Abstract
Increased prevalence of antibiotic resistance in skin and soft tissue infections is a concerning public health challenge currently facing medical science. A combinatory, broad spectrum biocidal antiseptic has been developed (“ASP”) as a topically applied solution to potential resistant and polymicrobial infected wounds that may be encountered in this context. The ASP-105 designate was evaluated in vitro by determining the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), against different strains of methicillin-resistant Staphylococcus aureus (MRSA), resulting estimates of which approximated the positive control (bacitracin). To evaluate in vivo microbicide efficacy, we utilized a murine full thickness wound model to study bacterial infection and wound healing kinetics. Mice were experimentally wounded dorsally and infected with bioluminescent MRSA. The infected wound was splinted, dressed and treated topically with either ASP-105, vehicle (-control), or bacitracin. Bacterial burden and wound healing was monitored using an in vivo imaging system and evaluation of biofilm formation using scanning electron microscopy of wound dressing. Treatment with ASP-105 significantly reduced bacterial burdens in the first 3 days of infection and inhibited MRSA biofilm formation on the surgical dressing. Notably, treatment with ASP-105 resulted in a sterilizing effect of any detectable MRSA in nearly all (80%; 4/5) of treatment group. All mice receiving vehicle control developed highly MRSA-luminescent and purulent wound beds as a result of experimental infection. The ASP-105 therapy facilitated natural healing in the absence of MRSA infection. Results of this study suggests that that the novel “ASP” combinatory topical antiseptic can be used directly in wounds as a potent, broad-spectrum microbicide against drug resistant S. aureus without injury to the wound bed and impediment of natural restorative processes associated with wound healing. Further studies are warranted to test the effectiveness of this biocidal formulation against other recalcitrant bacterial and fungal pathogens in the context of serious wound infections, and to assess utility of use in both clinical and self-treat scenarios.
Highlights
With the skin being the body’s first line of defense, abrasions and penetrating wounds of the skin typically obtained in combat, a hospital, or even the community are prone to infection
We demonstrate that treatment with antiseptic has been developed (ASP)-105 inhibits the growth of CA-methicillin-resistant Staphylococcus aureus (MRSA) in the wound bed, reduces gross pathology, inhibits biofilm formation, and does not impair the wound healing process
Two bioluminescent strains of S. aureus Newman and CAMRSA MW2, and a luminescent strain of P. aeruginosa (PAO1) were used as exemplars to assess the feasibility of experimental infection of wounds and whether there was enough fidelity in the model to provide semi-quantitative representation of bacterial contamination
Summary
With the skin being the body’s first line of defense, abrasions and penetrating wounds of the skin typically obtained in combat, a hospital, or even the community are prone to infection. Rates of skin and soft tissue infections (SSTIs) are high as they are among the most common infection in both ambulatory and hospital settings (Hersh et al, 2008; Miller et al, 2015; Kaye et al, 2019). S. aureus is troubling in a clinical setting as it readily acquires antibiotic resistance mechanisms and has a propensity to form biofilms in the wound bed resulting in chronic infections (Clinton and Carter, 2015). With S. aureus infections so prominent in a clinical setting, patients undergoing a surgical procedure are at risk for infection. In the United States surgical site infections are the most common cause of hospital acquired infection (Ban et al, 2017). With a rise in antimicrobial resistance and the fact that alcohol alone does not generate lasting protection of the wound alternatives may be needed (Anderson et al, 2014)
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