iNAAN
Driving international collaboration for an innovative digital penicillin allergy toolkit
Principal investigator
Professor Jason Trubiano, Director, Department of Infectious Diseases and Immunology and Centre for Antibiotic Allergy and Research, Austin Health
Host organisation
Austin Health
Ten percent of the Australian population have a penicillin allergy – or do they? In fact, about 90% of that group are not truly allergic to penicillin, which means they are at risk of receiving the wrong treatment.
In addition, on a global scale antibiotic resistance is rising to dangerously high levels, and over-use of antibiotics is a contributing factor.
It’s a complex situation with many factors – a patient might have at one point had an allergic reaction to a specific drug (such as amoxicillin), or experienced a drug side effect that was interpreted as an allergic reaction. They may have been allergic to penicillin as a child but have since outgrown the allergy without knowing. Approximately 80% of people who have experienced an allergic reaction to penicillin will ‘outgrow’ the allergy after ten years.
Incorrect or ‘false’ antibiotic allergy labels result in inappropriate prescribing and increased use of broad-spectrum antibiotics, poor patient outcomes and a financial impact on the health system.
How can clinicians be supported in assessing antibiotic allergies?
When a patient is admitted to hospital, time is of the essence and a validated method for assessing a patient’s reported penicillin allergy is an important tool for clinicians.
Standard practice in the past has been to perform a skin-test procedure before proceeding to an oral challenge dose, if the skin-test is negative. Accessing penicillin skin-testing procedures in the inpatient setting requires time, trained clinicians and resources. Given the pressures of responding to an immediate issue of infection, many clinicians were therefore unable to test if a penicillin allergy truly exists, leaving limited antibiotic choices for common infections.
“Historically, skin-testing was commonly performed before proceeding to the oral challenge,” says Ms Elise Mitri, Project Manager, the International Network of Antibiotic Allergy Nations (iNAAN) study.
“The field of antibiotic allergy has been a rapidly evolving space over the past five to 10 years and now there are validated clinical decision rules and assessment tools that demonstrate that if you are assessed as having a ‘low risk’ allergy, you don't need to have a skin-test and can go straight to a direct oral challenge test as the delabelling strategy.”
Ms Elise Mitri
A direct oral challenge is very simple and efficient, because it can be undertaken by potentially any multidisciplinary clinician and only requires an hour or two observation period.
The challenge is supporting clinicians with a standardised way of assessing antibiotic allergies, enabling a risk-stratification to determine which patients are low-risk and appropriate for direct oral challenge, and then increasing the availability of penicillin allergy delabelling for hospitalised low-risk patients.
What if clinicians had a tool to help them assess the likelihood of a patient truly having a penicillin allergy and how severe that allergy is likely to be, so they could choose the most appropriate testing strategy?
This is what the International Network of Antibiotic Allergy Nations (iNAAN) is working on. A digital penicillin allergy toolkit to help clinicians decide whether a patient has a low-risk penicillin allergy and may therefore be a good candidate for an oral challenge would potentially deliver huge benefit to both patients and the broader health system.
Providing the basis for improved patient care and reduction in antibiotic resistance
Having solid data about the current situation regarding the burden of antibiotic allergies, their impact on antibiotic prescribing, and modes of antibiotic allergy testing, is key to effective antibiotic use policies and procedures.
The National Antibiotic Allergy Network (NAAN) has developed a framework for collaborative health services research in antibiotic allergy and part of this action is the formation of a database auditing inpatient antibiotic allergy testing, known as the International Network of Antibiotic Allergy Nations (iNAAN) study.
This database provides a platform for informing a standardised assessment and oral challenge procedure and a method for capturing the resulting data, which can then be used for auditing and improving hospital procedures and national policy.
This work will provide vital data to inform the National Allergy Strategy and National Allergy Centre for Excellence (NACE) in the future.
The database is complemented by a smartphone app (NAAN App) that clinicians can use to guide their decision-making. The app utilises published clinical assessment tools, such as the Antibiotic Allergy Assessment Tool and PEN-FAST clinical decision rule, to provide clinicians with a digital penicillin allergy toolkit and a platform to easily collect penicillin allergy phenotypic data, enabling a resultant risk-assessment. The app also allows oral challenge data collection at the point-of-care.
“The reason we're doing this is to help remove false or incorrect penicillin allergy labels. At the patient level and at the health service level, the improvements associated with delabelling are significant,” says Ms Mitri.
“If we can demonstrate that a patient is not allergic to penicillin, the patient will receive the most appropriate antibiotic for their infection or during surgical procedures, and they will be at a lower risk of antimicrobial resistance. More broadly, it can reduce hospital length of stay and health service costs. That's a significant benefit for the health service.”
The benefits extend even further into the broader community. In the longer term, increased public perceptions and information about opportunities for delabelling antibiotic allergies and therefore more appropriate antibiotic use could lead to a widespread reduction in antimicrobial resistance.
Supporting health service compliance with national standards
The NAAN smartphone app launched in November 2022 at the Austin Hospital, Peter MacCallum Cancer Centre and Albury Wodonga Health. Since then, the project has expanded its participating health services to include international sites.
“One of the biggest developments since the iNAAN platform launch is that we've got an implementation science angle applied to the study,” says Ms Mitri.
“As well as capturing clinical effectiveness outcomes, such as the safety and numbers of patients being delabelled via oral challenge, we’re examining the implementation of the intervention in health services, including the adoption of the digital penicillin allergy toolkit.”
The project team is assessing the adoption of the digital penicillin allergy toolkit (NAAN app) to safely and effectively assess a patient’s penicillin allergy and where appropriate, utilise direct oral challenge as the testing strategy.
This assessment of adoption takes into account the number of hospitals that have picked up the intervention, how many clinicians are using the penicillin allergy toolkit to phenotype and risk-assess their patients and help decide whether or not they're appropriate to receive a challenge, and what multi-disciplinary clinicians are doing it.
The project team is also analysing the sustainability of the NAAN app over time at health services. This is done by collecting data on the number of assessments and challenges that sites are able to perform over time and whether that's sustained – in other words, whether the app is user friendly and makes it easier for the health service to implement penicillin allergy programs within routine clinical care and comply with the national standards for antibiotic allergy documentation in the medical record.
“Our National Safety and Quality Health Service (NSQHS) standards in Australia recommended that when a patient comes into the hospital and they report an antibiotic allergy, we should have the drug, the date, the severity and the reaction type documented in the medical record,” says Ms Mitri. “This helps to ensure patient safety by preventing inadvertent medication exposure, but also enables us to work out what alternate antibiotics a patient can safely receive while in hospital.”
The iNAAN platform enables sites to audit the accuracy and completeness of their own antibiotic allergy documentation, both pre- and post-allergy assessment, so they can demonstrate how their own health service is meeting the national standards for documentation of antibiotic allergies.
Ms Elise Mitri
Enabling a broad view of the antibiotic allergy landscape
Once sites are activated in the iNAAN study, they start submitting data to the iNAAN database via the NAAN app. In return, they receive regular electronic audit and feedback reports about their own health service every two months, enabling them to look at their own local clinical effectiveness and implementation outcomes.
This enables each health service to review the number of challenges they’re performing, the safety of those challenges, and which disciplines are actually conducting the assessment and then performing the challenges. The reports encompass benchmarking, enabling sites to compare their own outcomes with other comparable health services across Australia.
“We've had a number of focus groups and surveys about how acceptable the NAAN app is, to help clinicians assess patients at the bedside and decide whether or not someone is safe or appropriate for an oral challenge. The feedback on the NAAN app has been very positive. Additionally, we have obtained valuable feedback on the design and content of the health service reports. These focus groups have helped to inform improvements in the reports to ensure they meet the needs of clinicians and health services” says Ms Mitri.
A more extensive audit of the clinical effectiveness and sustainability of the digital penicillin allergy toolkit across all sites will be possible over time thanks to BioGrid’s platform, which will enable access to de-identified, aggregated data for the health services as they build up the data they contribute to the database.
BioGrid’s secure platform underpins the iNAAN study
The iNAAN project team had a choice – build their own database or find a partner with the expertise to help them. Doing it themselves would have cost triple, and BioGrid’s secure data storage and handling, along with existing ethics approval for the platform, made it a compelling proposition.
BioGrid makes the database very attractive to sites that are considering coming on board, as they tick all the boxes in terms of data security, data storage, the coding of data to remove identifying information, and the governance that exists for the platform
Professor Jason Trubiano, Principal Investigator for iNAAN
“In addition, the BioGrid relationship presents exciting possibilities in the future to link data from other studies with the iNAAN database to examine the relationship between penicillin allergy and other health factors.”
The data collected by the app is not stored locally, but is safely transferred via the cloud to a REDCap database securely hosted by BioGrid.
Rapid expansion of iNAAN into international sites
From its launch at three sites in 2022, iNAAN has now been activated in 38 sites in Australia and internationally. The sites span Australia, Canada, Hong Kong, Malaysia, South Africa, the United Kingdom, and the United States. New Zealand is also scheduled to come on board within the next couple of months.
“Our collaborators across all sites are really motivated to be involved and uptake has been very rapid. It’s really exciting because it’s a true multidisciplinary, international study involving allergists and immunologists, infectious diseases physicians, other non- allergist medical practitioners, pharmacists and nurses or nurse practitioners, all with a unified goal of implementing low-risk penicillin allergy delabelling programs,” says Ms Mitri.
“With one in 10 patients reporting a penicillin allergy, tackling this problem does require a multidisciplinary effort.”
The iNAAN database will provide a large, international evidence base for demonstrating that low-risk penicillin allergy delabelling may potentially be performed by any trained clinician, hopefully further increasing the uptake of these programs within health services.
“The toolkit is designed to support clinical decision-making, but ultimately the final decision about whether to perform an oral challenge is up to the clinician. Having data and evidence to support multi-disciplinary penicillin allergy delabelling is important to inform future expansion of these programs,” says Ms Mitri.
Right now there are no national or international standards for the optimal approach to performing an antibiotic allergy oral challenge, so the study team hope the iNAAN database will provide evidence to inform the design and implementation of standards for an approach to penicillin oral challenge, as well as introducing evidence about how penicillin allergy delabelling correlates with longer-term antimicrobial prescribing and antimicrobial resistance outcomes.
For more information about BioGrid’s data sharing platform, explore the rest of the BioGrid website.
Other active REDCap databases implemented and supported by BioGrid:
- Australia and Aotearora New Zealand Thoracic Clinical Quality (ANZTHOR) Registry
- Australian Bladder Cancer (ABC) Registry
- Penile Cancer Registry (PCR)
- Stafford Fox Rare Cancer (SFRC) Registry