The World Health Organization has listed antimicrobial resistance as one of the top threats facing health today. The over-prescription of antibiotics, use of biocides in commercial products, and misuse of antimicrobials have led to drug-resistant microbes, and stronger pharmaceuticals are often necessary to fight infections. In this work, the results of an extensive screening of biocide combinations to inactivate pathogens is described. Group IB metal ions (Ag, Cu, Au) were mixed with 210 different antibiotics that act on proteins, nucleic acids, cell wall, cell membrane, folate synthesis, among others. Wild-type E. coli was exposed to the metal alone, the biocide alone, and the metal mixed with biocide. Relative growth at 16 hours was compared for all three to determine if lethality of the metal-biocide combination was greater than the individual metal or antibiotic. Synergism was observed using the coefficient of drug interaction (CDI) and checkerboard assays. Among the 210 antibiotics tested, trends were observed for various classes mixed with Ag+, Cu2+, and Au3+ that are in agreement with published studies. New biocide/metal interactions were also observed that will require additional testing to evaluate mode of action and optimum concentrations. The work demonstrates that this approach for rapid drug screening can be used to study biocide mixtures, and should be used to combat pathogenic survival.

Rapid screening of synergistic combinations of group IB metals and antibiotics for E. coli inactivation

2019 Spring National Meeting

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