Gordon H. Sun, MD, MS

April 29, 2014

Cardiac Risk with Azithromycin

Despite the patient's comorbidities, he most likely can be treated safely as an outpatient. Using the British Thoracic Society Community Acquired Pneumonia Severity Calculations and Guidelines (CURB-65) system,[23] this patient scores a 0 out of 5 (no confusion, normal blood urea nitrogen level, respiratory rate < 30 breaths/min, blood pressure > 90/60 mm Hg, age < 65 years). For outpatient therapy in patients with cardiopulmonary comorbidities, the IDSA/ATS guideline for community-acquired pneumonia recommends fluoroquinolones, such as levofloxacin.[20]

Although the guideline also suggests a combination of a beta-lactam antibiotic and a macrolide as an alternative to fluoroquinolone therapy, one relatively recent concern is the side effect profile of azithromycin and other macrolides, particularly with respect to patients with cardiac disease. Large epidemiologic studies of Tennessee Medicaid patients[24] and US veterans[25] identified a significantly increased risk for serious arrhythmias and cardiovascular-related mortality with the use of azithromycin compared with amoxicillin. The Tennessee study led to a March 2013 safety alert from the FDA that azithromycin could trigger fatal QT interval prolongation and torsades de pointes.[26]

Of note, a third epidemiologic study conducted in a general population of Danish adults found no association between azithromycin use and increased risk for cardiovascular-related death.[27] However, in contrast to the first 2 studies, the cohort in the Danish study was generally younger and healthier. Thus, the cardiovascular risk associated with azithromycin use may be more pronounced in older people or those with cardiac or electrolyte comorbidities, such as existing QT interval prolongation and hypokalemia.

In the illustrated case, azithromycin would probably not be a good option, given the patient's known history of atrial fibrillation. An acceptable alternative to fluoroquinolone therapy for this patient would include a beta-lactam antibiotic combined with doxycycline (but neither as monotherapy).


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