Short and extended provocation tests have similar negative predictive value in non-immediate hypersensitivity to beta-lactams in children

Abstract

Introduction and objectives: Drug provocation tests (DPTs) are the gold-standard method to diagnose non-immediate hypersensitivity reactions (NIHSR) to beta-lactam antibiotics (BL) in children. Our aim was to compare the negative predictive value (NPV) of one-day (short) DPT versus 3-7 days (extended) DPT for the diagnosis of NIHSR to BL in paediatric age. A secondary aim was to compare confidence on drug re-exposure after short and extended negative DPTs.

Methods: The occurrence of HSR on drug re-exposure and drug refusal after negative diagnostic DPTs were evaluated in children/adolescents with a history of NIHSR to BL using a questionnaire performed six months to ten years after DPT. Patients were divided into two groups according to the protocol performed: short DPT vs. extended DPT.

Results: We enrolled 212 children and adolescents (86 females, 126 males, mean age at DPT 5.52 years, p25=3 years, p75=7.25 years): 69 tested with short DPT, and 143 with extended DPT. The NPV of both types of DPT together was 95.2%. The NPV of short DPT was 97.5% and the NPV of extended DPT was 93.8% (p=0.419). After negative DPT, beta-lactams were refused by carers in 14.75% of the children requiring subsequent treatment, 6.98% in the short DPT group and 18.99% in the extended DPT group (p=0.074).

Conclusions: In our paediatric sample, prolonging drug administration did not increase the NPV of diagnostic DPT for NIHSR to BL or reduce drug refusal. Altogether, the data here reported suggest that, however intuitive, prolonging DPT is not beneficial in the parameters analysed.

Keywords: Beta-lactams; Children; Drug provocation test; Duration of drug provocation; Negative predictive value; Non-immediate hypersensitivity.