A multimodel regime for evaluating effectiveness of antimicrobial wound care products in microbial biofilms.

Microbial biofilms have become increasingly recognized as a cause of wound chronicity. There are several topical antimicrobial wound care products available for use; however, their effectiveness has routinely been demonstrated with planktonic microorganisms. There is no target reference value for antimicrobial effectiveness of wound care products in biofilm models. In addition, data on antimicrobial activity of products in biofilm models are scattered across many test methods in a variety of studies. The aim of this work is to directly compare commercial products containing the commonly used topical antimicrobial agents iodine, silver, polyhexamethylene biguanide, octenidine, hypochlorous acid, benzalkonium chloride, and a surfactant-based topical containing poloxamer 188. Five different in vitro biofilm models of varied complexity were used, incorporating several bacterial pathogens such as Staphylococcus, Enterococcus, Streptococcus, Pseudomonas, Acinetobacter, Klebsiella, and Enterobacter. The fungal pathogens Candida albicans and Candida auris were also evaluated. A multispecies bacterial biofilm model was also used to evaluate the products. Additionally, C. albicans was used in combination with S. aureus and P. aeruginosa in a multikingdom version of the polymicrobial biofilm model. Statistically significant differences in antimicrobial performance were observed between treatments in each model and changing microbial growth conditions or combinations of organisms resulted in significant performance differences for some treatments. The iodine and benzalkonium chloride-containing products were overall the most effective in vitro and were then selected for in vivo evaluation in an infected immunocompromised murine model. Unexpectedly, the iodine product was statistically (P > .05) no different than the untreated control, while the benzalkonium chloride containing product significantly (P < .05) reduced the biofilm compared to untreated control. This body of work demonstrates the importance of not only evaluating antimicrobial wound care products in biofilm models but also the importance of using several different models to gain a comprehensive understanding of products' effectiveness.

Effect on Microbial Growth of a New Skin Protectant Formulation.

Objective: Evaluate the effect of a new investigational skin protectant formulation on the growth of various microorganisms in vitro. Approach: An in vitro laboratory assay with various species of gram-positive bacteria, gram-negative bacteria, and yeast grown on agar plates was used to verify that a new investigational product used for the management of incontinence-associated dermatitis (IAD) does not support microbial growth. Results: The investigational product did not support the growth of all organisms tested for 48 h in these assays. The results demonstrate the barrier properties of this investigational formulation against bacteria and yeast that are relevant to incontinent patients. Innovation: IAD accompanied by skin damage is difficult to manage with currently available products. A new skin protectant that can be applied as a liquid and polymerizes into a breathable film in situ even in the presence of exudate (as shown previously) has been developed and tested to ensure that it does not support microbial growth. Conclusion: This work verifies that this new product does not support microbial growth in vitro using organisms relevant for the intended application.

Nitric oxide levels in wound fluid may reflect the healing trajectory.

We analyzed nitric oxide metabolites (nitrate and nitrite, NOx) and other biomarkers in human wound fluids and correlated these markers with wound healing status (progressing or worsening) based on patient's wound history. Samples were collected pre- and postcleansing from patients with wounds of various etiologies and analyzed for NOx, matrix metalloproteinase activity, and elastase activity. A laboratory method was developed to analyze NOx which can detect at least 5 µM in samples as small as 10 µL. A nitrate-free sample collection device was identified to match the sensitivity of this new assay (most "nitrate-free" products tested contained nitrate levels higher than this detection limit when extracted in such a small volume). The correlation between pre- and postcleansing biomarker values, and the diagnostic potential of the biomarkers to wound progress were analyzed. Fifty wounds provided samples that were suitable for NOx analysis. The pre- and postcleansing values for NOx showed good correlation (r = 0.72); the correlation was not very strong for matrix metalloproteinase and elastase. Data analysis showed that NOx represents the best metabolite to discriminate between worsening and progressing wounds, and suggested that a two cut point diagnostic test using NOx is better than a single cut point test to identify progressing from worsening wounds.