The Risk of Aortic Dissection and Aneurysm in Patients Taking Oral Fluoroquinolones

Barbara Wells Trautner, MD, PhD, associate professor, director of clinical research, Baylor College of Medicine, explains the risk of aortic dissection and aneurysm in patients taking oral fluoroquinolones.

Interview transcript (slightly modified for readability):

There were actually 2 studies that came out in 2015. One, in JAMA Internal Medicine was performed in Korea, and the other was a study in Canada. Both are very large data studies, and both show there is an increased risk of aneurysm and dissection during the time patients are taking fluoroquinolones. However, both are observational, or database, cohort studies and they can’t prove causation. Now, what was interesting about the Canadian study is they actually did a test with a cohort of patients that got no antibiotics, a cohort of patients that got amoxicillin as their test, and a cohort that got fluoroquinolones. The risk of aneurysm in the amoxicillin group was 1.5 times higher than the no antibiotic group and the fluoroquinolones group risk of aneurysm was 2.4 times higher than the no antibiotic group. Yet, the fact that there were “negative-tracers” which was amoxicillin showed an increased risk of aneurysm, when we really don’t postulate a mechanism, shows that there is some confounding in that study that’s not subtracted out by all the adjustments made.

In other words, there’s probably some increase related to the fluoroquinolones since there was some increase in their control group, amoxicillin, in addition to the no antibiotic group. Sicker patients are getting antibiotics and sicker patients also get aneurysms. So, it’s entirely possible there is a real association, but we need to find the biologic causation behind it. I should say, there’s a new study that came out in 2018 in the BMJ looking at data in the Swedish database and they actually compared everyone on amoxicillin and everyone fluoroquinolones and also found an increased risk of aneurysm in patients on fluoroquinolones.

I work on antibiotics research for asymptomatic bacteria and I work on antibiotics research for urinary tract infection (UTI). Even though they are not a first-line antibiotic for UTI, fluoroquinolones are the most commonly prescribed agent for UTI, despite the fact that the guidelines don’t make list them as a first-choice drug and there’s a warning against using fluoroquinolones in uncomplicated UTI. I’ve been working on multiple projects to improve antibiotic stewardship in outpatient settings, which is basically telling people please don’t use fluoroquinolones as your first choice and then along comes these 3 studies that say, “hey fluoroquinolones may be related to aneurysms getting worse.” Add to that I work part of my time in direct clinical research in the department of surgery at Baylor and our vice chair for research is an aortic surgeon, and so, in his lab, he found that mice were predisposed to getting aneurysms if you gave them fluoroquinolones. It actually gave them aneurysms that ruptured compared to the mice who didn’t get fluoroquinolones. So, he said to me, “Barbra do aneurysm patients get fluoroquinolones?” and I said, “Oh sure it’s 1 of our most commonly used antibiotics. I’m sure aneurysm patients are getting fluoroquinolones.” He asked how many and I didn’t know leading to the study that we’re presenting today at SHEA.

[For our research] we asked the question, “Are aneurysm patients being exposed to fluoroquinolones,” because if it turns out there is a real relationship between fluoroquinolones and aneurysm, the first group of patients that should not be getting fluoroquinolones are those with aneurysms.

We looked at a database of 22 million patient hospitalizations—400 hospitals across the United States—and we sorted all patients out with aneurysm. We also got a second, smaller cohort of patients with morphea syndrome because that predisposes them to aneurysm. Out of all aneurysm patients, we looked at their hospitalization in an inpatient database and found that 20% of their hospitalizations, 1 in 5, get fluoroquinolones. That’s really the punchline, aneurysm patients are indeed getting fluoroquinolones and if you want to know the inpatient rate, it’s 1 in 5 hospitalizations. Now, we’re missing the outpatient data and that’s probably even higher on that, and it really didn’t make much difference if they were a dissection patient before the repair or after the repair of the aneurysm; all these patients with aneurysms are getting quinolones.

[For our research, we then asked,] what puts a patient at risk if you’re an aneurysm patient to get fluoroquinolones and, not surprisingly, if you have a UTI or pneumonia in your diagnosis, your odds of getting fluoroquinolones are much higher. The bottom line is if it turns out there is an association between fluoroquinolone use and aneurysm development worsening, the aneurysm patients that are most at risk are going to be the ones with pneumonia or UTI’s. Therefore, part of your stewardship program has to tell practitioners to be hesitant to put a patient with pneumonia or a UTI on a fluoroquinolone.