Resveratrol reverts tolerance and restores susceptibility to chlorhexidine and benzalkonium in gram-negative bacteria, gram-positive bacteria and yeasts
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University of Naples "Federico II" Department of Public Health, University of Naples, "Federico II" Via S. Pansini 5, Naples, Italy Italy
University of Naples "Federico II" 2Department of Chemical Sciences, University of Naples, "Federico II" Via Cintia 4, Naples, Italy Italy
Institute of Biostructures and Bioimaging, National Research Council, CNR Naples, Italy; Italy
Eliana De Gregorio
Publication date: 2023-04-26
Popul. Med. 2023;5(Supplement):A952
1. Introduction:
The spread of microorganisms causing health-care associated infection (HAI) is contributed by their intrinsic tolerance to a variety of biocides used as antiseptics or disinfectants. The aim of the study was to: (i) analyze the susceptibility to CHX and BZK biocides in a panel of reference strains and clinical isolates of Gram-negative bacteria, Gram-positive bacteria and yeasts; (ii) identify non-toxic compounds, which can restore susceptibility to CHX and BZK in the above pathogens.

2. Materials and Methods:
MIC (mg/L) and MBC (mg/L) values of CHX and BZK were determined by a broth microdilution method. In vitro combination studies were carried out using the checkerboard method. The combined effects were determined by calculating the fractional inhibitory concentration (FIC) index.

3. Results:
The natural monomeric stilbenoid resveratrol (RV) from 32 to 256 mg/L decreased dose-dependently CHX MIC and MBC in 33 selected strains, while not restored CHX susceptibility in Klebsiella pneumoniae ATCC 700603, all Pseudomonas aeruginosa and Candida spp. strains. RV up to 128 mg/L decreased dose-dependently BZK MIC and MBC, but not restored BZK susceptibility in 3 Burkholderia spp., Enterocobacter cloacae ATCC 13047, K. pneumoniae ATCC 700603, Stenotrophomonas maltophilia K279 and all P. aeruginosa strains. Furthermore, CHX and BZK combination in the presence of RV at 64 mg/L restored CHX or BZK susceptibility in all strains and showed a synergic in 20 out 21 strains and additive effect in 1 out 21 strains.

4. Conclusions:
A synergic microbicidal effect was observed when the two biocides were combined with RV in a panel of Gram-negative bacteria, Gram-positive bacteria and yeasts. RV reverts tolerance and restores susceptibility to CHX and BZK in the majority of microorganisms. The combination of RV, CHX and BZK may represent a useful strategy to maintain susceptibility to biocides in several nosocomial pathogens.

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