title: Glycyrrhizic Acid Decreases Gentamicin-Resistance in Vancomycin-Resistant Enterococci.
abstract: The resistance of commensal bacteria against first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. Particularly vancomycin-resistantEnterococcus faeciumrepresents an increasing clinical problem in the treatment of infectious diseases and hinders adequate antibiotic stewardship. In consideration of the lack of novel antibiotic compounds, the development of resistance-modifying agents, however, can mitigate the spread of bacterial drug resistance and might possibly extend the useful application indices of an existing licensed antibiotic. Given that saponins modify the local chemical environment at cell membranes and might modify the uptake or mode of action of antibiotics in bacteria, we investigated the influence of the triterpenoid saponin glycyrrhizic acid ofGlycyrrhiza glabraon the susceptibility of vancomycin-resistant enterococci against the aminoglycoside antibiotic gentamicin in 47 clinical isolates by applying the checkerboard method. The fractional inhibitory concentration indices values were determined between 0.016 and ≤ 0.5 (synergy is accepted with values ≤ 0.5). Glycyrrhizic acid at the subinhibitory concentration of 2.4 mM was found to reduce the minimal inhibitory concentration of gentamicin in intrinsically resistantE. faeciumstrains down to 6.25 % of the minimal inhibitory concentration of gentamicin alone, whereas relatively low concentrations of glycyrrhizic acid (18 µM) resulted in increased susceptibilities for someE. faeciumisolates to gentamicin. In conclusion, our study points towards a therapeutic potential of glycyrrhizic acid in co-application with gentamicin for defined local bacterial infections caused by vancomycin resistantEnterococcusstrains.
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heymann
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Melzig
authors.affiliation: Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016984:Enterococcus faecium / Q000187:drug effects*; D005839:Gentamicins / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D008826:Microbial Sensitivity Tests; D020713:Vancomycin Resistance / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D019695:Glycyrrhizic Acid