<p>The Alfred Hospital in Melbourne, Australia, has reported an ongoing outbreak of infections caused by multidrug-resistant <i>Enterobacter cloacae</i> complex (ECC). Phage therapy is a promising strategy to treat antimicrobial-resistant infections. Utilizing the hospital’s isolate collection, built over the past decade, we established an initial 3-phage cocktail with 54% ECC coverage. We then iteratively improved this product by enhancing phage killing efficiency using phage adaptation and expanded host range through targeted phage isolation against low-coverage ECC isolates. This optimization yielded Entelli-02, containing five well-characterized virulent phages that target clinical ECC isolates via distinct bacterial cell surface receptors. Entelli-02 exhibits 88% host coverage against The Alfred Hospital’s ECC isolate collection (<i>n</i> = 206), confirmed by plaque formation and reduced bacterial load in septicaemic mice by &gt;99%. We produced this cocktail as a therapeutic-grade product, ready for clinical use. Entelli-02 represents a hospital-specific phage cocktail with frontline efficacy and on-demand availability.</p>

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Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections

  • Dinesh Subedi,
  • Fernando Gordillo Altamirano,
  • Rylee Deehan,
  • Avindya Perera,
  • Ruzeen Patwa,
  • Xenia Kostoulias,
  • Denis Korneev,
  • Luke Blakeway,
  • Nenad Macesic,
  • Anton Y. Peleg,
  • Jeremy J. Barr

摘要

The Alfred Hospital in Melbourne, Australia, has reported an ongoing outbreak of infections caused by multidrug-resistant Enterobacter cloacae complex (ECC). Phage therapy is a promising strategy to treat antimicrobial-resistant infections. Utilizing the hospital’s isolate collection, built over the past decade, we established an initial 3-phage cocktail with 54% ECC coverage. We then iteratively improved this product by enhancing phage killing efficiency using phage adaptation and expanded host range through targeted phage isolation against low-coverage ECC isolates. This optimization yielded Entelli-02, containing five well-characterized virulent phages that target clinical ECC isolates via distinct bacterial cell surface receptors. Entelli-02 exhibits 88% host coverage against The Alfred Hospital’s ECC isolate collection (n = 206), confirmed by plaque formation and reduced bacterial load in septicaemic mice by >99%. We produced this cocktail as a therapeutic-grade product, ready for clinical use. Entelli-02 represents a hospital-specific phage cocktail with frontline efficacy and on-demand availability.