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.
Key words
Glycyrrhizic acid - vancomycin-resistant enterococci - combination effect - synergism
- saponins - gentamicin
