[In vitro antibacterial activity of piperacillin-tazobactam in combination with netilmicin or amikacin against Enterobacteriaceae resistant to amoxicillin]

Pathol Biol (Paris). 1995 Mar;43(3):208-14.
[Article in French]

Abstract

The antibacterial in vitro activity of piperacillin and tazobactam (in a concentration ratio of 8/1) was studied in combination with netilmicin or amikacin by a microtiter checkerboard assay against 162 strains of Enterobacteriaceae. These strains were selected for their resistance pattern to beta-lactam antibiotics and their beta-lactamases were characterized by the mean of isoelectric focusing in comparison with reference strains. A comparison of the MICs of piperacillin, alone and in combination, assessed the efficacy of tazobactam as beta-lactamase inhibitor, particularly when a TEM-1 beta-lactamase was produced. When the strains were sensitive to the aminoglycosides (111 netilmicin-sensitive ones and 131 amikacin-sensitive ones), we observed 55% of synergistic effects and 45% of additions with the combinations piperacillin-tazobactam-netilmicin or amikacin. A synergistic effect was usually encountered with P. mirabilis, P. vulgaris, M. morganii and with the strains of E. coli, E. cloacae and S. marcescens which produced a cephalosporinase only. Among the 51 strains that were intermediate or resistant to netilmicin, 8 ones were inhibited by piperacillin-tazobactam-netilmicin at therapeutic levels (3 synergisms, 5 additions). Among the 31 strains that were intermediate or resistant to amikacin, 24 ones (18 synergisms, 6 additions) were inhibited by piperacillin-tazobactam-amikacin at therapeutic concentrations. In most of the cases, the combination of piperacillin-tazobactam with an aminoglycoside enhanced the antibacterial activity of these agents by decreasing the concentrations necessary to inhibit the strains.

MeSH terms

  • Amikacin / pharmacology*
  • Amoxicillin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Microbial
  • Drug Synergism
  • Drug Therapy, Combination / pharmacology
  • Enterobacteriaceae / drug effects*
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Netilmicin / pharmacology*
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / pharmacology
  • Piperacillin / pharmacology*
  • Tazobactam
  • beta-Lactamase Inhibitors

Substances

  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • Netilmicin
  • Amoxicillin
  • Amikacin
  • Penicillanic Acid
  • Tazobactam
  • Piperacillin