Bottom Line:

Consider alternative antibiotic in patients with aortic pathology and in those who are prone to developing AA/AD, such as those with Marfan’s, smokers, elderly men, and/or hypertension.  Think about placing AA/AD higher on the differential in patients presenting with the classic symptoms, risk factors, and recent FQ exposure, as FQs may increase risk of AA/AD.

Study #1 (Pasternak et al)

• Retrospective cohort; investigated the risk of AA/AD, comparing treatment episodes of FQ use with episodes of amoxicillin use
• 66% increased rate of AA/AD → Hazard ratio = 1.66 (95% CI 1.12-2.46) developing AA/AD within 60 days of FQ use
• Secondary analyses demonstrated the following: no increased risk of AA/AD associated with FQ use in days 61-120 from start of treatment; 41% of AA in FQ group occurred in first 10 days from start of treatment; and, HR in FQ group was 1.90 for AA and only 0.93 for AD, with AAA being most common.
• Limitations: Observational study cannot prove causation and has inherent bias, but it’s unethical to do RCT and impractical given such low incidence of AA/AD; investigators reliance on filled prescriptions in order to define drug exposure (noncompliance with FQ use would bias results towards the null hypothesis)

Study #2 (Lee et al)

• Retrospective case-crossover analysis; evaluate the association between FQ treatment and AA/AD
• OR of FQ exposure 2.71 vs. in control was OR 0.75 (no increase in risk)
• Additionally, they found that the longer the exposure to FQ, the higher the risk of AA/AD compared to those with exposure <3days (3-14 days OR 2.41, CI 1.25-4.65; >14 days OR 2.83, CI 1.06-7.57, p<0.01), and that the highest risk of AA/AD was within 60 days of FQ exposure (OR 2.70, CI 1.87-21.40), whereas there was no significant association between FQ exposure and risk of AA/AD when hazard period was extended out to 120-180 days.
• Limitations: As with study #1, a filled prescription does not equal medication adherence. Potential for ascertainment bias, since patients who are being treated with FQ (e.g., for pneumonia) may undergo additional imaging, leading to the diagnosis of AA.

BONUS: ALTERNATIVE ABX!

• Diverticulitis? Ditch cipro-Flagyl for Augmentin (if outpatient) or ceftriaxone-Flagyl (inpatient)
• Infectious diarrhea? Use azithro instead of cipro
• Complicated UTI? Think Keflex or Bactrim DS instead of an FQ!

References:

Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ. 2018;360:k678. Published 2018 Mar 8. doi:10.1136/bmj.k678

Lee C-C, Lee M-TG, Hsieh R, et al. Oral fluoroquinolones and the risk of aortic dissection. J Am Coll Cardol 2018;72:1369-78.