Beyond delabeling: long-term penicillin use and avoidance following negative penicillin challenge in children

Background Penicillin allergy labels are frequently reported in children and contribute to avoidance of first-line antibiotic therapy. In appropriately selected pediatric patients, direct penicillin challenge is an increasingly used strategy for allergy evaluation and delabeling. However, whether successful delabeling translates into subsequent penicillin use in routine clinical practice remains poorly understood. Purpose This study evaluated long-term antibiotic use after successful penicillin allergy delabeling in children, focusing on subsequent penicillin reuse, continued avoidance, and factors associated with subsequent reuse. Methods We conducted a retrospective cohort study of 305 children referred for penicillin allergy evaluation at the Hillel Yaffe Pediatric Allergy Clinic between 2019 and 2023. Patients underwent risk-stratified skin testing and/or direct oral challenge according to institutional protocol, followed by a 5-day home treatment when indicated. Long-term outcomes, including subsequent penicillin reuse and any adverse reactions following challenge, were assessed via structured telephone interviews with caregivers. Results The median age at index reaction was 4 years; reactions were predominantly nonimmediate (59.6%) and cutaneous (98.0%). Oral provocation testing was performed in 93.8% of patients and was well tolerated in 98.6%. Full tolerance, defined as negative clinic challenge and negative 5-day home treatment, was documented in 79.7% of the cohort. Among fully tolerant children with follow-up, 63.7% subsequently reused penicillin, whereas 36.3% had no documented subsequent use. No subsequent allergic reactions were reported among children who reused penicillin. Younger age and shorter time since provocation were independently associated with greater likelihood of subsequent penicillin reuse. Conclusion Direct oral challenge was safe and successfully established penicillin tolerance in most children. However, successful delabeling did not consistently translate into subsequent penicillin use, highlighting a clinically important gap between diagnostic delabeling and its real-world implementation. Improved post-delabeling communication, documentation, and integration into antimicrobial stewardship may help maximize the clinical benefit of penicillin allergy delabeling.