title: Pharmacokinetic/pharmacodynamic evaluation of linezolid for the treatment of staphylococcal infections in critically ill patients.
abstract: Several studies have demonstrated that the ideal therapeutic effect of linezolid cannot be achieved in critically ill patients with the recommended standard dosing regimen of 600 mg every 12 h (q12h). Moreover, the optimal strategy for successful treatment is still lacking. This study analysed factors influencing the efficacy of linezolid treatment and determined the target for successful treatment by logistic regression in 27 critically ill patients with staphylococcal infection who received linezolid 600 mg q12h. The results showed that only the 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) ratio was significantly associated with staphylococcal eradication. Reaching 80% bacterial eradication required an AUC24/MIC of 120.5, defining the therapeutic target. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>99.9%) for the standard dosing regimen at MIC ≤ 1 mg/L, the PTA was almost 0 at MIC = 2 mg/L, thus the dosing regimen required adjustment. In addition, if the dosing regimen was adjusted to 600 mg every 8 h or 600 mg every 6 h, the major staphylococci (except for MRSA and MSSA) exhibited a cumulative fraction of response of >80%, showing a higher treatment success. These findings indicate that a strategy of high linezolid dosage may be needed to increase the probability of successful treatment at MIC > 1 mg/L. The role of therapeutic drug monitoring should be encouraged for optimising linezolid exposure in critically ill patients.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of 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 Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Central Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Sun
authors.affiliation: Central Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of 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: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016638:Critical Illness; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D000069349:Linezolid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013210:Staphylococcus / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid
keywords: Critically ill patients; Linezolid; Staphylococcal infection