Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit

JAMA. 2010 Jun 9;303(22):2260-4. doi: 10.1001/jama.2010.757.


Context: Linezolid resistance is extremely uncommon in Staphylococcus aureus.

Objective: To report an outbreak with linezolid and methicillin-resistant S. aureus (LRSA) in an intensive care department and the effective control measures taken.

Design, setting, and patients: Outbreak study of consecutive critically ill patients colonized and/or infected with LRSA at an intensive care department of a 1000-bed tertiary care university teaching hospital in Madrid, Spain. Patients were placed under strict contact isolation. Daily updates of outbreak data and recommendations for the use of linezolid were issued. Extensive environmental sampling and screening of the hands of health care workers were performed.

Main outcome measures: Linezolid use and clinical and epidemiological characteristics and outcomes using minimal inhibitory concentrations, pulsed-field gel electrophoresis, and polymerase chain reaction of LRSA isolates.

Results: Between April 13 and June 26, 2008, 12 patients with LRSA were identified. In 6 patients, LRSA caused ventilator-associated pneumonia and in 3 patients it caused bacteremia. Isolates were susceptible to trimethoprim-sulfamethoxazole, glycopeptides, tigecycline, and daptomycin. Genotyping identified 1 predominant clone and 3 other types. Cfr-mediated linezolid resistance was demonstrated in all isolates. Potential hospital staff carriers and environmental samples were negative except for one. Six patients died, 5 of them in the intensive care unit, with 1 death attributed to LRSA infection. Linezolid use decreased from 202 defined daily doses in April 2008 to 25 defined daily doses in July 2008. Between July 2008 and April 2010, no new cases have been identified in the weekly surveillance cultures or diagnostic samples.

Conclusions: The first clinical outbreak, to our knowledge, with LRSA mediated by the cfr gene developed at our center, was associated with nosocomial transmission and extensive usage of linezolid. Reduction of linezolid use and infection-control measures were associated with the termination of the outbreak.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology*
  • Acetamides / therapeutic use
  • Adult
  • Aged
  • Anti-Infective Agents / pharmacology*
  • Anti-Infective Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Disease Outbreaks*
  • Drug Resistance, Bacterial*
  • Female
  • Genotype
  • Hospitals, Teaching
  • Humans
  • Intensive Care Units
  • Linezolid
  • Male
  • Middle Aged
  • Oxazolidinones / pharmacology*
  • Oxazolidinones / therapeutic use
  • Spain / epidemiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / epidemiology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / isolation & purification


  • Acetamides
  • Anti-Infective Agents
  • Bacterial Proteins
  • CFR protein, Staphylococcus aureus
  • Oxazolidinones
  • Linezolid