Antimicrobial resistance (AMR) is becoming a leading cause of death worldwide. Phage therapy is a potential solution to this crisis. Currently, phage therapy applications are either individually tailored for a given patient’s infection or utilise pre-established cocktails of lytic phages with activity against clinically relevant bacterial species. However, these approaches are either too specific or too broad to maintain high antimicrobial activity. Therefore, there is a need to develop a standardised approach that combines academic phage research, clinical insights, and AMR data to create institution-specific phage cocktails that demonstrate front-line efficacy and ensure their availability when required.
Through an integrated academic-clinical approach, we identified Enterobacter cloacae complex (ECC), which is an emerging multi-drug resistant pathogen, as a priority nosocomial pathogen responsible for considerable morbidity and mortality at The Alfred Hospital in Melbourne, Australia. Utilising a strain collection over the last decade (n=206) in this centre, we tailored our phage isolation and refined killing efficiency using phage co-evolution and improved host coverage by targeting the phage search to those strains where the phage coverage was originally low.
This iterative process led to the creation of a phage product, “Entelli-02”, containing a combination of five genetically and phenotypically characterised lytic phages that target nearly complete (99%) clinical ECC strains through distinct mechanisms, by targeting different bacterial receptors. Entelli-02 contains phages that exhibit broad host coverage against The Alfred Hospital's ECC strain collection and is effective at reducing bacterial loads in ECC septicaemic mice.
Collectively, we developed a standardised approach that integrates academic phage research and clinical insights to produce a phage-based product that demonstrates both front-line efficacy while ensuring its availability for clinical deployment when required. This innovative strategy provides a template for developing tailored phage therapies against challenging nosocomial pathogens