Microbiologists develop bespoke phage therapy to combat antimicrobial resistance

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In a major advance for infectious disease treatment, researchers  have developed a bespoke phage therapy product that uses bacterial viruses, known as "bacteriophages," to combat a highly problematic, antimicrobial-resistant bacteria.

The treatment, named Entelli-02, is a five-phage cocktail designed specifically to target Enterobacter cloacae complex (ECC), a group of bacteria responsible for severe, often difficult-to-treat infections.

The study, published in Nature Microbiology    represents a new approach for precision medicine in hospitals battling antimicrobial resistance (AMR).

This is the first time they have designed and developed a clinical-ready phage therapy product tailored to an AMR bacterial pathogen at a local hospital. Entelli-02 is not just a scientific achievement, it's a clinical tool built for frontline use against deadly, drug-resistant, bacterial pathogens.

Enterobacter infections are notoriously difficult to treat and have been linked to more than 200,000 deaths globally in 2019. They have emerged in hospitals around the world and have the capacity to develop resistance to many of the last-line antibiotics.

Using a decade's worth of bacterial isolates, the research team developed and produced Entelli-02 through a rigorous process of phage isolation, genetics and preclinical testing.

They  initially began with three phages in our cocktail, but through iterative design, they improved the cocktail by genetically adapting the viruses to expand their host range, followed by selection of two additional phages with improved treatment outcomes.

The final product, Entelli-02, contains five phages that can kill a broad range of Enterobacter isolates and reduce bacterial loads in infected mice by over 99%. 

Entelli-02 was manufactured as a therapeutic-grade phage product at the Monash Phage Foundry, meeting sterility and safety standards for intravenous use.

This is a blueprint for how hospitals can respond to AMR outbreaks with precision therapies.

Entelli-02 is now available for compassionate use and sets the stage for future clinical trials using phage products. The team hopes this hospital-specific phage cocktail model can be replicated in other hospitals facing similar AMR threats.

Dinesh Subedi et al, Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections, Nature Microbiology (2025). DOI: 10.1038/s41564-025-02130-4