title: Risk factors for thrombocytopenia in adult chinese patients receiving linezolid therapy.
abstract: BACKGROUND
  Linezolid (LZD), an oxazolidinone antibiotic agent, has excellent activity and bioavailability against most methicillin-sensitive and methicillin-resistant gram-positive bacteria. Although LZD is generally well tolerated, several studies have found adverse hematologic effects, of which thrombocytopenia is of most concern.
  
  
  OBJECTIVE
  To investigate the risk factors for thrombocytopenia in patients who received oral or parenteral LZD therapy between February 1 and November 30, 2010.
  
  
  METHODS
  Data were extracted retrospectively from the electronic medical records in our hospital information system. Thrombocytopenia was defined as either a final platelet count of <100 × 10(9)/L (criterion 1) or a 25% reduction from the baseline platelet count (criterion 2). Risk factors were determined using logistic regression analysis, and clinical features were predicted using receiver operating characteristic curves.
  
  
  RESULTS
  The study included 254 patients, with mean (SD) age of 59 (17.66) years. The duration of LZD therapy was 9.43 (5.63) days. Thrombocytopenia developed in 69 patients (27.2%), as defined by criterion 1, and in 127 patients (50%), as defined by criterion 2. At univariate analysis, age, weight, creatinine clearance, serum albumin concentration, baseline platelet count, daily dosage, and concomitant use of caspofungin, levofloxacin, and meropenem were significant risk factors for thrombocytopenia. At multivariate analysis and using ROC curves, daily dose ≥18.75 mg/kg, baseline platelet count ≤181 × 10(9)/L, duration of LZD therapy ≥10 days, and concomitant use of caspofungin and levofloxacin were independent risk factors for thrombocytopenia as defined by criterion 1, whereas creatinine clearance ≤88.39 mL/min/1.73 m(2), serum albumin concentration ≤33.5 g/L, daily dose ≥18.46 mg/kg, and caspofungin were independent risk factors for thrombocytopenia as defined by criterion 2.
  
  
  CONCLUSIONS
  The incidence of LZD-related thrombocytopenia in the Chinese population is much higher than that suggested by the drug instructions. Low pretreatment platelet count, low body weight, low serum albumin concentration, long-term drug administration, advanced age, renal insufficiency, and concomitant use of caspofungin, levofloxacin, and meropenem have been identified as risk factors. Although predictors have been proposed for use in clinical practice to screen for patients at high risk who require intensified monitoring, further research on the dosage-based pharmacokinetics and pharmacodynamics of LZD are urgently needed.
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Guo
authors.affiliation: Department of Medical Statistics, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiutang
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
keywords: baseline platelet count; daily dosage; linezolid; risk factor; serum albumin; thrombocytopenia