Sodium ibuprofenate: antibacterial activities and potential β-lactamase inhibition in critical Gram-negative bacteria

To evaluate the antibacterial and antibiofilm activities of sodium ibuprofenate (NaI) and its hypertonic variant (NaIHS) against multidrug-resistant Gram-negative bacteria (MDR-GNB) and explore their potential to inhibit β-lactamase enzymes.

Antibacterial activity was assessed using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill assays. Antibiofilm activity was evaluated by measuring bacterial viability and biomass reduction in preformed biofilms. Scanning electron microscopy (SEM) was used to observe membrane effects. Molecular docking and molecular dynamics simulations were conducted to analyze the binding affinity of ibuprofen to the active sites of β-lactamases (CTX-M-15, KPC-2, OXA-23).

NaI exhibited bactericidal activity at concentrations of 25-75 mm, with Acinetobacter baumannii being the most susceptible. NaCl (≥0.5 M) enhanced bactericidal efficacy and lowered MBCs. Time-kill assays indicated rapid bacterial eradication within 2 hours, with NaIHS achieving similar results at lower concentrations. SEM confirmed membrane disruption. Both formulations reduced bacterial viability in biofilms, with NaIHS showing greater efficiency. In silico studies suggest ibuprofen may inhibit β-lactamases, with enhanced interactions in saline environments.

Sodium ibuprofenate, particularly in its hypertonic form, demonstrates strong antibacterial, antibiofilm, and potential β-lactamase inhibitory activity, making it a promising candidate for treating MDR-GNB infections.