Resistance to linezolid is mediated by the cfr gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus

Clin Infect Dis. 2010 Mar 15;50(6):821-5. doi: 10.1086/650574.


Background: From April through June 2008, we identified 12 patients in the intensive care unit and 3 patients on other wards infected with methicillin-resistant Staphylococcus aureus that was also resistant to linezolid. We investigated the mechanism of resistance--point mutations in domain V of 23S ribosomal RNA (rRNA) or presence of the cfr gene--involved in the outbreak.

Methods: Strains for the study were obtained in the intensive care unit and other wards. Minimal inhibitory concentrations were determined using automated methods, the E-test, or dilution in Mueller-Hinton agar in accordance with Clinical and Laboratory Standards Institute guidelines. Strains were genotyped using pulsed-field gel electrophoresis and were sequenced to determine the presence of point mutations in 23S rRNA. The presence of the cfr gene was determined by specific polymerase chain reaction.

Results: The minimal inhibitory concentrations of linezolid ranged from 16 mg/L to 32 mg/L, and all the strains were susceptible to tigecycline, vancomycin, and daptomycin. Typing of strains sequentially isolated by pulsed-field gel electrophoresis showed that each patient carried only 1 clonal type of linezolid-resistant, methicillin-resistant S. aureus as detected by sequential isolations. The presence of the cfr gene was confirmed in all the isolates. Furthermore, sequencing of domain V of 23S rRNA showed that the most common mechanism of linezolid resistance reported to date, mutation G2576T, was not detected in any of the strains analyzed.

Conclusions: We report the presence of the cfr gene underlying the resistance mechanism involved in a clinical outbreak of linezolid-resistant S. aureus.

MeSH terms

  • Acetamides / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bacterial Typing Techniques
  • DNA Fingerprinting
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Disease Outbreaks*
  • Drug Resistance, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Genotype
  • Humans
  • Linezolid
  • Methicillin-Resistant Staphylococcus aureus / classification
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Microbial Sensitivity Tests
  • Oxazolidinones / pharmacology*
  • Polymerase Chain Reaction
  • RNA, Ribosomal, 23S / genetics
  • Sequence Analysis, DNA
  • Staphylococcal Infections / epidemiology
  • Staphylococcal Infections / microbiology*


  • Acetamides
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • CFR protein, Staphylococcus aureus
  • DNA, Bacterial
  • DNA, Ribosomal
  • Oxazolidinones
  • RNA, Ribosomal, 23S
  • Linezolid