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

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; 95% confidence interval [CI] 1.06-1.31; P < .05), 1.12 (levofloxacin → ciprofloxacin; 95% CI, 1.01-1.23; P < .05), and 1.31 (moxifloxacin → ciprofloxacin; 95% CI, 1.12-1.54; P < .05).

CONCLUSION

Potential cross-drug reactions between ciprofloxacin, levofloxacin, and moxifloxacin were rare (∼2%) and slightly increased the odds of subsequent reaction in some drug pairs. These findings suggest class-wide avoidance may be unnecessary and support drug challenge as a safe strategy in selected patients. Interpretation of our findings should be cautious, as this is an International Classification of Diseases, Tenth Revision code-based approach without detailed mechanisms.