title: The efficacy and safety of linezolid as treatment for Staphylococcus aureus infections in compassionate use patients who are intolerant of, or who have failed to respond to, vancomycin.
abstract: OBJECTIVE
  The incidence of infections caused by methicillin-resistant Staphylococcus aureus continues to increase annually. Unfortunately, only a few therapeutic agents are available for the treatment of patients with such infections and all of the existing drugs have limitations. A pressing need exists, therefore, to identify new antibiotics for use in this clinical setting. The efficacy and safety of linezolid were studied in a compassionate use treatment programme and the results of treating a subset of patients with S. aureus infections are presented here.
  
  
  METHODS
  Patients received linezolid in a dosage of 600 mg intravenously (iv) and/or orally twice daily. Clinical and bacteriological responses were assessed after a minimum of 7 days and following completion of therapy.
  
  
  RESULTS
  Seven hundred and ninety-six patients who suffered 828 episodes of infection were enrolled in the linezolid compassionate use protocol. Of these, 183 patients received linezolid for 191 infections caused by S. aureus; in 151 cases, patients were intolerant of vancomycin, had a mixed S. aureus/vancomycin-resistant enterococcal infection or had no iv access, and, in 40 cases, patients had failed to respond to treatment with vancomycin. The median age of the patients was 57 years (range 14-93 years) and 53.9% were female. The predominant sites of infection were as follows: bone or joint (27.2%); skin and skin structure (25.1%); bloodstream (20.9%); and lower respiratory tract (12.6%). The clinical success rates in the clinically evaluable and all-treated populations were 83.9% and 62.3%, respectively, whereas the bacteriological eradication rates were 76.9% and 70.2% in the bacteriologically evaluable and all-treated populations, respectively. Linezolid was well tolerated. In 76 (39.8%) of the 191 episodes of infection, patients experienced one or more adverse events or exhibited one or more abnormal laboratory results; in 35 (18.3%) of the 191 cases it was necessary to discontinue treatment. Gastrointestinal tract-related symptoms (nausea, vomiting and diarrhoea) were the most common possibly or probably related adverse events and the most common reasons for drug discontinuation.
  
  
  CONCLUSIONS
  Linezolid was effective and well tolerated in patients with S. aureus infections who were enrolled in this compassionate use protocol.
authors.affiliation: CPL Associates, LLC, 3980 Sheridan Drive, Suite 501, Amherst, NY 14226, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Moise
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Mary C
authors.initials: MC
authors.lastname: Birmingham
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Schentag
mesh_terms: D000081:Acetamides / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use*; D020713:Vancomycin Resistance / Q000502:physiology*
chemical_list: D000081:Acetamides; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid