Synergistic Activity of Eugenol, Cinnamaldehyde and Carvacrol in Combination with Different Antimicrobial Molecules Against MultiDrug-Resistant Gram-Negative Clinical Isolates

Background/Objectives: WHO has identified Carbapenem-Resistant Acinetobacter baumannii (CRAb) and carbapenem-producing Enterobacterales (CPE) as the “critical priority” group of MDR organisms for which new therapeutic strategies are urgently needed. Here, we evaluated in vitro synergistic activity of eugenol, cinnamaldehyde and carvacrol in combination with β-lactams, gentamicin, or colistin against multidrug-resistant (MDR) Gram-negative bacteria (GNB). Methods: We selected seven MDR-GNB clinical isolates inclining CRAb, ESBL-producing and CPE clinical isolates displaying different antimicrobial susceptibility profiles. The genomes of clinical isolates were characterized by whole-genome sequencing and synergy testing was performed with checkerboard assay. Results: Our results demonstrated that eugenol, cinnamaldehyde and carvacrol in combination with colistin exhibited high synergistic activity against MDR-GNB clinical isolates (37.5-50%), while the effect was almost indifferent in combination with different β-lactam molecules or gentamicin (87.5-100%). Synergistic interaction of eugenol, cinnamaldehyde and carvacrol with colistin induced a statistically significant reduction (p