In a new study of US veterans, azithromycin and levofloxacin were associated with increased risk for mortality and arrhythmias when compared with amoxicillin.
The elevated risks were present for azithromycin within the first 5 days of treatment, and for levofloxacin within the first 10 days of treatment.
In March 2013, the FDA issued a safety advisory stating that azithromycin may potentially cause fatal arrhythmias, especially in patients with risk factors, including existing QT interval prolongation, low levels of potassium or magnesium in the blood, slow heart rate and use of antiarrhythmic drugs. The statement noted that the risks were similar for fluoroquinolones such as levofloxacin.
Gowtham A. Rao, MD, PhD, MPH, from the University of South Carolina, and colleagues conducted a retrospective cohort study of US veterans aged 30 to 74 years (mean age, 56.8 years) who received an exclusive dispensation from the Department of Veterans Affairs of amoxicillin (n=979,380), azithromycin (n=594,792) or levofloxacin (n=201,798) between September 1999 and April 2012. Azithromycin was generally dispensed for 5 days, whereas amoxicillin and levofloxacin were generally dispensed for 10 days.
The endpoints were all-cause mortality and serious cardiac arrhythmia, defined as long QT syndrome, ventricular tachycardia, ventricular fibrillation, ventricular flutter or cardiac arrest.
To minimize confounding, the researchers adjusted for a number of covariates, including race/ethnicity, age, sex, indication for antibiotics, comorbidities, laboratory findings and medication.
During treatment days 1 to 5, patients who received azithromycin had increased risk for mortality (HR=1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR=1.77; 95% CI, 1.2-2.62) compared with patients who received amoxicillin. There was no difference between the groups during treatment days 6 to 10.
During treatment days 1 to 5, patients who received levofloxacin had increased risk for mortality (HR=2.49; 95% CI, 1.56-3.79) and serious arrhythmias (HR=2.43; 95% CI, 1.56-3.79) compared with patients who received amoxicillin. The elevated risk remained during treatment days 6 to 10 (HR for mortality=1.95; 95% CI, 1.32-2.88; HR for serious arrhythmias=1.75; 95% CI, 1.09-2.82).
According to Rao and colleagues, because only three antibiotics were investigated, the study cannot determine whether any other antibiotics might be safer.
However, they noted, “there are usually multiple antibiotic choices available for older patients, especially those with cardiac comorbidities; physicians may consider prescribing medications other than azithromycin and levofloxacin.”
Disclosure: The researchers report no relevant financial disclosures.