Contribution of β-lactamase and efflux pump overproduction to tazobactam-piperacillin resistance in clinical isolates of Escherichia coli

Int J Antimicrob Agents. 2020 Apr;55(4):105919. doi: 10.1016/j.ijantimicag.2020.105919. Epub 2020 Feb 13.


Introduction: Tazobactam-piperacillin (TZP) is a mixture of a broad-spectrum penicillin and an irreversible β-lactamase inhibitor. TZP is effective against Gram-negative bacteria that produce extended-spectrum β-lactamases, and it is used as a first-line or second-line drug to treat serious infections.

Methods: This study identified three TZP-resistant and two TZP-intermediate strains among 514 clinical isolates of Escherichia coli.

Results: These five isolates possessed one or more β-lactamase genes, blaTEM-1, blaCTX-M-2, blaCTX-M-14, and/or blaCMY-8. The expression levels of β-lactamase genes and acrAB genes in the strains were examined by using real-time reverse transcription PCR. The total enzymatic piperacillin-degrading activity in cells was determined. Two TZP-resistance mechanisms were identified: hyperproduction of TEM-1 in the two resistant strains; and simultaneous high production of β-lactamase and efflux pump AcrAB in the two TZP-intermediate isolates. The latter are an international high-risk clone O25b:H4-ST131-H30R.

Conclusion: TZP resistance is still rare in clinical isolates of E. coli. However, resistance can develop on high production and/or combinations of known antimicrobial resistance mechanisms in different ways.

Keywords: AcrAB; Antimicrobial resistance; Extended-spectrum β-lactamase; Tazobactam-piperacillin.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carrier Proteins / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Proteins / genetics
  • Genome, Bacterial / genetics
  • Humans
  • Membrane Transport Proteins / genetics*
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Piperacillin, Tazobactam Drug Combination / pharmacology*
  • Whole Genome Sequencing
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / genetics*


  • AcrAB-TolC protein, E coli
  • Anti-Bacterial Agents
  • Carrier Proteins
  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • beta-Lactamase Inhibitors
  • Piperacillin, Tazobactam Drug Combination
  • beta-lactamase CTX-2
  • beta-Lactamases
  • beta-lactamase TEM-1