# Development of a Unique Antibiofilm Therapy for Diabetic Foot Ulcer Infections

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2020 · —

## Abstract

RELEVANCE: For patients within the VA healthcare system, diabetic foot ulcers constitute a significant portion
of treatment and therapy. Among all complications in patients with diabetes none is more common, costly and
complex than foot infections. When these wounds are complicated by biofilm-forming bacteria, the problem
becomes particularly challenging as biofilms contribute to chronic, difficult-to-treat infections that lead to
morbidity and amputation. In cases of infected diabetic foot ulcers and chronic wounds, two of the most common
pathogens cultured are Staphylococcus aureus (with methicillin-resistant S. aureus (MRSA) of particular
concern) and Pseudomonas aeruginosa—organisms that readily form biofilms. To address these problems, we
have synthesized and developed CZ compounds. CZs are a patented and unique first-in-class series of
antibiofilm antibiotics with reduced risk of resistance development that disperse and kill well-established biofilms.
They also work synergistically with traditional antibiotics, which provides the potential to not only address the
problem of biofilm-related infections, but to improve current clinical treatments.
OBJECTIVES: The immediate objective is to test the efficacy of an innovative antibiofilm therapy to treat and
prevent biofilm-related infection in a diabetic pig excision wound model. Long-term, the objective is to translate
this technology for testing CZs in the clinic. With the collaboration of Larry Meyer, MD, PhD and Don Granger
MD who treat VA patients regularly—a large portion of which suffer from diabetic foot ulcers—once in vivo animal
data is collected, our group can work with the FDA to perform investigator-initiated studies and directly translate
the technology to the clinic to reduce morbidity, cost, duration of hospitalization/clinic visits, and the length of
rehabilitation in our Veterans.
HYPOTHESES: 1) When used as a topical gel, CZ compounds will treat and prevent monomicrobial and
polymicrobial biofilm-related infection of MRSA or P. aeruginosa in a diabetic pig excision wound model. 2) CZ
compounds will act synergistically with antibiotics that are currently used clinically and will improve their ability
to treat and prevent biofilm-related infections caused by MRSA and P. aeruginosa in a diabetic pig excision
wound model.
PROCEDURES: Aim 1a: Will focus on in vitro optimization against monomicrobial and polymicrobial biofilms of
methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa. In vitro efficacy profiles of CZs have
been well-documented, which is important because this means that the success of Aim 1b and Aim 2 will not be
solely dependent on the success of Aim 1a. Nevertheless, in Aim 1a we propose to perform in vitro analysis of
the CZ technology to optimize dose and gel formulation to eradicate monomicrobial and polymicrobial biofilms.
Aim 1b: Will involve in vivo analysis of CZ efficacy against monomicrobial and polymicrobial biofilm-related
infections in di...

## Key facts

- **NIH application ID:** 10174764
- **Project number:** 5I01RX002287-05
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Dustin Lee Williams
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174764

## Citation

> US National Institutes of Health, RePORTER application 10174764, Development of a Unique Antibiofilm Therapy for Diabetic Foot Ulcer Infections (5I01RX002287-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10174764. Licensed CC0.

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