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. 2014 Mar-Apr;12(2):121-7.
doi: 10.1370/afm.1601.

Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death

Gowtham A Rao  1 , Joshua R Mann, Azza Shoaibi, Charles Lee Bennett, Georges Nahhas, S Scott Sutton, Sony Jacob, Scott M Strayer
Affiliations

Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death

Gowtham A Rao et al. Ann Fam Med. 2014 Mar-Apr.

Abstract

Purpose: Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin.

Methods: We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days.

Results: During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82).

Conclusions: Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.

Keywords: amoxicillin; arrhythmia; azithromycin; cause of death; levofloxacin.

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Figures

Figure 1
Figure 1
Cumulative incidence of all-cause death among patients by antibiotic type over 10 days (crude). HR = hazard ratio.
Figure 2
Figure 2
Cumulative incidence of all-cause death among patients by antibiotic type over 10 days (IPTW). HR = hazard ratio; IPTW = inverse probability treatment weights.
Figure 3
Figure 3
Cumulative incidence of serious cardiac arrhythmias among patients by antibiotic type over 10 days (crude). HR = hazard ratio.
Figure 4
Figure 4
Cumulative incidence of serious cardiac arrhythmias among patients by antibiotic type over 10 days (IPTW). HR = hazard ratio; IPTW = inverse probability treatment weights.
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