Vaccination can prevent infection – but is only available for a small number of infectious agents. For infections that are not prevented, antimicrobials (mostly antibiotics, with a few antivirals and antifungals) offer the possibility of treatment.
Now, however, antibiotics are failing due to growing antimicrobial resistance (AMR) and the R&D pipeline for new antibiotics has all but dried up. As the World Health Organization has warned, this threatens “an end to modern medicine as we know it”. Common infections will once again become untreatable. Cancer treatments and transplants will become increasingly unsafe and even routine operations and procedures will carry high risk of untreatable infection, sepsis, and mortality. By 2050, antibiotic resistant infections are projected to become the leading cause of death worldwide resulting in approximately 10 million deaths annually. The social and economic costs will be enormous.
Phage therapy offers a third approach to infectious disease control. Phages (also known as bacteriophages) are viruses that prey on bacteria. They remain completely effective against antibiotic resistant bacterial strains, offering a last defence against otherwise untreatable infection. Phage therapy also brings a number of critical advantages over antibiotic treatment. With careful preparation to remove impurities, they are non-toxic to humans. Unlike antibiotics, each phage is highly precise in the specific bacteria that it targets, meaning that treatment has fewer effects on the healthy bacteria in our bodies. They can be used on their own or in combination with other phages and antibiotics to increase efficacy even more.
Our primary goal is to establish phage therapy within a framework of approved indications based on clinical trials and a sound understanding of the underlying physiology. Phages will be available for prevention of disease as sole or adjunctive therapy, and as the go-to therapy when antibiotics are
inadequate (e.g., in chronic respiratory and medical device infections) or fail completely due to AMR.
We will achieve this through the creation of Phage Australia, a national industry ecosystem of genomics and informatics, diagnostics, clinical trials, manufacturing and internationally networked biobanks. Phage Australia will provide both empiric preparations designed by understanding the common pathogens and their phage susceptibilities, and bespoke therapies guided by precision diagnostics. The same diagnostic tools used to make initial therapeutic choices will help us to screen for new phages (i.e., to add to biobanks) and to monitor therapy. We will work to develop bioinformatics-driven phage optimisation, and to develop phages with new capacities and therapeutic potential.
New capacities in biotechnology, genomics, laboratory robotics, informatics, and synthetic biology make this the perfect time to bring a hitherto arcane science into the modern pharmacopoeia. Our newly established surveillance and biobanking programs provide ideal complementary infrastructure. By tapping into the global phage market, projected to reach $1.4 billion by 2026, Phage Australia will become a commercially sustainability entity, pioneering and delivering phage therapeutics, and putting Australia at the forefront of the third great revolution in the control of infectious disease.
Lin RC, Sacher JC, Ceyssens PJ, Zheng J, Khalid A, Iredell JR; Australian Phage Biobanking Network. Phage Biobank: present challenges and future perspectives. Curr Opin Biotechnol. 2021 68:221-230.
Khalid A, Lin RCY, Iredell JR. A phage therapy guide for clinicians and basic scientists: background and highlighting applications for developing countries. Front Microbiol. 2021 11:599906.
Venturini C, Ben Zakour NL, Bowring B, Morales S, Cole R, Kovach Z, Branston S, Kettle E, Thomson N, Iredell JR. Fine capsule variation affects bacteriophage susceptibility in Klebsiella pneumoniae ST258. FASEB J. 2020 34(8):10801-10817.
Petrovic Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR; Westmead Bacteriophage Therapy Team. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol. 2020 5(3):465-472.
Venturini C, Zingali T, Wyrsch ER, Bowring B, Iredell J, Partridge SR, Djordjevic SP. Diversity of P1 phage-like elements in multidrug resistant Escherichia coli. Sci Rep. 2019 9(1):18861.
Petrovic Fabijan A, Khalid A, Maddocks S, Ho J, Gilbey T, Sandaradura I, Lin RC, Ben Zakour N, Venturini C, Bowring B, Iredell JR. Phage therapy for severe bacterial infections: a narrative review. Med J Aust. 2020 212(6):279-285.
Maddocks S, Fabijan AP, Ho J, Lin RCY, Ben Zakour NL, Dugan C, Kliman I, Branston S, Morales S, Iredell JR. Bacteriophage therapy of ventilator-associated pneumonia and empyema caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2019 200(9):1179-1181.
Fabijan AP, Ben Zakour NL, Ho J, Lin RCY, Iredell J; Westmead Bacteriophage Therapy Team (WBTT) and AmpliPhi Biosciences Corporation. Polyclonal Staphylococcus aureus bacteremia. Ann Intern Med. 2019 171(12):940-941.
Gilbey T, Ho J, Cooley LA, Petrovic Fabijan A, Iredell JR. Adjunctive bacteriophage therapy for prosthetic valve endocarditis due to Staphylococcus aureus. Med J Aust. 2019 211(3):142-143.e1.
Khawaldeh A, Morales S, Dillon B, Alavidze Z, Ginn AN, Thomas L, Chapman SJ, Dublanchet A, Smithyman A, Iredell JR. Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection. J Med Microbiol. 2011 60(Pt11):1697-1700.
Clinical Nodes
- Adelaide Queen Elizabeth Hospital, Dr Morgyn Warner
- Alfred Hospital, Prof Anton Peleg
- Children’s Hospital Westmead, Dr Ameneh Khatami
- Telethon Kids / Perth Children’s Hospital, Prof Stephen Stick
- Royal Brisbane and Women’s Hospital, Prof David Paterson
- Westmead Hospital, Prof Jon Iredell
- Royal Perth Hospital / Fiona Stanley Hospital, Dr Chris Heath
- Royal Melbourne Hospital, Prof Deborah Williamson
Jon is an Infectious Disease Physician and Microbiologist who divides his time between Westmead Hospital in a combined Infectious Diseases and Microbiology Department and his research which is supported by the NHMRC at the University of Sydney.
His major interests are in critical infection, including the study of bacterial septic shock, and in bacterial genetics and ecology. Formal affiliations are (1) Conjoint Professor of Medicine and Microbiology, Sydney Medical School The University of Sydney/The Westmead Institute for Medical Research and the Marie Bashir Institute, (2) Senior Staff Specialist, Western Sydney and Westmead Hospital and Deputy Director Microbiology, Pathology West (NSW Pathology) and Institute of Clinical Pathology and Medical Research, (3) Director, Centre for Infectious Diseases and Microbiology at Westmead Institute for Medical Research. List of publications.
Deputy Director of Phage Australia (MRFF Frontier 2021), Stream 1 co-convenor, IP Commercialisation Working Group.
Ruby CY Lin is the Genomic Chair of the Scientific Advisory Committee of Westmead Precinct Hub (2 teaching hospitals and 3 Medical Research Institutes) and current Vice President of the Australasian Genomic Technologies Association (AGTA). She helps organisations build academic-industry hybrid teams and has secured over $6.4 million in research funding in the disciplines of genomics, cardiovascular diseases, obesity, cancer biology, tissue and pathogen biobanking, phage banking as well as phage therapy. She was a NHMRC Peter Doherty Postdoctoral Fellow (2005-8) and UNSW Global Postdoctoral Fellow (2009-14). Her research profile and publications can be referenced at ResearchGate, ORCID and Google Scholar. She officially handles @agtaGenomics and @Iredell_lab Twitter accounts and is active on LinkedIn.
During her time as the president of AGTA (2013-5), she continued to implement co-convenors for its annual meeting with a quiet room for delegates with carer duties, ECR-MCR pairing to chair sessions and 50:50 gender balanced international and local invites. AGTA proudly continues this equity diversity and inclusion guidelines in its conferences, workshops and symposiums. She is a GEDI (Gender Equality, Diversity and Inclusion) committee member of AAMRI (Association of Australian Medical Research Institutes), part of UNSW Women in Research and STEM Women (Australian Academy of Science) and advocates for girls and women in STEMM and does pro bono career coaching. She is on the Phage Futures Advisory Board, Convenor of AGTA2022 Sunshine Coast and part of organising committee for International Genetics Congress 2023 Melbourne and International Society for Viruses of Microorganisms 2024 Cairns.
Ameneh, BHB, MBChB, DipPaeds, MD, FRACP, is a senior lecturer in Child and Adolescent Health for The University of Sydney, based at The Children’s Hospital at Westmead where she also works as a paediatric infectious diseases specialist.
Her research focus is on novel therapeutic options for difficult to treat infections in paediatrics and optimisation of antimicrobial therapy for children with cystic fibrosis. She was the first clinician in Australia to treat a child with intravenous phage therapy in October 2019 for a highly resistant Pseudomonas aeruginosa bone infection and has been overseeing the planning and treatment of other patients using phages against Mycobacterium abscessus (including the first use of a genetically modified phage in Australia) through collaborations with Prof Iredell and the Westmead Institute for Medical Research and the Sydney Children’s Hospital Network cystic fibrosis teams.
Ameneh is the paediatric representative for the Australasian Society for Infectious Diseases Clinical Research Network with a goal to increase involvement of children in clinical research, particularly early phase studies. She is also the Phage Therapy content expert for the Sydney Children’s Hospital Network Advanced Therapeutics Steering Committee. Her other areas of research include investigating the immunological response to influenza and COVID-19 vaccination in healthcare workers, the burden of enteric fever in Western Sydney and improving molecular diagnostics of osteoarticular infections in children.
Jennifer is Director of Biobanking with NSW Health Pathology and conjoint Professor of Molecular Oncology in the Faculty of Medicine and Health at the University of Sydney.
She has spent much of her scientific career analysing childhood and adult cancers at a molecular level. Has published over 100 peer-reviewed publications, which have been cited more than 3,200 times. Her current research interests include the analysis of human biobank research outputs and the identification of predictors of biobank success, and the detection and analysis of incorrectly reported nucleotide sequence reagents in the biomedical research literature. Professor Byrne was named as one of the journal Nature’s “10 people who mattered in 2017”, for identifying and reporting numerous flawed cancer research papers.
Rob is a Matthew Flinders Fellow in Bioinformatics, College of Science and Engineering.
Rob received his BSc (Hons) from De Montfort University, Leicester, England, and then completed a PhD at the Nitrogen Fixation Laboratory at the University of Sussex, England exploring the regulation of nitrogen fixation in Klebsiella pneumoniae. He moved to the US as a PostDoc, first at the University of Pennsylvania in Philadelphia studying enterotoxigenic E. coli, and then at the University of Illinois, Urbana-Champaign studying the genomics and pathogenesis of Salmonella, work that he continued as an Assistant Professor at the University of Tennessee Health Sciences Center in Memphis, TN. Working with Argonne National Labs and the Fellowship for the Interpretation of Genomes (FIG) he developed the RAST and MG-RAST systems for bacterial genome and metagenome annotation.
In 2006, Rob took a position in the Departments of Computer Science and Biology at San Diego State University, and his work there led to breakthroughs in our understanding of how viruses interact with their hosts, and how viruses from around the world carry important genetic information. Rob has continued to push current sequencing and bioinformatics technologies, in 2013 took a next-generation sequencing machine to the remote Southern Line Islands to explore metagenomics of coral reefs in real-time. In 2014 Rob’s team identified a virus that is present in the intestines of approximately half the people in the world, and in 2019 Rob assembled a consortium of 115 colleagues from every continent to demonstrate the global spread of the virus.
In addition to science and teaching Rob is also an advanced scientific SCUBA diver having led teams to study Coral Reefs all over the world. In his spare time, he is a cyclist, black-diamond skiier and an avid international yachtsman, navigating in long-distance offshore races, including navigating the 2019 TransPac race from Los Angeles to Honolulu finishing 4th out of 89 boats.
Dr Heath is an Infectious Diseases Physician & Clinical Microbiologist (PathWest Laboratory Medicine) at both Fiona Stanley Hospital (FSH) & Royal Perth Hospital (RPH) in Perth, WA.
Dr Heath was the inaugural Head of Infectious Diseases at RPH from 1997 until 2017. He has extensive experience with expertise in clinical infectious diseases and in diagnostic laboratory microbiology. Chris has active research interests in infections in the immunocompromised host, clinical and laboratory mycology, hospital-acquired infections and control of MRO’s, antimicrobial stewardship, contemporary diagnostics involving innovative technologies, microbial genomics and phylogenetics, and novel antimicrobials for emerging drug resistance – including bacteriophages. Dr Heath is an adjunct Clinical Associate Professor of Medicine at the University of WA.
Trevor is the Director of the Centre to Impact AMR, a transdisciplinary research centre focussed on delivering sustainable solutions to the problem of AMR.
He also leads the Bacterial Cell Biology Lab at Monash University, investigating details of the structure and function of bacterial cell envelopes, the evolution of drug-resistance in Klebsiella and the role that phages play in limiting and reversing this dreadful trait. The work has impact in future treatments of urinary tract infections, pneumonia, liver disease and sepsis.
His lab uses bioinformatics and machine-learning to characterize the physical properties of phages from information embedded in their genomic sequences, and cryo-electron microscopy to image the structural features of phage particles. Phages are collected for study from local waterways in partnership with the Wurrundjeri Woi wurrung Cultural Heritage Aboriginal Corporation. Research activity (documented on Google Scholar) is enhanced through collaborative international Biobanks of phages and clinical bacterial isolates in the UK and China. Detailed investigation into the biology of the new waves of Klebsiella currently spreading across the globe relies on comparative genomics, biochemical characterization and evaluation of bacterial membrane proteins, and multi-‘omics assessments of these bacteria.
David Paterson is an Infectious Diseases Physician at the Royal Brisbane and Women’s Hospital and is Director of the University of Queensland Centre for Clinical Research.
With more than 500 peer-reviewed publications he is Australia’s most cited Infectious Diseases Physician. His major interest is in the field of Antimicrobial Resistance (AMR) where he is ranked number four in the world (expertscape.com).
Anton Peleg is a Professor of Infectious Diseases and Microbiology, NHMRC Practitioner Fellow and Director of the Department of Infectious Diseases at The Alfred Hospital and Monash University, Melbourne, VIC.
He is Theme Leader for Infection and Immunity at Monash Academic Health Research and Translational Centre, and has recently been elected as a Fellow of the Australian Academy of Health and Medical Sciences.
He completed his infectious diseases clinical training in Australia in 2005 and then went to the USA for four years and worked at the Harvard-affiliated hospitals; Beth Israel Deaconess Medical Center and Massachusetts General Hospital. He completed a Masters of Public Health at Harvard School of Public Health, and also completed a PhD in Infectious Diseases and Microbiology with a focus on antimicrobial resistance (AMR) and genomics. He returned to Australia in 2010 as a clinician-scientist.
His research interests are in hospital-acquired infections, AMR and novel solutions, bacterial genomics, mechanisms of pathogenesis and infections in immunocompromised hosts. He is also an active clinician working in the area of hospital-acquired infections and transplant infectious diseases. He has received numerous national and international awards for his advanced research and contribution to Infectious Diseases and Microbiology.
Vitali is an academic pathologist with Sydney Medical School, The University of Sydney and Director of the Centre for Infectious Diseases and Microbiology-Public Health, a translational research hub funded by the NSW Ministry of Health.
As a clinical microbiologist he leads NSW Public Health Pathogen Genomics service at the Institute of Clinical Pathology and Medical Research-NSW Health Pathology, and supervises the NSW Enteric and Mycobacterium Reference Laboratories. He is a Faculty member for Westmead Institute for Medical Research (WIMR), a member of the Sydney Infectious Diseases Institute at the University of Sydney, and visiting senior research fellow at the Centre for Health Informatics, Macquarie University.
Stephen is the Northern Star Professor of Children’s Respiratory Health Research Professor Stick is a career clinician and clinical researcher, holds a NHMRC Practitioner Fellowship and is a Fellow of the Australian Academy of Health and Medical Science.
He graduated in Medicine from Cambridge University, completing his paediatric training in the UK before obtaining a PhD in respiratory physiology at the University of Western Australia.
Prof Stick was head of the Department of Respiratory and Sleep Medicine at Princess Margaret Hospital for Children from 1998-2016. He introduced a number of important clinical services, including the first accredited children’s sleep laboratory in Australia and specialist outreach services to the South West, Goldfields and North West of Western Australia. His contribution as Principal Investigator for the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) is internationally recognised and in 2015 he was awarded the Richard Talamo Distinguished Clinical Achievement Award, the highest research award of the US Cystic Fibrosis Foundation.
Prof Stick has had continuous research funding from the NHMRC since 1997 and currently holds over $14m in competitive research funding from national and international sources. His research focus has been the earliest manifestations of chronic respiratory diseases such as asthma and cystic fibrosis and developing interventions to prevent long term lung damage.
Steven is an infectious diseases physician with the Victorian Infectious Diseases Service and Co-Head of the Translational and Clinical Research at the Doherty Institute.
He conducts infectious diseases clinical trials and leads the Staphylococcus aureus Network Adaptive Platform Trial and the Australasian COVID-19 Trial. He chairs the Australasian Society of Infectious Diseases Clinical Research Network. Follow him @syctong.
Morgyn is an infectious diseases physician and clinical microbiologist at SA Pathology and the Central Adelaide Health Network in South Australia.
She is the head of the infectious diseases unit at The Queen Elizabeth Hospital, chair of the South Australian expert Group on Antimicrobial Resistance (SAGAAR) and a member and past chair of the Australian Commission on Safety and Quality in Healthcare’s antimicrobial stewardship advisory committee. Her clinical interests are in antimicrobial resistance, antimicrobial stewardship and infections in immunosuppressed hosts. Her research interests include optimisation of dosing of antimicrobials, applications of bacteriophage therapy, antimicrobial stewardship, and the human and environmental microbiome in relation to multiresistant bacteria transmission and infection.
Deborah is a Clinical and Public Health Microbiologist, Professor / Director of Microbiology at the Royal Melbourne Hospital and the Doherty Institute, Deputy Director of the Microbiological Diagnostic Unit Public Health Laboratory, and a Dame Kate Campbell Fellow in the Department of Microbiology and Immunology at the University of Melbourne.
She is an NHMRC Investigator Grant recipient, received a L’Oreal-UNESCO Women in Science Fellowship in 2017 and was awarded the Australasian Society for Infectious Diseases Frank Fenner Award in 2020.
Integrating Australian phage bioanking and therapeutic networks and delivering solutions for antimicrobial resistance.
Our primary goal is to establish phage therapy in the national pharmacopoiea. Phages will be available for prevention of disease as sole or adjunctive therapy, and as the go-to therapy when antibiotics are inadequate.
Phage Australia will build a national industry ecosystem of genomics and informatics, diagnostics, clinical trials, manufacturing and internationally networked biobanks.
Phage therapy is safe and well tolerated in severe sepsis and shock
Phages will often be sought when the situation is most dire, perhaps as a ‘rescue therapy or as additional or ‘adjunctive’ therapy. We have shown that this therapy is safe in treating more than a dozen people with very severe infection, including people with the most severe sepsis and people with infected heart valves and very severe lung disease.
We have treated people by administering as an aerosol (a ‘nebuliser’, just as would use for asthma) and by intravenous injection and carefully measured their response to infection and to administration of the phage therapy.
Each dose is monitored and adjusted if necessary so that we are confident that there are enough phages being delivered to the site of infection.
Phage therapy can be used with antibiotics
It is not unusual that people receiving phage therapy will already be on antibiotics. We measure the bacterial killing effect of adding the phage to the antibiotics before using the combination at the bedside. A boosting (‘synergistic’) effect is common.
Phages have been administered for therapeutic purposes in almost any way you can imagine. They can be given by mouth, by topical administration (e.g. in an ointment or dressing), by inhalation, by instillation into a specific site (e.g. bladder irrigation) and by injection.
We typically use two doses a day and typically treat for a couple of weeks.
So far we have treated dozens of adults and children, mostly by direct instillation (into the bladder or the airways), by inhalation (of an aerosol) and by injection. Our outcomes have all been published in peer-reviewed journals and are listed in our Publications section.
All our therapeutic interventions are monitored by hospital ethics and drug committees and the Therapeutic Goods Administration.
A referral is best made from your family doctor or your specialist to an infectious diseases specialist.
If the infection specialist can certify that all medical and surgical anti-infection strategies are optimised or exhausted, they may suggest a referral to one of our team for discussion.
We also require that non-phage anti-infective strategies be closely and independently monitored during the course of phage therapy and for a follow-up period of several weeks thereafter.
Group lead: Dr Ameneh Khatami, Senior Lecturer, Child and Adolescent Health, University of Sydney, Paediatric Infectious Diseases specialist, The Children’s Hospital at Westmead
Children were included in some large early studies of phage therapy. There have also been several published reports of children from all around the world receiving phage therapy for various infections, sometimes for very long durations. In all of these reports, no significant safety concerns were raised and the children all tolerated the treatment well. Because phage therapy use in children is a relatively new treatment and there have not been large numbers of children treated, we need to continue to monitor children closely under research conditions until we learn more about this therapy.
Because children are still growing and developing, clearing infections early will allow that growth and development to occur normally. This will improve quality of life and long-term burden of healthcare needs and in many circumstances, will also improve life expectancy.
Although the safety data has been very encouraging, it is very important that we better understand how the human immune system responds to phage therapy. Because children’s immune systems are still developing, they may respond differently to adults receiving phage therapy. Comparing information we learn from children, to what we can learn from adults will help us understand this new treatment better.
The Children’s hospital at Westmead was the first centre in Australia to treat a child with phage therapy in 2019 (featured on ABC 7.30 report) and we were the first to treat any patient in Australia with genetically-modified phage in 2020.
So far we have treated 3 children for different infections. This includes a child with a very drug-resistant bacterial (Pseudomonas aeruginosa) infection in the bone and joints of her lower leg, and 2 children with cystic fibrosis and Mycobacterium abscessus lung infection. These treatments, which have ranged between 2 weeks and 10 months, have been well tolerated and no significant side effects have occurred. Refer to kids advanced therapeutics for more information.
If you believe that you or a family member may be a suitable candidate for phage therapy, please see your family doctor in the first instance to discuss this and request a referral to an adult or paediatric infectious disease specialist. After reviewing you, the infectious disease specialist will be able to contact one of the clinicians in our group to discuss your case.
Phage therapy is an experimental method that is only available when all other approaches are already optimised and only under the auspices of a special access scheme defined by the Therapeutic Goods Administration or within a clinical trial.
If a TGA-approved indication exists, we follow a protocol that has been defined by consensus among expert physicians and may evolve over time as data are reviewed. If you are eligible to receive therapy, we require informed consent and a minimum data set (including blood tests) that is necessary for the monitoring of your treatment.
