Farmacologia

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

clinical therapeutics

Antibiotic Prevention of Acute Exacerbations of COPD
Richard P. Wenzel, M.D., Alpha A. Fowler III, M.D., and Michael B. Edmond, M.D., M.P.H., M.P.A.
This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism ofbenefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the authors’ clinical recommendations.

From the Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond. Address reprint requests to Dr. Wenzelat 1 Capital Sq., 830 E. Main St., Richmond, VA 23219, or at rwenzel@mcvh-vcu.edu.
N Engl J Med 2012;367:340-7. DOI: 10.1056/NEJMct1115170
Copyright © 2012 Massachusetts Medical Society.

A 55-year-old man presents with a history of recurrent exacerbations of chronic obstructive pulmonary disease (COPD) during the past year. These episodes were characterized by increased shortness of breath,cough, and sputum production. The diagnosis of COPD was made 2 years previously. Pulmonary-function testing then revealed a forced expiratory volume in 1 second (FEV1) of 50% of the predicted value after bronchodilator inhalation, with a ratio of FEV1 to forced vital capacity (FVC) of 60%. The patient had a 30-pack-year smoking history but stopped smoking after chronic lung disease was diagnosed.On the current visit, he is afebrile and has a resting pulse of 84 beats per minute. A careful review confirms that he is knowledgeable about proper inhaler use and that he is compliant with his medications, which include maintenance therapy with salmeterol and fluticasone as well as albuterol plus ipratropium as needed for intermittent therapy for increased dyspnea. His physician recommends theuse of azithromycin at a dose of 250 mg daily to reduce the frequency of acute exacerbations.

The Cl inic a l Probl em
An estimated 24 million persons in the United States have COPD on the basis of lung-function testing.1 Globally, COPD is the fourth leading cause of death,2 and in the United States it is the third most common cause of death and chronic complications.3 The average personwith COPD has one to two acute exacerbations each year, with wide variation from patient to patient.4 In 2000 in the United States, 726,000 patients were hospitalized with acute exacerbations of COPD.1 During an acute exacerbation, antibiotics are generally administered for 5 to 10 days,5 creating a national burden of 120 million to 480 million antibiotic-days annually. The median hospital stay perexacerbation has been estimated at 9 days.6 In a 2007 Canadian study, the median cost of a hospital stay after an acute exacerbation of COPD was $9,557 (Canadian dollars).7 Acute exacerbations of COPD requiring hospitalization are associated with a 30-day rate of death from any cause of 4 to 30%.6 A study in Sweden showed an all-cause mortality of 26% at 30 days and of 69% at 3 years.8 Acuteexacerbations also accelerate the progressive decline in lung function associated with COPD. Overall, the FEV1 falls by approximately 33 ml per year in patients with COPD.4 Each acute exacerbation increases the rate of decline by an additional 2 ml per year4 and by up to 7 ml per year in smokers.6
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n engl j med 367;4

nejm.org

july 26, 2012

The New England Journal of MedicineDownloaded from nejm.org on October 25, 2012. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. All rights reserved.

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