New treatment options for multiresistant gram negatives

Curr Opin Infect Dis. 2020 Apr;33(2):214-223. doi: 10.1097/QCO.0000000000000627.

Abstract

Purpose of review: Multidrug-resistant (MDR) Gram-negative bacteria infections are listed among the top public health threats of the current era. As a result, there has been an increase in efforts to develop new therapeutic agents against MDR Gram-negatives. The purpose of this review is to summarize the clinical and preclinical findings associated with recently approved drugs and the drugs in clinical development against ESBL and carbapenemase-producing Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii infections.

Recent findings: There are a number of ESBL active agents in late stage clinical development that can help spare carbapenems. Likewise, recently approved β-lactam/β-lactamase inhibitor combinations allow a change in the treatment of KPC and OXA-48 producers and carbapenem-resistant P. aeruginosa from colistin to new, safer agents. Treatment of Meta-beta-lactamase (MBL) producers remains an unmet need - apart from cefiderocol, most agents with MBL activity are still in clinical development. Among the few agents with carbapenem-resistant A. baumannii activity, durlobactam/sulbactam in phase III clinical trials provides hope.

Summary: Armamentarium against MDR Gram-negatives has expanded with the dominance of agents active against ESBL and KPC producers. There is a need to prioritize MBL producers and carbapenem-resistant A. baumannii, as well as the need for clinical trials to test the new agents against serious infections.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Resistance, Multiple, Bacterial*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology*
  • Humans

Substances

  • Anti-Bacterial Agents