# Development of Novel Ophthalmic Antibiotics

> **NIH NIH K08** · UNIVERSITY OF ROCHESTER · 2020 · $203,404

## Abstract

ABSTRACT
Bacterial keratitis is a vision threatening disease and contributes significantly to world blindness.
Given the severity of the disease, immediate, broad spectrum antibiotics such as fourth generation
fluoroquinolones are crucial for successful treatment. However, rising resistance coupled with limited
industry-driven drug development highlights the need for novel ophthalmic antimicrobial therapeutics.
The central goals of this proposal are to address the antimicrobial void through the development of
novel ophthalmic antibiotics. Preliminary data has demonstrated the promise of rifampicin+polymyxin
B/trimethoprim (PT), a combination of FDA-approved antibiotics that displays broad-spectrum,
synergistic activity with reduced propensity to develop resistance. A central goal of this proposal is to
advance rifampicin+PT with in vivo efficacy studies in order to move this combination toward the
FDA’s 505 (B)2 fast track approval process. However given the quickening pace of antibiotic
resistance, novel classes of drugs must also be concurrently developed. In that regard, a high
throughput chemical library screen for novel, first-in-class agents with activity against Pseudomonas
aeruginosa and Staphylococcus aureus, the most common causes of keratitis, has been initiated and
initial lead compounds identified. Importantly, the screening paradigm is designed to identify
compounds with anti-biofilm activity, a growth state that is notoriously challenging to eradicate in
human disease including ocular infections, and has not previously been the target of high throughput
drug discovery screens. As part of hit-to-lead prioritization, biologic and physiochemical studies will
be performed, a CRISPR-interference essential gene knock down strain set will be created in order to
facilitate the identification of cellular targets of lead compounds, and a mouse model of keratitis will
be established. These latter two tool systems directly enable the proposed research but also have
wide-ranging utility with respect to understanding essential genes/pathways in keratitis pathogenesis.
This research program provides advanced training in drug discovery that will simultaneously define
the clinical promise of rifampicin+PT, identify novel agents that kill biofilm-associated cells and
develop high yield tools for antimicrobial or pathogenesis studies. In addition, this proposal details a
career development plan for Dr. Rachel Wozniak, MD, PhD in order to facilitate her transition to
independence. Dedicated mentorship, course work and specialized seminars will contribute to an
expanding knowledge of experimental design and advanced research techniques. She has obtained
full institutional and departmental support for these endeavors had has demonstrated the necessary
skill set, work ethic and intellectual curiosity necessary for success.

## Key facts

- **NIH application ID:** 9934208
- **Project number:** 5K08EY029012-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Rachel A F Wozniak
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,404
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934208

## Citation

> US National Institutes of Health, RePORTER application 9934208, Development of Novel Ophthalmic Antibiotics (5K08EY029012-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934208. Licensed CC0.

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