In vivo efficacy of a unique first-in-class antibiofilm antibiotic for biofilm-related wound infections caused by Acinetobacter baumannii

Dustin L Williams; Brooke Kawaguchi; Nicholas B Taylor; Gina Allyn; Marissa A Badham; Jeffery C Rogers; Brittany R Peterson; Paul R Sebahar; Travis J Haussener; Hariprasada Reddy Kanna Reddy; Brad M Isaacson; Paul F Pasquina; Ryan E Looper

doi:10.1016/j.bioflm.2020.100032

In vivo efficacy of a unique first-in-class antibiofilm antibiotic for biofilm-related wound infections caused by Acinetobacter baumannii

Biofilm. 2020 Jul 17:2:100032. doi: 10.1016/j.bioflm.2020.100032. eCollection 2020 Dec.

Authors

Dustin L Williams^{1

2

3

4

5

6

7}, Brooke Kawaguchi^{1

2}, Nicholas B Taylor^{1

2}, Gina Allyn^{1

2}, Marissa A Badham^{1

2}, Jeffery C Rogers^{1

2}, Brittany R Peterson^{1

2}, Paul R Sebahar^{6

8}, Travis J Haussener^{6

8}, Hariprasada Reddy Kanna Reddy^{6

8}, Brad M Isaacson^{2

5

7

9}, Paul F Pasquina^{7

10}, Ryan E Looper^{6

8}

Affiliations

¹ George E. Wahlen Department of Veterans Affairs, Salt Lake City, UT, USA.
² Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA.
³ Department of Pathology, University of Utah, Salt Lake City, UT, USA.
⁴ Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
⁵ Department of Physical Medicine and Rehabilitation, Uniformed Services University, Bethesda, MD, USA.
⁶ Curza Global, Salt Lake City, UT, USA.
⁷ The Center for Rehabilitation Sciences Research, Uniformed Services University, Bethesda, MD, USA.
⁸ Department of Chemistry, University of Utah, Salt Lake City, UT, USA.
⁹ The Geneva Foundation, Tacoma, WA, USA.
¹⁰ Department of Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD, USA.

Abstract

Wounds complicated by biofilms challenge even the best clinical care and can delay a return to duty for service members. A major component of treatment in wounded warriors includes infected wound management. Yet, all antibiotic therapy options have been optimized against planktonic bacteria, leaving an important gap in biofilm-related wound care. We tested the efficacy of a unique compound (CZ-01179) specifically synthesized to eradicate biofilms. CZ-01179 was formulated as the active agent in a hydrogel, and tested in vitro and in vivo in a pig excision wound model for its ability to treat and prevent biofilm-related wound infection caused by Acinetobacter baumannii. Data indicated that compared to a clinical standard-silver sulfadiazine-CZ-01179 was much more effective at eradicating biofilms of A. baumannii in vitro and up to 6 days faster at eradicating biofilms in vivo. CZ-01179 belongs to a broader class of newly-synthesized antibiofilm agents (referred to as CZ compounds) with reduced risk of resistance development, specific efficacy against biofilms, and promising formulation potential for clinical applications. Given its broad spectrum and biofilm-specific nature, CZ-01179 gel may be a promising agent to increase the pipeline of products to treat and prevent biofilm-related wound infections.

Keywords: Antibiofilm agent; Biofilm; Experimental models; Infection; Military wound care.