Neurological adverse outcomes may be caused in part or in full by drugs, and these neurological outcomes can be unpredictable, severe, and sometime chronic. Many of these events manifest in the form of central and peripheral nervous system effects like headaches, dizziness, seizures, and muscle weakness after taking antibiotics. In particular, central nervous system (CNS) events such as headaches and dizziness, among others, have been reported in individuals taking fluoroquinolone (FQ) antibiotics, a widely used antibiotic class that is responsible for 33 million outpatient prescriptions in the US annually. Additionally, severe and sometimes permanent peripheral nervous system (PNS) events, such as peripheral neuropathy characterized by burning, numbness, pain, and muscle weakness, as well as the exacerbation of myasthenia gravis characterized by varying degrees of weakness or tingling have been reported in case studies and through patient reporting after FQ exposure. However, the potential association between FQ use and CNS/PNS dysfunction has yet to be adequately studied using population-based epidemiologic methods. Our study aims to investigate the potential association between FQ use and CNS and PNS dysfunction in the adult population. We also seek to develop predictive models for the occurrence of CNS and PNS dysfunction that can stratify FQ users with regard to risk. We will approach these aims using OptumInsight data, claims data from a commercially insured adult population. We will use propensity score matching to isolate the impact of FQ exposure on the development of neuropathy events, as well as Cox proportional hazards regression models to assess the risk of these events due to FQ use vs. the comparator drug while allowing for censoring. Finally, we will use model-building methods to approach the predictive models. This research will address an important neurological drug safety issue, and will help to inform physician prescribing decisions and FDA actions going forward. It will also provide crucial support as well as preliminary data for a planned postdoctoral mentored career development award, enabling an exceptional research trainee to prepare for a career as an academic investigator focusing on applying pharmacoepidemiologic research methods to the study of neuropharmacology.
Neurological adverse events of both the central (CNS) and peripheral nervous systems (PNS) have been reported due to antibiotic use, and many of these adverse events are listed in the prescribing information for certain antibiotic medications. Recently, the U.S. Food and Drug Administration (FDA) has given increased attention to fluoroquinolone (FQ)-class antibiotics, reporting that this antibiotic class might put individuals at increased risk of serious and potentially chronic neurological adverse events; however, limited epidemiologic evidence exploring this potential association exists in the past or current literature. Through the use of a propensity score-matched cohort study design, the current proposed research will evaluate the potential association between FQ use and CNS and PNS dysfunction in the adult population as well as predictors for the occurrence of CNS and PNS dysfunction, which will help to address an important neurological drug safety issue, and will help to inform physician prescribing decisions and FDA actions going forward.