Phage Therapy: A Promising Solution in the Battle Against Superbugs.

Ruby Lin and Jon Iredell

Our reliance on antibiotics is facing a significant challenge. Antimicrobial resistance (AMR), commonly known as the rise of "superbugs," has become a pressing global concern. Scientists are exploring phage therapy as an intriguing solution. As we approach the premier of the documentary, “Last Chance to Save a Life” on SBS (15th of February 2024), which showcases one of the patients we treated at Westmead Health Precinct, we take this opportunity to describe our ongoing endeavours to harness the power of phage therapy in the battle against antibiotic resistance.

Antimicrobial resistance occurs when bacteria develop the ability to resist drugs that were once effective in treating them. This renders traditional antibiotics less effective, and in some cases, completely ineffective. It's a global health concern because common infections can become life-threatening without effective treatment options.

Bacteriophages, or phages for short, are viruses that specifically target and infect bacteria. They can be thought of as "natural predators" of bacteria. In phage therapy, we isolate specific phages that can infect and kill the targeted bacteria. These phages multiply and destroy the bacteria, effectively eliminating the infection. Phage constantly evolve alongside bacteria, continually adapting to outsmart them. This makes them a potential long-term solution against evolving and resistant bacteria. The remarkable precision of phages in targeting specific bacteria is an incredibly efficient approach for developing personalised therapies within the realm of precision medicine. ?

Phage therapy has been used for over a century, in some countries, particularly in Eastern Europe, to treat bacterial infections. More recently, there have been successful cases of phage therapy being used to combat drug-resistant infections, such as those caused by superbugs like MRSA (Methicillin-resistant Staphylococcus aureus). Research is ongoing, and clinical trials are being conducted to further explore its potential.

Like all advanced therapies, phage therapy faces its own set of challenges. The process of matching the appropriate phages to target specific bacteria can be intricate. Moreover, regulatory processes and ensuring the safety and effectiveness of phage products require further focus. At the Westmead Health Precinct, we are actively addressing these challenges.

We co-founded Phage Australia with the goal of seamless integration of phage therapy into clinical services. This visionary initiative unites clinicians, infectious diseases physicians, phage biologists, researchers, scientists, and regulatory and biomanufacturing experts from both national and international domains. Through this collaborative effort, we are actively propelling the progress of phage therapy as a prospective clinical service within the public sector.

Since December 2021, patients in Australia have gained access to bacteriophage therapy through the Therapeutic Goods Administration (TGA) Special Access Scheme, with a permissive and supportive stance from the TGA. This pathway enables patients to receive this innovative treatment under the standardised treatment and monitoring protocol known as STAMP (Standardised Treatment and Monitoring Protocol). This significant development has opened doors for patients to benefit from phage therapy with the necessary oversight and support from regulatory authorities.

Here we provide an update on the progress of our phage therapy program. Prior to STAMP we treated 19 patients (2 Pseudomonas aeruginosa patients (VAP + UTI), 14 Staphylococcus aureus patients, 3 Paediatric patients (2 Mycobacterium abscessus and 1 Pseudomonas aeruginosa) between 2017-2021. Since national approval of the STAMP protocol in December 2021, we have received 80 requests for phage susceptibility testing, and 15 patients have been treated. The most common reasons for exclusion were absence of a suitable phage match (27%) or improvement of infection and no longer requiring phage therapy (33%). Of the 15 enrolled patients (9 male, 6 female; aged 8-81 years), infections were found in various sites, including bone/joint, pulmonary, sinus, endovascular, urinary tract, intra-abdominal, and disseminated. The target pathogens treated with phages included?Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella aerogenes, and Mycobacterium abscessus.

Under STAMP, a total of 23 batches of fourteen phages were used, either individually or in combination, after conducting phage susceptibility tests. These phage preparations were administered through different routes, including intravenous, topical/instillations, nebulised, and oral. Fourteen patients (14/15 patients, 93%) had their phage preparations produced at The Westmead Institute for Medical Research. Clinical responses to the treatment varied with most patients experiencing clinical response (73%) ranging from clinical cure to partial improvement assessed at 2 weeks after phage therapy. In some cases, phage neutralisation activity in the patients’ serum was detected, indicating the presence of antibodies against the phages. No serious adverse events related to the treatment occurred (at the time of writing this article).

In Australia, we have achieved a significant milestone by treating a cohort of 34 patients using phage therapy, which marks the highest number of patients treated to date. This accomplishment underscores our commitment to advancing the field of phage therapy and providing innovative treatment options to patients in need. The utilisation of the STAMP protocol has further enhanced the standardisation and monitoring of these therapeutic interventions, ensuring optimal patient care.

This progress in phage therapy highlights its potential as an alternative approach to combating antimicrobial resistance and treating difficult-to-treat infections. Ongoing research and clinical experiences will continue to shed light on the safety, efficacy, and broader applications of phage therapy in the future.

Closing thoughts:

Addressing antimicrobial resistance is an urgent global concern, and it is imperative that we explore alternative solutions such as phage therapy. Advancing our knowledge of phages and their potential applications is crucial for developing effective treatments against highly resistant bacterial strains. Staying abreast of the latest scientific advancements and providing support to research endeavours are pivotal in shaping the future of medical interventions. We express sincere appreciation to our esteemed funders and donors for their invaluable contributions to this scientific pursuit (NSW Health/OHMR; Hooper Shaw Foundation, MRFF Frontiers Stage 1).

Disclaimer:

The information provided in this article is for educational purposes only and should not be considered as medical advice. Consult a healthcare professional for personalised guidance regarding your health and treatment options.

Acknowledgement:

Graeme Loy, Mark Mclean, Jean-Frederic Levesque, Tony Penna, Anne O’Neill, Laura Collie, Julia Warning, Sian Hope, Ameneh Khatami, Susan Maddocks, Stephanie Lynch, Nouri Ben Zakour, Holly Sinclair, Clinton Colaco, Indy Sandaradura, Karen Swensen, Ali Khalid, Hélène Lebhar, Chris Marquis, Joey Lai, Ruwani Dissanayake, Jessica Sacher, Jan Zheng, Tony Lai, Tim Gilbey, Steve Petrovski, Rabeya Rahmatullah, Carina Lauter, Kiran Bosco, Aleksandra Petrovic Fabijan, Brian Chong, Bernard Hudson, Shirley Wong, Tim Gilbey, Hien Duong, Morgyn Warner, Emily Tucker, Jeremy Barr, Anthony Kicic, Stephen Stick, Anton Peleg, Shinwon Lee, Nicki Mileham, Heejoon Myung, Greg German, Ran Nir-Paz, Ronan Hazan, Graham Hatfull, Jean-Paul Pirnay, Pieter-Jan Ceyssans, Rob Lavigne, Jeroen Wagemans, Lars Hansen, Nikoline S. Olsen, Mark Rees, Nicholas McKay, Ed Hendriks and TGA Phage Therapy Regulatory Working Group.