Potentiation of cefotaxime against methicillin-resistant Staphylococcus aureus (MRSA) with the application of a novel adjuvant

One of the current strategies to overcome methicillin-resistant Staphylococcus aureus (MRSA) and to minimise the need for new antibiotics is the application of adjuvant in antibiotic therapy. In the present work, cefotaxime (CTX), a third-generation antibiotic was successfully incorporated into a nanofiber mat and applied in combination with an adjuvant including boric acid (BA), borax (BX), and phenylboronic acid (PBA). The antibacterial activity of the developed formulations against Staphylococcus aureus strains including methicillin-susceptible S. aureus MSSA (ATCC® 25923™), oxacillin-sensitive S. aureus OSSA (ATCC® 29213™) and methicillin-resistant S. aureus MRSA (ATCC® 43300™) were evaluated by Kirby–Bauer disc diffusion and minimum inhibitory concentration (MIC) methods. PBA markedly decreased the MIC of CTX from 16 µg ml -1 to 0.125 µg ml -1 leading to a 128-fold reduction in its MIC value. BA and BX demonstrated a 16-fold and an 8-fold reduction in the MIC value of CTX, respectively, when used for the treatment of MRSA ATCC 43300. The combination of CTX with any of the available commercial ß-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam) did not produce an effect against MRSA ATCC 43300. Cytotoxicity was assessed using MTT assay on human umbilical vein endothelial cells (HUVECs) and the results showed no statistically significant toxic effect for the developed formulations. These novel findings suggest that PBA, a non-toxic and inexpensive compound, possesses structural similarities with β-lactam and may represent promising molecules to reverse resistance to CTX. This method can overcome the need to develop new antibiotics and render them more effective against MRSA. Graphical abstract