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Novel polysaccharide compound improves wound healing in a MRSA-infected porcine wound model
Isaac James, MD; Debra Bourne, MD; Mayara Silva, MD; Peng Chang, MD; Sheri Wang, BS; Damian Grybowski, BS; Gabriella DiBernardo, BS; Phillip Gallo, PhD; Latha Satish, PhD; Stacy Townsend, PhD; Shenda Baker, PhD; Kacey Marra, PhD; J. Peter Rubin, MD
University of Pittsburgh Dept. of Plastic Surgery
2016-02-01
Presenter: Isaac James
Affidavit:
This data has not been previously published or presented at a major meeting. The work below represents the original work of the individual submitting to the degree described.
Director Name: Not a resident
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the most common etiology of wound infection in the US, causing considerable morbidity and mortality costing more than $10-billion annually. SYN01 is a non-toxic, polycationic polysaccharide which disrupts biofilms and prevents bacterial colonization in vitro. It is low cost, stable at room-temperature, and not associated with bacterial resistance. We sought to investigate the therapeutic potential of SYN01 in porcine MRSA-infected wounds.
METHODS: Full-thickness excisional wounds 4cm in diameter (n=20) were created on the backs of Yorkshire pigs. Each wound received either 10^5 or 10^8 CFU of a clinical MRSA isolate (Xen31, ATCC:33591). Wounds were covered for 30min to allow bacterial adherence then treated with SYN01 or saline. Individual wound treatments were randomized to account for differences in healing between anatomic sites. Tegaderm dressings were used to prevent cross-contamination. Treatments were reapplied at 48hrs. Sacrifice occurred at 5d. Punch biopsies from each wound were homogenized, serially diluted, and plated to agar for CFU quantification. Wound contraction was assessed via surface area tracing.
RESULTS: All wounds developed clinically significant MRSA infection by 48hr. Compared to controls, SYN01 reduced bacterial load 1.5-fold (p=0.12) and 8-fold (p<0.005) in the 10^5 and 10^8 CFU groups respectively. SYN01-treated wounds trended toward faster closure vs control in 10^5 (13.0%+/-6.2%) and 10^8 (9.6%+/-1.9%) CFU groups.
CONCLUSIONS: SYN01 reduced bacterial load and enhanced wound closure in MRSA-infected porcine wounds. SYN01 appears to confer greater benefit with high bacterial load and may provide a promising therapeutic option for treating and preventing severe wound infections.
