AUTHOR=Song Xiangqing , Han Mi 

TITLE=Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.874401

DOI=10.3389/fcimb.2022.874401

ISSN=2235-2988

ABSTRACT=<sec><title>Objective</title><p>The study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) <italic>vs.</italic> intermittent infusion (II) <italic>vs.</italic> continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.</p></sec><sec><title>Methods</title><p>With PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated. Using the Monte Carlo simulations, the vancomycin population PK parameters derived from critical patients, the PD parameter for MRSA isolates [i.e., minimum inhibitory concentration (MIC)], and the dosing parameters of these regimens were integrated into a robust mdel of vancomycin PK/PD index, defined as a ratio of the daily area under the curve (AUC<sub>0–24</sub>) to MIC (i.e., AUC<sub>0–24</sub>/MIC), to estimate the probability of target attainment (PTA) of these regimens against MRSA isolates with an MIC of 0.5, 1, 2, 4, and 8 mg/L in patients with varying renal function. The PTA at an AUC<sub>0–24</sub>/MIC ratio of &gt;400, 400–600, and &gt;600 was estimated. A regimen with a PTA of ≥90% at an AUC<sub>0–24</sub>/MIC ratio of 400–600, which is supposed to maximize both efficacy and safety, was considered optimal.</p></sec><sec><title>Results</title><p>At the same daily dose, almost only the OTSI regimens showed a PTA of ≥90% at an AUC<sub>0–24</sub>/MIC ratio of 400–600, and this profile seems evident especially in patients with creatinine clearance (<italic>CL</italic><sub>cr</sub>) of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. However, for patients with <italic>CL</italic><sub>cr</sub> of &lt;60 ml/min and for isolates with an MIC of ≥4 mg/L, the II regimens often displayed a higher or even ≥90% PTA at an AUC<sub>0–24</sub>/MIC ratio of &gt;400 and of &gt;600. The CI regimens frequently afforded a reduced PTA at an AUC<sub>0–24</sub>/MIC ratio of &gt;400 and of &gt;600, regardless of <italic>CL</italic><sub>cr</sub> and MIC.</p></sec><sec><title>Conclusions</title><p>The data indicated that the OTSI regimens allowed preferred PK/PD exposure in terms of both efficacy and safety, and thus should be focused more on, especially in patients with <italic>CL</italic><sub>cr</sub> of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L.</p></sec>