Publication Date
5-1-2023
Journal
Kidney Medicine
DOI
10.1016/j.xkme.2023.100618
PMID
37113163
PMCID
PMC10127135
PubMedCentral® Posted Date
2-15-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Azithromycin, dialysate potassium, fluoroquinolones, hemodialysis, sudden cardiac death, USRDS
Abstract
RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin.
STUDY DESIGN: Retrospective observational cohort study using a new-user study design.
SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017).
EXPOSURE: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (
OUTCOMES: Sudden cardiac death (14 days).
ANALYTICAL APPROACH: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs.
RESULTS: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96,
LIMITATIONS: Residual confounding.
CONCLUSIONS: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.
Graphical Abstract
Included in
Diseases Commons, Infectious Disease Commons, Medical Sciences Commons, Nephrology Commons
Comments
See editorial "Individualization of Serum-to-Dialysate Potassium Concentrations to Reduce the Risk of Sudden Cardiac Death Conferred by QT-Prolonging Antibiotics in Patients Receiving Hemodialysis", 100638.
Associated Data