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Special Communication | Clinician's Corner

Update on the Treatment of Tuberculosis and Latent Tuberculosis Infection

Henry M. Blumberg, MD; Michael K. Leonard, MD; Robert M. Jasmer, MD
JAMA. 2005;293(22):2776-2784. doi:10.1001/jama.293.22.2776.
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Tuberculosis (TB) has emerged as a global public health epidemic. Despite decreasing numbers of cases in the United States since 1992, TB remains a serious public health problem among certain patient populations and is highly prevalent in many urban areas. The responsibility for prescribing an appropriate drug regimen and ensuring that treatment is completed is assigned to the public health program or the clinician not to the patient. The initial prescribed regimen for the treatment of TB usually consists of 4 drugs: isoniazid, rifampin, pyrazinamide, and ethambutol. The minimum length for the treatment of drug-susceptible TB with a rifampin-based regimen is 6 to 9 months. Providing medications directly to the patient and watching him/her swallow the anti-TB drugs, which is termed directly observed therapy, is recommended for all patients diagnosed with TB and can help ensure higher completion rates, prevent the emergence of drug resistant TB, and enhance TB control. There has been renewed interest in the treatment of those with latent TB infection as a TB-control strategy in the United States for eliminating the large reservoir of individuals at risk for progression to TB. The 2 broad categories of persons who should be tested for latent TB infection are those who are likely to have been recently infected (such as contacts to infectious TB cases) and persons who are at increased risk of progression to TB disease following infection with Mycobacterium tuberculosis (eg, human immunodeficiency virus infection and selected medical conditions; recent immigrants to the United States from high TB-burden countries). The preferred regimen for the treatment of latent TB infection is 9 months of isoniazid. There is now renewed interest in and great need for the development of new drugs to treat TB and latent TB infection.

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Figure 1. Treatment Completion Rates for Pulmonary Tuberculosis
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Error bars indicate range. DOT indicates directly observed therapy; TB, tuberculosis. Source: Chauk et al.9

Figure 2. Treatment Algorithm for Drug-Susceptible Pulmonary TB5
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Patients in whom tuberculosis (TB) is proved or strongly suspected should have treatment initiated with isoniazid, rifampin, pyrazinamide, and ethambutol for the initial 2 months of treatment. A repeat acid-fast bacilli (AFB) smear and culture should be performed when the initial 2 months of drug treatment has been completed. If cavitation was present on the initial chest radiograph and the TB culture was positive after 2 months of therapy, the continuation phase should be extended to 7 months (total treatment: 9 months). If cavitation was present on the initial chest radiograph but the TB culture was negative at 2 months, the total length of therapy should be 6 months (2 months of initial therapy and 4 months in the continuation phase). If a patient was infected with human immunodeficiency virus (HIV) and his/her CD4 cell count was lower than 100/μL, the continuation phase should consist of isoniazid and rifampin daily or 3 times weekly. In patients without HIV, without cavitation on chest radiograph, and negative AFB smears at completion of initial 2-month treatment, the continuation phase may consist of either (1) once-weekly isoniazid and rifapentine or (2) isoniazid and rifampin daily or twice weekly (total treatment: 6 months). In patients who took isoniazid and rifapentine and whose 2-month cultures were positive, treatment should be extended 3 months (total treatment: 9 months). Asterisk indicates ethambutol may be discontinued when results of drug susceptibility testing indicate no drug resistance. Dagger indicates pyrazinamide may be discontinued after it has been taken for 2 months. Double dagger indicates rifapentine should not be used in patients who have HIV and TB or in patients with extrapulmonary TB. Section symbol indicates therapy should be extended to 9 months if the 2-month culture was positive. Source: Blumberg et al.5

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