Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives

Curr Opin Infect Dis. 2023 Dec 1;36(6):615-622. doi: 10.1097/QCO.0000000000000984. Epub 2023 Oct 16.

Abstract

Purpose of review: Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB.

Recent findings: Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii . Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti- Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide β-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound.

Summary: Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Cefepime / pharmacology
  • Cefepime / therapeutic use
  • Cephalosporins / therapeutic use
  • Gram-Negative Bacteria
  • Gram-Negative Bacterial Infections* / drug therapy
  • Gram-Negative Bacterial Infections* / microbiology
  • Humans
  • Microbial Sensitivity Tests

Substances

  • Cefepime
  • Anti-Bacterial Agents
  • Cephalosporins