title: Clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill intensive care unit patients.
abstract: Severely ill Intensive Care Unit (ICU) patients have an increased risk of developing multiresistant Gram-positive infections, largely due to the inappropriate use of antimicrobials. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid, an antibiotic against Gram-positive infections, was characterised in eight critically ill patients admitted to the ICU. Remarkable variation amongst patients in the PK parameters of linezolid was observed, including a 5-7-fold difference in peak serum concentration (C(max)) (mean±standard deviation 15.70±6.58 mg/L) and 12-h area under the serum concentration-time curve (AUC(0-12)) (96.73±56.45 mg h/L), although the minimum inhibitory concentration (MIC) was similar amongst patients. In particular, variation amongst patients was found in the ratio of AUC(0-24)/MIC (range 31.66-216.82, mean 96.73) and the percentage of time that the serum concentration exceeded the MIC (T>MIC) (range 53.4-100%), two parameters used to predict linezolid efficacy. These variations highlight the importance of individual monitoring of linezolid PK/PD properties in critically ill patients. Furthermore, it was observed that regardless of AUC(0-24)/MIC and T>MIC values, the clinical and microbiological responses of patients were primarily affected by the individual's pathophysiological condition. In summary, these findings point to highly variable PK/PD properties of linezolid in severely ill patients, providing the rationale for targeting linezolid dosage to each individual patient's specific properties. An optimal dosage regimen based on individual PK/PD properties and pathophysiological conditions will help reduce the occurrence of resistance in Gram-positive bacteria.
authors: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Haiyan
authors: H
authors: Dong
authors: Xue
authors: X
authors: Wang
authors: Yalin
authors: Y
authors: Dong
authors: Jin'e
authors: J
authors: Lei
authors: Hao
authors: H
authors: Li
authors: Haisheng
authors: H
authors: You
authors: Maoyi
authors: M
authors: Wang
authors: Jianfeng
authors: J
authors: Xing
authors: Jinyao
authors: J
authors: Sun
authors: Huifang
authors: H
authors: Zhu
mesh_terms: D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007362:Intensive Care Units; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid