Antibiotics Elevate Risk of Death, Cardiac Arrhythmias

In a new study, the antibiotics azithromycin and levofloxacin were associated with greater risks of death and serious cardiac arrhythmias during standard lengths of prescriptions.

University of South Carolina School of Medicine researchers analyzed data from military veterans receiving outpatient treatment with amoxicillin (979,380 patients), azithromycin (594,792 patients), or levofloxacin (201,798 patients) within the Veterans Affairs healthcare system from September 1999 to April 2012. According to the authors, the average patient age was 56.5 years.
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Overall, the most common indications for antibiotic treatment were ear, nose, and throat infections (29.3 percent), chronic obstructive pulmonary disease (14 percent), and other respiratory infections (11 percent).

Throughout the first 5 days after a prescription was dispensed, investigators found the risk of all-cause death was 48 percent higher in the group taking azithromycin, with a 77 percent greater risk of serious arrhythmia among the same patient population. There were no longer any significant differences in risk 6 to 10 days after starting treatment, the authors noted.

Levofloxacin, which is typically administered for 10 days, was linked to bigger risks of death and serious arrhythmia throughout the first 10 days after starting treatment

“The key takeaway point for now is that prescribing antibiotics is not a benign intervention,” says Joshua Mann, MD, MPH, associate professor and preventive medicine residency director at the University of South Carolina School of Medicine, and study co-author.

“There are risks of adverse consequences, including increased antimicrobial resistance—which gets talked about most,” says Mann. “But it appears that, at least for some antibiotics, risk of cardiac arrhythmias and even death can also be increased. So I think primary care physicians and other healthcare providers should keep that in mind and avoid prescribing antibiotics unless they are truly indicated clinically.”

In the event an antibiotic is indicated, “it would appear, based on our study, that amoxicillin is likely a safer choice than azithromycin and levofloxacin,” he says, noting that more research is needed to compare risks across different types of antibiotics, “so providers can have more information about the relative risks of different treatment options.”

While the risk of death was greater with azithromycin and levofloxacin, the absolute risks were relatively low, according to the study authors, who report the risk of all-cause death was heightened during the first 5 days of treatment, and 6-to-10 days after the start of treatment. They add, however, that the risk of arrhythmia was comparable between levofloxacin and azithromycin.

“We believe that our findings are an important message of caution, especially because patients continue to receive antibiotics when not indicated or when inappropriate, such as non-bacterial 'cough,' says Gowtham Rao, MD, PhD, MPH, a preventive medicine physician at the University of South Carolina, and lead study author.

“All medications, even short-term antibiotics, are not free of serious adverse events, and thus risks and benefits should be individualized for each patient,” says Rao. “This should include doctor-patient shared decision making, where risks are discussed.”

—Mark McGraw

Reference

Rao G, Mann J, et al. Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death. Ann Fam Med. 2014.