HINES, IL – Prescriptions for fluoroquinolones have been dropping over the past decade at the VHA and elsewhere. A new study pointed out that reasons include both a greater emphasis on antimicrobial stewardship, as well as growing provider awareness of serious adverse drug reactions.

The report in Pharmacology Research & Perspectives described how, recently, aortic rupture and dissection, were added to the list of conditions linked to the antibiotics. The risks of tendon rupture, irreversible peripheral neuropathy, hypoglycemia, and, most recently, aortic rupture and dissection were already well understood, according to the study.

Researchers from the VA Center for Medication Safety in Hines, IL, and colleagues from around the United States cautioned that, while fluoroquinolone (FQ) prescribing is decreasing, “inappropriate use remains a concern; this includes utilization in patients at increased risk for adverse events.”

The articles recounted how, following the latest Food and Drug Administration warning in December 2018, the VA Center for Medication Safety performed an active surveillance project to assess the potential association between FQ use and aortic aneurysm/dissection, as well as acute myocardial infarction, ventricular arrhythmias, Achilles tendon rupture, peripheral neuropathy, and 30‐day all‐cause mortality in veterans.

The authors said the surveillance project detected the potential for an increased risk of aortic aneurysm/dissection, acute myocardial infarction, and 30‐day all‐cause mortality with FQs compared to both azithromycin and amoxicillin, which led to more comprehensive and rigorous study using methods that would adjust for additional potential confounding.

Researchers sought to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all-cause mortality vs other commonly used antibiotics.

To do that, they conducted a self-controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on VHA diagnosis codes from emergency department visits and hospitalizations and death in FY2014-FY2018. The veterans also received outpatient prescriptions for FQs. Used as comparison were patients receiving amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole-trimethoprim.

Essentially, the study determined the following:

  • The incidence of aortic aneurysm/dissection was significantly higher during fluoroquinolone vs amoxicillin and azithromycin risk periods.

  • Fluoroquinolones were associated with an increased risk of all‐cause mortality vs multiple antibiotics commonly used for outpatient infections.

  • A significantly increased risk of acute myocardial infarction or ventricular arrhythmias was not observed with fluoroquinolones vs each comparator antibiotic.


The study used a 30-day risk period after each antibiotic prescription to determine that adjusted incidence rate ratios (aIRRs) for FQs vs. each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, however, incidence was higher during FQ risk periods vs. amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods.

Furthermore, researchers observed a significantly increased risk of mortality with FQs vs. each antibiotic of interest. “FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all-cause mortality vs multiple antibiotics commonly used for outpatient infections,” the authors concluded. “Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.”

The study team emphasized that its findings have clinical implications and support the FDA’s recommendation that FQs should be avoided in patients with risk factors for AA/AD unless there are no viable alternatives. Those risk factors include smoking, advanced age, male sex, hypertension, and atherosclerosis.

The authors noted that, despite the evidence, recent research found that 20% of patients with known AA received FQs during a hospitalization before the repair. They posited that might mean providers were unaware or unconvinced of the potential risk.

“Also, the potential increased risk of all‐cause mortality with the FQs vs other antibiotics supports recommendations to limit FQ use,” they wrote. “However, given these recommendations, providers may prescribe alternative antibiotics that have other serious adverse effects. For example, sulfamethoxazole‐trimethoprim has been associated with hyperkalemia and renal failure, especially in elderly patients and those taking other medications that can raise serum potassium.”

Still, researchers added, “Although the differences in event rates are small, FQs should be reserved for serious infections where there are no suitable alternatives.”


  1. Aspinall SL, Sylvain NP, Zhao X, Zhang R, Dong D, Echevarria K, Glassman PA, Goetz MB, Miller DR, Cunningham FE. Serious cardiovascular adverse events with fluoroquinolones versus other antibiotics: A self-controlled case series analysis. Pharmacol Res Perspect. 2020 Dec;8(6):e00664. doi: 10.1002/prp2.664. PMID: 33047487; PMCID: PMC7550792.