Azithromycin use may increase the risk for sudden cardiac death in patients receiving in-center hemodialysis, a new study confirms.
The rate of sudden cardiac death in the hemodialysis population is more than 20 times higher than that in the general population, Jennifer E. Flythe, MD, MPH, of the University of North Carolina Kidney Center at Chapel Hill and colleagues noted in a report in Kidney International. Structural heart disease, conduction abnormalities, and electrolyte derangements are common among patients on hemodialysis, they pointed out, and may amplify the proarrhythmic effects of QT-prolonging medications frequently prescribed to patients on hemodialysis.
Using data from the United States Renal Data System (2007-2017), the investigators examined the cardiac safety of azithromycin compared with amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin, a fluoroquinolone antibiotic known to prolong the QT-interval. They studied 2 cohorts, one comparing azithromycin with amoxicillin-based antibiotics and the other comparing azithromycin with levofloxacin.
The azithromycin vs amoxicillin-based treatment cohort included 282,899 patients receiving in-center hemodialysis who had 381,306 azithromycin and 344,125 amoxicillin-based treatment episodes. Compared with amoxicillin-based antibiotics, azithromycin was significantly associated with a 70% higher risk of sudden cardiac death due to cardiac arrhythmia or cardiac arrest in patients on hemodialysis during the 5 days of therapy, Dr Flythe and her colleagues reported. They calculated that 1 additional sudden cardiac death event would occur during the first 5 days of therapy for every 4000 treatment episodes when azithromycin was prescribed rather than an amoxicillin-based antibiotic.
The azithromycin vs levofloxacin cohort included 245,143 patients receiving in-center hemodialysis. This group had 387,382 azithromycin and 167,175 levofloxacin treatment episodes. Compared with levofloxacin, azithromycin was significantly associated with a 21% lower risk of sudden cardiac death within 5 days. The risk of sudden cardiac death particularly increased when levofloxacin was prescribed at higher doses than recommended for patients on hemodialysis (500 mg initial dose, followed by 250 mg every 48 hours). The investigators calculated that 1 fewer sudden cardiac death event would occur during the first 5 days of therapy for every 5921 treatment episodes when azithromycin was prescribed rather than levofloxacin.
Compared with amoxicillin-based antibiotics, azithromycin was significantly associated with a 1.7-fold increased risk for sudden cardiac death within 5 days and levofloxacin with a 2.2-fold increased risk. Clinicians may still choose to use azithryomycin or levofloxacin because of their efficacy.
“When selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks,” according to Dr Flythe’s team. They recommended electrocardiographic monitoring before and during therapy when prescribing QT-prolonging medications of any therapeutic class to this population.
Disclosure: This research was supported by Fresenius Medical Care, North America. Please see the original reference for a full list of disclosures.
Assimon MM, Pun PH, Wang L, et al. Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure. Kidney Int. Published online June 23, 2022. doi:10.1016/j.kint.2022.05.024