# Potential Synergistic Inhibition of _Enterococcus faecalis_ by Essential Oils and Antibiotics
## 4 Discussion
There was also an enhanced antimicrobial effect when CN2.5% cinnamon EO was combined with 5% streptomycin (2.5 mg/mL), where the combined solution produced significantly increased antimicrobial effect comparable to that of 10% streptomycin (5 mg/mL) solution alone. Such enhancements were not observed with kanamycin/gentamicin/ampicillin combined with CN2.5% EO solution. The CN1.25% combined with 5% antibiotic solutions did not produce enhanced antimicrobial effects as their ZOI values were not significantly different than those for either one or both or their individual component solutions. For CL50% EO combined with 5% antibiotic solutions, there was no improvement in the antimicrobial effects of the combined solution beyond the effects observed for their individual component solutions. The enhanced antimicrobial effects of combining antibiotics with cinnamon or clove EOs have been reported previously in Escherichia coli, pseudomonas aeruginosa, and in methicillin-resistant Staphylococcus aureus [54; 55]. In our study, using the Kirby-Bauer disk diffusion test, we report that 5% concentration of aminoglycoside-class antibiotics (kanamycin, streptomycin, gentamicin) combined with 5% cinnamon EO produced significantly enhanced antimicrobial effect than 10% concentration of corresponding antibiotics alone against _E. faecalis_. The limitation of the present study is that since the MIC and the MBC values were not measured, it is not possible to define whether our enhanced antimicrobial observations show strictly synergistic or additive effects. However, based on our data, it may be reasonable to infer the presence of additive-like synergism where the 5% antibiotic + CN5% EO shows a significant increase in antimicrobial response compared to the 10% concentration antibiotic alone. Acquisition of antibiotic resistance by _E. faecalis_ is reported to be associated in part with its ability to synthesize \(\upbeta\)-lactamase, incorporate aminoglycoside-resistant genes aac(6\({}^{\prime}\))-Ie-aph(2\({}^{\prime\prime}\))-Ia and aph(2\({}^{\prime}\))-Ib, and upregulate expression of low-affinity penicillin-binding protein Pbp5, and with the presence of ATP-binding cassette multidrug efflux pump EfraB [56; 57; 58; 59; 60]. These adaptations, along with its ability to survive in biologically inhospitable environments, make _E. faecalis_ an ideal candidate to thrive and persist at sites in and around endodontic infections. The antimicrobial and antibacterial properties observed in EOs, such as cinnamon and clove oils, involve disruption of bacterial genes, non-specific permeabilization of the cell membrane, and inhibition of transmembrane proton motif force and ATPase via anti-quorum sensing effects [32]. Our in vitro data show that the enhanced antimicrobial effects observed against _E. faecalis_ by combining the antibiotics with cinnamon and clove EOs, presumably by interfering with the antibiotic-resistant cellular mechanisms, may be a suitable and practical approach to reduce the prevalence and incidence of persistent dental infections and treatment failures. Exploration of such strategies in in vivo and clinical studies to assess the efficacy, safety, and duration of their effects should be examined in future studies.