In Vitro Efficiency of the piperacillin/tazobactam Combination Against Inhibitor-Resistant TEM- And Complex Mutant TEM-producing Clinical Strains of Escherichia Coli

J Antimicrob Chemother. 2011 May;66(5):1052-6. doi: 10.1093/jac/dkr045. Epub 2011 Feb 28.


Objectives: We investigated the bacteriostatic and bactericidal activities of piperacillin/tazobactam against 16 clinical Escherichia coli producing inhibitor-resistant TEM β-lactamases (IRT; 13/16) and complex mutant TEM enzymes (CMT; 3/16).

Methods: Bacteriostatic activity was evaluated by three methods (disc diffusion, Vitek2 automated system, MIC determination by a microdilution method) and a time-killing study was used to investigate the bactericidal effect against standard (5 × 10(5) cfu/mL) and high inocula (5 × 10(6) cfu/mL).

Results: Piperacillin/tazobactam was bacteriostatic against most of the tested strains (15/16). Using a high inoculum, the piperacillin/tazobactam combination was not bactericidal against the 13 IRT-producing strains and one of the CMT-producing strains (1/3). A loss of bactericidal activity was still observed for seven IRT-producing strains (7/13) with a standard bacterial inoculum (<99.9% killing over 24 h).

Conclusions: Despite usual in vitro bacteriostatic activity, the piperacillin/tazobactam combination was not bactericidal against most IRT-producing clinical strains of E. coli, especially for the treatment of a high bacterial inoculum. This possible loss of bactericidal effect should be brought to the attention of physicians and may require high dosing regimens for the treatment of severe infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology*
  • Escherichia coli / growth & development
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / biosynthesis
  • Escherichia coli Proteins / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Mutant Proteins / biosynthesis
  • Mutant Proteins / genetics
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology
  • Piperacillin / pharmacology
  • Piperacillin, Tazobactam Drug Combination
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / genetics


  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Mutant Proteins
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • beta-Lactamases
  • Piperacillin