In vitro and in vivo antimicrobial activities of tazobactam/piperacillin

Abstract

The antimicrobial activity of tazobactam/piperacillin (TAZ/PIPC), a combination of tazobactam (TAZ) and piperacillin (PIPC) at a ratio of 1: 4, was compared with that of 8 β-lactam antibiotics. The MIC90s (μg/ml) of TAZ/PIPC and PIPC against clinical isolates were as follows: Staphylococcus aureus: 4, 8; Streptococcus pyogenes:≦0.06, ≦0.06; Enterococcus faecalis: 2, 4; Escherichia coli: 0.25, >128; Morganella morganii: 4, 32; Providencia rettgeri: 2, 16 μg/ml; respectively. TAZ/PIPC exhibited excellent antimicrobial activity against both β-lactamase-producing and non-producing strains. The therapeutic efficacy of TAZ/PIPC was superior to that of PIPC against systemic or urinary tract infections in mice caused by various β-lactamase producing bacteria such as E. coli, Citrobacter freundii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The PIPC concentration was measured in the kidneys of mice with UTI due to E. coli KU-3 producing β-lactamase after subcutaneous administration of PIPC alone at 40 mg/kg and TAZ/PIPC containing TAZ at 10 mg/kg. The concentration of PIPC in the kidneys of mice treated with TAZ/PIPC was 2-3 times higher than that of PIPC alone. This indicates that PIPC of TAZ/PIPC is hardly inactivated by β-lactamase in the infected region because of TAZ, a β-lactamase inhibitor. These results show that TAZ/PIPC is a useful drug for the treatment of infections, especially those due to β-lactamase-producing bacteria. © 1994, Japanese Society of Chemotherapy. All rights reserved.