A LARGE international study found that penicillin allergy testing using direct oral challenge (DOC) safely removed incorrect allergy labels and reduced World Health Organisation (WHO)-restricted antibiotic prescribing in hospitalised patients.
Around one in 10 hospitalised patients report a penicillin allergy, yet most of these labels are inaccurate, often leading clinicians to prescribe broader-spectrum or less effective antibiotics. This contributes to antimicrobial resistance and poorer clinical outcomes, making improved diagnostic strategies a priority.
Penicillin Allergy Testing Improves Clinical Prescribing
In this prospective, multicentre study across 40 hospitals in eight countries, researchers evaluated over 5,000 adult inpatients with reported penicillin allergy. Participants were assessed using a digital toolkit, and some underwent DOC, a supervised method of confirming whether a true allergy exists.
Among the 1,573 patients who received DOC, 95.5% were safely “delabelled,” meaning they were no longer considered allergic. Only 4.5% had a positive test, and serious adverse events were rare, occurring in just 0.4% of cases.
Importantly, penicillin allergy testing had a clear impact on prescribing behaviour.
Patients who underwent DOC were significantly more likely to receive penicillin at 90 days (risk ratio: 13.25; 95% CI: 7.82–22.46) and less likely to be prescribed WHO “Watch” or “Reserve” antibiotics (risk ratio: 0.73; 95% CI: 0.60–0.89).
These findings highlight the role of accurate allergy assessment in supporting antibiotic stewardship.
Implementation Challenges and Future Impact
The study also assessed real-world implementation. Within six months of introducing the digital assessment tool, 77 clinicians had adopted it into practice, demonstrating moderate but promising uptake.
However, not all eligible patients underwent DOC, reflecting ongoing logistical and clinical barriers, such as staffing, training, and risk perception. As an observational study emulating a target trial, the findings may also be influenced by selection bias.
Despite these limitations, the results suggest that penicillin allergy testing using DOC is both safe and effective when implemented in routine care. Wider adoption could reduce unnecessary use of restricted antibiotics, improve patient outcomes, and help tackle antimicrobial resistance.
Future research will likely focus on scaling these approaches and integrating them more consistently into hospital workflows, ensuring that inaccurate allergy labels no longer compromise optimal treatment decisions.
Reference
Mitri EA et al. Direct oral challenge for penicillin allergy: the International Network of Antibiotic Allergy Nations (iNAAN) study. Clin Infect Dis. 2026; DOI:10.1093/cid/ciag082.
Featured image: mitsyko1971 on Adobe Stock
