Direct oral penicillin challenge in secondary care with low-risk patients: the SPACE mixed-methods study with cost-effectiveness analysis.

Background: One in five inpatients carries a penicillin allergy label. However, 90-95% of labels are incorrect. Penicillin allergy labels lead to increased risk for serious hospital infections and longer hospital stay and are associated with higher estimated healthcare costs. Penicillin allergy testing is onerous and requires a specialist. Routine inpatient testing is not available. Recent evidence suggests that a direct oral penicillin challenge delivered by non-allergy specialists is safe in 'low risk' patients, who are highly unlikely to be allergic based on history.

Aims: To explore behaviour, attitudes and acceptability of patients, healthcare professionals and managers regarding a direct oral penicillin challenge in 'low risk' patients. To inform development of an implementation framework and determine potential cost-effectiveness.

Methods: This study (1 May 2021-30 April 2023) involved delivery of direct oral penicillin challenge by non-allergy specialists across three clinical settings (medical/infectious diseases wards, presurgical and haematology-oncology units) at three hospitals. The study had three workstreams: Workstream 1: Screening for potential suitability. Patients were stratified into 'low risk' and 'high risk'. 'Low-risk' patients underwent direct oral penicillin challenge. Workstream 2: One-to-one semistructured interviews with patients ( = 43) and focus group ( = 28) discussions with stakeholders. Workstream 3: Care pathway mapping, decision-analytic modelling and value of information analysis were carried out to determine potential cost-effectiveness of direct oral penicillin challenge.

Results: One thousand and fifty-four of 2257 screened patients were eligible, 270 of 643 approached patients consented (42%). Two hundred and fifty-nine patients were risk-stratified (155 'low risk'; 104 'high risk'). Of the 155 'low risk' patients, 126 underwent direct oral penicillin challenge, 122 (97%) were de-labelled with no serious allergic reactions and 43 patients were interviewed. Low-risk patients accepted their allergy labels, had limited knowledge of the adverse impact and most were keen to have their labels reviewed. Healthcare professionals demonstrated a risk-averse approach, although would engage in the intervention with training, resource availability and a governance framework in place. The total costs of the direct oral penicillin challenge pathway were higher than the costs of direct oral penicillin challenge alone (£940 vs. £98-288 per patient). There were minimal expected savings in antibiotic and hospital costs in the short term and potentially large healthcare cost savings over 5 years.

Limitations: Relatively small sample size for direct oral penicillin challenge, poor conversion rate, particularly in acute settings, patients with limited English language proficiency could not be included and the study was not sufficiently powered and controlled to conduct a cost-effectiveness evaluation.

Conclusions: This first multicentre United Kingdom study showed that non-allergy specialist-led direct oral penicillin challenge is feasible in secondary care. A high proportion of direct oral penicillin challenges were successful, with positive feedback from patients. Majority of screened patients did not progress through the study pathway. Going forward, a multipronged approach is needed to enhance equitability of direct oral penicillin challenge in routine practice. Follow-up mechanisms to consider the intervention during a clinically stable state and a governance framework for those lacking capacity to consent are needed. The cost of delivering a direct oral penicillin challenge pathway in its entirety is significantly higher than the costs of performing direct oral penicillin challenge per se.

Future Work: A randomised controlled trial with long-term follow-up is needed to determine the cost-effectiveness of direct oral penicillin challenge.

Study Registration: This study is registered as ISRCTN55524365.

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129069) and is published in full in ; Vol. 13, No. 9. See the NIHR Funding and Awards website for further award information.