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Original Investigation
April 29, 2019

Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy

Author Affiliations
  • 1Division of Population Health and Genomics, University of Dundee, Dundee, United Kingdom
  • 2Department of Pharmacovigilance and Epidemiology, European Medicines Agency, London, United Kingdom
  • 3William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
JAMA Neurol. 2019;76(7):827-833. doi:10.1001/jamaneurol.2019.0887
Key Points

Question  What is the risk of peripheral neuropathy following exposure to fluoroquinolone or amoxicillin-clavulanate antibiotics?

Findings  This nested case-control study of 5357 incident peripheral neuropathy cases and 17 285 matched controls showed that current use of systemic fluoroquinolone antibiotics increased the risk of peripheral neuropathy by 47%, causing an additional 2.4 cases per 10 000 patients per year of current use. Risk appeared to be greater with cumulative exposure, among men, and among those older than 60 years of age but was not significantly associated with amoxicillin-clavulanate.

Meaning  Health care professionals should consider the potential risk of peripheral neuropathy when prescribing fluoroquinolone antibiotics.


Importance  Peripheral neuropathy has been associated with systemic fluoroquinolone exposure, but risk has been poorly quantified.

Objective  To calculate relative and absolute risk estimates for the association of fluoroquinolone exposure with peripheral neuropathy and to examine how risk may be affected by timing of fluoroquinolone exposure and by other risk factors.

Design, Setting, and Participants  This nested case-control study used anonymized data from all patients routinely registered with general practices in The Health Improvement Network database, a large primary care population database in the United Kingdom, from January 1, 1999, to December 31, 2015. Data analyses were conducted January 8, 2018. The cohort consisted of 1 338 900 adults issued 1 or more prescriptions of fluoroquinolone (34.3%) or amoxicillin-clavulanate (65.7%) antibiotics. Adults with incident peripheral neuropathy were matched (on age, sex, general practice, and calendar time) with up to 4 controls by using incidence density sampling selected from a cohort prescribed oral fluoroquinolone or amoxicillin-clavulanate antibiotics. Incidence rate ratios of peripheral neuropathy were calculated for fluoroquinolone and for amoxicillin-clavulanate exposure and compared with nonexposure among patients without diabetes, with sensitivity analyses testing the consistency of the results. Population mean–adjusted rate differences were then estimated, including the number needed to harm for various durations of fluoroquinolone therapy.

Exposures  Current and cumulative exposure to oral fluoroquinolone or amoxicillin-clavulanate antibiotics.

Main Outcomes and Measures  Incident peripheral neuropathy cases recorded in electronic medical records.

Results  In total, 5357 patients with incident peripheral neuropathy (mean [SD] age, 65.6 [14.7] years; 2809 women [52.4%]) were matched to 17 285 controls (mean [SD] age, 64.4 [15.2] years; 9485 women [54.9%]) without diabetes. Current oral fluoroquinolone exposure was associated with an increased relative incidence of peripheral neuropathy compared with nonexposure (adjusted incident rate ratio, 1.47; 95% CI, 1.13-1.92). Risk increased by approximately 3% for each additional day of current fluoroquinolone exposure and persisted for up to 180 days following exposure. No significant increased risk was observed with oral amoxicillin-clavulanate exposure. The absolute risk with current oral fluoroquinolone exposure was 2.4 (95% CI, 1.8-3.1) per 10 000 patients per year of current use. The number needed to harm for a 10-day course was 152 083 patients (95% CI, 117 742-202 778) and was greatest among men and among patients older than 60 years.

Conclusions and Relevance  The results of the present study suggested that oral fluoroquinolone therapy was associated with an increased risk of incident peripheral neuropathy that may depend on the timing of the exposure and the cumulative dose. Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotics.