Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control study in Italy

Int J Antimicrob Agents. 2015 Mar;45(3):255-61. doi: 10.1016/j.ijantimicag.2014.12.008. Epub 2014 Dec 30.

Abstract

The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case-case-control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp. group were compared with control patients to determine the clinical features and factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp. strains underwent molecular typing. Compared with the LIN-S group, central venous catheters were the main source of infection in the LIN-R group. The LIN-R and LIN-S groups showed a similar incidence of severe sepsis or septic shock, and both showed a higher incidence of these compared with the control group. Overall, patients in the LIN-R group had a higher 30-day mortality rate. Multivariate analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at least two antibiotics and hospitalisation in the previous 90 days as independent risk factors associated with isolation of a LIN-R strain. The G2576T mutation in domain V of 23S rRNA was the principal mechanism of resistance; only one strain of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together with L4 insertion (71GGR72) and L3 substitution (H146Q). LIN-R strains are associated with severe impairment of clinical conditions and unfavourable patient outcomes. Reinforcement of infection control measures may have an important role in preventing these infections.

Keywords: Bacteraemia; Central venous catheter; Linezolid; PFGE analysis; Staphylococcal infection.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Bacteremia / epidemiology
  • Bacteremia / microbiology*
  • Case-Control Studies
  • Catheter-Related Infections / epidemiology
  • Catheter-Related Infections / microbiology*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Drug Resistance, Bacterial*
  • Female
  • Humans
  • Italy / epidemiology
  • Linezolid
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Molecular Typing
  • Oxazolidinones / pharmacology*
  • Point Mutation
  • RNA, Ribosomal, 23S / genetics
  • Retrospective Studies
  • Risk Factors
  • Sequence Analysis, DNA
  • Staphylococcal Infections / epidemiology
  • Staphylococcal Infections / microbiology*
  • Staphylococcus / classification
  • Staphylococcus / drug effects*
  • Staphylococcus / genetics
  • Staphylococcus / isolation & purification
  • Survival Analysis
  • Young Adult

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • DNA, Bacterial
  • DNA, Ribosomal
  • Oxazolidinones
  • RNA, Ribosomal, 23S
  • Linezolid