The role of new β-lactamase inhibitors in gram-negative infections

Curr Opin Infect Dis. 2019 Dec;32(6):638-646. doi: 10.1097/QCO.0000000000000600.

Abstract

Purpose of review: In recent years, traditional β-lactams have dramatically reduced their effectiveness against gram-negative bacteria mainly because of their ability to express multiple β-lactamase or carabapenemases that are not hydrolyzed by the old β-lactam inhibitors (BLIs) such as clavulanic acid, tazobactam, and sulbactam. New BLIs molecules have been developed to face the need of compounds that are active against multidrug or pandrug resistant gram-negative pathogens. The aim of this review is to summarize the new generation of BLIs and β-lactams combinations.

Recent findings: A number of new molecules with activity against Ambler class A (e.g., extended-spectrum β-lactamases, serine carbapenemases), class C (e.g., AmpC), or class D (e.g., oxacillinase-48) have been recently approved in combination with old β-lactams for the treatment of multidrug-resistant bacteria, and other agents are under investigation. These new compounds include diazabicyclooctanones non-β-lactam inhibitors (e.g., avibactam, relebactam, nacubactam) and boronic acid inhibitors (e.g., vaborbactam).

Summary: Newly approved and investigational new BLIs are expected to offer many advantages for the management of patients with multidrug-resistant gram-negative pathogens. Promising characteristics of new compounds include high activity against multi drug resistance gram-negative bacteria and a favorable safety profile.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Disease Management
  • Drug Therapy, Combination
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology*
  • Humans
  • Treatment Outcome
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors