The preferred antitubercular regimen in susceptible cases consists of an initial 2-month treatment with four drugs (isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin) followed by a 4-month phase of isoniazid and rifampin. Total treatment time is typically 6 months. If the local prevalence of isoniazid resistance is less than 4%, and the patient is not from an area with a high prevalence of drug resistance, then ethambutol (or streptomycin) may be withheld from the first phase. If cultures show that the organism is fully drug susceptible, then the ethambutol (or streptomycin) may be discontinued.Prior to the initiation of therapy, patients should have sufficient material obtained for culture to particularly ensure that susceptibility testing can be undertaken. In addition, baseline laboratory studies should be performed, including measurement of liver-associated enzymes, total bilirubin, and a complete blood cell count. All patients diagnosed with tuberculosis should be offered HIV testing. If treatment with pyrazinamide is considered, a baseline uric acid level should be obtained, and if ethambutol is to be used, both visual acuity and color perception should be evaluated.
Directly Observed TherapyStudies have shown that clinicians are unable to predict patient compliance. Patient compliance is one of the key factors in treatment success and in the prevention of drug resistance. Directly observed therapy implies that a health care provider is present when the patient takes the medications. Although labor intensive, directly observed therapy is effective, especially when intermittent dosing regimens are chosen. It may take place in an office or clinic setting, or may consist of outreach workers who travel to the patient’s residence. If the patient remains noncompliant with therapy, the local health department should be contacted to mobilize additional resources.
HIV InfectionTreatment of tuberculosis in the HIV-infected patient is complicated by drug interactions, particularly for patients on antiretroviral therapy. The administration of rifampin with certain protease inhibitors and non-nucleoside reverse transcriptase inhibitors can cause elevations in levels of rifampin, and sub-therapeutic levels of the antiretroviral agents. One should not discontinue antiretroviral therapy so that rifampin can be used to treat tuberculosis. Instead, rifabutin can be substituted for rifampin and used in combination with the protease inhibitors indinavir or nelfinavir as well as most available non-nucleoside reverse transcriptase inhibitors. Rifabutin should not be used with the protease inhibitor ritonavir or the non-nucleoside reverse transcriptase inhibitor delavirdine. If a regimen that does not contain rifabutin or rifampin is desired, a regimen consisting of isoniazid, pyrazinamide, and streptomycin for 9 months, with ethambutol added for the first 2 months, is recommended. Given the complexities of antiretroviral therapy and the potential for drug interactions, patients with HIV infection and tuberculosis should be referred to clinicians who are experienced in the treatment of both infections.
PregnancyPregnant women diagnosed with tuberculosis should be treated promptly. The preferred initial regimen is isoniazid, rifampin, and ethambutol. Streptomycin should not be used because of known teratogenic effects. The safety of pyrazinamide in pregnancy is unknown, and this drug should be avoided. Once the organism is known to be susceptible, ethambutol can be discontinued. The duration of treatment with regimens without pyranzinamide is typically 9 months.*62/348/5*
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