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New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams

Juan C Vázquez-Ucha1, Jorge Arca-Suárez1, Germán Bou1

  • 1Servicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC-CICA), Complejo Hospitalario Universitario A Coruña (CHUAC), As Xubias 84, 15006 A Coruña, Spain.

International Journal of Molecular Sciences
|December 9, 2020
PubMed

Insights

New carbapenemase inhibitors and β-lactam/β-lactamase inhibitor combinations show promise for treating difficult infections. These advancements are crucial in combating antimicrobial resistance, particularly against metallo-β-lactamases and carbapenem-hydrolysing class D β-lactamases.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Carbapenem resistance is a critical global health threat, complicating treatment of hospital-acquired infections.
  • Carbapenemase production (e.g., VIM, IMP, NDM, KPC, OXA) is a primary mechanism of resistance.
  • Existing treatments are increasingly ineffective against carbapenem-resistant pathogens.

Purpose of the Study:

  • To review promising carbapenemase inhibitors and their development status.
  • To highlight β-lactam/β-lactamase inhibitor combinations for treating priority pathogens.
  • To assess the potential of new agents against metallo-β-lactamases and class D carbapenemases.

Main Methods:

  • Literature review of preclinical and clinical data on carbapenemase inhibitors.
  • Analysis of inhibitor spectrum of activity and developmental stage.
  • Focus on β-lactam/β-lactamase inhibitor combinations.

Main Results:

  • Several novel carbapenemase inhibitors are in development.
  • Approved agents like avibactam, relebactam, and vaborbactam offer new treatment options.
  • New combinations show potential against critical carbapenemase-producing pathogens.

Conclusions:

  • Emerging carbapenemase inhibitors and combinations represent significant progress against antimicrobial resistance.
  • These advancements are vital for addressing infections caused by metallo-β-lactamases and class D carbapenemases.
  • Further development is needed to overcome resistance challenges.
Keywords:
antibiotic resistancecarbapenem resistancecarbapenemaseinhibitormetallo-β-lactamasesserine-β-lactamases

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