Allergy De-labelling: An Important Antimicrobial Stewardship Intervention

World AMR Awareness Week (WAAW) is a global campaign held from 18 to 24 November each year to raise awareness and drive action against antimicrobial resistance (AMR). Recognising WAAW provides an opportunity to reflect on strategies to optimise antimicrobial use.

Antimicrobial stewardship (AMS) initiatives often have a strong focus on reducing the inappropriate prescribing of antimicrobials. For example, encouraging the avoidance of antibiotics for asymptomatic bacteriuria or for minor self-limiting infections. However, the impact of penicillin allergy delabelling should not be underestimated.

In many cases, a documented penicillin allergy is accepted at face value. However, evidence shows that penicillin allergy labels are often inaccurate or outdated. Some studies suggest that this may be the case for around 90% of allergy labels. Removing inaccurate allergy labels can improve patient outcomes, increase access to first-line antibiotic therapy, optimise prescribing, and help combat AMR.

The Scale of the Problem in Australia

The Australasian Society of Clinical Immunology and Allergy (ASCIA) state that around 10% of the population reports a penicillin allergy. However, fewer than 1% of people are thought to be truly allergic and more than 90% of people with a penicillin allergy label can tolerate penicillin following appropriate assessment and testing.

Inaccurate allergy labels can originate when a patient experiences a non-immune-related adverse reaction. Gastrointestinal adverse effects, such as vomiting and diarrhoea, are commonly experienced in association with antibiotic therapy. Coincidental reactions can also occur, such as a non-allergic viral exanthem. In both of these cases, these reactions may be mistakenly attributed to an allergic reaction.

Another consideration is the possibility that an allergy has resolved. True penicillin allergy can wane over time, with studies showing that 80% of patients with IgE-mediated penicillin allergy lose that sensitivity after 10 years. The implication is that some historical allergy labels may no longer reflect current risk.

Why Allergy Labels Matter

An inaccurate penicillin allergy label can affect prescribing decisions throughout a patient’s lifetime. When penicillins are avoided, they are often replaced with broader-spectrum antibiotics such as fluoroquinolones, glycopeptides or carbapenems. The unnecessary use of broad-spectrum antibiotics directly undermines efforts to preserve the effectiveness of existing antimicrobial agents.

Overall, antibiotic allergy labels are associated with:

• Greater AMR, including higher rates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) colonisation or infection;
• Increased risk of Clostridioides difficile infection;
• Increased surgical site infection rates;
• Longer hospital stays;
• Higher readmission rates; and
• Increased healthcare costs.

De-labelling as an AMS Strategy

Penicillin allergy delabelling is the process of identifying and removing an inaccurate allergy label after appropriate assessment. De-labelling can range from careful review of a patient’s allergy history through to formal allergy testing or supervised oral challenge, depending on the nature of the reported reaction and local protocols.

Australian healthcare services have demonstrated the benefits of this approach. A Victorian antibiotic allergy de-labelling program studied patients undergoing oral penicillin challenge and found that 97% of these patients had a negative result. De-labelling of penicillin allergy resulted in a significant change in the use of preferred antibiotics and appropriate prescribing. Outcomes in the de-labelled patients included a ten-fold increase in the use of narrow-spectrum penicillins and a reduction in the use of restricted antibiotics.

While the benefits of penicillin allergy de-labelling are well established, patient safety remains paramount. De-labelling should only occur after an appropriate assessment of the reported reaction and, where indicated, supervised allergy testing or oral challenge. Patients with a history suggestive of severe delayed hypersensitivity reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), serum sickness-like reactions, or organ-specific immune reactions require specialist assessment and should not undergo direct oral challenge. Careful patient selection helps minimise risks while maximising the benefits of de-labelling programs.

Assessing risk

Validated tools, such as PEN-FAST, can be used to assess penicillin allergy risk. This tool helps clinicians to rapidly assess risk and support penicillin allergy de-labelling programs.

A score of less than three indicates a low risk of penicillin allergy. Studies suggest that low-risk patients may be suitable for direct oral penicillin challenge without prior skin testing. However, this should only ever be conducted in accordance with local protocols, governance requirements, and appropriate clinical supervision.

The PEN-FAST tool has been validated for use in adults and may be useful in adolescents. However, it should not be used to assess allergy risk in children. An alternative tool, the Beta-lactam antibiotic allergy assessment tool, has been validated for use in both adults and children. This tool utilises patient-reported signs and symptoms to assign an accurate phenotype to the allergy and recommendations for management of the allergy. This tool can be used by any health professional and was validated by junior doctors, senior doctors, pharmacists, specialist nurses, and haematology/oncology nurses.

Patients with a history of severe penicillin allergy should not undergo direct oral challenge without prior skin testing.

Aligning with Australian Standards

Penicillin allergy assessment and documentation are increasingly recognised as important components of AMS programs.

The Australian Commission on Safety and Quality in Health Care (the Commission) identifies optimisation of antimicrobial use as a key strategy for reducing AMR. They produce a range of resources to support antibiotic allergy assessment and AMS in general.

All healthcare staff can help identify and address inaccurate antibiotic allergy labels, improving patient care and supporting AMS.

Key actions include:

• Clarifying reported allergy histories and reaction details;
• Distinguishing side effects from true allergic reactions;
• Identifying patients who may benefit from referral for further assessment;
• Encouraging discussion of allergy labels with the treating team;
• Ensuring allergy information is accurately documented and updated; and
• Supporting local allergy assessment, testing, or antibiotic challenge programs where available.

By working together, prescribers, pharmacists, and nurses can help ensure patients receive the most appropriate antibiotic therapy.

Following successful de-labelling, allergy records should be updated across all relevant medical records and patients should be informed of the outcome to reduce the risk of the incorrect allergy label being reintroduced in the future.

A Key Message for World AMR Awareness Week

Antimicrobial resistance is often described as one of the greatest threats to modern healthcare. While new antibiotics are limited, improving how existing antibiotics are used remains one of the most effective defences.

True antibiotic allergies are uncommon and frequently over-reported. Beta-lactam antibiotics, such as penicillins and cephalosporins, are among the safest and most effective treatments for many infections and should only be avoided when there is a strong suspicion of a genuine allergy. Over-diagnosis of allergy can lead to poorer antibiotic choices, including unnecessary use of broader-spectrum antibiotics, which may be less effective, more toxic, and further contribute to AMR.

An inaccurate penicillin allergy label can persist for decades, influencing countless prescribing decisions. By questioning, assessing and appropriately removing incorrect allergy labels, healthcare professionals can improve patient outcomes while strengthening AMS efforts.

Effective penicillin allergy de-labelling requires a balanced approach that maximises access to preferred antibiotics while maintaining patient safety. Accurate history-taking, appropriate risk stratification, adherence to local protocols, and careful documentation are critical to minimising the risk of inappropriate de-labelling. Addressing penicillin allergy labels through systematic assessment and evidence-based de-labelling is an important AMS activity. It has the potential to improve individual patient outcomes, enhance access to first-line antimicrobial therapy, reduce unnecessary broad-spectrum antibiotic use, and help minimise AMR.