title: Risks of cardiac arrhythmia and mortality among patients using new-generation macrolides, fluoroquinolones, and β-lactam/β-lactamase inhibitors: a Taiwanese nationwide study.
abstract: 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.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei.
authors.forename: Hsu-Wen
authors.initials: HW
authors.lastname: Chou
authors.affiliation: College of Medicine, I-Shou University and Department of Internal Medicine, E-Da Hospital, Kaohsiung Department of Internal Medicine, National Taiwan University Hospital, Taipei.
authors.forename: Jiun-Ling
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei Department of Internal Medicine, National Taiwan University Hospital, Taipei.
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei Department of Internal Medicine, National Taiwan University Hospital, Taipei Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu.
authors.forename: Chao-Lun
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei Center for Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital.
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Lai
authors.affiliation: Graduate Institute of Oncology, College of Medicine, National Taiwan University Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: K Arnold
authors.initials: KA
authors.lastname: Chan
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality*; D017963:Azithromycin / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000401:mortality*; D002939:Ciprofloxacin / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D015897:Comorbidity; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D064704:Levofloxacin / Q000009:adverse effects* / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D000077266:Moxifloxacin; D012306:Risk; D013624:Taiwan; D065093:beta-Lactamase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D065093:beta-Lactamase Inhibitors; D002939:Ciprofloxacin; D064704:Levofloxacin; D019980:Amoxicillin-Potassium Clavulanate Combination; D017963:Azithromycin; D017291:Clarithromycin; D000077266:Moxifloxacin
keywords: azithromycin; cardiovascular death; levofloxacin.; moxifloxacin; ventricular arrhythmia