Comparison of fixed concentration and fixed ratio options for testing susceptibility of gram-negative bacilli to piperacillin and piperacillin/tazobactam

Eur J Clin Microbiol Infect Dis. 1992 Aug;11(8):728-32. doi: 10.1007/BF01989979.

Abstract

Piperacillin combined with tazobactam was tested at both a fixed ratio (8:1) and fixed tazobactam concentration (4 micrograms/ml) against 2,685 consecutively isolated gram-negative bacilli and 56 highly piperacillin-resistant isolates. Tazobactam significantly enhanced the spectrum of piperacillin activity. Overall, at a concentration of 16 micrograms/ml piperacillin alone inhibited 78.8% of the Enterobacteriaceae isolates compared to inhibition of 92.7% and 95.5% by the 8:1 ratio and fixed (4 micrograms/ml) tazobactam combinations, respectively. In MIC tests the two combination options performed comparably against both routine and highly piperacillin-resistant isolates. Synergistic inhibition was observed for comparable numbers of isolates with the two combination options, the most marked effect being seen in the more highly piperacillin-resistant isolates. Both testing options are supported by the available human pharmacokinetic data; however the 8:1 ratio of piperacillin to tazobactam may be preferable given that the clinical formulation contains the two compounds in an 8:1 ratio and this ratio is maintained in vivo.

MeSH terms

  • Drug Synergism
  • Drug Therapy, Combination / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Microbial Sensitivity Tests / methods
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / pharmacology
  • Piperacillin / administration & dosage
  • Piperacillin / pharmacology*
  • Tazobactam
  • beta-Lactamase Inhibitors

Substances

  • beta-Lactamase Inhibitors
  • Penicillanic Acid
  • Tazobactam
  • Piperacillin