Both acute and chronic cutaneous wounds are often difficult to treat due to the high-risk for bacterial contamination. Once hospitalized, open wounds are at a high-risk for developing hospital-associated infections caused by multi drug-resistant bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Treating these infections is challenging, not only because of antibiotic resistance, but also due to the production of biofilms. New treatment strategies are needed that will help in both stimulating the wound healing process, as well as preventing and eliminating bacterial wound infections. Fusaricidins are naturally occurring cyclic lipopeptides with antimicrobial properties that have shown to be effective against a variety of fungi and Gram-positive bacteria, with low toxicity. Continuing with our efforts toward the identification of novel cyclic lipopeptides Fusaricidin analogs, herein we report the synthesis and evaluation of the antimicrobial activity for two novel cyclic lipopeptides (CLP), CLP 2605-4 and CLP 2612-8.1 against methicillin resistant S. aureus and P. aeruginosa, respectively, in in vivo porcine full thickness wound model. Both CLPs were able to reduce bacterial counts by approximately 3 log CFU/g by the last assessment day. Peptide 2612-8.1 slightly enhanced the wound healing, however, wounds treated with peptide 2605-4, have shown higher levels of inflammation and impaired wound healing process. This study highlights the importance of identifying new antimicrobials that can combat bacterial infection while not impeding tissue repair.

A variety of wound matrix materials that are designed to help heal both acute and chronic wounds are currently available. Because wounds often encounter opportunistic microbes that can delay healing, the effectiveness of these materials is often suboptimal, resulting in delayed or compromised wound healing. The importance of reducing and controlling wound microbes is well recognised and there are several antimicrobial options available to address this unmet clinical need. This study compares the antimicrobial and wound healing capabilities, both in vivo and in vitro against methicillin-resistant Staphylococcus aureus (MRSA) USA 300, for the following compounds: Collagen Wound Matrix-Anti Microbial (CWM-AM); Collagen Wound Matrix-Anti Microbial XT (CWM-AM XT); Antimicrobial Hydrofiber Wound Dressing (AHWD); Dermal Scaffold with Silver (DRSAg); Collagen Extracellular Matrix (CEM); Collagen Wound Matrix (CWM); Matrix Wound Dressing with Silver (MWDAg); Cadexomer Iodine Gel (CIG); Triple Antibiotic Ointment (TAO); and Antimicrobial Wound Gel (AWG). For the in vitro zone of inhibition assay, AWG and CIG had the largest diffused areas, followed by CWM-AM and CWM-AM XT. Furthermore, CWM-AM, CWM-AM XT, AWG, and CIG exhibited a persistent antimicrobial activity for up to 10 days after incubation. However, in the cytotoxicity studies performed using human fibroblasts, CWM-AM and CWM-AM XT had no detrimental effects in cell proliferation and viability, while AWG and CIG were cytotoxic and prohibitive for cell proliferation. Treatments were then assessed for microbiology and wound healing efficacy using an in vivo porcine deep reticular dermal wound model. CWM-AM XT displayed the greatest in vivo antimicrobial activity against MRSA USA300 and expedited the reepithelialisation at a faster rate than other treatment groups. This study shows that a novel collagen matrix containing an antimicrobial agent can reduce the bacterial load and support healing.

BACKGROUNDWound cleansing is an important component of wound management.PURPOSEThis study was conducted to examine the effect of a wound management solution (WMS) containing hypochlorous acid (HOCl) on methicillin-resistant Staphylococcus aureus (MRSA) and healing when used in conjunction with debridement.METHODSNineteen (19) deep reticular dermal wounds (22 mm × 22 mm × 3 mm deep) were created on the paravertebral and thoracic areas of 3 female pigs using a specialized electrokeratome. Wounds were separated by at least 5 cm to 7 cm of unwounded skin and inoculated with MRSA. After 72 hours, all wounds were debrided with a curette and irrigated with either the WMS or sterile saline solution twice per day from day 0 to day 4. Wounds then were irrigated once a day until the completion of the study (day 11). Wound tissue specimens were taken using punch biopsy for microbiological and histological analysis on days 4, 8, and 11 post treatment. Percent of wound epithelialized, epithelial thickness (cell layers µm), white cell infiltrate (1 = absent, 2 = mild, 3 = moderate, 4 = marked, 5 = exuberant), and percent of granulation tissue formation were calculated and assessed. Microbiology and histology results were analyzed for significant differences between treatments and among assessment days using one-way analysis of variance and student t-tests. A P value ≤ .05 was considered significant.RESULTSThe WMS effected a bacterial reduction (P ≤ .05) of more than 2.74 ± 0.43 and 1.03 ± 0.22 Log CFU/g in all assessment days compared with baseline before and after debridement, respectively. Percent epithelialization was significantly different between treatments on day 8, only 78.3% and 67.8% for HOCl and saline, respectively (P ≤ .05). No significant differences between treatments were observed for epithelial thickness or granulation tissue formation.CONCLUSIONThe combination of debridement and HOCl wound irrigation can significantly reduce MRSA contamination and facilitate the healing process compared to saline irrigation. Clinical studies are needed to confirm these results.