Assessing Pediatric Cephalosporin Allergic Reactions Through Direct Graded Oral Challenges

Cephalosporins are commonly used to treat pediatric bacterial infections. Prevalence estimates for suspected cephalosporin allergy vary. The present study sought to assess whether direct graded oral challenges (GOCs) are appropriate for the diagnosis of cephalosporin allergy in children.From 2013 to 2023, 136 pediatric patients with index reactions to cephalosporins were recruited from 4 Canadian allergy clinics as part of the B-Lactam and other Antibiotics in Children: Tests, Assessment, and Management study. Demographic, clinical reaction, and management data were collected via questionnaire. The median age at index reaction was 2.2 years, and the median age at GOC was 3.9 years. Cefprozil represented the most frequent cephalosporin, followed by cephalexin and cefixime. One fourth of patients had previous exposure to the cephalosporin associated with their index reaction.The B-Lactam and other Antibiotics in Children: Tests, Assessment, and Management study was observational, with retrospective and prospective arms. Adverse reactions were retrospectively characterized. Challenge outcomes and subsequent antibiotic use were prospectively investigated. The GOC was a 2-step, nonblinded observed challenge. The challenge dose was based on weight and was administered as 10%, followed by 20 minutes of observation, followed by 90% within the clinic. Adverse reactions were classified as mild (oral mucosa or skin symptoms), moderate, or severe (cardiovascular or respiratory symptoms). Anaphylaxis was defined as involvement of at least 2 organ systems or hypotension within 2 hours. Following a negative challenge, patients were discharged after 1 hour and were asked to report any nonimmediate adverse symptoms within 1 week. Follow-ups were conducted 1 week after GOC, and for up to 5 years to assess subsequent antibiotic use.Patients underwent a GOC to their respective index cephalosporin. Direct GOC resulted in 5.1% of patients reporting symptoms within 1 hour (immediate) and 4.4% of patients reporting symptoms between 1 and <8 hours following GOC (nonimmediate). Among the 7 immediate reactions, 6 occurred within less than 5 minutes. Among the 6 nonimmediate reactions, 3 occurred between 1- and 8-hour following GOC, whereas the other 3 occurred more than 8 hours after the GOC. One patient was diagnosed with anaphylaxis and treated with epinephrine. Among patients with a negative GOC, 51.2% of families were contacted at least once over the subsequent 5 years. Within the followed patient population, 50.8% had used antibiotics, and 3 reported adverse antibiotic reactions. Following a negative GOC, 2 adverse reactions were to amoxicillin, whereas 1 was to a cephalosporin.Direct GOC is a safe and efficacious strategy to diagnose cephalosporin allergy in children.Previously reported diagnostic tests for cephalosporin allergy include intradermal testing and GOC. Nonstandardized intradermal testing has significant limitations. Adverse reactions in the studied population were infrequent, and the report of only one severe adverse reaction is reassuring. The authors note an association between positive GOCs and a longer interval between the index reaction and GOC. The authors suggest T lymphocyte sensitization and an expanded pool of memory cells as a possible etiology for this finding. Additional and larger studies are needed to clarify and further explore this association.