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A 32-year-old man is evaluated because of a 2-month history of fever, night sweats, weight loss, and cough. Ten months ago, he was incarcerated because of drug possession charges related to injection drug use. At that time, a tuberculin skin test and serologic studies for HIV were negative. A follow-up HIV test 6 weeks later was also negative. Since release from jail, he has been drug-free, lives alone, and is employed as a nighttime office janitor.
On physical examination, he has an occasional cough and appears chronically ill. Temperature is 38 °C (100.4 °F); other vital signs are normal. Fine crackles are auscultated over the right posterior thorax. A chest radiograph shows a right upper lobe infiltrate with a small cavity. A stained sputum specimen is positive for acid-fast organisms; sputum culture results are pending.
Which of the following is the most appropriate initial therapy for this patient?
A Isoniazid, pyrazinamide, and ethambutol
B Isoniazid, pyrazinamide, and ethionamide
C Isoniazid alone for 9 months
D Isoniazid, rifampin, pyrazinamide, and ethambutol
E No therapy until cultures confirm Mycobacterium tuberculosis
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D Isoniazid, rifampin, pyrazinamide, and ethambutol
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Using more than one medication to treat active TB. The standard initial treatment combines 4 medications to prevent multidrug-resistant TB. People who have latent TB may take one or two antibiotics.
Treating active TB for a minimum of 6 months and longer if necessary. Treatment for latent TB usually lasts 9 months with isoniazid or 4 months with rifampin.
Using direct observation treatment. This may mean daily visits with a health professional who watches you take your medication. A cure for TB requires you to take all doses of the antibiotics. These visits ensure that people follow medication instructions, which is helpful because of the long treatment course for TB.
Trying a different combination of medications if the treatment is not working because of drug resistance (when tests show that TB-causing bacteria are still active).
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(Correct Answer = D)
Key Point
When initiating antituberculous therapy, a four-drug regimen must be used if the probability of resistance to isoniazid is greater than 4%.
The initial treatment of this patient with active tuberculosis must include four antituberculous drugs. Therapy cannot be delayed until a definitive diagnosis of tuberculosis is made because that might take weeks and the infection could worsen or spread to other persons in the interim.
The American Thoracic Society, U.S. Centers for Disease Control and Prevention, and the Infectious Diseases Society of America have published recommendations for the management of tuberculosis. These guidelines are associated with published performance indicators that allow assessment of tuberculosis treatment by practitioners, although in most areas of the United States treatment can be effectively administered by municipal health authorities using directly observed treatment to minimize poor adherence and breakthrough or recurrent infection.
The guidelines recommend one of the following drug combinations: 1) isoniazid, rifampin, and pyrazinamide; 2) isoniazid, rifampin, pyrazinamide, and ethambutol; or 3) isoniazid, rifampin, pyrazinamide, and streptomycin. The guidelines also recommend that if the probability of resistance to isoniazid is greater than 4%, a fourth drug must be included to decrease the possibility of selecting for further drug-resistant mycobacteria. When susceptibility tests become available and the organism is shown to be susceptible to isoniazid, rifampin, and pyrazinamide, the fourth drug can eventually be stopped.
As of 1997, 84% of the U.S. population met the threshold of greater than 4% resistance to isoniazid. Consequently, unless there is compelling evidence to the contrary, most patients with newly diagnosed tuberculosis in the United States are treated, at least initially, with four-drug therapy. The patient described in this clinical scenario is most likely to have acquired his infection in prison. Because the likelihood of isoniazid resistance is extremely high in the prison population, initial treatment with a four-drug regimen is the best option.
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