Phage therapy
Antibiotics and resistance
Antibiotics treat bacterial infections by killing the bacteria outright or stopping them from reproducing.
They work by targeting specific parts of bacteria, such as their cell wall or the processes they use to grow and multiply.
How antibiotic resistance can arise
Bacteria naturally mutate as they replicate. Occasionally a mutation will help them to survive antibiotics that would normally kill them.
When antibiotics are used, susceptible bacteria die off, but resistant ones survive and multiply. Bacteria can also pass these resistance genes directly to other bacteria, allowing resistance to spread quickly through a population.
Antibiotics can also become less effective over time due to:
- use of antibiotics for a nonbacterial infection or
- incomplete use of the full course of prescribed antibiotics.
The World Health Organization recognises antimicrobial (antibiotic) resistance as one of the top global public health threats facing the world today.
How phage therapy helps fight antibiotic resistance
Phages or bacteriophages are tiny viruses that target bacteria. They can be found everywhere, including in soil, water and inside the human body.
Unlike antibiotics, which can wipe out both harmful and helpful bacteria, phages are highly specific. Each phage only recognises and attacks one type of bacteria (or a small handful of related strains). This makes them a very safe and highly targeted way to fight bacterial infections while leaving both the patient's own cells and helpful bacteria unharmed.
Phages target and attach to bacteria by a lock-and-key mechanism:
- Binding proteins on the phage match to unique markers on specific bacteria.
- If they match, the phage attaches and infects the bacteria – otherwise it will drift away.
- After infecting the bacteria, the phage copies itself until the bacterial cell bursts, releasing new phages to infect more of the same bacteria.
Human cells do not have these markers, so phage can’t infect them.
What happens in phage therapy
Currently phage therapy is individualised to each patient.
The delivery method depends on the type and location of the infection and can include:
- intravenous (through a drip)
- nebulisation (into the lungs)
- topical application
- drains
- intranasal washes, or
- catheter-based (into the urinary bladder) administration.
Treatment length varies too, ranging from around a week for acute (sudden, short-term) infections to several weeks for chronic or recurrent infections, though a 2-week course is more common.
Phage therapy in Australia
While it has been used around the world for over 100 years, phage therapy is currently considered an experimental treatment in Australia.
On a compassionate-use basis and through the STAMP clinical trial, phage therapy has already been used to successfully treat patients with severe infections when no other options remained.
Special access and clinical trial cases
Cystic fibrosis and lung infections
Two teenagers with cystic fibrosis and lung infections caused by Mycobacterium abscessus bacteria were given special access to phage therapy. Treated at the Sydney Children's Hospitals Network in collaboration with the University of Pittsburgh, one patient received phage through an IV drip for 7 months. The other patient received phage both through an IV drip for 10 months and twice directly into the lungs via a bronchoscope.
Both patients showed some improvement in their symptoms, and the infection went away completely in one of them.1
Bone and joint infection
One 7-year-old child with long-lasting (chronic) bone and joint infection caused by Pseudomonas aeruginosa was given special access to phage therapy and treated at The Children's Hospital at Westmead. Alongside antibiotics, the patient was given phage through an IV drip once or twice daily for 2 weeks.
There was some improvement in the child’s pain 2 weeks after treatment. After a few months, there was significant improvement in the child’s pain and mobility.2
Learn more about the case on the EMBO podcast.
Staphylococcus aureus infections
A total of 13 patients with serious or life-threatening Staphylococcus aureus infections were granted access to phage therapy through either clinical trial or special regulatory pathways that allow doctors to access unapproved treatments in urgent cases. The patients were treated with a combination of phages through an IV drip, alongside their antibiotics, twice daily for 2 weeks.
Bacterial levels dropped during treatment and doctors found the phage therapy was safe, with patients experiencing no side effects.3
Standardised Treatment And Monitoring Protocol (STAMP) Study
Led by Associate Professor Ameneh Khatami (Sydney Children's Hospitals Network) and Professor Jon Iredell (Western Sydney LHD), STAMP is a clinical trial to assess the method of delivery, safety and tolerability of bacteriophage therapy for adult and paediatric patients.
Doctors access phage therapy for patients through special regulatory pathways and phages are matched to the specific bacteria causing their infection. The treatment course is developed by a team of clinicians and scientists and patients are carefully observed for safety and efficacy outcomes.4,5 Learn more about the STAMP trial and what happens during treatment.
Since 2022, 17 paediatric and adult hospitals across Australia have treated 12 kids (4 at our Network) and 33 adults with a variety of serious or life-threatening infections. Patient outcomes are currently being analysed and will be released soon.
SABRE-Phi
Funded by an NHMRC award and led by Associate Professor Ameneh Khatami (Sydney Children's Hospitals Network) and Professor Jon Iredell (Western Sydney LHD), SABRE-Phi is an upcoming clinical trial embedded within the SNAP trial, assessing the safety and effectiveness of phage therapy for persistent staphylococcalbacteraemia (bloodstream infection).
References
1 Rebekah M Dedrick, Bailey E Smith, et al. Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease. Clinical Infectious Diseases. 2023; 76(1): 103–112.
2 Khatami, A., Lin, RCY, et al. Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child. EMBO Mol Med. 2021;13.
3 Petrovic Fabijan A, Lin RCY, et al. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nature microbiology. 2020;5(3):465-72.
4 STAMP Trial Australia New Zealand Clinical Trials Registration
5 Khatami A, Foley DA, et al. Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial. BMJ Open 2022;12:e065401
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