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Preventing severe antibiotic allergy

 

Dr Jason Trubiano is Director of Antimicrobial Stewardship and Drug and Antibiotic Allergy Services, at Austin Health’s Department of Infectious Diseases and Centre for Antibiotic Allergy.

In 2018, Jason was selected to take part in Melbourne Genomics’ Medical Specialists Immersion Program. His project explores genomic associations with severe antibiotic allergy in hospital settings.

We asked Jason a few questions about the project.

 

Tell us about your project with Melbourne Genomics.

PIPA – Predictors, Immunopathogenesis and Prescribing in Antibiotic allergy – examines the burden, severity and solutions to antibiotic allergy in the hospital setting.

A significant part related to Melbourne Genomics was to better understand the role of HLA (human leukocyte antigen) and other genetic predictors, in severe cutaneous adverse reactions (SCAR) – a form of drug allergy resulting in up to 25 per cent mortality. (HLA helps the immune system distinguish the body’s own proteins from those made by foreign invaders, such as virus and bacteria.)

The Melbourne Genomics fellowship allowed me to spend time at Vanderbilt University (Nashville, Tennessee) and understand the important components required to examine HLA and genomic predictors of drug allergy – including the importance of phenotyping (clinical assessment) to genotyping. I wanted to gain a better understanding of the techniques involved in DNA extraction/biobanking, HLA typing and the development of whole-of-hospital genetic biobanks – which exists at Vanderbilt.

This funding enabled me to spend time with world experts in drug allergy pharmacogenomics and to develop skills to bring back to Melbourne.

What was your ultimate goal?

The ultimate goal was to develop a well-phenotyped cohort of patients with antibiotic-associated SCAR in Australia and examine the HLA and genomic predictors in collaboration with institutions such as Vanderbilt.

What did you learn?

We were able to develop a DNA biobank at Austin Health, in collaboration with sites around Victoria. This DNA biobank has enabled us to explore HLA associations with particular antibiotic-associated SCAR. As such, our international collaboration has identified a HLA closely associated with a common antibiotic-associated SCAR. This finding is about to be published. 

Why is this area of research important?

At present, antibiotic allergy is associated with inferior patient and hospital outcomes. Severe allergic cases are associated with a mortality rate of 25 per cent, and require use of second-line antibiotics. There are no readily available screening or diagnostic tests for patients with SCAR. The ultimate goal would be to prevent this disease by screening patients before they are given antibiotics.

How has the research project helped your career and how will it help the field of genomics?

The project has helped me develop a local biobank of patients to explore HLA and genomic associations with severe drug allergy. Further, it has built a platform for a national registry to be created to examine genomic predictors for a range of antibiotic allergies – AUS-SCAR.

How has the project influence your future research career?

This project has opened my eyes to the role genomics can play in the prevention and detection of severe antibiotic allergy. My future studies are focused on finding genomic strategies for the prevention and diagnosis of SCAR.