Treatment of Tuberculosis and Latent Tuberculosis Infection
abstract & commentary
By Joseph E. Scherger, MD, MPH
Clinical Professor, University of California, San Diego
Dr. Scherger reports no financial interests in this field of study.
Synopsis: The treatment of pulmonary tuberculosis is divided into an initial phase of 4 drugs for 2 months (isoniazid, rifampin, pyrazinamide, and ethambutol) followed by continuation phase depending on culture results and patient risk. The treatment of latent tuberculosis now consists of 9 months of isoniazid, with rifampin as an alternative for 4-6 months in patients not tolerant of isoniazid. Special populations, such as HIV-positive patients, require special consideration in treatment.
Source: Blumberg HM, et al. Update on the treatment of tuberculosis and latent tuberculosis infection. JAMA. 2005;293:2776-2784.
Tuberculosis (TB) remains an important public health problem in the United States and globally. Most patients in the United States diagnosed with tuberculosis today were not born in the United States. HIV-infected persons remain an important subgroup with TB, and all patients with a new diagnosis of TB should be tested for HIV. TB should remain high on the differential diagnosis of any patient with fever, cough, sputum production and a positive chest x-ray with localized infiltrates. TB in other sites such as bone, meninges, and pericardium should also be kept in mind. Specimens must be obtained to confirm the diagnosis and test for drug susceptibility.
The treatment of tuberculosis has been refined to a 2-month initial phase and a 4-7 month continuation phase depending on severity of infection and patient risk factors. The initial phase consists of 4 drugs: isoniazid, rifampin, pyrazinamide and ethambutol; given for 8 weeks. Direct observation therapy is highly recommended, and alternative programs of 3, 5, and 7 days a week are available. Specimens are obtained for culture after 2 months to help guide the continuation therapy. If cultures are negative at 2 months, the continuation phase may be limited to 4 months. If not, the continuation phase should be 7 months for a total of 9 months of therapy.
Two drugs are used for continuation therapy—isoniazid and rifampin or isoniazid and rifapentine. Dosage schedules are available of 1, 2, 3 or 7 days a week. Direct observation therapy is again recommended for all patients to ensure completion of therapy and the avoidance of drug resistant organisms due to partial treatment. HIV positive patients should not be given the once weekly therapy with isoniazid and rifapentine, and if the CD4 count is below 100, they should not be given the 2-day-a-week therapy.
The treatment of latent TB infection remains an important means of controlling tuberculosis in both individual patients and society. Two broad categories of patients are highly recommended for treatment for latent infection: recently infected patients (such as contacts of persons with active tuberculosis), and recent immigrants to the United States from high prevalence countries. HIV positive patients should also be treated for latent infection if present. A chest x-ray and a symptom review for extrapulmonary involvement should be done to rule out active infection. Nine months of therapy with isoniazid is currently recommended for latent infection. Clinical observation for hepatitis is done, including patient education for warning signs and symptoms. Baseline and monthly liver function tests are not necessary. Treatment should be stopped only if transaminase levels are higher than 5 times normal in an asymptomatic patient, and higher than 3 times normal in a patient with symptoms. Pyridoxine 25-50 mg is given to prevent neuropathy only in patients predisposed to this complication such as with diabetes, uremia, malnutrition, and HIV-positive patients
For patients who cannot tolerate isoniazid, or have isoniazid resistant infection, rifampin alone can be used to treat latent infection for 4 months in adults and 6 months in children.
Commentary
I currently work in a program which assesses physician competence. We present a series of cases in a standardized format. One case is a middle aged man with 6 weeks of fever and productive cough. A right upper lobe infiltrate is seen on chest x-ray. Alarmingly, many physicians treat this patient with antibiotics and send him home. Some admit the patient to the hospital for antibiotics, with no skin testing, acid fast smears or cultures, and not in isolation. Today, many physicians are not sensitive to the risk of tuberculosis infection. Much harm is done when a patient with active tuberculosis infects health care workers, family members and other patients. Tuberculosis is still with us in large numbers, and should be considered in a wide range of patients, especially among immigrants to the United States and those persons at risk for sexually transmitted disease (including HIV).
This JAMA source was part of a special issue on tuberculosis (June 8, 2005, www.jama.com). The Centers for Disease Control and Prevention, the American Thoracic Society and the Infectious Disease Society of America have joined together to provide these current recommendations. This summary has only given the highlights. For more details, the JAMA article is highly recommended.
The treatment of pulmonary tuberculosis is divided into an initial phase of four drugs for two months.
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