In patients with hemodialysis-dependent kidney failure, treatment with the macrolide antibiotic azithromycin is associated with an increased risk of sudden cardiac death (SCD), reports a preproof paper in Kidney International.
Using data from the US Renal Data System, the researchers performed a cohort study to assess the cardiac safety of azithromycin compared with amoxicillin-based antibiotics in patients on hemodialysis from 2007 through 2017. A separate cohort study compared azithromycin with levofloxacin, a fluoroquinolone antibiotic that, like azithromycin, is known to prolong the QT interval.
The two studies included 381,306 treatment episodes with azithromycin versus 344,125 with amoxicillin-based antibiotics and 387,382 treatment episodes with azithromycin versus 167,175 with levofloxacin. The main outcome of interest was the 5-day risk of SCD.
Compared with amoxicillin or amoxicillin/clavulanic acid, azithromycin was associated with a significantly increased risk of SCD (weighted hazard ratio [HR], 1.70). Absolute risk was also higher with azithromycin (weighted incidence, 36.5 vs. 15.5 per 100 treatment episodes). For the first 5 days, azithromycin would result in one additional case of SCD for every 4000 treatment episodes compared with amoxicillin.
In the second cohort study, azithromycin was associated with a lower risk of SCD compared with levofloxacin. The weighted HR for azithromycin was 0.79, with an absolute risk difference of −18.9 per 100,000 treatment episodes. Compared with levofloxacin, azithromycin would avoid one case of SCD during the first 5 days per 5921 treatment episodes.
Azithromycin is a broad-spectrum macrolide antibiotic, widely used for respiratory infections, and has a known QT-prolonging potential. Hemodialysis patients may be especially susceptible to this QT-prolonging effect and its potential consequences, including SCD.
This large analysis of US hemodialysis patients shows a higher risk of SCD after starting treatment with azithromycin compared with amoxicillin-based antibiotics. Azithromycin is associated with a lower SCD risk than levofloxacin in the same patient population. The investigators conclude: “When selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks” [Assimon MM, et al. Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure. Kidney Int, published online ahead of print June 22, 2022; doi: 10.1016/j.kint.2022.05.024; https://www.kidney-international.org/article/S0085-2538 (22)00461-6/fulltext].