{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T21:36:28Z","timestamp":1770500188564,"version":"3.49.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"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. Microbiol."],"abstract":"<jats:p>The increasing emergence of bacterial strains with high VAN MICs (BS<jats:sub><jats:italic>H<\/jats:italic><\/jats:sub><jats:sub>\u2013<\/jats:sub><jats:sub><jats:italic>V<\/jats:italic><\/jats:sub><jats:sub><jats:italic>AN\u2013<\/jats:italic><\/jats:sub><jats:sub><jats:italic>M<\/jats:italic><\/jats:sub>), such as <jats:italic>Enterococcus faecalis<\/jats:italic>, <jats:italic>Enterococcus faecium<\/jats:italic>, <jats:italic>Staphylococcus aureus<\/jats:italic>, <jats:italic>Staphylococcus epidermidis<\/jats:italic>, and <jats:italic>Streptococcus bovis<\/jats:italic>, results in growing concern that VAN is not effective against these isolates. Due to the limited data on VAN against BS<jats:sub><jats:italic>H\u2013VAN\u2013M<\/jats:italic><\/jats:sub> and the application limits of drugs currently considered to be effective for BS<jats:sub><jats:italic>H\u2013VAN\u2013M<\/jats:italic><\/jats:sub>, exploration of \u201cnew usages for old drugs\u201d is reasonable to improve and maximize the efficacy of existing antibiotics. This study aimed to construct a novel dosing strategy to mine the competence of VAN in the management of BS<jats:sub><jats:italic>H\u2013VAN\u2013M<\/jats:italic><\/jats:sub> infections. Herein, we optimized the traditional intermittent i.v. infusion (TIII) method to create an optimal two-step infusion (OTSI). With pharmacokinetic (PK)\/pharmacodynamic (PD) modeling at the targeted ratio of the daily area under the concentration-time curve (AUC<jats:sub>0<\/jats:sub><jats:sub>\u2013<\/jats:sub><jats:sub>24<\/jats:sub>) to the minimum inhibitory concentration (MIC) (AUC<jats:sub>0<\/jats:sub><jats:sub>\u2013<\/jats:sub><jats:sub>24<\/jats:sub>\/MIC) of 400, we used Monte Carlo simulations to evaluate the efficacy of 25 VAN regimens (including 15 OTSI regimens and 10 TIII regimens with daily doses of up to 6 g) to treat pneumonia, meningitis, sternal osteomyelitis, mastitis, pleuritis, bacteremia, and bacterial pericarditis resulting from isolates with MICs of \u226464 mg\/L and to the current <jats:italic>E. faecalis<\/jats:italic>, <jats:italic>E. faecium<\/jats:italic>, <jats:italic>S. aureus<\/jats:italic>, <jats:italic>S. epidermidis<\/jats:italic>, and <jats:italic>S. bovis<\/jats:italic> populations with a pooled MIC distribution. Our data indicated that 4 g\/day VAN, with an OTSI but not a TIII, for mastitis, pleuritis, bacteremia, and bacterial pericarditis due to isolates with MICs of \u22644 mg\/L or to the current <jats:italic>E. faecalis<\/jats:italic>, <jats:italic>S. aureus<\/jats:italic>, <jats:italic>S. epidermidis<\/jats:italic>, and <jats:italic>S. bovis<\/jats:italic> populations achieved the desired PK\/PD exposure at the AUC<jats:sub>0<\/jats:sub><jats:sub>\u2013<\/jats:sub><jats:sub>24<\/jats:sub>\/MIC target of 400. This study suggests the superiority and feasibility of OTSI relative to TIII for the competence mining of VAN against BS<jats:sub><jats:italic>H\u2013VAN\u2013M<\/jats:italic><\/jats:sub> from the perspective of PK\/PD and provides a new resource for understanding how PK\/PD modeling shapes the performance of VAN to meet the growing challenges of BS<jats:sub><jats:italic>H\u2013VAN\u2013M<\/jats:italic><\/jats:sub> infections.<\/jats:p>","DOI":"10.3389\/fmicb.2021.649757","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T06:21:41Z","timestamp":1619072501000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Competence Mining of Vancomycin (VAN) in the Management of Infections Due to Bacterial Strains With High VAN Minimum Inhibitory Concentrations (MICs): A Novel Dosing Strategy Based on Pharmacokinetic\/Pharmacodynamic Modeling"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiangqing","family":"Song","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meizi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1128\/aac.44.5.1356-1358.2000","article-title":"Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit.","volume":"44","author":"Alban\u00e8se","year":"2000","journal-title":"Antimicrob. 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