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Updated: Nov 17, 2025

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Published on: May 31, 2021
Outcome of drug provocation testing in children with suspected beta-lactam hypersensitivity
Si Hui Goh1, Kok Wee Chong1, Wen Chin Chiang1
1Allergy Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore.
Insights
Evaluating suspected beta-lactam (BL) hypersensitivity in children via drug provocation tests (DPT) is crucial. Our findings show that directly performing DPT is a safe and effective approach for diagnosing BL hypersensitivity in pediatric patients.
Area of Science:
- Pediatric Allergy and Immunology
- Clinical Pharmacology
- Drug Hypersensitivity Research
Background:
- Beta-lactam (BL) hypersensitivity suspicion often relies on parental reports, necessitating accurate diagnostic evaluations.
- Incorrect labeling of BL hypersensitivity can lead to significant clinical consequences for children.
Purpose of the Study:
- To investigate the outcomes of drug provocation tests (DPT) in children with suspected beta-lactam hypersensitivity.
- To assess the safety and efficacy of DPT as a diagnostic tool in pediatric allergy.
Main Methods:
- Retrospective analysis of 120 children undergoing BL DPT at a Singaporean pediatric allergy center (August 2016 - December 2017).
- Classification of suspected reactions into immediate (≤1 hour) or delayed (>1 hour) onset.
- Skin prick testing (SPT) preceded DPT for immediate reactions if SPT was negative; delayed reactions underwent direct DPT.
Main Results:
- 121 suspected reactions were reported, with delayed reactions being most common (66%).
- Amoxicillin (45%) and amoxicillin-clavulanate (37%) were the most frequently implicated drugs.
- Drug provocation tests yielded negative results in 93% of diagnostic cases, with all observed reactions being mild.
Conclusions:
- Directly performing diagnostic DPT is a safe and effective strategy for evaluating suspected childhood beta-lactam hypersensitivity.
- Prior skin tests may not be essential for children with non-severe suspected reactions, simplifying the diagnostic pathway.
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.
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