Enterococcal endophthalmitis leads to poor visual prognosis. In addition, reports of endophthalmitis caused by drug-resistant bacteria are increasing; therefore, it is necessary to develop novel treatment and prophylactic methods to substitute the use of antibacterial drugs. Bacteriophages (phages) are viruses that infect and lyse bacteria, and phage therapy utilizes their lytic activity to treat bacterial infection. In this study, we examined the effectiveness of phage therapy against enterococcal endophthalmitis. The administration of Enterococcus phage phiEF24C-P2 into the vitreous body of mouse models of vancomycin-susceptible and vancomycin-resistant Enterococcus (VRE) -associated endophthalmitis led to the improvement of inflammation in the eyes, suppression of viable Enterococcus count, and maintenance of retinal structure and function. Next, phiEF7H, phiEF14H1, and phiEF19G were isolated as phages with lytic activity against a wide range of Enterococcus strains, including VRE. Based on genome analysis results, they were classified into the family Herelleviridae and genus Kochikohdavirus. Since no lysogenic, toxic, or drug resistance genes were detected, they could be considered suitable for phage therapy. These phages demonstrated therapeutic effects in mouse models of enterococcal endophthalmitis. Furthermore, the intracameral administration of phage phiEF24C-P2 into rabbit models of postcataract surgery endophthalmitis revealed that it could suppress the onset of endophthalmitis without causing retinal dysfunction.
These results suggested that phage therapy is a potential novel treatment and prophylactic method against endophthalmitis that can substitute the use of antibacterial drugs.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 127: 1022-1030,2023.