Risks of cardiac arrhythmia and mortality among patients using new-generation macrolides, fluoroquinolones, and β-lactam/β-lactamase inhibitors: a Taiwanese nationwide study

Clin Infect Dis. 2015 Feb 15;60(4):566-77. doi: 10.1093/cid/ciu914. Epub 2014 Nov 18.


Background: Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics.

Methods: Between January 2001 and November 2011, a total of 10 684 100 patients were prescribed oral azithromycin, clarithromycin, moxifloxacin, levofloxacin, ciprofloxacin, or amoxicillin-clavulanate at outpatient visits. A logistic regression model adjusted for propensity score was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse cardiac outcomes occurring within 7 days after the initiation of antibiotic treatment.

Results: Compared with amoxicillin-clavulanate treatment, the use of azithromycin and moxifloxacin was associated with significant increases in the risks of ventricular arrhythmia and cardiovascular death. The adjusted ORs for ventricular arrhythmia were 4.32 (95% CI, 2.95-6.33) for azithromycin, 3.30 (95% CI, 2.07-5.25) for moxifloxacin, and 1.41 (95% CI, .91-2.18) for levofloxacin. For cardiovascular death, the adjusted ORs for azithromycin, moxifloxacin, and levofloxacin were 2.62 (95% CI, 1.69-4.06), 2.31 (95% CI, 1.39-3.84), and 1.77 (95% CI, 1.22-2.59), respectively. No association was noted between clarithromycin or ciprofloxacin and adverse cardiac outcomes.

Conclusions: Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves.

Keywords: azithromycin; cardiovascular death; levofloxacin.; moxifloxacin; ventricular arrhythmia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / epidemiology*
  • Arrhythmias, Cardiac / mortality*
  • Azithromycin / adverse effects*
  • Azithromycin / therapeutic use
  • Cardiovascular Diseases / mortality*
  • Ciprofloxacin / therapeutic use
  • Clarithromycin / therapeutic use
  • Comorbidity
  • Female
  • Fluoroquinolones / adverse effects*
  • Fluoroquinolones / therapeutic use
  • Humans
  • Levofloxacin / adverse effects*
  • Levofloxacin / therapeutic use
  • Logistic Models
  • Male
  • Moxifloxacin
  • Risk
  • Taiwan
  • beta-Lactamase Inhibitors / adverse effects*
  • beta-Lactamase Inhibitors / therapeutic use


  • Anti-Bacterial Agents
  • Fluoroquinolones
  • beta-Lactamase Inhibitors
  • Ciprofloxacin
  • Levofloxacin
  • Amoxicillin-Potassium Clavulanate Combination
  • Azithromycin
  • Clarithromycin
  • Moxifloxacin