Evolving resistance landscape in gram-negative pathogens: An update on β-lactam and β-lactam-inhibitor treatment combinations for carbapenem-resistant organisms

Pharmacotherapy. 2024 Aug;44(8):658-674. doi: 10.1002/phar.2950. Epub 2024 Jul 1.

Abstract

Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β-lactamases including MBL and OXA-enzymes.

Keywords: Acinetobacter baumannii; Pseudomonas aeruginosa; Enterobacterales; β‐lactamase; β‐lactamase inhibitor.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Carbapenems* / pharmacology
  • Carbapenems* / therapeutic use
  • Gram-Negative Bacteria* / drug effects
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • beta-Lactam Resistance
  • beta-Lactamase Inhibitors* / pharmacology
  • beta-Lactamase Inhibitors* / therapeutic use
  • beta-Lactamases
  • beta-Lactams* / pharmacology
  • beta-Lactams* / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • Carbapenems
  • beta-Lactamases