Respiratory fluroquinolone treatment associated with increased short-term risk of sudden cardiac death compared to amoxicillin-based antibiotics

1. Amongst patients receiving hemodialysis, treatment with a respiratory fluoroquinolone is associated with an increased risk of sudden cardiac death when compared to an amoxicillin-based antibiotic.

Evidence Rating Level: 2 (Good)

Study Rundown: Fluroquinolones antibiotics are a mainstay of treating respiratory pathogens and are generally well tolerated. However, they are one of the most common medications to cause QT interval prolongation. Associations between these medications and risk of serious arrythmias and cardiovascular death are not yet well established in literature. One population that is extremely susceptible to sudden cardiac death is patients receiving hemodialysis for renal failure. This is because risk factors known to enhance QT interval prolonging potential such as electrolyte disturbance are highly prevalent amongst this population. However, there is a lack of evidence linking fluroquinolones to adverse cardiac events in patients receiving hemodialysis for renal failure. Therefore, this retrospective cohort study aims to evaluate the cardiac safety of respiratory fluroquinolones amongst individuals receiving hemodialysis.

This study made use of data from the US Renal Data System, which was a national surveillance system that collects information on individuals with kidney failure in the United States. The comparator utilized in this study was amoxicillin-based antibiotics as they are also used to treat respiratory infections but have not shown to cause QT prolongation. Exposure to fluroquinolone and amoxicillin-based antibiotics was identified amongst patients receiving hemodialysis. Total of 626,322 antibiotic episodes among 264,968 adults receiving hemodialysis were included. Patients were followed and evaluated for outcomes at 5, 7, 10, and 14 days. The primary outcome was sudden cardiac death. It was found that compared to amoxicillin-based antibiotics, fluroquinolones were associated with a higher 5-day risk of sudden cardiac death. This association was maintained in the 7, 10, and 14-day follow-ups. The secondary outcomes measured were a composite of sudden cardiac death or hospitalized ventricular arrythmia, cardiovascular mortality, or all-cause mortality. Similarly, analysis revealed that fluroquinolone treatment was associated with increased risk of all the above secondary outcomes at all time points. Hospitalization for fracture was utilized as a negative control and the study did not find that fluroquinolones or amoxicillin-based antibiotics were associated with risk of hospitalized fracture.

Prior literature examining this research question consisted of mainly case reports, and thus, this is one of the first cohort studies examining such a relationship. One of its greatest strength is the large sample size, allowing for increased validity. Another strength was accounting for potential confounders such as demographic data, comorbid conditions, and other medications used by the patients. Finally, this comparison reflects an important treatment decision often encountered by clinicians when managing respiratory infections. One limitation of the study is that although certain confounders were accounted for, there are other variables that could not be controlled or ascertained. For example, the study was unable to evaluate whether patients received appropriate doses of fluroquinolones. This is largely due to the retrospective nature of the study. Additionally, these results cannot be extrapolated to patients excluded from this study such as those with recent hospitalization. Overall, although this study demonstrates that fluroquinolones may be associated with an increased risk of sudden cardiac death in patients receiving hemodialysis, more studies with improved methodology are needed to confirm these results.

Click to read the study in JAMA Cardiology

Relevant Reading:  Fluoroquinolones and cardiovascular risk: a systematic review, meta-analysis and network meta-analysis

In-Depth [retrospective cohort study]: A total of 626 322 antibiotic treatment episodes among 264 968 unique adults (mean(SD) age= 61(15) years; 129 732 (49.0%) women) were included in the study. 251 726 were respiratory fluoroquinolone treatment episodes (148 417 patients, 40.2%) and 374 596 were amoxicillin-based antibiotic treatment episodes (180 887 patients, 59.8%). In the 5-day follow-up, the respiratory fluroquinolone treatment was associated with a higher risk of sudden cardiac death compared to the amoxicillin-based antibiotic treatment (weighted HR: 1.95; 95% CI: 1.57-2.41). Similar results were found with 7-day (weighted HR: 1.83; 95% CI: 1.54-2.17), 10-day (weighted HR: 1.71; 95% CI: 1.48-1.97) and 14-day (weighted HR: 1.64; 95% CI: 1.45-1.85) follow-ups. Sudden cardiac death or hospitalization due to ventricular arrhythmia was increased in the fluroquinolone group at 5, 7, 10, and 14 days (weighted HR (95% CI): 1.92 (1.57-2.34), 1.79 (1.52-2.11), 1.69 (1.47-1.94), and 1.61 (1.43-1.80) respectively). Similar results were found for cardiac death at 5, 7, 10, and 14 days where in patients on fluroquinolone showed an increased association (weighted HR (95% CI): 1.89 (1.57-2.27), 1.75 (1.50-2.04), 1.66 (1.47-1.88), and 1.62 (1.46-1.79) respectively). Finally, fluroquinolones were also associated with increased risk of all cause death at 5, 7, 10, and 14 days (weighted HR (95% CI): 2.17 (1.88-2.50), 1.98 (1.76-2.22), 1.83 (1.67-2.00), and 1.75 (1.63-1.89) respectively).

Image: PD

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