Association of Infections and Use of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection

Abstract

Importance: Prior observational studies have suggested that fluoroquinolone use may be associated with more than 2-fold increased risk of aortic aneurysm or aortic dissection (AA/AD). These studies, however, did not fully consider the role of coexisting infections and the risk of fluoroquinolones relative to other antibiotics.

Objective: To estimate the risk of AA/AD associated with infections and to assess the comparative risk of AA/AD associated with fluoroquinolones vs other antibiotics with similar indication profiles among patients with the same types of infections.

Designs, settings, and participants: This nested case-control study identified 21 651 176 adult patients from a nationwide population-based health insurance claims database from January 1, 2009, to November 30, 2015. Each incident case of AA/AD was matched with 10 control individuals by age, sex, and follow-up duration in the database using risk-set sampling. Analysis of the data was conducted from April 2019 to March 2020.

Exposures: Infections and antibiotic use within a 60-day risk window before the occurrence of AA/AD.

Main outcomes and measures: Conditional logistic regression was used to estimate the odds ratios (ORs) and 95% CIs comparing infections for which fluoroquinolones are commonly used with no infection within a 60-day risk window before outcome occurrence, adjusting for baseline confounders and concomitant antibiotic use. The adjusted ORs comparing fluoroquinolones with antibiotics with similar indication profiles within patients with indicated infections were also estimated.

Results: A total of 28 948 cases and 289 480 matched controls were included (71.37% male; mean [SD] age, 67.41 [15.03] years). Among these, the adjusted OR of AA/AD for any indicated infections was 1.73 (95% CI, 1.66-1.81). Septicemia (OR, 3.16; 95% CI, 2.63-3.78) and intra-abdominal infection (OR, 2.99; 95% CI, 2.45-3.65) had the highest increased risk. Fluoroquinolones were not associated with an increased AA/AD risk when compared with combined amoxicillin-clavulanate or combined ampicillin-sulbactam (OR, 1.01; 95% CI, 0.82-1.24) or with extended-spectrum cephalosporins (OR, 0.88; 95% CI, 0.70-1.11) among patients with indicated infections. The null findings for fluoroquinolone use remained robust in different subgroup and sensitivity analyses.

Conclusions and relevance: These results highlight the importance of accounting for coexisting infections while examining the safety of antibiotics using real-world data; the findings suggest that concerns about AA/AD risk should not deter fluoroquinolone use for patients with indicated infections.

Figure.. Risk of Aortic Aneurysm and Aortic Dissection Associated With Fluoroquinolone Monotherapy vs Comparison Antibiotic Monotherapy Among Patients With Indicated Infections Restricted to Those With Potentially High-risk Characteristics

Odds ratios (ORs) are adjusted for matching factors of age, sex, duration of follow-up in the database, and type of infection and for baseline covariates, including hypertension, ischemic heart disease, valve disorder, ischemic stroke, disorders of lipid metabolism, chronic obstructive pulmonary disease, chronic kidney disease, Charlson comorbidity score, tobacco smoking, claims-based frailty index, any episodes of infections, any use of fluoroquinolones, and any use of nonfluoroquinolone antibiotics measured between cohort entry and 60 days before the index date.