title: Subtherapeutic linezolid concentrations in a patient with morbid obesity and methicillin-resistant Staphylococcus aureus pneumonia: case report and review of the literature.
abstract: OBJECTIVE
  To report a case of subtherapeutic linezolid concentrations in a patient with morbid obesity.
  
  
  METHODS
  A 34-year-old male with morbid obesity (265 kg, body mass index 82 kg/m(2)) was admitted for severe sepsis due to respiratory failure requiring emergent intubation and treatment of community-acquired pneumonia. Admission tracheal aspirate culture revealed methicillin-resistant Staphylococcus aureus (MRSA) for which vancomycin was prescribed. Therapy subsequently was changed to linezolid, because the patient's clinical status worsened, with significant hypoxia (partial pressure of arterial oxygen/fraction of inspired oxygen [PaO2/FiO2] ratio 145), increasing leukocytosis (white blood cell count from 10,800/μL on admission to 15,400/μL on hospital day 6), and persistent fever (38.3 °C). After 48 hours of linezolid monotherapy, the patient remained febrile with continued leukocytosis, worsening hypoxemia, and a persistently positive MRSA culture from a repeat endotracheal aspirate. Linezolid serum concentrations were obtained and vancomycin was reinstituted, after which the patient began to improve (afebrile, improving PaO2/FiO2 ratio, decreasing leukocytosis). On hospital day 12, the patient removed his endotracheal tube, and a sputum sample was obtained for culture. The patient's clinical status subsequently declined, prompting addition of cefepime to his antibiotic regimen. This sputum culture revealed not only MRSA, but also quinolone-resistant Escherichia coli. After completing treatment for both organisms the patient was discharged home.
  
  
  CONCLUSIONS
  Limited data on linezolid dosing in the morbidly obese population show lower serum drug concentrations than those in nonobese patients, but no clinical failure has been reported when treating MRSA skin and soft tissue infections or MRSA tracheitis. In our patient, low steady-state linezolid serum concentrations (peak 4.13 μg/mL [reference 15-27] and trough 1.27 μg/mL [reference 2-9]) were thought to contribute to his poor clinical response.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of subtherapeutic linezolid concentrations correlated with decreased clinical effectiveness when during treatment of MRSA pneumonia in a patient with morbid obesity.
authors.affiliation: Critical Care, Department of Pharmacy Services, Virginia Commonwealth University Health System, Richmond, VA, USA. kmuzevich@mcvh-vcu.edu
authors.forename: Katie M
authors.initials: KM
authors.lastname: Muzevich
authors.forename: Kimberly B
authors.initials: KB
authors.lastname: Lee
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000627:therapeutic use*; D000328:Adult; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D009767:Obesity, Morbid / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D023303:Oxazolidinones / Q000097:blood* / Q000627:therapeutic use*; D011023:Pneumonia, Staphylococcal / Q000097:blood* / Q000188:drug therapy
chemical_list: D000081:Acetamides; D023303:Oxazolidinones; D000069349:Linezolid