Susceptibility of Clinical Isolates to Expanded-Spectrum β-Lactams Alone and in the Presence of β-Lactamase Inhibitors

Tazobactam and BRL 42715 are relatively new penems which inhibit a wide range of plasmid- as well as chromosomally mediated bacterial β-lactamases that include Richmond and Sykes type I, II, III, IV and V β-lactamases, staphylococcal penicillins and extended-spectrum β-lactamases. However, clavulanic acid, which is a potent inhibitor of class III β-lactamases, is one of the first discovered compounds. We used a total of 645 recent clinical isolates, consisting of 305 Enterobacteriaceae, 180 gram-positive cocci and 160 other gram-negative bacteria to evaluate the ability of β-lactamase inhibitors for potentiation of piperacillin, ticarcillin and amoxycillin. Minimum inhibitory concentrations for all the 42 strains of methicillin-susceptible Staphylococcus aureus were reduced 4- to 16-fold in the presence of β-lactamase inhibitors. They were also highly effective in inhibiting the β-lactamase of a wide variety of gram-negative bacteria, thereby changing their MIC values for amoxycillin, ticarcillin and piperacillin from a ‘resistant’ to a ‘susceptible’ range. Commonly resistant bacteria like Klebsiella, Enterobacter, Serratia,Acinetobacter and Pseudomonas were rendered susceptible to piperacillin and ticarcillin in the presence of clavulanic acid, tazobactam and BRL 42715. Of the commercially available formulations for clinical use, piperacillin/tazobactam (TazocinTM) was found to be more inhibitory towards both gram-positive and gram-negative bacteria.