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前房内注射莫西沙星:对人眼细胞的体外安全性

Intracameral moxifloxacin: in vitro safety on human ocular cells.

作者信息

Kernt Marcus, Neubauer Aljoscha S, Liegl Raffael G, Lackerbauer Carl A, Eibl Kirsten H, Alge Claudia S, Ulbig Michael W, A Anselm Kampik

机构信息

Department of Ophthalmology, Ludwig-Maximilians-Universität, Munich, Germany.

出版信息

Cornea. 2009 Jun;28(5):553-61. doi: 10.1097/ICO.0b013e318191447b.

Abstract

PURPOSE

The fourth-generation fluoroquinolone, moxifloxacin, covers most gram-positive and gram-negative isolates causing endophthalmitis. It is safe and effective for systemic and topical use, but only limited data are available on prophylactic intracameral administration to prevent endophthalmitis. This study uses a cell culture model to investigate the safety of moxifloxacin for intracameral application.

METHODS

Endothelial toxicity of moxifloxacin was evaluated in cultured human corneas. Possible toxic effects of moxifloxacin (10-750 microg/mL) in corneal endothelial cells (CEC), primary human trabecular meshwork cells (TMC), and primary human retinal pigment epithelial (RPE) cells were evaluated after 24 hours and under conditions of oxidative and inflammatory stress by treatment with tumor necrosis factor alpha, lipopolysaccharides, or interleukin-6. Toxicity was evaluated by tetrazolium dye reduction assay, and cell viability was quantified by a microscopic live-dead assay.

RESULTS

No corneal endothelial toxicity could be detected after 30 days of treatment with 500 microg/mL moxifloxacin. Concentrations up to 150 microg/mL had no influence on CEC, TMC, or RPE cell proliferation or on cell viability when administered for 24 hours. After preincubation with tumor necrosis factor alpha, lipopolysaccharides, or interleukin-6 for 24 hours and subsequent treatment with moxifloxacin at concentrations from 10 to 150 microg/mL for 24 hours, no significant decrease in proliferation or viability was observed. Hydrogen peroxide exposure did not increase cellular toxicity.

CONCLUSIONS

This study showed no significant toxicity for moxifloxacin on CEC, TMC, RPE cells, or human corneal endothelium for concentrations up to 150 microg/mL. The minimum inhibitory concentration of moxifloxacin to inhibit 90% of pathogens commonly encountered in endophthalmitis is known to be in the range of 0.25-2.5 microg/mL. Therefore, prophylactic intracameral use of moxifloxacin at concentrations up to 150 microg/mL may be safely used to prevent endophthalmitis after intraocular surgery.

摘要

目的

第四代氟喹诺酮类药物莫西沙星对引起眼内炎的大多数革兰氏阳性和革兰氏阴性分离菌株均有覆盖作用。它全身及局部使用均安全有效,但关于其前房内预防性给药预防眼内炎的数据有限。本研究采用细胞培养模型来研究莫西沙星前房内应用的安全性。

方法

在培养的人角膜中评估莫西沙星的内皮毒性。在24小时后以及在通过用肿瘤坏死因子α、脂多糖或白细胞介素-6处理造成氧化和炎症应激的条件下,评估莫西沙星(10 - 750微克/毫升)对角膜内皮细胞(CEC)、原代人小梁网细胞(TMC)和原代人视网膜色素上皮(RPE)细胞的可能毒性作用。通过四唑盐染料还原试验评估毒性,并通过显微镜下活死细胞试验对细胞活力进行定量。

结果

用500微克/毫升莫西沙星治疗30天后未检测到角膜内皮毒性。浓度高达150微克/毫升时,给药24小时对CEC、TMC或RPE细胞增殖或细胞活力均无影响。在用肿瘤坏死因子α、脂多糖或白细胞介素-6预孵育24小时,随后用浓度为10至150微克/毫升的莫西沙星处理24小时后,未观察到增殖或活力有显著下降。过氧化氢暴露并未增加细胞毒性。

结论

本研究表明,浓度高达150微克/毫升时,莫西沙星对CEC、TMC、RPE细胞或人角膜内皮无显著毒性。已知莫西沙星抑制眼内炎中常见病原体90%的最低抑菌浓度在0.25 - 2.5微克/毫升范围内。因此,浓度高达150微克/毫升的莫西沙星前房内预防性应用可安全用于预防眼内手术后的眼内炎。

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