Clinical Question

Is the use of azithromycin (Zithromax) for older patients hospitalized with pneumonia associated with increased mortality or an increased risk of cardiovascular events?

Bottom Line

For older patients hospitalized with pneumonia, the use of combination antibiotic therapy including azithromycin is associated with decreased mortality but an increased risk of myocardial infarction (MI). You would need to treat 21 patients with azithromycin to prevent one death within 90 days; you would need to treat 144 patients to cause one MI. This results in a net benefit of seven deaths prevented for one nonfatal MI induced with the use of azithromycin. (Level of Evidence = 2b)

Synopsis

Using data from the Veterans Administration health care system, these authors examined the association of azithromycin with death and cardiovascular outcomes in older patients who were hospitalized with pneumonia. Patients included in the study were at least 65 years of age who received antibiotic therapy per guidelines from the Infectious Diseases Society of America and the American Thoracic Society for the treatment of community-acquired pneumonia. Primary outcomes were death at 30 days and at 90 days, as well as cardiovascular events within 90 days. The cohort was divided into those who received combination therapy (which included azithromycin) and those who received other guideline-concordant antibiotics.

Subsequently, propensity scores were used to match patients based on potential confounders—such as age, intensive care unit admission, and history of cardiac disease—that could affect the severity of illness or outcomes. Almost 64,000 patients were included in the propensity-matched analysis. Patients had a mean age of 78 years, 16% were admitted to the intensive care unit, and 5% received invasive mechanical ventilation. In this cohort, 90-day mortality was lower for azithromycin users (17% vs. 22%; odds ratio [OR] = 0.76; 95% confidence interval [CI], 0.73 to 0.80). Although azithromycin users had more MIs (5.1% vs. 4.4%; OR = 1.17; 95% CI, 1.08 to 1.25), there were no statistically significant differences in overall cardiac events, cardiac arrhythmias, or heart failure.

Study design: Cohort (retrospective)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Reference: MortensenEMHalmEAPughMJet alAssociation of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia. JAMA2014; 311( 21): 2199– 2208.