{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:01:50Z","timestamp":1784739710851,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The study aimed to evaluate and compare the pharmacokinetic\/pharmacodynamic (PK\/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) <jats:italic>vs.<\/jats:italic> intermittent infusion (II) <jats:italic>vs.<\/jats:italic> continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats: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\u00a0g 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<jats:sub>0\u201324<\/jats:sub>) to MIC (i.e., AUC<jats:sub>0\u201324<\/jats: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<jats:sub>0\u201324<\/jats:sub>\/MIC ratio of &amp;gt;400, 400\u2013600, and &amp;gt;600 was estimated. A regimen with a PTA of \u226590% at an AUC<jats:sub>0\u201324<\/jats:sub>\/MIC ratio of 400\u2013600, which is supposed to maximize both efficacy and safety, was considered optimal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the same daily dose, almost only the OTSI regimens showed a PTA of \u226590% at an AUC<jats:sub>0\u201324<\/jats:sub>\/MIC ratio of 400\u2013600, and this profile seems evident especially in patients with creatinine clearance (<jats:italic>CL<\/jats:italic><jats:sub>cr<\/jats:sub>) of \u226560 ml\/min and for isolates with an MIC of \u22642 mg\/L. However, for patients with <jats:italic>CL<\/jats:italic><jats:sub>cr<\/jats:sub> of &amp;lt;60 ml\/min and for isolates with an MIC of \u22654 mg\/L, the II regimens often displayed a higher or even \u226590% PTA at an AUC<jats:sub>0\u201324<\/jats:sub>\/MIC ratio of &amp;gt;400 and of &amp;gt;600. The CI regimens frequently afforded a reduced PTA at an AUC<jats:sub>0\u201324<\/jats:sub>\/MIC ratio of &amp;gt;400 and of &amp;gt;600, regardless of <jats:italic>CL<\/jats:italic><jats:sub>cr<\/jats:sub> and MIC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats: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 <jats:italic>CL<\/jats:italic><jats:sub>cr<\/jats:sub> of \u226560 ml\/min and for isolates with an MIC of \u22642 mg\/L.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2022.874401","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T06:06:47Z","timestamp":1657174007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"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"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiangqing","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e254","DOI":"10.1097\/BCR.0b013e31825042fa","article-title":"Serum Vancomycin Levels Resulting From Continuous or Intermittent Infusion in Critically Ill Burn Patients With or Without Continuous Renal Replacement Therapy","volume":"33","author":"Akers","year":"2012","journal-title":"J. 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