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.
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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.
- 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
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.