Novel silver-cerium EDTA complexes with high antimicrobial and antibiofilm efficacy.

Abstract: Introduction: Biofilms often show increased tolerance to antimicrobials and antibiotics in comparison to their planktonic counterparts, which impose significant challenges for clinical infection control. This indicates the urgent need for new targeted technologies and emerging therapeutic strategies. In this study, novel silver-cerium EDTA complexes (Ag-Ce MMC) were synthesised and their antibacterial/antibiofilm efficacies were tested by multiple in vitro microbial and biofilm models on different platforms. Method: A variety of in vitro microbial and biofilm models were utilized to evaluate the ability of Ag-Ce MMC in different platforms (liquid/gel/fabric) to sequester microbes, prevent dissemination, and manage bioburden. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Ag-Ce MMC and it’s the mixtures with surfactant Poloxamer P188 and P407 were determined using a broth microdilution method against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. CDC Bioreactor and artificial wound slough (AWS) models were used to evaluate antibacterial killing efficacy towards established P. aeruginosa and Staphylococcus aureus biofilms using more challenging, wound-like models. Biofilms in different models were treated with liquid and gel samples for pre-defined contact times before being transferred to the appropriate neutraliser, sonicated, serial diluted 1:10 in PBS and plated onto TSA in duplicate. Results / Discussion: Following MIC and MBC testing of Ag-Ce MMC and the components alone, increased antimicrobial potency was found with all complexes tested. Checkerboard assays showed synergistic interactions between Ag-Ce MMC with poloxamer P188 and P407 against P. aeruginosa, S. aureus, and C. albicans. CDC and AWS biofilm models demonstrated strong antibiofilm activity of Ag-Ce MMC against P. aeruginosa and S. aureus. The Ag-Ce MMC loaded gels (Carbopol and poloxamer) demonstrated superiority in both CDC and AWS biofilm models, as reduced P. aeruginosa growth to the limit of detection (completely killed). Conclusion: The data generated within the in vitro biofilm models demonstrate that the Ag-Ce MMC complexes are the promising reagents for effective biofilm management and control in wound care.

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