Antibiotics that don't prolong QT interval and minimize potassium gradient reduce SCD risk in hemodialysis patients

Selecting antibiotics that do not prolong the QT interval when appropriate and minimizing the potassium gradient during QT-prolonging antibiotic therapy may be necessary to reduce the already high risk of SCD borne by patients receiving maintenance hemodialysis.

The study has highlighted an essential finding that the Selection of antibiotics not prolonging QT interval when appropriate and minimizing the potassium gradient during QT-prolonging antibiotic therapy is a crucial step in reducing the already high risk of SCD borne by patients on maintenance hemodialysis.

Management with QT interval-prolonging antibiotics is tied to greater risk of sudden cardiac death or SCD among those with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients (promoting large potassium shifts) augments the proarrhythmic effects.

Considering this background, researchers investigated whether the serum-to-dialysate gradient is associated with modifying the cardiac safety of azithromycin and, separately, levofloxacin/moxifloxacin. The design of this study was a Retrospective observational cohort study using a new-user study design.

The study included patients from USRDS 2007-2017 adult Medicare patients. The exposure had Azithromycin or Fluoroquinolone vs Amoxicillin exposure. Sudden cardiac death (14 days) was the outcome measured by them.

The study Results are:

• There were 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes.
• Azithromycin versus amoxicillin-based antibiotic treatment caused a higher risk of sudden cardiac death overall, with an HR of 1.68.
• The risk was higher when the serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L with an HR of 2.22 vs 1.43.
• The Findings were similar for levofloxacin and moxifloxacin, which are other QT-prolonging antibiotics.

The main limitation of the study was Residual confounding.

Concluding further, they said azithromycin treatment and, separately, respiratory fluoroquinolones heightened the risk of sudden cardiac death, which was augmented in the setting of larger serum-to-dialysate potassium gradients.

We found that azithromycin (a QT-prolonging antibiotic) had a higher risk of sudden death than amoxicillin-based antibiotics (non–QT-prolonging antibiotics).

They said that minimising the serum-to-dialysate potassium gradient during hemodialysis may reduce the sudden death risk tied to QT-prolonging antibiotics.

Further reading:

QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis. https://doi.org/10.1016/j.xkme.2023.100618