In a significant breakthrough for the treatment of infectious diseases, researchers from Monash University and The Alfred have developed a targeted phage therapy product aimed at combating antimicrobial-resistant bacteria. Named Entelli-02, this innovative five-phage cocktail specifically targets the Enterobacter cloacae complex (ECC), a group of bacteria known for causing severe, often hard-to-treat infections. The findings of this study were published in the esteemed journal Nature Microbiology.
Led by Professor Jeremy J. Barr from the Monash University School of Biological Sciences, with Professor Anton Peleg from the Department of Infectious Diseases at The Alfred as a co-senior author, this research marks a pioneering approach to precision medicine in the ongoing battle against antimicrobial resistance (AMR). As Professor Barr stated, “This is the first time we’ve designed and developed a clinical-ready phage therapy product tailored to an AMR bacterial pathogen at a local hospital.”
The urgency of this innovation is underscored by the fact that Enterobacter infections are notoriously difficult to treat, contributing to over 200,000 deaths globally in 2019. These infections have become prevalent in hospitals worldwide and display a worrying ability to develop resistance to many last-line antibiotics.
The formulation of Entelli-02 involved a decade’s worth of bacterial isolates. Lead author Dr. Dinesh Subedi explained the rigorous process required to produce this therapy. “We initially began with three phages in our cocktail, but through iterative design, we improved the cocktail by genetically adapting the viruses to expand their host range,” he said. This careful development led to the inclusion of two additional phages, enhancing the treatment’s effectiveness. The final product has been shown to kill a broad range of Enterobacter isolates, reducing bacterial loads in infected mice by over 99 percent.
Manufactured at the Monash Phage Foundry, Entelli-02 meets the necessary sterility and safety standards for intravenous use, under Australia’s Therapeutic Goods Administration Special Access Scheme. Professor Barr remarked, “This is a blueprint for how hospitals can respond to AMR outbreaks with precision therapies.”
Professor Peleg emphasized the significance of this advancement, stating, “We’re bridging the gap between broad-spectrum antimicrobial treatments and personalized phage therapy to deliver a ready-to-use solution that’s both targeted and scalable.” With the development of this off-the-shelf product, healthcare providers now have a prompt solution for some of the most challenging infections.
The research is a collaborative effort between Monash University’s Centre to Impact AMR, The Alfred’s Department of Infectious Diseases, and the Monash Biomedicine Discovery Institute. Key contributors also include Dr. Fernando Gordillo Altamirano and Professor Peleg.
Currently, Entelli-02 is available for compassionate use and sets the foundation for future clinical trials involving phage products. The research team aims to replicate this hospital-specific phage cocktail model in other medical facilities facing similar AMR challenges.
As Professor Barr highlighted, “Antibiotic resistance is one of the biggest challenges in modern medicine.” With the introduction of Entelli-02, the team demonstrates that phage therapy can be a precise and powerful tool, ready for clinical deployment. The full paper detailing this research can be accessed in Nature Microbiology under the title “Rational design of a hospital specific phage cocktail to treat Enterobacter cloacae complex infections” (DOI: 10.1038/s41564-025-02130-4).
