title: Macrolide antibiotics and the risk of ventricular arrhythmia in older adults.
abstract: BACKGROUND
  Many respiratory tract infections are treated with macrolide antibiotics. Regulatory agencies warn that these antibiotics increase the risk of ventricular arrhythmia. We examined the 30-day risk of ventricular arrhythmia and all-cause mortality associated with macrolide antibiotics relative to nonmacrolide antibiotics.
  
  
  METHODS
  We conducted a population-based retrospective cohort study involving older adults (age > 65 yr) with a new prescription for an oral macrolide antibiotic (azithromycin, clarithromycin or erythromycin) in Ontario from 2002 to 2013. Our primary outcome was a hospital encounter with ventricular arrhythmia within 30 days after a new prescription. Our secondary outcome was 30-day all-cause mortality. We matched patients 1:1 using propensity scores to patients prescribed nonmacrolide antibiotics (amoxicillin, cefuroxime or levofloxacin). We used conditional logistic regression to measure the association between macrolide exposure and outcomes, and repeated the analysis in 4 subgroups defined by the presence or absence of chronic kidney disease, congestive heart failure, coronary artery disease and concurrent use of a drug known to prolong the QT interval.
  
  
  RESULTS
  Compared with nonmacrolide antibiotics, macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia (0.03% v. 0.03%; relative risk [RR] 1.06, 95% confidence interval [CI] 0.83-1.36) and were associated with a lower risk of all-cause mortality (0.62% v. 0.76%; RR 0.82, 95% CI 0.78-0.86). These associations were similar in all subgroups.
  
  
  CONCLUSIONS
  Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated.
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
authors.forename: Mai H
authors.initials: MH
authors.lastname: Trac
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
authors.forename: Eric
authors.initials: E
authors.lastname: McArthur
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
authors.forename: Racquel
authors.initials: R
authors.lastname: Jandoc
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Dixon
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Nash
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Hackam
authors.affiliation: Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont. amit.garg@lhsc.on.ca.
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D017963:Azithromycin / Q000009:adverse effects; D017291:Clarithromycin / Q000009:adverse effects; D015331:Cohort Studies; D004917:Erythromycin / Q000009:adverse effects; D005260:Female; D006801:Humans; D016015:Logistic Models; D018942:Macrolides / Q000009:adverse effects*; D008297:Male; D009864:Ontario; D057216:Propensity Score; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin