title: High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia.
abstract: OBJECTIVE
  Thrombocytopenia is sometimes observed during linezolid therapy. Here, we aimed to investigate the factors affecting linezolid-induced thrombocytopenia.
  
  
  METHODS
  A prospective observational study was performed between October 2009 and February 2011; 30 patients were included. Plasma linezolid trough concentrations were measured on days 3, 7 and 14 after initial drug administration. Platelet counts and haemoglobin levels were also monitored.
  
  
  RESULTS
  Thrombocytopenia occurred in 17 patients (56.7%). Median linezolid trough concentrations on day 3 were significantly higher in patients with renal impairment (creatinine clearance <60 mL/min) than in patients without renal impairment (14.7 versus 4.8 mg/L; P < 0.0001). Median linezolid trough concentrations on day 3 in patients who developed thrombocytopenia were also significantly higher than those in patients who did not (13.4 versus 4.3 mg/L, P < 0.0001). Development of thrombocytopenia occurred significantly more frequently in patients with linezolid trough concentration >7.5 mg/L (OR, 90.0; P < 0.0001) and renal impairment (OR, 39.0; P = 0.0002). The Kaplan-Meier plot showed that the median time from the initiation of therapy to development of thrombocytopenia was 11 days.
  
  
  CONCLUSIONS
  Patients with renal impairment are more likely to have a high plasma linezolid concentration. In addition, a high plasma linezolid concentration and renal impairment significantly affected the development of linezolid-induced thrombocytopenia. Further studies are required to evaluate whether therapeutic drug monitoring-guided dosage adjustment of linezolid decreases the adverse effects while maintaining treatment efficacy in patients with renal dysfunction.
authors.affiliation: Department of Infection Control and Prevention, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nukui
authors.forename: Shuji
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Koh
authors.initials: K
authors.lastname: Okamoto
authors.forename: Takehito
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hisaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nahoko
authors.initials: N
authors.lastname: Yata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yotsuyanagi
authors.forename: Kyoji
authors.initials: K
authors.lastname: Moriya
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D007677:Kidney Function Tests; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid
keywords: adverse effects; anti-MRSA agents; haematological toxicity; renal dysfunction; therapeutic drug monitoring