Outcome of drug provocation testing in children with suspected beta-lactam hypersensitivity

Abstract

Background: Suspicion of beta-lactam (BL) hypersensitivity is often based on parental report. Evaluation is important as incorrect labelling has clinical consequence.

Objective: To describe the outcomes of drug provocation test (DPT) in children with suspected hypersensitivity.

Methods: A retrospective study of patients who completed BL DPT from 1 August 2016 to 31 December 2017 at a paediatric allergy centre in Singapore. Suspected hypersensitivity reactions were classified as immediate (onset ≤1 hour) or delayed (onset > 1 hour). Patients with immediate reactions underwent skin prick test (SPT) followed by DPT if SPT was negative. Patients with delayed reactions underwent DPT directly.

Results: We identified 120 children who reported 121 suspected hypersensitivity reactions. The median age at reaction was 2.0 years (interquartile range [IQR], 1.0-5.0 years) and the median age at DPT was 7.4 years (IQR, 4.2-11.1 years). The timing of suspected hypersensitivity reaction was immediate in 21% (25 of 121), delayed in 66% (80 of 121), and uncertain in 13% (16 of 121). Commonly implicated drugs were amoxicillin in 45% (54 of 121), amoxicillin-clavulanate in 37% (45 of 121), and cephalexin in 8% (10 of 121). Commonly reported symptoms were maculopapular rash 44% (53 of 121), urticaria 34% (41 of 121), and angioedema 22% (27 of 121). All SPTs (n = 26) were negative. There were 118 diagnostic DPTs to index drug and 3 DPTs to alternative drug. A negative challenge result was obtained in 93% (110 of 118) of diagnostic DPTs: 92% (96 of 104) and 100% (14 of 14) of DPTs to penicillin group and cephalosporins respectively. All challenge reactions were mild.

Conclusion: Our study supports the opinion that prior skin tests may not be necessary for children who report nonsevere reactions and directly performing diagnostic DPT is a safe approach in the evaluation of suspected childhood BL hypersensitivity.

Keywords: Antibiotic allergy; Child; Drug allergy; Drug hypersensitivity; Oral provocation test.

Fig. 1. Outcome of drug provocation test (DPT). ^*One patient had a suspected cefazolin DHR. As the patient's parent declined any evaluation of cephalosporin hypersensitivity, the patient underwent amoxicillin DPT. ⁺One patient had a suspected cefixime DHR. As cefixime was unavailable in hospital formulary, the patient underwent ceftibuten DPT. One patient had cefepime hypersensitivity confirmed on IDT and underwent cefuroxime DPT. (Described in section Case Description).