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

초록

This study was designed to assess the effect of beta-lactam/beta-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 (STAS) and clinically isolated multidrug-resistant (MDR) S. Typhimurium CCARM 8009 (STMDR). Compared to the control, the minimum inhibitory concentrations (MICs) of AMP against STAS and CEF against STMDR were decreased from 32 to 16 mu g/mL and 0.25 to 0.125 mu g/mL, respectively, in the presence of SUL. The numbers of STMDR treated with AMP + SUL and CEF + SUL were effectively reduced by more than 2 logs after 4 h of incubation at 37 degrees C. The beta-lactamase activities of STAS and STMDR treated with AMP and CEF were reduced from 3.3 to 2.6 mu mol/min/mL and from 8.3 to 3.4 mu mol/min/mL, respectively, in the presence of SUL. The biofilm cell numbers of STAS and STMDR were reduced at all treatments after 24 h of incubation at 37 degrees C. The biofilm cell numbers of STAS and STMDR 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 STAS treated with AMP + SUL, while no significant differences in the relative fitness were observed in STMDR. This study suggests that beta-lactamase inhibitors (BLIs) could be used for controlling biofilm formation of beta-lactamase-producing multidrug-resistant S. Typhimurium.

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