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使用PROSE装置增强靶向抗生素递送治疗氟喹诺酮耐药性角膜炎

Resolution of fluoroquinolone-resistant keratitis with a PROSE device for enhanced targeted antibiotic delivery.

作者信息

Zhai Hualei, Bispo Paulo J M, Kobashi Hidenaga, Jacobs Deborah S, Gilmore Michael S, Ciolino Joseph B

机构信息

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, USA.

Infectious Diseases Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, USA.

出版信息

Am J Ophthalmol Case Rep. 2018 Sep 12;12:73-75. doi: 10.1016/j.ajoc.2018.09.006. eCollection 2018 Dec.

Abstract

PURPOSE

To report the resolution of a fluoroquinolone-resistant keratitis with use of a prosthetic replacement of the ocular surface ecosystem (PROSE) device for enhanced targeted delivery of moxifloxiacin.

OBSERVATIONS

A 62-year-old female presented with a 3-day history of pain, photophobia, and declining vision in left eye. The patient had a 2-year history of binocular PROSE treatment for ocular chronic graft-vs-host disease (cGVHD). A corneal ulcer was diagnosed and treated with topical 0.5% moxifloxacin solution 6 times per day, with continued wear of the PROSE device. After 4 days, worsening symptoms led to an increase in application of moxifloxicin to every 2 hours while awake. The drug was administered by removal of the device, cleaning and replenishing the reservoir with sterile saline, and adding one drop of the drug to the reservoir prior to reinsertion. Four days later, the corneal surface was epithelialized with only small subepithelial infiltrate remaining. The corneal culture grew an isolate carrying multiple mutations in the topoisomerase genes. These mutations were correlated with varying levels of resistance to ciprofloxacin (256 μg/mL), levofloxacin (8 μg/mL), and moxifloxacin (16 μg/mL).

CONCLUSIONS AND IMPORTANCE

Although the infecting strain exhibited resistance to fluoroquinolones, the infection resolved when moxifloxacin was combined with PROSE therapy. Frequent dosing to the PROSE reservoir is likely to increase fluoroquinolone bioavailability and may represent a valuable approach to overcome antibiotic resistance.

摘要

目的

报告使用眼表生态系统假体置换(PROSE)装置增强莫西沙星靶向递送治疗耐氟喹诺酮类角膜炎的疗效。

观察结果

一名62岁女性,左眼疼痛、畏光且视力下降3天。该患者有双眼PROSE治疗眼部慢性移植物抗宿主病(cGVHD)2年的病史。诊断为角膜溃疡,每天局部应用0.5%莫西沙星溶液6次,同时继续佩戴PROSE装置。4天后,症状恶化,导致清醒时莫西沙星的应用增加至每2小时一次。给药方法是取下装置,用无菌盐水清洁并补充储液器,在重新插入前向储液器中加入一滴药物。4天后,角膜表面上皮化,仅残留少量上皮下浸润。角膜培养物培养出一种在拓扑异构酶基因中携带多个突变的分离株。这些突变与对环丙沙星(256μg/mL)、左氧氟沙星(8μg/mL)和莫西沙星(16μg/mL)的不同程度耐药相关。

结论与意义

尽管感染菌株对氟喹诺酮类药物耐药,但当莫西沙星与PROSE疗法联合使用时,感染得到解决。频繁向PROSE储液器给药可能会提高氟喹诺酮类药物的生物利用度,可能是克服抗生素耐药性的一种有价值的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8b2/6159334/066243d850b8/gr1.jpg

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