Direct Oral Challenge for Immediate and Non-Immediate <b>β</b>-Lactam Allergy in Children: A Real-World Multicenter Study

To evaluate the safety and efficacy in using direct oral drug provocation test (DODPT) in delabeling beta-lactam antibiotic (BLA) allergy in children with both immediate and nonimmediate reactions.The study consisted of 2133 children across 15 hospitals in Spain from November 2016 to March 2023 with suspected BLA before age 15. Approximately 1346 of the children were 1 to 6 years old. Amoxicillin or amoxicillin/clavulanic acid was the BLA suspected in 2029 of the children. There was history of anaphylaxis in 14 children and Stevens-Johnson syndrome in one child.Skin tests or in vitro tests could be performed before DODPT, with positive tests considered confirmation of BLA allergy if DODPT was not subsequently performed. The attending physician determined both duration and mode of DODPT per case, ranging from at the hospital for one day to continued at home for several days. Allergy was ruled out if no reaction occurred. If signs or symptoms were observed, the attending physician defined the result as positive (allergy confirmed) or equivocal and then determined whether to repeat or extend the study.DODPT was performed on 2014 patients and 1863 tolerated. Of patients, 145 had signs or symptoms related to DODPT. Only 4 (0.2%) had a severe reaction (2 with anaphylaxis and 2 with drug-induced enterocolitis syndrome). The other 141 had mild reactions, which resolved following treatment with antihistamines and/or corticosteroids. In 58 of the 145 patients, a positive DODPT confirmed diagnosis of BLA allergy. In 87 of the 145, manifestations were equivocal and a second DODPT was performed in 57 patients. Fifty-two tolerated the repeat DODPT, whereas 5 had mild skin reactions. The other 30 had parental refusal or were lost to follow-up. Ultimately, BLA was ruled out in 1938 patients (90.9% of the total cohort, 96.4% of those completing the study).DODPT is a safe and effective test to rule out BLA allergy in children with history of immediate and nonimmediate mild reactions. BLA was confirmed in less than 5% of the population that completed the study. Among those with mild or equivocal reaction to the initial DODPT, a repeat DODPT was tolerated in the vast majority.DODPT allowed removal of BLA allergy label in most children (>95% of the population completing the study). This study illustrates that the those with initial equivocal results upon DODPT should undergo repeat DODPT to facilitate BLA allergy label removal. Delabeling BLA allergy in children will reduce costs and morbidity associated with unnecessary use of alternative antibiotics.