Antibiofilm Activity of β-Lactam/β-Lactamase Inhibitor Combination against Multidrug-Resistant Salmonella Typhimurium

This study was designed to assess the effect of β-lactam/β-lactamase inhibitor combinations on the inhibition of biofilm formation of Salmonella Typhimurium. The anti-planktonic and anti-biofilm activities of ampicillin (AMP), ceftriaxone (CEF), and combination treatments of antibiotics and sulbactam (AMP + SUL and CEF + SUL) were evaluated against antibiotic-sensitive S. Typhimurium ATCC 19585 (ST(AS)) and clinically isolated multidrug-resistant (MDR) S. Typhimurium CCARM 8009 (ST(MDR)). Compared to the control, the minimum inhibitory concentrations (MICs) of AMP against ST(AS) and CEF against ST(MDR) were decreased from 32 to 16 μg/mL and 0.25 to 0.125 μg/mL, respectively, in the presence of SUL. The numbers of ST(MDR) treated with AMP + SUL and CEF + SUL were effectively reduced by more than 2 logs after 4 h of incubation at 37 °C. The β-lactamase activities of ST(AS) and ST(MDR) treated with AMP and CEF were reduced from 3.3 to 2.6 μmol/min/mL and from 8.3 to 3.4 μmol/min/mL, respectively, in the presence of SUL. The biofilm cell numbers of ST(AS) and ST(MDR) were reduced at all treatments after 24 h of incubation at 37 °C. The biofilm cell numbers of ST(AS) and ST(MDR) were reduced by more than 2 logs in the presence of SUL compared to the AMP and CEF alone. The lowest relative fitness level was 0.6 in ST(AS) treated with AMP + SUL, while no significant differences in the relative fitness were observed in ST(MDR). This study suggests that β-lactamase inhibitors (BLIs) could be used for controlling biofilm formation of β-lactamase-producing multidrug-resistant S. Typhimurium.