Real-World Patterns of Delayed Cutaneous Adverse Reactions to Antimicrobial Therapy in Children: A Case Series and FAERS Analysis Across Age Groups.

Background/Objectives: Cutaneous adverse drug reactions (CADRs) account for approximately 45% of all adverse drug reactions. Although most are self-limiting, some may progress to severe cutaneous adverse reactions (SCARs). In children, delayed rashes associated with antimicrobial therapy, particularly beta-lactams, are often misclassified as drug allergies, leading to unnecessary antibiotic avoidance and potentially suboptimal antimicrobial prescribing. This study aimed to characterize delayed antimicrobial-associated CADRs in children and to investigate reporting patterns and factors associated with their clinical management across age groups. Methods: Real-world data from pediatric patients hospitalized in 2023 at the "Ospedale dei Bambini Vittore Buzzi" (Milan, Italy) were integrated with Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS). Only cases with documented treatment durations were included. Clinical characteristics, antimicrobial exposure patterns, and factors associated with the reporting of delayed rashes were evaluated. Results: Five pediatric patients developed delayed CADRs after 19-22 days of antimicrobial therapy. Infectious and immunological investigations were negative, and symptoms resolved following drug discontinuation. FAERS analysis identified 97 delayed rash reports, associated with prolonged treatment duration, frequent polytherapy, and higher reporting rates for vancomycin, teicoplanin, and beta-lactam combination regimens. Logistic regression showed that age and polypharmacy were significantly associated with reporting patterns of delayed rash and therapy continuation among reported cases. Conclusions: Among reported cases, delayed antimicrobial-associated CADRs were associated with age and polypharmacy. Improved recognition of these reactions may facilitate appropriate clinical management, support more informed prescribing decisions, and reduce inappropriate antibiotic allergy labeling. Further studies are needed to validate these findings and refine risk-based management strategies in pediatric patients.