Planta Med 2016; 82(18): 1540-1545
DOI: 10.1055/s-0042-114781
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Glycyrrhizic Acid Decreases Gentamicin-Resistance in Vancomycin-Resistant Enterococci

Sebastian Schmidt
1   Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
,
Kerstin Heymann
1   Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
,
Matthias F. Melzig
1   Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
,
Stefan Bereswill
2   Institute of Microbiology and Hygiene, Charité – University Medicine Berlin, Berlin, Germany
,
Markus M. Heimesaat
2   Institute of Microbiology and Hygiene, Charité – University Medicine Berlin, Berlin, Germany
› Author Affiliations
Further Information

Publication History

received 23 May 2016
revised 21 July 2016

accepted 04 August 2016

Publication Date:
23 August 2016 (online)

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-resistant Enterococcus faecium represents 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 of Glycyrrhiza glabra on 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 resistant E. faecium strains 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 some E. faecium isolates 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 resistant Enterococcus strains.

 
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