In a significant breakthrough for treating infectious diseases, researchers from Monash University and The Alfred have developed a novel phage therapy product designed to combat drug-resistant bacteria. The innovative treatment, named Entelli-02, consists of a five-phage cocktail specifically targeting the Enterobacter cloacae complex (ECC), a group of bacteria notorious for causing severe and often difficult-to-treat infections. This research was detailed in a recent publication in Nature Microbiology.
Leading the study was 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 and Monash University serving as co-senior author. This work represents a pioneering approach to precision medicine in hospitals facing the growing challenge of antimicrobial resistance (AMR).
“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,” stated Professor Barr. He emphasized that Entelli-02 is not merely a scientific achievement but a practical tool meant for frontline use against dangerous, drug-resistant bacterial pathogens.
Enterobacter infections pose a considerable challenge to healthcare systems. In 2019 alone, they were linked to over 200,000 deaths globally. These infections have proliferated in hospitals and exhibit a troubling capacity to develop resistance to many last-line antibiotics.
The development of Entelli-02 involved a decade’s worth of bacterial isolates. The lead author of the study, Dr. Dinesh Subedi, explained that the research team went through a meticulous process of phage isolation, genetic modification, and preclinical testing. “We initially began with three phages in our cocktail. Through iterative design, we improved the cocktail by genetically adapting the viruses to expand their host range, followed by selecting two additional phages with improved treatment outcomes,” Dr. Subedi noted.
The final product, Entelli-02, incorporates five phages capable of eradicating a wide range of Enterobacter isolates. In preclinical tests, it successfully reduced bacterial loads in infected mice by over 99 percent.
Entelli-02 was manufactured as a therapeutic-grade phage product at the Monash Phage Foundry. It meets the sterility and safety standards for intravenous use under Australia’s Therapeutic Goods Administration Special Access Scheme. Professor Barr added, “This is a blueprint for how hospitals can respond to AMR outbreaks with precision therapies.”
Professor Peleg highlighted the collaboration’s goal: “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.” He noted that the team is now prepared with an off-the-shelf product that can promptly assist in treating some of the most challenging infections.
The research was a collective effort involving Monash University’s Centre to Impact AMR, the Department of Infectious Diseases at The Alfred, and the Monash Biomedicine Discovery Institute. Key contributors to the project included Dr. Dinesh Subedi, Dr. Fernando Gordillo Altamirano, and Professor Anton Peleg.
Currently, Entelli-02 is available for compassionate use, paving the way for future clinical trials of phage products. The research team is optimistic that this hospital-specific phage cocktail model can be replicated in other medical institutions facing similar AMR challenges.
“Antibiotic resistance is one of the biggest challenges in modern medicine,” Professor Barr remarked. “With Entelli-02, we’re demonstrating that phage therapy can be precise, powerful, and ready for clinical deployment.”
For further details, the full study is published in Nature Microbiology, titled “Rational design of a hospital specific phage cocktail to treat Enterobacter cloacae complex infections” (DOI: 10.1038/s41564-025-02130-4).
