In vitro and in vivo efficacy of YTR-830H and piperacillin combinations versus beta-lactamase-producing bacteria.

YTR-830H, a beta-lactamase inhibitor, is a non-amino penicillanic sulfone. In vitro synergistic activity with piperacillin was determined for 226 beta-lactamase producing clinical cultures. Combination of piperacillin: YTR in ratios of 2:1, 4:1, and 8:1 were highly effective vs Escherichia coli, Proteus, Providencia, Morganella, Staphylococcus, and Bacteroides. Minimum inhibitory concentrations (MICs) of piperacillin were reduced from the resistant to susceptible range. The higher ratios were less effective vs Enterobacter, Serratia, and Citrobacter. YTR-830H was not antagonistic with piperacillin. Combinations of 2:1, 4:1, and 8:1 increased the therapeutic effectiveness of piperacillin 8 - to 36 - fold against acute lethal infections produced in mice with piperacillin-resistant Escherichia coli, Klebsiella pneumoniae, Morganella morganii, and Staphylococcus aureus.