Azithromycin, levofloxacin associated with increased cardiac risk versus amoxicillin

Azithromycin and levofloxacin were both associated with increased cardiac risk compared with amoxicillin, a recent study found.

Researchers conducted a retrospective cohort study among U.S. veterans to determine whether azithromycin or levofloxacin would result in increased risk for cardiovascular death and cardiac arrhythmia versus amoxicillin. Patients between ages 30 and 74 who were treated at a Department of Veterans Affairs facility, including medical centers and outpatient clinics, between September 1999 and April 2012 and who received exclusive outpatient dispensing of amoxicillin, azithromycin, or levofloxacin were included. Amoxicillin and levofloxacin were usually dispensed for at least 10 days; azithromycin was usually dispensed for 5 days. The study's primary and secondary endpoints were all-cause mortality and serious cardiac arrhythmia. The study results were published in the March/April Annals of Family Medicine.

Throughout the study period, 979,380 patients were prescribed amoxicillin, 594,792 were prescribed azithromycin, and 201,798 were prescribed levofloxacin. The mean age of the cohort was 56.5 years; 71% of patients were white, 18.4% were black, and 88% were men. In the first 5 days of treatment, risk for death and serious arrhythmia was significantly higher in patients taking azithromycin compared with amoxicillin (hazard ratios, 1.48 [95% CI, 1.05 to 2.09] and 1.77 [95% CI, 1.20 to 2.62], respectively). Risks did not differ significantly between patients taking these 2 drugs on days 6 to 10. Patients taking levofloxacin also had a higher risk for death and serious cardiac arrhythmia than those taking amoxicillin during days 1 to 5 (hazard ratios, 2.49 [95% CI, 1.7 to 3.64] and 2.43 [95% CI, 1.56 to 3.79], respectively), but this increase in risk persisted during days 6 to 10 (hazard ratios, 1.95 [95% CI, 1.32 to 2.88] and 1.75 [95% CI, 1.09 to 2.82], respectively).

The authors noted that their results might have been affected by residual unmeasured confounding and that the differences in mortality may have reflected differences in the reasons for antibiotic use, among other limitations. However, they concluded that their results show an increase in cardiac risk with azithromycin and levofloxacin and support recent safety announcements from the FDA and from industry about these drugs. “There are usually multiple antibiotic choices available for older patients, especially those with cardiac comorbidities,” the authors wrote. “Physicians may consider prescribing medications other than azithromycin and levofloxacin.”