Evaluation of Diagnosis, Cross-Reactivity, and Risk Factors in Pediatric Patients With Macrolide Allergy

Abstract

Background

Macrolide antibiotics are generally considered safe in children, but allergic reactions can still occur. This study aims to evaluate the sensitivity and specificity of intradermal test (IDT) used to detect macrolide allergy in pediatric patients, investigate the rate of cross-reactivity between clarithromycin and azithromycin, and identify factors influencing the development of macrolide allergy.

Methods

A total of 102 patients with suspected clarithromycin and azithromycin allergy were included in the study. Characteristics of the reactions and results of skin and drug oral provocation test (OPT) were recorded.

Results

Clarithromycin was confirmed as the culprit drug in 8 (9%) of 88 patients, and azithromycin in 1 (7.1%) of 14 patients. The cross-reactivity between clarithromycin and azithromycin determined 11.1%. In patients with immediate-type reactions, IDT performed at a concentration of 0.05 mg/mL demonstrated a sensitivity of 33.3% (95% CI: 0.0%–66.7%) and a specificity of 92.7% (95% CI: 82.9%–100%). When a higher concentration of 0.5 mg/mL was used, sensitivity increased to 100% (95% CI: 0.0%–100%), while specificity decreased to 78.9% (95% CI: 65.8%–92.1%) respectively. According to univariate logistic regression analysis, patients with a history of previous non-macrolide drug allergy (p: 0.003, Odds Ratio [OR]: 41, 95% CI: 3.6–456.5) and family history of drug allergy (p = 0.026, OR: 5.2, 95% CI: 1.2–22.5) were at a significantly higher risk of developing macrolide allergy.

Conclusions

Although IDT at a concentration of 0.05 mg/mL showed higher specificity (92.7%) compared to 0.5 mg/mL (78.9%), given its limited sensitivity, OPT is still required to confirm the diagnosis.