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Associate Professor Jon Iredell

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Professor Jon Iredell

Jon Iredell has comprehensive training in intensive care, infectious diseases and clinical microbiology, combined with a PhD in molecular bacteriology. He is an NHMRC Practitioner Fellow and heads the NHMRC (National Health and Medical Research Council) Centre for Research Excellence in Critical Infection, which conducts basic and clinical research and provides a course in advanced clinical microbiology/infectious diseases in critical care (short course in Critical Infection; contact: critical.infection@sydney.edu.au).

Jon also heads the Bacteriology, Antibiotic Resistance, and Rapid Diagnostics group which, studies the ecology of bacterial resistance genes, translates these into diagnostic targets, and studies the effects of antibiotics on the microflora.

He provides a clinical service as a senior Microbiologist and as Director of Infectious Diseases, at the Centre for Infectious Diseases and Microbiology at Westmead Hospital and is a member of the Antimicrobial Resistance Advisory Committee of the NHMRC and the Gene Technology Technical Advisory Committee of the OGTR (Office of the Gene Technology Regulator).

Jon was the inaugural Division 1 Chair (Medical and Veterinary Microbiology) of the Australian Society for Microbiology (ASM) and was awarded the ASM/ BioMerieux Antibiotic Resistance award in 2007. He is conjoint Professor of Medicine and Microbiology and Deputy Post-Graduate Coordinator at the Sydney Medical School (Western).

The trajectory of the Bacteriology, Anitbiotic Resistance and Rapid Diagnostic group is:

  • to understand the key genetic ecology of antibiotic resistance, particularly genetic associations and the relative fluxes via major transmission vehicles, eg: plasmids;
  • to understand the real impact of antibiotics on the microflora, both at whole gut ecology level, including selection of resistance, and at level of mobile genes and their vehicles (eg: plasmid ecology) – this work has major implications for national antibiotic policy and screening strategies; and
  • to marry high-throughput technology for epidemiological screening with high-speed accurate diagnosis in the critically ill, especially for septic shock and central-line associated blood stream infections. These areas are completely novel, not having been achieved anywhere in the world, and supported by external grants (NHMRC).

Professor Jon Iredell's research has been published in major medical journals including, the Journal of Clinical Microbiology, New England Journal of Medicine and Antimicrobial Agents and Chemotherapy.

Click here for a full listing of Professor Iredell's publications.

A critical look at infection


(Iredell, Sorrell, Gilbert, Booy, Kerridge, Dwyer, Webb, Sintchenko, Jones, Bennett)

The Hon Mark Butler, Federal Minister for Mental Health and Ageing, opened the Centre for Research Excellence in Critical Infection at a ceremony at the Westmead Millennium Institute in 2011, funded for 5 years at $500,000 per annum. Two research Fellows joined us from the ICDDR in Dhaka and have just begun work in the Department.

Direct support goes to the Paediatric Active Enhanced Surveillance Unit (PAEDS) and researchers in the Centre for Value Ethics and the Law in Medicine and to conduct clinical trials and microbiology surveillance and research on this campus.

A colloquium was held on 25 November 2011 at the Sydney Law School to review plans, among which is the inaugural short course in critical infection (May 11-12), the first of its kind, aimed at Intensivists wishing to learn relevant Microbiology and Infectious Diseases. We expect this to be an important step forward in antibiotic stewardship in 2012. Email: critical.infection@sydney.edu.au.

Recent work in our group has shown that:

  • Previous assumptions about antibiotic homogeneity as a driver of antibiotic resistance, founded on little or no empiric evidence and on simplistic mathematical models, cannot be experimentally confirmed in a carefully controlled prospective study.
  • Cefepime, widely used in critical care in Australia, and associated with a much-debated and unexplained attributable mortality in severe sepsis, but much greater in vitro efficacy against pathogens such as P. aeruginosa, is the strongest single risk factor for colonisation and infection with MRSA and P. aeruginosa in an ICU antibiotic exposure study involving two major Intensive Care units with >2000 admissions in two capital cities (presented at Australian Society for Microbiology 2001; submitted).
  • Conjugative (self-mobilising) antibiotic resistance plasmids of some subtypes are very restricted in diversity compared to antibiotic-sensitive plasmids of the same type. The addictive nature of these plasmids leads to important questions about ecological balance in the plasmid gene pool, especially given the linked relationships between certain antibiotic resistance plasmids and pathogenic E. coli/ eg ST131 E coli with CTXM-15 IncF ESBL plasmids – this work has been done with NHMRC funding using modern high-throuput 'deep sequencing' methods including Illumina and Roche 454 technologies and led to several important recent publications (AAC - Partridge/ Iredell).

Recent work in our group (Iredell/Partridge) has demonstrated that:

  • A number of new genes are emerging from the Asian gene pool in the Australian microflora (eg pan-aminoglycoside resistance due to methylase genes; new carbapenemases such as KPC and NDM).
  • Most of this emergence is silent –not detected reliably by phenotypic methods
  • The mobilised/ captured antibiotic resistance gene pool (eg ESBL) in Enterobacteriaceae is relatively limited and predictable and can be utilised as genetic targets for both screening and diagnosis – an opportunity to rescue the situation.
  • The genetic basis for antibiotic resistance to ESBL, aminoglycosides, carbapenems and AmpC enzymes in E. coli and K. pneumoniae can be accurately defined, with ~98% positive and negative predictive value (invited presentation American Society for Microbiology ASMET2 Puerto Rico 2011; also AAC – Zong et al; JCM – Ellem et al). This is crucially important as it allows us to use genetic targets to predict antibiotic resistance accurately.
  • In addition to ('next-gen') genomics approaches, we have developed innovative bioinformatics solutions to manage such data and published this in Microbiology, Bioinformatics and computational biology journals (eg Database (Oxford). 2011 Dec 2;2011:bar054; FEMS Microbiol Rev. 2011 Sep;35(5):820-55. Bioinformatics. 2011 Mar 15;27(6):791-6.

MALDI-TOF (Iredell/Chen): Our group helped pioneer the application of mass spectroscopic identification in the routine laboratory of bacteria (Kok et al 2011) and yeasts (Pinto et al 2011). MT-PCR (Iredell): Our group helped pioneer the use of multiplex-tandem PCR in Microbiology, in collaboration from 2004 with Keith Stanley, who invented and published the method in late 2005 and developed a successful startup company (AusDiagnostics). This has has led to several joint publications and NHMRC grants.

This platform (MT-PCR) was the main instrument used in the 2009 pandemic at Westmead and several other places for identification and (at Westmead) subtyping of influenza. It is now being deployed to:

  • Rapidly identify the subtype of Gram-positive cocci in blood culture of critically ill patients eg VRE, MRSA, Streptcocci – shortening time to identification by 12 hours or more – this has a measurable mortality benefit in septic shock.
  • Quantify bacteraemia and cytokine profiles in order to predict outcomes in the context of resuscitated septic shock, as part of an NHMRC grant in conjunction with the ANZICS Clinical Trials Group.

The impact of this work is to tie the targeting of antibiotic genes to rapid diagnosis and for the first time ever, move to point-of-care testing for the patient with septic shock.