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 Fukushima
Author Information
Tatsuma Kishimoto: Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan. ORCID
Waka Ishida: Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.
Ken Fukuda: Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan k.fukuda@kochi-u.ac.jp.
Isana Nakajima: Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.
Takashi Suzuki: Department of Ophthalmology, Toho University, Tokyo, Japan.
Jumpei Uchiyama: Laboratory of Veterinary Microbiology I, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
Shigenobu Matsuzaki: Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.
Daisuke Todokoro: Department of Ophthalmology, Gunma University Graduate School of Medicine, Gunma, Japan.
Masanori Daibata: Department of Microbiology and Infection, Kochi Medical School, Kochi University, Kochi, Japan.
Atsuki Fukushima: Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.
Endophthalmitis due to infection with spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant 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 Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with -related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 10 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 10 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 .
