Developments in the pharmacokinetic/pharmacodynamic index of linezolid: a step toward dose optimization using Monte Carlo simulation in critically ill patients

SummaryObjectivesThis 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.MethodsA Monte Carlo simulation involving 10 000 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 24 h/minimum inhibitory concentration).ResultsAs 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 2 mg/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.ConclusionsThese 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 ≥2 mg/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.