Fluoroquinolones Show No Greater Risk of Peripheral Neuropathy Than Cephalosporins: Study

Prospective analyses were carried out to identify the potential association between systemic fluoroquinolone prescription use and the development of peripheral neuropathy in comparison with cephalosporin prescriptions by conducting parallel population-based cohort studies in UK primary care electronic medical records from the CPRD Aurum and GOLD database from April 1, 1997, to December 31, 2019.

For the study, the cohort comprised of adult patients 18 years of age or above who did not have any underlying history of diabetes mellitus and peripheral neuropathy and were prescribed with either systemic fluoroquinolones or cephalosporins. The analysis of hazard ratios (aHR) for incidence of peripheral neuropathy within 60 days of prescription was done using inverse probability of treatment weighting with stabilized propensity scores in Cox proportional hazards regression model.

Sensitivity of the study design methodologically was tested by computing hazard ratios for a positive control endpoint of tendon rupture within 60 days of prescription. Risk difference was calculated using the weighted Aalen-Johansen estimator.

Key findings:

• Meta-analysis involving almost 4 million UK general practice patients (2,933,982 in Aurum; 995,457 in GOLD) revealed no association for peripheral neuropathy along with positive control validation.
• In their first treatment episode, 1,002,004 patients (34.2%) in Aurum and 381,734 (38.3%) in GOLD were treated with fluoroquinolones.
• The pooled adjusted hazard ratio for incident peripheral neuropathy during 60 days after prescribing was near-null at the first treatment episode (pooled aHR 0.96; 95% CI, 0.77–1.20) and during all treatment episodes altogether (pooled aHR 1.05; 95% CI, 0.92–1.20).
• In contrast to the neuropathy outcome, hazard ratios were significantly elevated for the positive control outcome of incident tendon rupture during 60 days at the first treatment episode (pooled aHR 1.98; 95% CI, 1.55–2.53) and during all treatment episodes (pooled aHR 1.76; 95% CI, 1.52–2.04), which proved the ability of the study to reveal the true drug-induced adverse event.
• The Aurum group consisted of patients whose median age was 49.5 years (IQR 34.1–67.5), and 63.7% of them were females (n = 1,868,793), while in the GOLD group the median age was 51.5 years (IQR 35.6–68.0) with 63.5% female representation (n = 632,033).

In summary, dual database cohort studies of primary care have shown that there is no significant difference in the risk of peripheral neuropathy between systemic fluoroquinolones and cephalosporins. The conclusions from this study show that although positive controls have reconfirmed the known risk of tendon rupture, the findings have provided clinical reassurance about the safety of peripheral nerves with fluoroquinolones.

reference:

Brown, J. P., Wing, K., Mansfield, K. E., Evans, S. J. W., Leyrat, C., Smeeth, L., Wong, A. Y. S., Galwey, N. W., & Douglas, I. J. (2026). Association Between Systemic Fluoroquinolones and Risk of Peripheral Neuropathy. Neurology, 107(10), e218699. https://doi.org/10.1212/wnl.0000000000218699