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Published on: April 18, 2019

FPI-1523, a novel β-lactamase inhibitor, enhances imipenem activity against carbapenemase-producing Enterobacterales

Zeyong Zhong1, Jingchun Kong2, Yichi Zhang2

  • 1Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.

Journal of Global Antimicrobial Resistance
|July 8, 2026
PubMed
Abstract

Insights

The novel β-lactamase inhibitor FPI-1523 combined with imipenem shows significant antimicrobial activity against carbapenem-resistant Enterobacterales (CRE). This combination restores imipenem susceptibility in most CRE strains, demonstrating safety and efficacy.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Carbapenem-resistant Enterobacterales (CRE) pose a significant global health threat due to limited treatment options.
  • The emergence of carbapenemases necessitates the development of novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the in vitro and in vivo antimicrobial activity of FPI-1523, a novel β-lactamase inhibitor, in combination with imipenem against CRE.
  • To assess the safety profile of the FPI-1523 and imipenem combination.

Main Methods:

  • Antimicrobial susceptibility testing, time-kill assays, and Galleria mellonella infection model were used to assess antibacterial effects.
  • Hemolysis assays and cytotoxicity experiments evaluated drug safety.
  • Modified carbapenem inactivation and carbapenemase inhibition assays explored the mechanism of action.

Main Results:

  • The FPI-1523 and imipenem combination restored imipenem susceptibility in 75% of CRE strains, including those producing KPC, NDM, and IMP carbapenemases.
  • FPI-1523 demonstrated intrinsic antimicrobial activity against E. cloacae and E. coli.
  • In vivo studies in Galleria mellonella confirmed significant antibacterial effects and safety of the combination.

Conclusions:

  • The combination of FPI-1523 and imipenem exhibits potent antibacterial activity against a wide range of carbapenemase-producing CRE.
  • FPI-1523 effectively inhibits carbapenemase activity, with potential monotherapy benefits for class B carbapenemase-producing strains.
Keywords:
Carbapenem-resistant EnterobacteralesFPI-1523Imipenem

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