Given the limited number of effective antibiotics available and the requirement for multiple antibiotics in the face of considerable antimicrobial resistance, it is important to understand the safety profile of fluoroquinolones. As a first-line antibiotic, it is frequently indicated for its broad antimicrobial spectrum in primary care and hospital settings. However, emerging safety concerns about increased risks for complications, such as aortic aneurysm/dissection, retinal detachment and tendon disorders, have restricted fluoroquinolone use by the US FDA and European Medicine Agency. However, research findings have been conflicting, and causality is unclear. Researchers based in London used multiple analyses and multiple databases to estimate the association of systemic fluoroquinolone use with acute uveitis or retinal detachment. Their findings, which were published yesterday in JAMA Ophthalmology, did not support an association of systemic fluoroquinolone use with a substantially increased risk of uveitis or retinal detachment.¹

Individuals with conditions leading to elevated risk of retinal detachment, such as cataracts or diabetes, may be more likely to receive oral fluoroquinolones (e.g., for prophylaxis for cataract surgery or to treat diabetes-associated urinary tract infections). Photo: Mark Dunbar, OD. Click image to enlarge.

This cohort study used data from the Clinical Practice Research Datalink Aurum and GOLD UK primary care records databases, which were linked to hospital admissions data. Adults prescribed fluoroquinolone or a comparator antibiotic, cephalosporin, were included. Adults with uveitis or retinal detachment were analyzed in a separate, self-controlled case series. In total, 3,001,256 individuals in Aurum (63.1% women; median age: 51) and 434,754 in GOLD (63.5% women; median age: 53) were included.

For uveitis, the pooled adjusted hazard ratios (HRs) for the use of fluoroquinolone vs. cephalosporin were 0.91 at first treatment episode and 1.07 over all treatment episodes. For retinal detachment, the pooled adjusted HRs were 1.37 at first treatment episode and 1.18 over all treatment episodes. For uveitis, the pooled adjusted RRs for fluoroquinolone use vs. nonuse were 1.13 for one to 29 days of exposure, 1.16 for 30 to 59 days, and 0.98 for 60 days for longer. For retinal detachment, pooled adjusted RRs for fluoroquinolone use vs. nonuse were 1.15 for one to 29 days of exposure, 0.94 for 30 to 59 days and 1.03 for 60 days or longer.

“Although we cannot rule out a small increase in risk of uveitis or retinal detachment with systemic fluoroquinolones, it is apparent from the estimated risk differences that any increase in absolute risk would be minimal (less than one in 10,000 treatment episodes) and of questionable clinical importance,” the researchers wrote in their paper.¹

A commentary also published in JAMA Ophthalmology also highlighted that, “To optimize the benefits of existing cohort data, analytic plans to emulate clinical trial designs can address selection bias and confounding by indication in observational data and have the potential to provide unbiased estimates of either treatment effectiveness or safety concerns.”²