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Daptomycin Resistance Occurs Predominantly in vanA-Type Vancomycin-Resistant Enterococcus faecium in Australasia and

Lucy Li1, Charlie Higgs1, Adrianna M Turner1

  • 1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.

Frontiers in Microbiology
|November 8, 2021
PubMed

Insights

Daptomycin-resistant vancomycin-resistant Enterococcus faecium (VREfm) is a growing concern. This study identified genetic markers for resistance and demonstrated reduced daptomycin treatment efficacy in a mouse model.

Area of Science:

  • Infectious Diseases
  • Antimicrobial Resistance
  • Genomics

Background:

  • Healthcare-associated infections caused by vancomycin-resistant Enterococcus faecium (VREfm) pose significant clinical challenges.
  • Daptomycin is a last-resort antibiotic for multidrug-resistant VREfm, making daptomycin resistance a serious clinical concern.

Purpose of the Study:

  • To investigate the prevalence, genetic basis, and clinical impact of daptomycin resistance in VREfm isolates.
  • To identify genetic signatures associated with daptomycin resistance in VREfm.

Main Methods:

  • Phenotypic daptomycin susceptibility testing on 324 E. faecium isolates.
  • Whole genome sequencing to identify genetic mutations and resistance mechanisms.
  • Evaluation of daptomycin treatment efficacy in a mouse model of VREfm bacteremia.

Main Results:

  • Approximately 15% of study isolates exhibited daptomycin resistance.
  • A strong association was found between vanA-VREfm and daptomycin resistance (95% of resistant isolates harbored vanA).
  • Novel mutations in liaR, liaS, rpoB, rpoC, and dltC genes were identified in daptomycin-resistant isolates, with 70% carrying mutations in liaR, rpoB, rpoC, or dltC.
  • Daptomycin-resistant VREfm demonstrated reduced treatment efficacy in a mouse model.

Conclusions:

  • The study identified key genetic determinants of daptomycin resistance in VREfm, including mutations in liaR, rpoB, rpoC, and dltC.
  • Daptomycin resistance in VREfm impacts treatment efficacy, highlighting the need for enhanced surveillance and alternative therapeutic strategies.
Keywords:
Enterococcus faeciumbacteraemiadaptomycin-resistancesingle nucleotide polymorphisms (SNPs)vanA

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