Purpose

Preclinical evaluation of the therapeutic potential of antimicrobial 265 nm UVC for infectious keratitis.

Methods

Four experiments explored UVC: 1) impact on bacterial and fungal lawns on agar, in individual or mixed culture, 2) bacterial inactivation dose in an in vitro deep corneal infection model, 3) dose validation in an ex vivo porcine keratitis model and 4) efficacy in a masked, randomised, controlled murine keratitis trial using bioluminescent Pseudomonas aeruginosa.

Results

Minimum effective UVC exposures ranged between 2 s and 5 s for lawn bacteria and fungi in individual or mixed culture. Significant P. aeruginosa growth inhibition in the in vitro infection model was achieved with 15 s UVC, that resulted in a >3.5 log₁₀ reduction of bacteria in a subsequent ex vivo keratitis model (p < 0.05). Bioluminescence fell below baseline levels in all treated animals, within 8 h of treatment (p < 0.05), in the in vivo study. Re-epithelialisation with corneal clarity occurred within 24 h in 75% of UVC-treated cases, with no relapse at 48 h. On plating, bacteria were recovered only from untreated controls.

Conclusions

UVC inhibited all tested bacteria and fungi, including mixed culture and strains linked to antibiotic resistance, in vitro, with exposures of ≤ 5 s. In vitro and ex vivo testing confirmed therapeutic potential of 15 s UVC. In vivo, 15 s UVC administered in two doses, 4 h apart, proved effective in treating murine bacterial keratitis.

中文翻译：

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UVC治疗感染性角膜炎疗效的临床前确认

目的

抗菌 265 nm UVC 对感染性角膜炎的治疗潜力的临床前评估。

方法

四项实验探讨了 UVC：1) 在单独或混合培养物中对琼脂上细菌和真菌菌苔的影响，2)体外深层角膜感染模型中的细菌灭活剂量，3) 离体猪角膜炎模型中的剂量验证，4 )使用生物发光铜绿假单胞菌进行的隐蔽、随机、对照小鼠角膜炎试验的疗效。

结果

对于单独培养或混合培养的草坪细菌和真菌来说，最小有效 UVC 照射时间范围为 2 秒至 5 秒。15 s UVC 在体外感染模型中实现了显着的铜绿假单胞菌生长抑制，导致随后的离体角膜炎模型中细菌减少>3.5 log _{10 (p < 0.05)。}在体内研究中，所有接受治疗的动物在治疗后 8 小时内生物发光均降至基线水平以下 (p < 0.05) 。75% 的 UVC 治疗病例在 24 小时内出现角膜透明的再上皮化，48 小时没有复发。在平板上，仅从未经处理的对照中回收细菌。

结论

UVC 可在体外抑制所有测试的细菌和真菌，包括混合培养物和与抗生素耐药性相关的菌株，且暴露时间≤ 5 秒。体外和离体测试证实了 15 秒 UVC 的治疗潜力。在体内， 15 s UVC 分两次给药（间隔 4 小时）被证明可有效治疗小鼠细菌性角膜炎。