Spread of clonal linezolid-resistant Staphylococcus epidermidis in an intensive care unit associated with linezolid exposure

Eur J Clin Microbiol Infect Dis. 2020 Jul;39(7):1271-1277. doi: 10.1007/s10096-020-03842-7. Epub 2020 Feb 14.

Abstract

The aim of the study was to determine factors associated with spread of linezolid (LNZ)-resistant Staphylococcus epidermidis isolates in a surgical intensive care unit (ICU). A case-control study was conducted in one French adult surgical ICU. From January 2012 to December 2016, patients with at least a single positive LNZ-resistant S. epidermidis blood culture were matched to control with LNZ-susceptible S. epidermidis blood culture in a 1:4 manner. Cases were compared to controls regarding baseline clinical characteristics and LNZ exposure before positive blood culture. Bacterial isolates were genotyped by using pulsed-field gel electrophoresis (PFGE) and MLST. We identified 13 LNZ-resistant S. epidermidis isolates, 1 in 2012, 3 in 2014, 6 in 2015, and 3 in 2016. LNZ use increased steadily from 8 DDDs/100 patient days in 2010 to 19 in 2013 and further decrease by more of 50% in 2015 and 2016. The only independent risk factors associated to LNZ-resistant S. epidermidis isolation were length of stay in ICU before infection (OR 1.45; 95% CI 1.07-1.98), prior exposure to LNZ (OR 109; 95% CI 3.9-3034), and Charlson comorbidities score (OR 3.19; 95% CI 1.11-9.14). PFGE typing showed that all LNZ-resistant isolates were clonal belonging to ST2 and that LNZ-susceptible isolates were highly diverse. We report herein that previous exposure to LNZ substantially increased the risk of occurrence of LNZ resistance in S. epidermidis even in the case of clonal spread of LNZ-resistant isolates. These findings highlight the need for reducing the use of LNZ to preserve its efficacy in the future.

Keywords: Antibiotic resistance; Genotyping; Linezolid; Risk factors; Staphylococcus epidermidis.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Case-Control Studies
  • Cross Infection / microbiology
  • Cross Infection / transmission
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial* / genetics
  • Female
  • Genotype
  • Humans
  • Intensive Care Units
  • Linezolid / therapeutic use*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Molecular Epidemiology
  • Risk Factors
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / epidemiology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / transmission
  • Staphylococcus epidermidis / drug effects*
  • Staphylococcus epidermidis / genetics*
  • Staphylococcus epidermidis / isolation & purification

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Linezolid