Improving Corneal Ulcer Outcomes with Unbiased Pathogen and Antimicrobial Resistance Detection

项目总结/摘要 感染性角膜溃疡影响所有年龄段，并导致全球范围内的显著视力发病率。经验性 用广谱抗微生物剂治疗而不考虑抗微生物剂耐药性目前是标准的 照顾。这要么是因为常规微生物检测的病原体鉴定不理想， 测试并没有完全完成。而经验性治疗是感染性角膜炎的首选实践模式 在世界范围内，这与抗菌剂管理的目标和理想背道而驰。在此，我们建议加强 提高对感染性角膜炎发病机制和抗生素耐药性的认识 诊断学和治疗学，具有以下目的。在第一个目标中，我们将在全球范围内监测 所有导致感染性角膜炎的微生物。我们预计病因谱将随着 地理位置此外，季节性将影响病原体概况和疾病结果。第二 目的是确定角膜溃疡病原体中抗菌素耐药性（AMR）的频率和丰富程度 并将这些发现与表型相关联。我们预计AMR将因全球位置而异，并预测临床 结果。最后，我们将定义感染性角膜炎的局部免疫反应。我们假设免疫 特征可以预测病原体类型和临床结果。继发于感染性角膜炎的角膜混浊 仍然是全球失明的主要原因之一，我们预计这项研究将指导临床医生 关于角膜感染的最佳管理，以减少全球的经济和眼部健康负担。

PROJECT SUMMARY/ABSTRACT Infectious corneal ulcers affect all ages and contribute to significant visual morbidity worldwide. Empiric treatment with broad spectrum antimicrobials without regard for antimicrobial resistance is presently standard of care. This is either because pathogen identification with routine microbiological testing is suboptimal or testing is not done altogether. While empiric treatment is the preferred practice pattern for infectious keratitis worldwide, this is contrary to the goals and ideals of antimicrobial stewardship. Here, we propose to enhance the understanding of the pathogenesis of infectious keratitis and antibiotic resistance profiles to improve diagnostics and therapeutics with the following aims. In the first aim, we will perform worldwide surveillance of all organisms responsible for infectious keratitis. We expect the spectrum of etiology will vary significantly with geographic location. In addition, seasonality will affect pathogen profile and disease outcomes. The second aim will determine the frequency and richness of antimicrobial resistance (AMR) in corneal ulcer pathogens and correlate those findings with phenotypes. We expect AMR will differ by global location and predict clinical outcome. Finally, we will define the local immune response in infectious keratitis. We hypothesize that immune signatures can predict pathogen types and clinical outcome. Corneal opacity secondary to infectious keratitis remains one of the leading causes of blindness worldwide and we anticipate this research will guide clinicians on the best management for corneal infection to reduce both the financial and ocular health burden globally.