Anti-Biofilm Activity of Combinations of Cinnamic Acid and Its Derivatives with Cloxacillin Against Methicillin-Resistant Staphylococcus epidermidis

<i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>) poses a significant clinical challenge, particularly in the context of biofilm-associated infections, with increasing antibiotic resistance further complicating infection eradication. In the present study, the effects of cinnamic acid and its derivatives (ferulic acid, <i>p</i>-coumaric acid, and sinapic acid), alone and in combination with the β-lactam antibiotic cloxacillin, on biofilm formation by a single methicillin-resistant <i>S. epidermidis</i> (MRSE) clinical strain were explored. The expression of the biofilm-associated <i>icaADBC</i> operon genes and the <i>icaR</i> repressor gene was assessed using Real-Time PCR as an exploratory analysis under sub-minimal inhibitory concentrations (sub-MICs) of the tested compounds. Furthermore, confocal microscopy was used to qualitatively assess selected structural changes in the biofilm. Their occurrence was demonstrated depending on the fractional inhibitory concentration (FIC) levels used. The results revealed variable and nonlinear patterns of gene expression in response to the tested concentrations. Additionally, compound-dependent differences in anti-biofilm-related responses were observed. Overall, the findings provide insight into the potential influence of cinnamic acid derivatives combined with cloxacillin on biofilm-associated processes in <i>S. epidermidis</i>.