Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.
Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan
Antimicrob Agents Chemother. 2019 Oct 22;63(11). doi: 10.1128/AAC.01088-19. Print 2019 Nov.
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 .
由 spp. 引起的眼内炎进展迅速，常导致严重且不可逆转的视力丧失。鉴于耐万古霉素的 spp. 引起的这种情况的频率一直在增加，迫切需要开发新的治疗方法。我们已经在万古霉素敏感（EF24）或万古霉素耐药（VRE2） 株引起的小鼠眼内炎模型中证明了噬菌体 ΦEF24C-P2 的治疗潜力。噬菌体 ΦEF24C-P2 在浊度降低测定中快速且显著地裂解 EF24、VRE2 和源自与 -相关的术后眼内炎患者的临床分离株。通过将 EF24 或 VRE2（1×10 个细胞）注入玻璃体来诱导小鼠眼内炎。眼内活菌数量增加到>1×10 CFU，感染后 24 小时，髓过氧化物酶活性增加表明中性粒细胞浸润到眼内。基于眼底可见度丧失以及眼内活菌数量和髓过氧化物酶活性水平的临床评分均显著降低，在 EF24 或 VRE2 注射后 6 小时通过玻璃体内注射 ΦEF24C-P2。虽然组织病理学分析显示在载体处理的眼中有大量炎症细胞和视网膜脱离浸润，但在噬菌体处理的眼中这些细胞的数量大大减少，视网膜结构完整性得以保留。因此，我们的结果表明，玻璃体内噬菌体治疗可能是治疗万古霉素敏感或耐药 株引起的眼内炎的一种潜在方法。
