Antimicrobial resistance is one of the most pressing challenges in modern medicine, making once-treatable infections increasingly lethal. Enterobacter infections, for example, are difficult to treat and have been linked to more than 200,000 deaths globally in 2019. These bacteria have emerged in hospitals worldwide with the capacity to evade even last-line antibiotics. Now, scientists have created a novel virus-based treatment that significantly reduced bacterial loads in preclinical models.

Researchers at Monash University (Melbourne, Australia) and The Alfred (Melbourne, Australia) have developed Entelli-02, a therapeutic phage cocktail designed to target Enterobacter cloacae complex (ECC), a group of bacteria responsible for severe hospital infections. The product, developed at the Monash Phage Foundry, meets strict sterility and safety standards for intravenous use under Australia’s Therapeutic Goods Administration Special Access Scheme. It represents the first hospital-specific, clinical-ready phage therapy for antimicrobial-resistant pathogens.

The research team began with a three-phage cocktail, iteratively improving it through genetic adaptation and selection. Over a decade’s worth of bacterial isolates were studied, leading to the addition of two more phages with enhanced host range and treatment outcomes. The findings, published in Nature Microbiology, show that the final five-phage product was able to kill a broad range of Enterobacter isolates and demonstrated an ability to reduce bacterial loads in infected mice by more than 99 percent.

The therapy offers a blueprint for hospitals to respond to AMR outbreaks with precision medicine, bridging the gap between broad-spectrum antibiotics and tailored phage treatments. Entelli-02 is already available for compassionate use, setting the stage for future clinical trials. Researchers hope this model of hospital-specific phage cocktails can be replicated worldwide to tackle similar antimicrobial resistance threats.

“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,” said Professor Barr, senior author of the study. “This is a blueprint for how hospitals can respond to AMR outbreaks with precision therapies. 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.”

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