# Antibiofilm Potential of Natural Essential Oils
## 5 Synergistic Effect of EO and Antibiotics
[57] studied the ABF activity of _Cinammonun zyelanicum_, _Mentha_\(\times\)_piperta_, _O. vulgare_, and _T. vulgaris_ EOs on _S. aureus_ ATCC 29213, _E. faecalis_ ATCC 29212, _S. epidermidis_ IG4, _S. aureus_ IG22 BF, and synergistic effect in combination with antibiotic drugs (norfloxacin, oxacillin, and gentamicin). The association of EOs-antibiotics showed a strong destruction of the BF growth of the four bacterial species considered, wherein the interaction of norfloxacin with EOs was the most effective. The authors demonstrated that the amount of antibiotic can be significantly reduced by EOs, thus adding to the achievement of the desired therapeutic effects. Furthermore, they noted the large reduction in the quantities of EOs employed to attain the association with respect to the quantity of the EOs used alone to inhibit the strain. [PERSON] et al. [58] report that there is a potential synergistic effect between _M._\(\times\)_piperta_ EO (MPEO) and three widely used antibiotics (gentamicin, oxacillin, norfloxacin) on _S. aureus_ ATCC 29213, _E. faecalis_ ATCC 29212, _S. epidermidis_ IG4, _S. aureus_ IG22 BFs formation and growth. All the combinations of MPEO with antibiotics are able to produce a substantial inhibition of bacterial BF growth. [PERSON] et al. [34] found reduced MIC values for _Foeniculum vulgare_ Mill. EO (FEO) in combination with H\({}_{2}\)O\({}_{2}\) compared to FEO alone in BF formation by reference _S. aureus_ strains. The coupled use of FEO and H\({}_{2}\)O\({}_{2}\) exerted synergistic effects on all reference strains (MSSA and MRSA). Sub-inhibitory concentrations of FEO (0.5 MIC and 0.25 MIC) alone and in combination with 0.5 MIC H\({}_{2}\)O\({}_{2}\) significantly inhibited BF formation by _S. aureus_ and suppressed the metabolic activity of the attached cells. It seems that the combination of FEO containing 80% trans-anethole and H\({}_{2}\)O\({}_{2}\) affords potential possibilities for trial use in wound treatment. EOs-drug mixtures can be a good option for topical applications. Topical antiseptics seem to be more beneficial compared to systemic antibiotics because they do not cause multidrug resistance, have a broader spectrum of AM activity, and are less likely to cause allergic reactions [50]. In turn, [PERSON] et al. [33] investigated the possible synergism of EOs and antibiotics against _S. aureus_, using EO from _Croton conduplicatus_ Kunth (EOCC), oxacillin (OXA), and ampicillin (AMP). MIC values of EOCC were 256 and 512 \(\upmu\)g/mL for methicillin-sensitive and resistant _S. aureus_ strains (MSSA and MRSA), respectively. The combinations of EOCC with OxA and AMP were synergistic (OXA/EOCC and AMP/EOCC combined decreased the OXA MIC and AMPMIC to 0.5 and 0.25 for MSSA, respectively, and OXA/EOCC and AMP/EOCC combined decreased the OXA MIC and the AMP MIC to 1 and 0.5 for MRSA, respectively) and could modify the resistance profile of MSSA and MRSA strains. The combinations of EOCC with OXA and AMP were able to reverse resistance to these antibiotics, indicating that at concentrations lower than MIC, OXA and AMP became active against the strains when combined with EOCC. The results indicated that EOCC was also able to partially inhibit biofilm formation by damaging the cell membrane with extravasation of intracellular contents, whereas beta-lactam antibiotics act by inhibiting penicillin-binding proteins. The synergistic effect of EOs and antibiotics can be associated with the creation of complex chemical products that can be very effective in inhibiting many species of microorganisms by preventing the synthesis of the cell wall or can lead to lysis and ultimately death. Mixing EOs with antibiotics strengthens their antibacterial effects, raising the possibility of reducing the dose of the drug, which reduces side effects. They also increase antibiotic spectrum, preventing the development of resistance and reducing toxicity, often showing antibacterial effects better than estimated for each antibiotic separately [54].