Therapeutic effects of intravitreously administered bacteriophage in a mouse model of endophthalmitis caused by vancomycin-sensitive or -resistant enterococcus faecalis

Tatsuma Kishimoto, Waka Ishida, Ken Fukuda, Isana Nakajima, Takashi Suzuki, Jumpei Uchiyama, Shigenobu Matsuzaki, Daisuke Todokoro, Masanori Daibata, Atsuki Fukushimaa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ϕEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis. Phage ϕEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 * 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 * 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ϕEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

Original languageEnglish
Article numbere01088-19
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number11
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Bacteriophage therapy
  • Endophthalmitis
  • Enterococcus
  • Mouse
  • Ophthalmology

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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