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Treatment of Severe Acute Bacterial Keratitis in Rabbits Using Continuous Topical Ocular Instillation with Norvancomycin
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2021-02-16 , DOI: 10.2147/dddt.s295874 Wenxiang Lin 1, 2 , Libei Zhao 2 , Qian Tan 1, 2 , Ding Lin 1, 2
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2021-02-16 , DOI: 10.2147/dddt.s295874 Wenxiang Lin 1, 2 , Libei Zhao 2 , Qian Tan 1, 2 , Ding Lin 1, 2
Affiliation
Purpose: Efficacy of norvancomycin (NVCM) through continuous topical ocular instillation drug delivery (CTOIDD) system for treating severe acute bacterial keratitis infection with Staphylococcus aureus was investigated.
Methods: Rabbits with bacterial keratitis were treated using CTOIDD with NVCM (n=13), topical NVCM eye drops (n=11), and CTOIDD with saline (n=8). Clinical signs of keratitis in all groups were assessed consecutively for a week. Bacterial quantification of excised corneas was counted on the fourth and eighth days. Histopathologic examinations were performed to assess inflammatory cell infiltration on the eighth day.
Results: All signs of bacterial keratitis were alleviated in CTOIDD with NVCM according to criteria, and the CTOIDD-NVCM group had significantly less inflammation than CTOIDD-saline (p< 0.05), and eye drop-NVCM (p< 0.05). Two eyes in the eye drop-NVCM group, four eyes in the CTOIDD-saline group had corneal perforation (CP), while none of the rabbits showed CP in the CTOIDD-NVCM group. Bacterial counts were significantly less in the CTOIDD with NVCM group in comparison to the eye drop-NVCM (p< 0.05), and CTOIDD-saline (p< 0.05) groups. Severe inflammation and marked inflammatory cell infiltration were found in histopathologic examinations in the CTOIDD-saline and eye drop-NVCM groups, while significantly less inflammation was documented in the CTOIDD-NVCM (p< 0.05) group.
Conclusion: CTOIDD with NVCM effectively reduced the severity and treated acute bacterial S. aureus keratitis infection in a rabbit model. The presented approach of CTOIDD with NVCM appears to be a promising therapeutic approach for severe acute bacterial keratitis.
Keywords: severe acute bacterial keratitis, continuous topical instillation, eye drop, norvancomycin, rabbit eyes
中文翻译：
去甲万古霉素连续眼部滴眼治疗兔重症急性细菌性角膜炎
目的：研究去甲万古霉素（NVCM）通过连续局部眼部滴注给药（CTOIDD）系统治疗金黄色葡萄球菌感染的严重急性细菌性角膜炎的疗效。
方法：用 CTOIDD 加 NVCM (n=13)、局部 NVCM 滴眼液 (n=11) 和 CTOIDD 加盐水 (n=8) 治疗患有细菌性角膜炎的兔子。连续一周评估所有组的角膜炎临床症状。在第 4 天和第 8 天对切除的角膜进行细菌定量计数。在第八天进行组织病理学检查以评估炎性细胞浸润。
结果：根据标准，CTOIDD联合NVCM所有细菌性角膜炎症状均得到缓解，CTOIDD-NVCM组炎症明显低于CTOIDD-生理盐水（p <0.05）和滴眼剂-NVCM（p <0.05）。滴眼液-NVCM组2只眼，CTIOIDD-生理盐水组4只眼出现角膜穿孔（CP），而CTOIDD-NVCM组家兔均未出现CP。与滴眼液-NVCM ( p < 0.05) 和 CTOIDD-生理盐水 ( p< 0.05) 组。CTIOIDD-生理盐水组和滴眼液-NVCM组的组织病理学检查发现严重炎症和明显的炎症细胞浸润，而CTOIDD-NVCM组的炎症明显减少（p < 0.05）。
结论： CTOIDD 联合 NVCM 可有效降低兔模型急性细菌性金黄色葡萄球菌角膜炎感染的严重程度并治疗。所提出的 CTOIDD 与 NVCM 的方法似乎是治疗严重急性细菌性角膜炎的有希望的方法。
关键词：重症急性细菌性角膜炎，持续局部滴注，滴眼液，去甲万古霉素，兔眼
更新日期：2021-04-20
Methods: Rabbits with bacterial keratitis were treated using CTOIDD with NVCM (n=13), topical NVCM eye drops (n=11), and CTOIDD with saline (n=8). Clinical signs of keratitis in all groups were assessed consecutively for a week. Bacterial quantification of excised corneas was counted on the fourth and eighth days. Histopathologic examinations were performed to assess inflammatory cell infiltration on the eighth day.
Results: All signs of bacterial keratitis were alleviated in CTOIDD with NVCM according to criteria, and the CTOIDD-NVCM group had significantly less inflammation than CTOIDD-saline (p< 0.05), and eye drop-NVCM (p< 0.05). Two eyes in the eye drop-NVCM group, four eyes in the CTOIDD-saline group had corneal perforation (CP), while none of the rabbits showed CP in the CTOIDD-NVCM group. Bacterial counts were significantly less in the CTOIDD with NVCM group in comparison to the eye drop-NVCM (p< 0.05), and CTOIDD-saline (p< 0.05) groups. Severe inflammation and marked inflammatory cell infiltration were found in histopathologic examinations in the CTOIDD-saline and eye drop-NVCM groups, while significantly less inflammation was documented in the CTOIDD-NVCM (p< 0.05) group.
Conclusion: CTOIDD with NVCM effectively reduced the severity and treated acute bacterial S. aureus keratitis infection in a rabbit model. The presented approach of CTOIDD with NVCM appears to be a promising therapeutic approach for severe acute bacterial keratitis.
Keywords: severe acute bacterial keratitis, continuous topical instillation, eye drop, norvancomycin, rabbit eyes
中文翻译：
去甲万古霉素连续眼部滴眼治疗兔重症急性细菌性角膜炎
目的：研究去甲万古霉素（NVCM）通过连续局部眼部滴注给药（CTOIDD）系统治疗金黄色葡萄球菌感染的严重急性细菌性角膜炎的疗效。
方法：用 CTOIDD 加 NVCM (n=13)、局部 NVCM 滴眼液 (n=11) 和 CTOIDD 加盐水 (n=8) 治疗患有细菌性角膜炎的兔子。连续一周评估所有组的角膜炎临床症状。在第 4 天和第 8 天对切除的角膜进行细菌定量计数。在第八天进行组织病理学检查以评估炎性细胞浸润。
结果：根据标准，CTOIDD联合NVCM所有细菌性角膜炎症状均得到缓解，CTOIDD-NVCM组炎症明显低于CTOIDD-生理盐水（p <0.05）和滴眼剂-NVCM（p <0.05）。滴眼液-NVCM组2只眼，CTIOIDD-生理盐水组4只眼出现角膜穿孔（CP），而CTOIDD-NVCM组家兔均未出现CP。与滴眼液-NVCM ( p < 0.05) 和 CTOIDD-生理盐水 ( p< 0.05) 组。CTIOIDD-生理盐水组和滴眼液-NVCM组的组织病理学检查发现严重炎症和明显的炎症细胞浸润，而CTOIDD-NVCM组的炎症明显减少（p < 0.05）。
结论： CTOIDD 联合 NVCM 可有效降低兔模型急性细菌性金黄色葡萄球菌角膜炎感染的严重程度并治疗。所提出的 CTOIDD 与 NVCM 的方法似乎是治疗严重急性细菌性角膜炎的有希望的方法。
关键词：重症急性细菌性角膜炎，持续局部滴注，滴眼液，去甲万古霉素，兔眼
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