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

Abstract

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Library and Google Scholar were searched from inception to 28 June 2020 (updated November 2020) to find published and unpublished studies that reported direct oral challenge for the purpose of removal of penicillin allergy labels.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.

Patients with questionable penicillin (beta-lactam) allergy: Causes and solutions

“…So far, guidelines recommend direct provocation only in children after the development of uncomplicated exanthema [ 43 ]. Two systematic reviews also examined the safety and efficacy of direct oral provocation by allergists and non-allergists in adults [ 33 , 34 ]. However, data for use in immediate reactions are still insufficient.…”

“…A less resource-intensive method uses direct oral provocation in patients with a history of low risk for non-severe BLA. The direct oral provocation test has also been performed outside of allergy centers [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Such testing is useful when 1) there is a low risk of triggering a reaction, and 2) a severe reaction can be largely excluded.…”

Does my patient need an allergy evaluation for penicillin allergy?

“…A direct or graded amoxicillin challenge under medical observation may be performed in low-risk patients, ie, a PEN-FAST score of 2 or less. 3,7,8 Before performing such a procedure, it is essential to obtain informed consent and ensure appropriate monitoring and access to medications used to treat allergic reactions. If no reaction occurs during the observation period, the patient can subsequently take any type of penicillin without restriction.…”

An algorithm for safe de‐labelling of antibiotic allergy in adult hospital in‐patients

“…The Scottish Antimicrobial Prescribing Group (SAPG), therefore, convened a multi‐professional steering group including lay representatives to scope, develop and test a process for penicillin allergy de‐labelling (PADL) across several hospitals. The Scoping work involved audits () to confirm the prevalence and nature of reported penicillin allergy in the Scottish in‐patient population and a systematic review of the safety and efficacy of oral challenge 3 . Risk‐assessment development involved the development of a risk algorithm (Figure 1) using an iterative process along with supporting information for clinical teams and patients (Figure ; ).…”