Class A carbapenemases

Jan Walther-Rasmussen1, Niels Høiby

  • 1Department of Clinical Microbiology, 9301, Rigshospitalet, National University Hospital, Copenhagen, Denmark. jawalras@mail.tele.dk

Insights

Carbapenem resistance in Enterobacteriaceae is rising due to prevalent class A beta-lactamases. These enzymes, like KPC and GES, inactivate carbapenems, limiting treatment options for serious infections.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Carbapenems (imipenem, meropenem) are crucial for treating infections caused by extended-spectrum beta-lactamase (ESBL)-producing enterobacteria.
  • Emergence of carbapenem-inactivating enzymes threatens the efficacy of these last-resort antibiotics.
  • Carbapenem resistance in Enterobacteriaceae, though rare, is increasing due to prevalent class A beta-lactamases.

Purpose of the Study:

  • To review the classification and prevalence of class A carbapenemases in Enterobacteriaceae.
  • To understand the genetic basis and location of carbapenemase genes.
  • To discuss the enzymatic activity and inhibition of these resistance enzymes.

Main Methods:

  • Phylogenetic analysis to classify class A carbapenemases.
  • Review of genetic mechanisms (plasmid-borne, chromosomal, integrons, transposable elements).
  • Enzymatic activity profiling and classification using the Bush-Jacoby-Medeiros system.

Main Results:

  • Class A carbapenemases are phylogenetically grouped into six types (GES, KPC, SME, IMI/NMC-A, SHV-38, SFC-1).
  • Genes encoding these enzymes are found on plasmids or chromosomes, often associated with mobile genetic elements like integrons and transposons.
  • These enzymes hydrolyze various beta-lactams, including carbapenems, and are classified into four phenotypic groups (2br, 2be, 2e, 2f).

Conclusions:

  • Class A carbapenemases are a growing threat to carbapenem efficacy in Enterobacteriaceae.
  • Understanding their genetic and enzymatic diversity is crucial for surveillance and treatment strategies.
  • These enzymes remain susceptible to inhibition by clavulanate and tazobactam, similar to other class A beta-lactamases.

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