title: Developments in the pharmacokinetic/pharmacodynamic index of linezolid: a step toward dose optimization using Monte Carlo simulation in critically ill patients.
abstract: OBJECTIVE
  This study evaluated the efficacy of the pharmacokinetic/pharmacodynamic (PK/PD) index for increasing the success rate of linezolid treatment based on Monte Carlo simulation, and compared differences between the calculated PK/PD breakpoints and those defined by committee for critically ill patients with linezolid treatment.
  
  
  METHODS
  A Monte Carlo simulation involving 10000 subjects was used to analyze the pharmacokinetic parameters and microbiological data of linezolid for an effectiveness evaluation at the corresponding AUC24/MIC values (area under the serum concentration-time curve over 24h/minimum inhibitory concentration).
  
  
  RESULTS
  As the PK/PD index of linezolid increased from 80 to 120, the corresponding probability of target attainment (PTA) decreased from 99.91% to 18.97%, with a MIC of 2mg/l. Furthermore, the cumulative fraction of response (CFR) reached <90% for several pathogens at an AUC24/MIC of 100-120, revealing a relatively lower efficacy with recommended linezolid dosing.
  
  
  CONCLUSIONS
  These findings reveal that the target AUC24/MIC value of 80-120 requires further classification for more accurate assessment of the linezolid dose regimen. At a MIC of ≥2mg/l, the clinical outcome varies greatly for different AUC24/MIC values when applying the same dose of linezolid. In such cases, we suggest optimized adjustment of the linezolid dosage regimen.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Xie
authors.affiliation: Central Intensive Care Unit, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jinyue
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhaoyingren@sohu.com.
authors.forename: Yingren
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: dongyalin@mail.xjtu.edu.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D003198:Computer Simulation; D016638:Critical Illness; D054796:Drug Dosage Calculations; D024901:Drug Resistance, Multiple, Bacterial; D016983:Enterococcus / Q000187:drug effects / Q000502:physiology; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D009010:Monte Carlo Method; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000502:physiology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid
keywords: Critically ill patients; Dose optimization; Linezolid; Monte Carlo simulation; Pharmacokinetic/pharmacodynamic (PK/PD)