniazid and rifampin is demonstrated, the second phase of treatment should consist of isoniazid and rifampin for an additional 4 months.

If DOT is used, medications may be dosed intermittently. Several options exist for 6-month, intermittent regimens:

  • Four-drug therapy, administered daily for 8 weeks, may be followed by therapy with isoniazid and rifampin given two or three times a week for 16 weeks (if susceptibility to isoniazid and rifampin is demonstrated)9;
  • Four-drug therapy, administered daily for 2 weeks and then two times a week for 6 weeks, may be followed by therapy with isoniazid and rifampin given two times a week for 16 weeks (if susceptibility to isoniazid and rifampin is demonstrated)9;
  • Four-drug therapy may be administered three times a week throughout the 6-month treatment period. All four drugs should be continued throughout the course of treatment in this regimen10.

When isoniazid, pyrazinamide, and ethambutol or streptomycin are given two or three times a week instead of every day, their dosages must be increased. However, the dose of rifampin is the same whether the drug is given daily or intermittently.

Alternatively, a 9-month regimen of isoniazid and rifampin is acceptable for persons who cannot or should not take pyrazinamide (e.g., pregnant women). Again, streptomycin (except in pregnant women) or ethambutol should be included initially unless there is little possibility of drug resistance (patient has no individual risk factors for drug resistance and resides in an area where the prevalence of isoniazid-resistant TB < 4%). If susceptibility to isoniazid and rifampin is demonstrated, isoniazid and rifampin may be given twice weekly after an initial 4-8 weeks of daily treatment11.

For adults with smear- and culture-negative pulmonary TB (i.e., TB diagnosed only clinically), a 4-month regimen of isoniazid and rifampin combined with pyrazinamide for the first 2 months, may be used when drug resistance is unlikely12,13.

HIV-Positive Persons
(See table 4)

Management of HIV-related TB disease is complex, and the clinical and public health consequences associated with the failure of treatment are serious. 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.

Published guidelines recommend the use of antiretroviral therapy for patients infected with HIV14. Widely used antiretroviral drugs available in the United States include the protease inhibitors (saquinavir, indinavir, ritonavir, efavirenz, and nelfinavir) and the nonnucleoside reverse transcriptase inhibitors (NNRTIs) (nevirapine and delavirdine). However, these inhibitors interact with rifamycin derivatives, such as rifampin and rifabutin, which are used to treat and prevent the mycobacterial infections commonly observed in HIV-positive patients. Of the rifamycins, rifampin has the most potent interactions; rifabutin has substantially fewer interactions. Because the most recent recommendations for the use of antiretroviral therapy strongly advise against interruptions of therapy16, and because non–rifampin-containing alternatives for TB treatment are available, previous antituberculosis therapy options that involved stopping antiretroviral therapy to allow the use of rifampin are no longer recommended. The other class of antiretroviral agents available in the U.S., nucleoside reverse transcriptase inhibitors (NRTIs), which include zidovudine, didanosine, zalcitabine, stavudine, lamivudine, and abacavir, are not contraindicated with the use of rifamycins and do not require dose adjustments.

The use of rifampin to treat TB is not generally recommended for patients who

  • Will start treatment with an antiretroviral regimen that includes a protease inhibitor or an NNRTI at the same time they begin treatment for TB, or
  • Have established HIV infection that is being maintained on such an antiretroviral regimen when TB is newly diagnosed and needs to be treated.

Two TB treatment options are currently recommended for these patients:

  1. A rifabutin-based regimen
    The initial phase of a 6-month TB regimen for patients who are receiving therapy with protease inhibitors or NNRTIs consists of isoniazid, rifabutin, pyrazinamide, and ethambutol for the first 2 months (8 weeks). The initial phase should be followed by isoniazid and rifabutin to complete 6 months if sensitivity to isoniazid and rifampin has been documented. Treatment should be prolonged to 9 months or longer for patients with delayed response to therapy.
  2. An alternative nonrifamycin regimen that includes streptomycin
    The initial phase of a 9-month TB regimen for patients for whom the use of rifamycins is limited or contraindicated for any reason (e.g., intolerance to rifamycins, patient/clinician decision not to combine antiretroviral therapy with rifabutin), consists of a 2-month induction phase of isoniazid, ethambutol, pyrazinamide, and streptomycin, followed by isoniazid, pyrazinamide, and streptomycin administered 2-3 times per week for 7 months (30 weeks). Every effort should be made to continue the administration of streptomycin for the total duration of treatment. If streptomycin is not used for the recommended 9 months, ethambutol should be added to the continuation phase of the regimen and treatment duration should be prolonged from 9 months (38 weeks) to 12 months (52 weeks).

A rifampin-based regimen continues to be recommended for the treatment of TB in HIV-positive patients

  • Who have not started antiretroviral therapy, and both the patient and the clinician agree that it would be prudent to wait before starting such therapy, or
  • For whom antiretroviral therapy with a protease inhibitor or NNRTI is not recommended.

The following treatment option is recommended for these patients:

  • The initial phase of a 6-month regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for the first 2 months (8 weeks), followed by isoniazid and rifampin to complete 6 months. Isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) can be administered for the entire 6-month treatment period (26 weeks). Treatment should be prolonged to 9 months or longer for patients with delayed response to therapy.

However, new data indicate that rifampin can be used for the treatment of active TB disease for patients whose antiretroviral regimen includes

  • The NNRTI efavirenz and two nucleoside reverse transcriptase inhibitors (NRTIs);
  • The protease inhibitor ritonavir and one or more NRTIs;
  • The combination of two protease inhibitors (ritonavir and either saquinavir hard-gel capsule or saquinavir soft-gel capsule).

All patients should receive monthly clinical evaluations to monitor their response to treatment and medication side effects. During the early phase of treatment, the interval between these evaluations may be shorter (e.g., every 2 weeks).

DOT and other adherence-promoting strategies should be used for all patients with HIV-related TB. Pyridoxine (vitamin B6) (25-50 mg daily or 50-100 mg twice weekly) should be administered to all HIV-positive patients who are undergoing TB treatment with isoniazid to reduce isoniazid-induced side effects in the central and peripheral nervous system.

Note: These recommendations are not intended to substitute for the judgment of an expert physician. As new antiretroviral agents or new data regarding existing agents result in changes in therapeutic options and preferences for antiretroviral therapy, these changes in turn may impact the recommendations for the prevention and treatment of TB for patients coinfected with HIV.

 


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination - http://www.cdc.gov/tb

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