Is it safe to use levofloxacin (a fluoroquinolone antibiotic) in an older adult patient with an aortic aneurysm and possible cardiovascular risk factors?

Levofloxacin Should Be Avoided in Patients with Aortic Aneurysm

Fluoroquinolones, including levofloxacin, are generally contraindicated in patients with aortic aneurysm and should only be used when there is a compelling indication with no alternative antibiotic available. 1, 2

Guideline-Based Recommendations

Primary Contraindication

• The Mayo Clinic Proceedings explicitly states that fluoroquinolones should be avoided in patients with thoracic aortic aneurysm due to increased risk of aortic complications. 1
• The European Society of Cardiology recommends avoiding fluoroquinolones unless there is a compelling indication with no alternative antibiotic option. 2
• This recommendation applies to all aortic aneurysms, including thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA). 1

FDA Black Box Warning Context

• The FDA has issued a boxed warning for levofloxacin regarding tendinitis and tendon rupture, with increased risk in patients over 60 years of age, those taking corticosteroids, and transplant recipients. 3
• While the FDA label does not specifically mention aortic aneurysm, the mechanism of collagen degradation that causes tendon complications also affects aortic tissue. 4, 5

Evidence Supporting Avoidance

Magnitude of Risk

• Levofloxacin use is associated with a 44% increased risk of aortic aneurysm or dissection compared to macrolide antibiotics (adjusted hazard ratio: 1.44; 95% CI: 1.19-1.52). 4
• A meta-analysis demonstrated that fluoroquinolones increase the combined risk of aortic aneurysm and dissection more than two-fold (relative risk = 2.11; 95% CI, 1.62-2.75). 6
• The risk for aortic aneurysm specifically is even higher (relative risk = 2.83; 95% CI, 2.02-3.95). 6

Temporal Relationship

• Current use (within 60 days) of fluoroquinolones carries the highest risk (rate ratio: 2.43; 95% CI, 1.83-3.22), with attenuated but persistent risk during past use (61-365 days prior). 5
• The association is primarily driven by aortic aneurysm cases (95.8% of events). 4

Mechanism of Harm

• Fluoroquinolones cause collagen degradation through inhibition of matrix metalloproteinases and disruption of extracellular matrix integrity. 5
• This mechanism directly compromises aortic wall structural integrity, particularly concerning in patients with pre-existing aneurysmal disease. 7, 6

Clinical Decision Algorithm

When Fluoroquinolone Use Is Being Considered:

1. First-line approach: Select an alternative antibiotic class (beta-lactams, macrolides, tetracyclines, or other non-fluoroquinolone options based on infection type and susceptibility). 1, 2

2. If no alternative exists:

   • Document the compelling indication and lack of alternatives in the medical record
   • Assess aneurysm size and stability (larger aneurysms ≥50-55 mm carry higher baseline rupture risk). 1
   • Consider infectious disease consultation for alternative regimens
   • Use the shortest effective duration possible 4

3. High-risk features that strengthen contraindication:

   • Aneurysm diameter approaching surgical threshold (≥50 mm women, ≥55 mm men) 1, 8
   • Rapid aneurysm growth (≥10 mm/year or ≥5 mm in 6 months) 8
   • Saccular morphology 1
   • Uncontrolled hypertension 1
   • Concurrent corticosteroid use (compounds both tendon and aortic risk) 3
   • Age >60 years 3, 5

Common Pitfalls to Avoid

• Do not assume that short-course fluoroquinolone therapy is safe: Even 7-14 days of exposure increases risk (adjusted hazard ratio: 1.47; 95% CI: 1.26-1.71). 4
• Do not overlook oral formulations: Oral fluoroquinolones are more likely to produce aortic adverse events than intravenous formulations. 7
• Do not forget to screen for undiagnosed aneurysms: In older adults with cardiovascular risk factors receiving fluoroquinolones for the first time, consider whether baseline aortic imaging has been performed, particularly if they meet screening criteria (men ≥65 years with smoking history). 1

Alternative Antibiotic Selection

When treating common infections in patients with aortic aneurysm:

• Respiratory tract infections: Consider macrolides, beta-lactams, or doxycycline instead of levofloxacin 4
• Urinary tract infections: Use trimethoprim-sulfamethoxazole, nitrofurantoin, or beta-lactams when susceptibility allows 4, 5
• Skin/soft tissue infections: Beta-lactams, clindamycin, or doxycycline are preferred 4