Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions

Eur J Clin Microbiol Infect Dis. 2021 Oct;40(10):2053-2068. doi: 10.1007/s10096-021-04296-1. Epub 2021 Jun 24.

Abstract

Carbapenem-resistant Enterobacterales (CRE) are a growing threat to human health worldwide. CRE often carry multiple resistance genes that limit treatment options and require longer durations of therapy, are more costly to treat, and necessitate therapies with increased toxicities when compared with carbapenem-susceptible strains. Here, we provide an overview of the mechanisms of resistance in CRE, the epidemiology of CRE infections worldwide, and available treatment options for CRE. We review recentlyapproved agents for the treatment of CRE, including ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and novel aminoglycosides and tetracyclines. We also discuss recent advances in phage therapy and antibiotics that are currently in development targeted to CRE. The potential for the development of resistance to these therapies remains high, and enhanced antimicrobial stewardship is imperative both to reduce the spread of CRE worldwide and to ensure continued access to efficacious treatment options.

Keywords: Antimicrobial resistance; CRE; Carbapenem-resistant; Carbapenemase; Enterobacterales.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Azabicyclo Compounds / therapeutic use
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Carbapenem-Resistant Enterobacteriaceae / genetics
  • Carbapenem-Resistant Enterobacteriaceae / physiology
  • Carbapenems / pharmacology
  • Ceftazidime / therapeutic use
  • Drug Combinations
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Humans

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Carbapenems
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime