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Potential limited cross-drug reaction among fluoroquinolones: A large database analysis by International Classification of Diseases, Tenth Revision code-based approach

Chiu CY, Chastain DB, Jeffres MN, Henao-Martínez AF

The journal of allergy and clinical immunology. Global, 2026

Abstract

Background: Fluoroquinolone allergy is the third most commonly reported antibiotic allergy. Cross-drug reactions among fluoroquinolones remain a clinical concern, although existing studies are limited by small sample sizes and a lack of control groups.

Objective: We aimed to assess the real-world frequency and risk of potential fluoroquinolone cross-drug reactions using a large health care database.

Methods: We performed a retrospective analysis using the TriNetX database in September 2025. Patients with an allergy label to ciprofloxacin, levofloxacin, or moxifloxacin who were subsequently exposed to a different fluoroquinolone were identified. Potential cross-drug reactions following the second fluoroquinolone exposure were assessed based on the International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. Odds ratios for potential cross-drug reactions were calculated.

Results: The frequencies of potential cross-drug reactions following a second fluoroquinolone exposure were as follows: 2.6% (index allergy to ciprofloxacin, subsequent allergy to levofloxacin), 1.5% (ciprofloxacin → moxifloxacin), 2.7% (levofloxacin → ciprofloxacin), 1.3% (levofloxacin → moxifloxacin), 2.9% (moxifloxacin → ciprofloxacin), and 2.9% (moxifloxacin → levofloxacin). Compared with patients without an index fluoroquinolone allergy, the odds of experiencing a potential cross-drug reaction were slightly higher in some drug pairs: 1.18 (ciprofloxacin → levofloxacin;…

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