The present investigation aimed to assess the combinational effect of commonly used antipyretics and antiseptics with ethanolic extracts of propolis (EEPs) on the growth inhibition of Staphylococcus aureus. The broth microdilution checkerboard assay revealed synergistic interactions between all investigated antipyretics, namely acetylsalicylic acid, ibuprofen, and acetaminophen, with EEPs samples. The values of the fractional inhibitory concentration (ΣFIC) index for all these combinations were <0.5. While, in the case of considered antiseptics, namely chlorhexidine, octenidine dihydrochloride, and 2-phenoxyethanol, the positive interaction was confirmed only for the last one (values of ΣFIC in the range 0.0625-0.25). Combinations of two other agents with all four samples of EEPs resulted in an important antagonistic effect (values of ΣFIC ≥ 4.5). Propolis is mostly dedicated to the treatment of skin/wound infections; thus, these findings are of particular practical importance. The outcomes of the study also support the hypothesis that the propolis's antimicrobial effect is due to the combined (synergistic) action of several ingredients rather than the presence of one component of high antibacterial activity. The composition of 13 ingredients of EEPs (at a concentration below the MIC (minimum inhibitory concentration) of the most active agent) exhibited considerably high anti-staphylococcal efficiency with MIC = 128 µg/mL.
Keywords: 2-phenoxyethanol; Staphylococcus aureus; acetaminophen; acetylsalicylic acid; chlorhexidine; ibuprofen; octenidine dihydrochloride; propolis; synergism.