A SUMMARY OF THE GUIDELINES FROM THE AMERICAN THORACIC SOCIETY AND THE CENTERS FOR DISEASE CONTROL (1993)
Treatment of active tuberculous infection:
Tuberculous disease refers to symptomatic infection with Mycobacterium tuberculosis (MTB) or, less commonly, Mycobacterium bovis as opposed to latent tuberculous infection, which refers to asymptomatic contamination with MTB.
Tuberculosis may be treated with a 6-month regimen consisting of isoniazid, rifampin, and pyrazinamide for 2 months followed by isoniazid and rifampin for an additional 4 months. This is the preferred therapy in patients infected with susceptible organisms who are compliant with therapy. Ethambutol, or streptomycin in children too young to inform medical personnel of drug-induced visual changes, should be included in the initial regimens until drug susceptibility results are available unless there is a low chance or incidence of drug resistance.
An alternative regimen includes 9 months of therapy with isoniazid and rifampin. This method of therapy is often used in patients who can not tolerate pyrazinamide. Ethambutol, or streptomycin in children too young to inform medical personnel of drug-induced visual changes, should be included in the initial regimen until drug susceptibility results are available, unless there is a low chance or incidence of drug resistance. If the infecting organism is found to be resistant to isoniazid on sensitivity testing, then therapy should include rifampin and ethambutol for a minimum of 12 months.
Adults who have active tuberculosis but are smear-negative and culture-negative, may be treated with a 4-month regimen of isoniazid and rifampin. This is provided that there is a low incidence of drug resistance.
Multidrug-resistant Mycobacterium tuberculosis (defined as those organisms with demonstrated resistance to at least isoniazid and rifampin on susceptibility testing) should be treated based on the results of susceptibility testing. An expert in tuberculosis infection (either an ifectious disease specialist or a pulmonologist) should be consulted to help manage these patients. Second line agents include streptomycin, para-aminosalicylic acid, ethionamide, cycloserine, kanamycin, capreomycin, ciprofloxacin, and ofloxacin.
Children should be treated similarly to adults except that dosage adjustments should be made in the individual medications. Therapy for extrapulmonary tuberculosis is similar to therapy for pulmonary disease. The exceptions are persons who have miliary disease, bone or joint involvement, or tuberculous meningitis. In these cases, therapy is similar except that it should be continued for a minimum of 12 months.
Pregnant women with active disease should receive treatment with isoniazid or rifampin and, if drug resistance is suspected, with ethambutol. These drugs are safe with no significant side effects to the fetus. Pyrazinamide should not be used during pregnancy because its teratogenic potential has not been determined. Breast-feeding during therapy should not be discouraged.
In cases of culture-positive disease, repeat cultures should be performed monthly until they are negative. Repeated culture testing is also recommended upon completion of therapy to ensure adequate treatment of disease. Cases of smear-negative and culture-negative active disease should be treated with 4 months of isoniazid and rifampin as outlined above, and response to therapy should be monitored with serial chest radiographs. A lack of radiographic response after 3 months may indicate prior inactive tuberculous infection.
Treatment of latent tuberculous infection:
Latent tuberculosis infection refers to asymptomatic contamination with Mycobacterium tuberculosis. These patients are PPD-positive but lack any of the characteristic symptoms associated with pulmonary tuberculous disease. Preventive therapy with isoniazid given for 6 to 9 months is an effective prophylaxis against the risk of future tuberculous disease in children and adults with tuberculous infection. It is believed that preventive therapy effectively decreases or eradicates mycobacterial contamination in healed or radiographically invisible lesions. Studies have shown that prophylactic therapy in PPD-positive persons persists for as long as 20 years, and, in the absence of reinfection, it is believed that the protective effect offered by prophylactic therapy persists for life. Studies by the US Public Health Service have shown that preventive therapy with INH decreases the incidence of active disease by 54-88%. It is advised that PPD-positive persons with any of the following conditions, regardless of age, should be considered candidates for prophylaxis: HIV-positive persons, persons with risk factors for HIV whose current HIV status is unknown, close contacts of persons with active tuberculous disease who are newly PPD-positive, recent skin test converters, and persons with medical conditions associated with an increased risk for tuberculous infection (diabetes mellitus, patients receiving steroid or other immunosuppressive therapy, intravenous drug abusers, hematologic and reticuloendothelial malignancies, end-stage renal disease, and conditions associated with rapid weight loss or chronic undernutrition). In some instances, certain individuals with negative PPDs are candidates for prophylaxis including children who are close contacts of infectious cases and HIV-infected adults who are anergic and at an increased risk for tuberculosis.
PPD-positive adults whose chest radiograph demonstrates fibrotic lesions likely representing old healed tuberculosis and adults with silicosis should receive either 4 months of multidrug chemotherapy (isoniazid plus rifampin) or 12 months of isoniazid. Persons who are HIV positive and in close contact with TB should undergo evaluation for evidence of tuberculosis. If the workup for active tuberculosis is negative, these persons should receive preventive therapy with isoniazid. Therefore, it is important to offer HIV testing to anyone who is in close contact to patients with active tuberculosis and admit to any risk factors that might increase the likelihood of HIV infection. The reason is that TB prophylaxis is administered differently to HIV-positive persons. Prophylaxis for HIV-positive patients (both children and adults) or patients with other conditions associated with immunosuppression entails 12 months of isoniazid therapy; however, 6 months of therapy is adequate in HIV-negative adults. HIV-negative children require 9 months of prophylaxis as per the Academy of Pediatrics.
Prophylactic therapy in pregnant women should be deferred until after delivery. Treatment of tuberculous infection is not a contraindication to breast-feeding, and infants who are breast-feeding from mothers on isoniazid therapy should not be considered adequately treated if they are PPD-positive.