1336. Fluoroquinolones and Collagen Associated Severe Toxicity
Session: Oral Abstract Session: Antimicrobial Stewardship in Older Adults
Saturday, October 10, 2015: 9:30 AM
Room: 25--ABC
Background: Fluoroquinolones (FQs) are the most commonly used antibiotic class, so rare complications can have significant public health consequences.  FQ-associated tendon ruptures have been well described, but other more severe collagen associated adverse events may also be possible.  We sought to confirm the association of FQs and tendon rupture, to clarify the potential association of FQs and retinal detachment, and to test for a previously unrecognized but potentially lethal association between FQs and aortic aneurysms.

Methods: longitudinal cohort study of all older adults turning 65 years between Apr 1 1997 and Mar 31 2012 in Ontario, Canada.   FQ use was measured as a time-varying covariate, with patients considered to be at risk during and 30 days following treatment.  Tendon ruptures, retinal detachments, and aortic aneurysm events diagnosed in province wide hospital and emergency room datasets in Ontario’s universal healthcare system.  Patients were followed until they experienced an outcome event, died, or reached the end of follow-up period (Mar 31 2014).  

Results: Among 1,744,360 eligible older adults, 657,950 (38%) received at least one FQ during follow up, amounting to 22,380,515 days of FQ treatment.  The patients experienced 37,338 (2.1%) tendon ruptures, 3,246 (0.2%) retinal detachments, and 18,391 (1.1%) aortic aneurysms.   Severe collagen-associated adverse events were more common during FQ treatment than control periods, including tendon ruptures (0.82 vs 0.26 per 100-person years (py), p<0.001), retinal detachments (0.03 vs 0.02 per 100-py, p=0.003) and aortic aneurysms (0.35 vs 0.13 per 100-py, p<0.001).  Current FQs were associated with increases in tendon rupture (HR 3.13, 95%CI 2.98-3.28; adjusted HR 2.40, 95%CI 2.24-2.57), and a similar increase in aortic aneurysms (HR 2.72, 95%CI 2.53-2.93; adjusted HR2.24, 95%CI 2.02-2.49), which was substantially greater in magnitude than the association of these outcomes with amoxicillin.  The hazard of retinal detachment was marginal (HR 1.28, 95%CI 0.99-1.65; adjusted HR 1.47, 95%CI 1.08-2.00), and not greater in magnitude than that observed with amoxicillin.

Conclusion: FQ treatment is indeed associated with subsequent tendon ruptures, and may also contribute to aortic aneurysms.

Nick Daneman, MD, MSc1,2,3, Hong Lu, PhD2 and Donald Redelmeier, MD, MSc2, (1)Division of Infectious Diseases & Clinical Epidemiology, University of Toronto, Toronto, ON, Canada, (2)Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, (3)Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Disclosures:

N. Daneman, None

H. Lu, None

D. Redelmeier, None

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