Safety and efficacy of de-labelling penicillin allergy in adults using direct oral challenge: a systematic review

Background: Approximately 10% of people have an unverified penicillin allergy, with multiple personal and public health consequences. Objectives: To assess the efficacy and safety of direct oral challenge, without prior skin testing, in this population. Methods: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Google Scholar were searched from inception to 28 June 2020 (updated November 2020) to find published and unpublished studies that reported direct oral challenge for the purpose of removal of penicillin allergy labels. Population weighted mean was used to calculate the proportion of patients who developed an immediate or delayed reaction to direct oral challenge across the studies. Results: Thirteen studies were included in the review, with a sample size of 1202 (range 7-328). Studies included inpatient and outpatient cohorts assessed as low risk for true allergy. In pooled analysis of all 13 studies there were 41/1202 (3.41%) mild immediate or delayed reactions to direct oral challenge. The population-weighted mean incidence of immediate or delayed reaction to an oral challenge across studies was also 3.41% (95% CI: 2.38%-4.43%). There were no reports of serious adverse reactions, 96.5% of patients could be de-labelled and many were subsequently successfully treated with penicillin. Conclusions: Direct oral challenge is safe and effective for de-labelling patients assessed as low risk for true allergy. Non-specialist clinicians competent in using an assessment algorithm can offer evaluation of penicillin allergy labels using direct oral challenge in appropriate patients. These measures will facilitate optimal infection treatment for patients, support antimicrobial stewardship, and minimize antimicrobial resistance.