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Optimizing phage therapy for carbapenem-resistant Enterobacter cloacae bacteremia: insights into dose and timing

Shi-Yong Fu1, Xiu-Zhen Chen2, Peng-Cheng Yi2

  • 1Department of Oncology, the Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine, Nanjing, China.

Antimicrobial Agents and Chemotherapy
|February 26, 2025
PubMed

Insights

Novel bacteriophages effectively treat multidrug-resistant Enterobacter cloacae complex infections. Optimizing phage cocktail dosing and timing, including prophylactic use, is crucial for combating carbapenem-resistant bacterial infections.

Area of Science:

  • Microbiology
  • Bacteriology
  • Phage Therapy

Background:

  • Rising prevalence of multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) infections, especially carbapenem-resistant strains.
  • Urgent need for alternative therapeutic strategies beyond conventional antibiotics.
  • Limited availability of well-characterized ECC-targeting phages and unexplored dosing/timing for phage cocktails.

Purpose of the Study:

  • Isolate and characterize novel lytic phages targeting ECC.
  • Evaluate the efficacy of a phage cocktail against E. cloacae bacteremia in a murine model.
  • Investigate the impact of phage dosing and administration timing on treatment outcomes.

Main Methods:

  • Isolation and characterization of three novel lytic phages.
  • Assessment of phage host range, including ФEBU8's activity against Enterobacter species and Acinetobacter baumannii.
  • Evaluation of ФECL22's stability (temperature, pH) and receptor identification (OmpA).
  • In vivo efficacy study using a mouse model of E. cloacae bacteremia with a phage cocktail (ФEBU8, ФECL22, ФECL30).

Main Results:

  • Three novel lytic phages were isolated and characterized.
  • ФEBU8 showed broad-spectrum activity; ФECL22 exhibited stability and a burst size of 19 PFU/cell.
  • The phage cocktail demonstrated dose-dependent efficacy in rescuing mice with E. cloacae bacteremia.
  • Immediate and prophylactic/therapeutic (-24 + 6) administration regimens achieved 100% survival.

Conclusions:

  • Dosing and timing are critical factors in optimizing phage therapy for carbapenem-resistant Enterobacter infections.
  • Prophylactic phage administration offers a significant therapeutic window and a promising strategy.
  • Novel phages and optimized phage cocktails represent a viable alternative for severe bacterial infections.
Keywords:
Enterobacter cloacae complexOmpAdose optimizationhost rangephage therapyprophylactic usereceptor

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