title: Antimicrobial potency of single and combined mupirocin and monoterpenes, thymol, menthol and 1,8-cineole against Staphylococcus aureus planktonic and biofilm growth.
abstract: Staphylococcus aureus is one of the most commonly isolated microbes in chronic rhinosinusitis (CRS) that can be complicated due to the formation of a staphylococcal biofilm. In this study, we investigated antimicrobial efficacy of single mupirocin and three types of monoterpenes (thymol, menthol and 1,8-cineole) as well as mupirocin-monoterpene combinations against S. aureus ATCC 29213 and 5 methicilin-resistant S. aureus strains (MRSA) grown in planktonic and biofilm form. MIC against planktonic bacteria as well as minimum biofilm-eliminating concentrations (MBECs) and minimum biofilm inhibitory concentrations (MBICs) were determined by TTC and MTT reduction assay, respectively. The MICs of mupirocin (0.125-0.156 μg ml(-1)) were three orders of magnitude lower than the MICs of monoterpenes, which were as follows: thymol (0.250-0.375 mg ml(-1)) > menthol (1 mg ml(-1)) > 1,8-cineole (4-8 mg ml(-1)). Mupirocin-monoterpene combinations showed indifferent effect as compared with MICs of single substances. Mupirocin (0.016-2 mg ml(-1)) failed to destroy the biofilm. The MBECs of thymol and menthol were two- to sixfold higher than their MICs, while 1,8-cineole exerted a weak antibiofilm effect with MBECs 16- to 64-fold higher than MICs. Mixture of mupirocin and 1,8 cineole exerted a potentiated biofilm-eliminating effect, mupirocin-menthol showed antagonism, while effect of thymol-mupirocin mixture was inconclusive. MBICs of antimicrobials were close to their MICs, except 1,8-cineole, MBIC was about three- to fivefold higher. Dominant synergy was observed for mixtures of mupirocin and menthol or thymol, whereas mupirocin-1,8-cineol exerted an indifferent or additive biofilm inhibitory effect. Particular combinations of mupirocin and the monoterpenes could be applied in CRS therapy in order to eliminate or prevent bacterial biofilm growth.
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Domagoj
authors.initials: D
authors.lastname: Kifer
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Vedran
authors.initials: V
authors.lastname: Mužinić
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Maja Šegvić
authors.initials: MŠ
authors.lastname: Klarić
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D000077591:Eucalyptol; D008610:Menthol / Q000008:administration & dosage / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D016712:Mupirocin / Q000008:administration & dosage / Q000494:pharmacology*; D010933:Plankton / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects*; D013943:Thymol / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D003511:Cyclohexanols; D039821:Monoterpenes; D008610:Menthol; D013943:Thymol; D016712:Mupirocin; D000077591:Eucalyptol