SULBACTAM (SBT): PERMANENT INACTIVATION OF VARIOUS TYPES OF β-LACTAMASES AND THE AFFINITY TO PENICILLIN-BINDING PROTEINS IN BACTERIA

Abstract

It was confirmed that β-lactamase-inhibitors that can manifest a synergy of antibacterial activities with β-lactamase-susceptible β-lactams are limited to those possessing an activity of permanent inactivation of the enzymes. Since sulbactam (SBT) inactivated the types of Ic, II, III (TEM), IV, and V (OXA) β-lactamases strongly and the type Ia enzyme moderately, a combination of SBT with cefoperazone (CPZ) showed marked antibacterial activities against P. vulgaris, P. cepacia, B. fragilis, E. coli carrying R (bla) plasmids, Klebsiella, and P. mirabilis. The activity of SBT to inactivate the type III β-lactamase, however, was weaker than that of clavulanic acid (CVA) in some extent. The combined drug exhibited some synergies to Serratia marcescens also, because of inactivation of the type Ia enzyme.
SBT competed for penicillin-binding proteins of Escherichia coli and Staphylococcus aureus with more than 25 μg/ml, resulting in stronger cell-lysis if combined with CPZ.