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• An AUC 24 /MIC of 100 was required to achieve a bacterial51 eradication rate of 80% for sepsis patients treated with linezolid. • An 800 mg/12 h (safety probability 66.8%) dosing regimen was appropriate for sepsis patients with normal renal function or mild kidney damage. • There is a high thrombocytopenia probability with 600 mg/12 h for sepsis patients on CRRT, so dosing should be adjusted based on TDM. Significant alterations in the pharmacokinetic characteristics of linezolid are often seen in sepsis patients. The study aimed to identify a target pharmacokinetics/pharmacodynamics (PK/PD) index of the efficacy of linezolid treatment, and to estimate the optimum dosage regimen of linezolid in sepsis patients. The PK data were modeled using the one-compartment model, which determined the target PK/PD index for successful treatment by logistic regression. The probability of thrombocytopenia was identified by establishing a logistic model. Different dosing regimens were evaluated using Monte Carlo simulation. Reaching 80% bacterial eradication required an AUC 24 /MIC of 100, which defined the therapeutic target. The proposed regimen to attain a cumulative fraction of response ≥80% was 800 mg/12 h (safety probability 66.8%) for sepsis patients with normal renal function or mild kidney damage. By contrast, the target cumulative fraction of response was attained with a standard dosing regimen in sepsis patients on continuous renal replacement therapy [600 mg/12 h (safety probability 49.7%)]. This study identified different dosing strategies to achieve target linezolid PK/PD values according to whether sepsis patients were treated with continuous renal replacement therapy. Due to the high incidence of thrombocytopenia in sepsis patients on continuous renal replacement therapy, therapeutic drug monitoring should be encouraged for optimizing linezolid exposure in sepsis patients. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to investigate the pharmacokinetic profile and safety of voriconazole treatment in patients with Child–Pugh class B and C cirrhosis. Methods Liver cirrhosis patients who had received the recommended voriconazole maintenance dose (group A) or halved maintenance dose (group B), orally or intravenously, were included. Voriconazole-related adverse events (AEs) were defined according to the Common Terminology Criteria for Adverse Events. Results A total of 110 trough plasma concentrations of voriconazole ( C min ) were measured in 78 patients. There was a significant difference in voriconazole C min between group A and group B ( C min , 6.95 ± 3.42 mg/l vs. 4.02 ± 2.00 mg/l; p < 0.001). No significant difference in voriconazole C min between Child–Pugh class B and C cirrhosis patients was observed in either of the two groups. The international normalized ratio and co-medication with a CYP2C19 inhibitor had a significant effect on voriconazole C min in group B. The incidence of AEs in group A was 26.5% and in group B was 15.9%, and 87.5% of AEs developed within 7 days after starting voriconazole treatment. Conclusions These results suggest that the recommended dose and halved maintenance dose may be inappropriate in patients with Child–Pugh class B and C cirrhosis due to the high C min , and that voriconazole C min should be monitored earlier to avoid AEs. [ABSTRACT FROM AUTHOR]