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

Introduction: Tazobactam-piperacillin (TZP) is a mixture of a broad-spectrum penicillin and an irreversible beta-lactamase inhibitor. TZP is effective against Gram-negative bacteria that produce extended-spectrum beta-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 beta-lactamase genes, bla(TEM-1), bla(CTX-M-2), bla(CTX-M-14), and/or bla(CMY-8). The expression levels of beta-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 beta-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. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.