Patients at Risk for Aortic Rupture Often Exposed to Fluoroquinolones during Hospitalization

Abstract

Several studies have indicated that fluoroquinolone use may be associated with an increased risk of aortic aneurysm or dissection (AAD). Because patients with AAD or Marfan syndrome are at increased risk for aortic rupture, we performed a retrospective cohort study to determine the prevalence of systemic fluoroquinolone exposure and predictors of fluoroquinolone use in these patients. Data were obtained from the advisory board billing and administrative database, which contained information on 22 million adult hospitalizations in the United States for the study period (2009 to 2015). International Classification of Diseases (9/10) and Current Procedural Terminology codes were used to identify patients who had AAD or Marfan syndrome or underwent aortic repair. We identified 136,789 admissions for AAD, which involved 99,818 unique patients, 20% of whom received fluoroquinolone during a hospital admission. Of the 7,045 patients with dissection, 18% were exposed to fluoroquinolone. Of the 27,876 AAD patients who underwent aortic repair, 19% received fluoroquinolone during a hospitalization before the repair. In the AAD patients, having a diagnosis of pneumonia or urinary tract infection increased the likelihood of receiving fluoroquinolone during admission by 46% and 40%, respectively (P < 0.001). Additionally, we identified 2,871 admissions for Marfan syndrome, which involved 1,872 patients, 14% of whom received fluoroquinolone during an admission. In these patients, pneumonia and urinary tract infections also increased the risk of fluoroquinolone exposure. If the deleterious effects of fluoroquinolone on aortic integrity are substantiated, reducing fluoroquinolone use in hospitalized patients with aortic disorders will become an urgent safety issue for antibiotic stewardship programs.

Transferable Mechanisms of Quinolone Resistance from 1998 Onward

“…There have been recent warnings regarding the possible development of aortic aneurysms and dissection in patients at risk as antibiotic-class-related severe adverse events (100,101). In this line, mice challenged with a high-fat diet and a low-dose angiotensin infusion exposed to ciprofloxacin were more prone to developing aortic destruction and aneurysms (102).…”

“…In this line, a curious phenomenon of paradoxical bacterial survival has been described in the presence of extremely high levels of (45,87,88,90,101,461). In several cases, these findings have led to the discontinuation of research, withdrawal from clinical practice, and strong restrictions to specific nonsystemic applications (such as topical or ophthalmic), to serious life-or limb-threatening infections, or to last-resort applications, such as compassionate use of several of these quinolones (45,100,454,462,463). Note that these regulations may differ among different countries.…”

“…Note that other quinolones may also be able to cause similar effects in specific cases or circumstances. d Most of the cases are related to ciprofloxacin treatment but proposed to be an antibiotic class effect (100,101).…”

Relationship between fluoroquinolones and the risk of aortic diseases: a meta-analysis of observational studies

“…Several studies showed that ciprofloxacin could inhibit collagen production in tenocytes [25,26]. Another study suggested that patients with aortic aneurysm, aortic dissection or Marfan syndrome had a higher risk for aortic rupture when exposed to fluoroquinolones [27]. Moreover, compared with intravenous fluoroquinolones, oral fluoroquinolones carried a higher risk of negative effects, and levofloxacin was associated with not only aortic aneurysm but also aortic dissection [28].…”

Relationship between fluoroquinolones and the risk of aortic diseases: a meta-analysis of observational studies

“…[25,26] Another study suggested that patients with aortic aneurysm, aortic dissection or Marfan syndrome had a higher risk for aortic rupture when exposed to fluoroquinolones. [27] Moreover, compared with intravenous fluoroquinolones, oral fluoroquinolones carried a higher risk of negative effects, and levofloxacin was associated with not only aortic aneurysm but also aortic dissection. [28] Based on these findings, future studies should focus on age stratification, the evaluation of individuals' fluoroquinolone with regard to the risk of aortic aneurysm or dissection and different exposure times, which may provide additional information because aortic diseases are rare adverse events that cannot be studied in randomized controlled trials.…”