Investigation of synergistic antibiotic-essential oil component combinations as a means to preserve the current antibiotic repertoire in Enterococcus sp.

Abstract

Aims To investigate synergistic combinations of Essential Oils (EOs) and vancomycin as potential antimicrobial formulations against Vancomycin-Sensitive Enterococcus faecium (VSE) and Vancomycin-Resistant E. faecium (VRE).

Methods and results Oregano, cumin and rosewood EOs and their major components carvacrol, cuminaldehyde and linalool were screened for synergistic interactions with vancomycin against VSE and VRE using the checkerboard method. Synergistic combinations were further investigated by a time-kill assay. A combination of 4.20 mM cuminaldehyde, 1.98 mM carvacrol and 0.031 mg/L vancomycin was synergistic against both VSE and VRE, reducing the Minimum Inhibitory Concentration (MIC) of vancomycin below the EUCAST (1) resistance breakpoint. The combination reduced VSE by 5.83 log10 and VRE by 5.07 log10 Colony Forming Units (CFU)/mL over 24 hours. In vivo efficacy of the combination against VRE was determined using a Galleria mellonella larvae assay. The combination did not significantly (p<0.05) improve survival of larvae compared to controls.

Conclusions A combination of carvacrol, cuminaldehyde and vancomycin was synergistic against VSE and VRE, reducing the effective dose of vancomycin. However, this combination was not significantly antimicrobial in vivo suggesting further drug development is required. Synergistic antibiotic-EO compound formulations may be a means to extend the life of antibiotics against resistant bacteria.

Significance of study Combining EO compounds with antibiotics may be a useful strategy to reduce the effective doses of antibiotics against antibiotic-resistant bacteria, thus preserving current antimicrobial therapies. This study identified a formulation that reduced the MIC of vancomycin below the resistance breakpoint, which could be a candidate for further investigation.