Analysis of Respiratory Fluoroquinolones and the Risk of Sudden Cardiac Death Among Patients Receiving Hemodialysis

JAMA Cardiol. 2022 Jan 1;7(1):75-83. doi: 10.1001/jamacardio.2021.4234.

Abstract

Importance: Respiratory fluoroquinolone antibiotics are some of the most common medications with QT interval-prolonging potential prescribed to patients with hemodialysis-dependent kidney failure-individuals who have a very high risk of sudden cardiac death (SCD). To date, there have been no large-scale, population-specific studies evaluating the cardiac safety of respiratory fluoroquinolones in the hemodialysis population.

Objective: To investigate the cardiac safety of respiratory fluoroquinolones among individuals with hemodialysis-dependent kidney failure.

Design, setting, and participants: A retrospective cohort study examining safety using an active comparator new-user design was conducted using administrative claims data from a US-wide kidney failure registry from January 1, 2007, to December 31, 2016, including 264 968 Medicare beneficiaries receiving in-center maintenance hemodialysis. Data analysis was performed from January 4 to August 16, 2021.

Exposures: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) vs amoxicillin-based (amoxicillin or amoxicillin with clavulanic acid) antibiotic treatment.

Main outcomes and measures: Sudden cardiac death within 5 days of outpatient initiation of a study antibiotic. Inverse probability of treatment-weighted survival models to estimate hazard ratios (HRs), risk differences (RDs), and corresponding 95% CIs. Death due to a cause other than SCD was treated as a competing event. Fracture was considered as a negative control outcome.

Results: The study cohort included 264 968 unique in-center hemodialysis patients and 626 322 study antibiotic treatment episodes: 251 726 respiratory fluoroquinolone treatment episodes (40.2%) and 374 596 amoxicillin-based treatment episodes (59.8%). Of the 264 968 patients, 135 236 (51.0%) were men, and the mean (SD) age was 61 (15) years. Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was associated with a higher relative and absolute 5-day risk of SCD (weighted HR, 1.95; 95% CI, 1.57-2.41; and weighted RD per 100 000 treatment episodes, 44.0; 95% CI, 31.0-59.2). Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was not associated with the 5-day risk of fracture.

Conclusions and relevance: In this study, compared with amoxicillin-based antibiotic treatment, respiratory fluoroquinolone treatment was associated with a higher short-term risk of SCD among patients with hemodialysis-dependent kidney failure. This finding suggests that decisions between the use of respiratory fluoroquinolones and amoxicillin-based antibiotics should be individualized, with prescribers considering both the clinical benefits and potential cardiac risks.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Death, Sudden, Cardiac / epidemiology*
  • Death, Sudden, Cardiac / etiology
  • Female
  • Fluoroquinolones / adverse effects*
  • Fluoroquinolones / pharmacokinetics
  • Follow-Up Studies
  • Humans
  • Incidence
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Population Surveillance*
  • Renal Dialysis*
  • Respiratory Tract Diseases / drug therapy*
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • United States / epidemiology

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones