Improving Corneal Ulcer Outcomes with Unbiased Pathogen and Antimicrobial Resistance Detection

项目概要/摘要 感染性角膜溃疡影响所有年龄段，并导致全世界严重的视力障碍。经验主义 目前标准做法是使用广谱抗菌药物治疗而不考虑抗菌药物耐药性 的照顾。这要么是因为常规微生物检测的病原体识别效果不佳，要么是 测试并未完全完成。虽然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，这与抗菌药物管理的目标和理想背道而驰。在此，我们建议加强 了解传染性角膜炎的发病机制和抗生素耐药性，以提高 诊断和治疗具有以下目的。第一个目标是，我们将在全球范围内对 所有引起传染性角膜炎的微生物。我们预计病因谱将随着不同因素而显着变化 地理位置。此外，季节性将影响病原体特征和疾病结果。第二个 目的将确定角膜溃疡病原体中抗菌素耐药性（AMR）的频率和丰富度 并将这些发现与表型相关联。我们预计 AMR 将因全球地点而异，并预测临床情况 结果。最后，我们将定义传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 仍然是全世界失明的主要原因之一，我们预计这项研究将为临床医生提供指导 探讨角膜感染的最佳管理方法，以减轻全球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.