<p><strong>BACKGROUND: </strong>Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones.</p>

<p><strong>PURPOSE: </strong>To evaluate the safety of fluoroquinolones with regard to risk of diagnosed neurological dysfunction.</p>

<p><strong>METHODS: </strong>We conducted a propensity score-matched inception cohort study using claims data from a commercially insured population (OptumInsight). Our study included adults prescribed an oral fluoroquinolone or comparator antibiotic between January 2004 and September 2015 for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, uncomplicated urinary tract infection, or acute bronchitis. Our outcomes were CNS dysfunction, and four separate but complementary PNS dysfunction outcomes. Cox proportional hazards models were estimated after matching on propensity scores fitted using the variables age, sex, epilepsy, hereditary peripheral neuropathy, renal dysfunction, diabetes, gabapentinoid use, statin use, isoniazid use, and chemotherapy use.</p>

<p><strong>RESULTS: </strong>Our cohort contained 976,568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator. Matching produced balance (standardized mean difference &lt; 0.1) on all variables included in the propensity score. The hazard ratio associated with fluoroquinolone exposure was 1.08 (95% confidence interval 1.05-1.11) for CNS dysfunction, and 1.09 (95% CI 1.07-1.11) for the most commonly occurring PNS dysfunction outcome.</p>

<p><strong>CONCLUSIONS: </strong>Fluoroquinolone antibiotic use was associated with the development of neurological dysfunction versus comparator antibiotic use in the adult population.</p>