Resistance to cefepime and cefpirome due to a 4-amino-acid deletion in the chromosome-encoded AmpC beta-lactamase of a Serratia marcescens clinical isolate

Antimicrob Agents Chemother. 2004 Mar;48(3):716-20. doi: 10.1128/AAC.48.3.716-720.2004.

Abstract

A multiresistant Serratia marcescens strain, HD, isolated from a patient with a urinary tract infection, was resistant to amino-, carboxy-, and ureidopenicillins, ceftazidime, and cefepime and was susceptible to cefotaxime and ceftriaxone, according to the guidelines of the NCCLS. No synergy was found between expanded-spectrum cephalosporins and clavulanic acid, according to the double-disk synergy test. The bla(AmpC) gene of the strain was amplified by PCR and cloned into Escherichia coli DH10B, giving rise to high-level resistance to ceftazidime, cefepime, and cefpirome. Sequencing analysis revealed that the bla(AmpC) gene from S. marcescens HD had a 12-nucleotide deletion compared to the bla(AmpC) gene from reference strain S. marcescens S3, leading to a 4-amino-acid deletion located in the H-10 helix of the beta-lactamase. Kinetic analysis showed that this enzyme significantly hydrolyzed ceftazidime, cefepime, and cefpirome. This work underlined that resistance to the latest expanded-spectrum cephalosporins may be mediated by structurally modified AmpC-type beta-lactamases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Cefepime
  • Cefpirome
  • Cephalosporin Resistance / genetics
  • Cephalosporinase / genetics
  • Cephalosporinase / metabolism
  • Cephalosporins / pharmacology*
  • Chromosomes, Bacterial / genetics*
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / genetics
  • Hydrolysis
  • Kinetics
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation / physiology*
  • Plasmids / genetics
  • Sequence Deletion*
  • Serratia Infections / microbiology*
  • Serratia marcescens / drug effects
  • Serratia marcescens / enzymology*
  • Serratia marcescens / genetics
  • beta-Lactamases / genetics*

Substances

  • Bacterial Proteins
  • Cephalosporins
  • Cefepime
  • Cephalosporinase
  • AmpC beta-lactamases
  • beta-Lactamases