局部用他唑仙的眼部渗透及其对兔铜绿假单胞菌诱导性角膜炎的治疗效果

Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits.

作者信息

Singh Sujaya, Agarwal Renu, Razak Zulhilmi Abdul, Ngu Robin, Nyein Lwin L, Vasudevan Sushil, Kapitonova Marina, Kadir Azida Juana, Visvaraja Subrayan

机构信息

1 Department of Ophthalmology, University of Malaya , Kuala Lumpur, Malaysia .

2 Center for Neuroscience Research , Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia .

出版信息

J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):214-223. doi: 10.1089/jop.2017.0098. Epub 2018 Jan 17.

DOI:10.1089/jop.2017.0098

PMID:29341837

Abstract

PURPOSE

Pseudomonas aeruginosa is the most common causative organism for contact lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With the emergence of resistant strains, it is important to investigate alternative therapies. Despite well-established efficacy of tazocin against systemic Pseudomonas infections, its topical use for the treatment of Pseudomonas keratitis has not been described, hence this study was aimed to find the ocular permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes.

METHODS

We investigated the ocular permeation of topical tazocin after single drop application in normal rabbit eyes by estimating piperacillin and tazobactam concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS method. Furthermore, we determined the efficacy of repeated dose administration of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in comparison to moxifloxacin. To determine the efficacy, clinical examination, histopathological examination, and estimation of bacterial load and inflammatory cytokines in cornea were done.

RESULTS

Significant corneal concentration of piperacillin and tazobactam was detected in normal rabbit corneas after single dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis, topical tazocin caused significant clinical and histopathological improvement. This improvement was associated with reduction in corneal bacterial load and inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group showed greater clinical response which was associated with higher interleukin (IL)-1β, lower tumor necrosis factor (TNF)-α, a comparable level of IL-8, greater reduction in corneal bacterial load, and lesser inflammatory cell infiltration.

CONCLUSION

Tazocin showed good ocular penetration and was effective in treatment of Pseudomonas induced keratitis in rabbits.

摘要

目的

铜绿假单胞菌是与隐形眼镜相关的角膜溃疡最常见的致病微生物，通常用氟喹诺酮类药物治疗。随着耐药菌株的出现，研究替代疗法很重要。尽管他唑仙对全身性铜绿假单胞菌感染的疗效已得到充分证实，但其局部用于治疗铜绿假单胞菌性角膜炎尚未见报道，因此本研究旨在研究他唑仙的眼内渗透性及其治疗兔眼角膜炎的疗效。

方法

我们通过使用经过验证的液相色谱 - 串联质谱法估计角膜、房水和玻璃体内哌拉西林和他唑巴坦的浓度，研究了在正常兔眼单次滴用后局部他唑仙的眼内渗透性。此外，我们确定了与莫西沙星相比，重复给药他唑仙对实验性诱导的兔铜绿假单胞菌性角膜炎的疗效。为了确定疗效，进行了临床检查、组织病理学检查以及角膜中细菌载量和炎性细胞因子的评估。

结果

用他唑仙单剂量治疗后，在正常兔角膜中检测到显著的哌拉西林和他唑巴坦角膜浓度。在患有铜绿假单胞菌诱导性角膜炎的兔中，局部使用他唑仙导致显著的临床和组织病理学改善。这种改善与角膜细菌载量和炎性细胞因子的减少有关。与0.5%的莫西沙星相比，他唑仙治疗组显示出更大的临床反应，这与更高的白细胞介素（IL）-1β、更低的肿瘤坏死因子（TNF）-α、相当水平的IL-8、角膜细菌载量的更大降低以及更少的炎性细胞浸润有关。