New study finds that use of azithromycin and levofloxacin are associated with significantly increased risk of death and serious arrhythmia, backing up a safety warning issued by the FDA in March 2013.

Short-term treatment with the antibiotics azithromycin and levofloxacin may increase the risk of serious cardiac arrhythmias and death, the results of a new study indicate.
Previous research has shown a relationship between treatment with azithromycin and an increased risk of cardiovascular death and all-cause mortality in Medicaid patients, especially those at a high risk for cardiovascular disease. These findings led the FDA to issue a public safety warning about the potential risks associated with the antibiotic and similar risks linked with levofloxacin.
Expanding on this research, the , published in the March/April 2014 issue of the Annals of Family Medicine, analyzed data from a cohort of veterans treated with azithromycin, levofloxacin, or amoxicillin and evaluated the risks of cardiac arrhythmia and death associated with use of each antibiotic. The analysis included 14 million patients who were treated at 140 Department of Veterans Affairs Medical Centers and 600 outpatient clinics from September 1999 through April 2012. Azithromycin was typically dispensed for 5 days, while amoxicillin and levofloxacin were generally dispensed for 10 days.  
The results indicated that treatment with either azithromycin or levofloxacin was associated with a significant increase in the risk of death and serious arrhythmia. Based on weighted analysis, 228 patients treated with azithromycin and 384 of those treated with levofloxacin per million antibiotics dispensed died after 5 days of treatment, compared with just 154 deaths in patients treated with amoxicillin. At 10 days after the start of treatment, 422 azithromycin patients and 714 levofloxacin patients died per million antibiotics dispensed, compared with 324 amoxicillin patients.
Within the first 5 days of treatment, patients receiving azithromycin had a 48% increased risk of death and a 77% increased risk of serious arrhythmia compared with patients who took amoxicillin. During days 6 to 10 after the beginning of treatment, however, the risk of both death and serious arrhythmia in patients receiving azithromycin were not significantly increased compared with those taking amoxicillin.
During the first 5 days of treatment, patients who received levofloxacin had a 149% increased risk of death and a 143% increased risk of serious arrhythmia compared with those who took amoxicillin. The increased risks associated with taking levofloxacin compared with taking amoxicillin remained significantly increased throughout the 10-day treatment period, with the risk of death increased 95% and the risk of serious arrhythmia increased 75%.
The findings support safety announcements from the manufacturer of azithromycin and the FDA, the authors note. They suggest that providers should consider the risks and benefits of the antibiotics before making prescribing decisions.
“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,” they conclude.