Should we Stop Prescribing Azithromycin in the ED?

In 2011, Azithromycin was the 7th most prescribed (55.3 million prescriptions) medication according to IMS Health.  There have been several publications indicating that the use of macrolide antibiotics, increase risk of serious ventricular arrhythmias and sudden cardiac death (FDA Adverse Event Reporting System). Specifically, 2 recent studies in the NEJM were published looking at the risk of Azithromycin with cardiovascular death and received lots of press.

Study #1: [1]

What they Did:

  • Retrospective, Observational Cohort Study
  • Tennessee Medicaid Cohort
  • Compared
    1. No antibiotics (1,391,180 prescriptions)
    2. Azithromycin (347,795 prescriptions)
    3. Amoxicillin (1,348,672 prescriptions)
  • Detect an increased risk of death

Primary Outcomes:

  • Cardiovascular death
  • Death from any cause


Cardiovascular Mortality Due to Azithromycin

  • Cardiovascular Risk Factors in This Study: Smoking, high BMI, poor diet, and low physical activity
  • NO statistically significant risk of death after the 5 day course of azithromycin completed


  • Observational, non-randomized clinical trial

Conclusion: During 5 days of azithromycin therapy, there is a small absolute increase in cardiovascular deaths and most pronounced in patients with a high baseline risk of cardiovascular disease

Study #2: [2]

What they Did:

  • Retrospective,  Observational Cohort Study
  • Danish Adults
  • Compared
    1. No antibiotics vs Azithromycin (1,102050 prescriptions compared in 1:1 ratio)
    2. Azithromycin vs Pencillin V (1,102,419 prescriptions vs 7,364,292 prescriptions)

Primary Outcomes:

  • Cardiovascular Death


  • No increase in cardiovascular death with recent or past use of azithromycin
  • No increase in cardiovascular death in patients with no history of cardiovascular disease
  • There is an increase in cardiovascular death in patients with a history of cardiovascular disease


  • Did not have information of known risk factors for cardiovascular disease (smoking and BMI)
  • Number of events in the subgroup analysis is low

Conclusion: Azithromycin use is not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults

Take Home Points:

  • In the second study the patient population had better cardiovascular health than the first study
  • The increased cardiovascular risk may be from the systemic infectious process and not azithromycin itself
  • You can still prescribe azithromycin, but remember the small increased risk of death in patients with cardiovascular disease and/or > 65 years of age


  1. Ray WA et al. Azithromycin and the Risk of Cardiovascular Death. NEJM 2012. PMID: 22591294
  2. Svanstrom H et al. Use of Azithromycin and Death from Cardiovascular Causes. NEJM 2013. PMID: 23635050

For more on this topic:

Cite this article as: Salim Rezaie, "Should we Stop Prescribing Azithromycin in the ED?", REBEL EM blog, November 19, 2013. Available at:

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