Reevaluating Pediatric Penicillin Allergy: Diagnosis, Clinical Impact, and De-labeling Strategies

Penicillin allergy is the most commonly reported drug allergy in children, yet the vast majority of these labels are incorrect.Approximately 5-10% of pediatric patients are reported to be penicillin-allergic, but over 90% are found to tolerate penicillins after thorough evaluation.Overdiagnosis of penicillin allergy in children leads to significant clinical and public health consequences, including the unnecessary use of broad-spectrum antibiotics, higher rates of antimicrobial resistance (e.g., Clostridioides difficile and methicillin-resistant Staphylococcus aureus infections), and increased healthcare costs.This narrative review examines the discrepancy between reported and true penicillin allergy prevalence in pediatrics and discusses the immunopathology of hypersensitivity reactions (Types I-IV).We outline current strategies for diagnosing penicillin allergy, from detailed history-taking and risk stratification to skin testing using non-irritating concentrations and drug provocation test, which remains the gold standard.We also review the evidence on -lactam cross-reactivity, clarifying that cross-allergy with cephalosporins and carbapenems is lower than historically thought and largely related to side-chain structures.The clinical impact of mislabeling children as penicillin-allergic is explored, highlighting the benefits of penicillin "de-labeling" programs and antibiotic stewardship interventions.Ongoing trials aim to demonstrate improved outcomes when incorrect allergy labels are removed.Finally, we address the challenges and practice gaps in lowresource settings, particularly in Asia, where limited access to allergy testing and specialist care complicates penicillin allergy management.By improving the accurate diagnosis of penicillin allergy in children, we can optimize antibiotic use, enhance patient safety, and combat antibiotic resistance.