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

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Updates:

Hitting bacteria hard and early with diverse phage cocktails may curb resistance

As multidrug antibiotic resistance emerges as a potent public health challenge, medical science has renewed attention on the potential for bacteriophage therapy. Bacteriophages, or phages, are viruses that target, infect and replicate inside bacteria, destroying them in the process. To help maximize the success rate of this approach, researchers recently modeled the dynamics of bacteriophage therapy to explain particular therapies and optimize the composition of bacteriophage cocktails.

Phage are the most prevalent organisms on the planet. They exist everywhere bacteria exist. However, each phage has evolved to narrowly target specific bacteria, and bacteria have evolved various mechanisms of resistance.
Phage cocktails—combinations of particular phages for a patient facing a specific bacterial infection—represent a complicated form of personalized medicine. Given the fast and complex dynamics of bacterial responses to phages, it is not typically known why a particular phage therapy succeeded or failed. As described in the journal PLOS Computational Biology, the research team developed a mathematical model that could describe effective phage cocktails and optimize their diversity and timing.
The researchers developed their mathematical model by building on an existing model calibrated with data from phage therapy in a live mouse. The mathematical model was extended to humans and included multiple phages infecting multiple bacterial strains with varying phage resistance.
The model was able to predict success based on several key factors. The bacteria's pretreatment resistance level was critical, as were the diversity of the phage cocktail and the timing of its delivery. Phage therapy is a complicated dynamic in which more infective phages can wipe out more sensitive (i.e., less resistant) bacteria faster. That leaves resistant bacteria to expand, and they can quickly evolve better resistance, mutating to avoid infection by the phage.

The team found that therapy is best served by a diversity of phages, which overwhelm the bacteria's ability to evolve resistance quickly enough. The team also focused on the timing of phage delivery, determining that immediate treatment with the full phage cocktail offered the most success. That creates a high genetic barrier to bacterial resistance, meaning that the bacteria would need to accumulate several genetic changes or mutations to survive the therapy.
The rapid evolution of resistance is the main challenge to therapy.
That capacity is why antibiotics may not work in the first place. For phage therapy to be effective, the cocktails should be diverse, sufficient and immediate. The approach amounts to 'hit the bacteria hard and early.

Rob J. de Boer et al, Towards modeling phage therapy, PLOS Computational Biology (2026). DOI: 10.1371/journal.pcbi.1014408