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They are administered intravenously (IV); however, \u22485 \u2013 10% of the total IV dose is released in the gastrointestinal (GI) tract via biliary excretion, driving resistance emergence in commensal <jats:italic>Enterococcus faecium<\/jats:italic> (<jats:italic>E. faecium<\/jats:italic>) populations. Here, it is reported that sevelamer (SEV), a Food and Drug Administration (FDA)\u2010approved anion\u2010exchange polymeric microparticle, captures anionic DAP within minutes and cationic VAN within hours, inactivating the antibacterial efficacy of DAP and VAN. In vitro SEV\u2010mediated VAN or DAP transient removal is successfully described by a diffusion\u2010adsorption mechanism. In vivo oral SEV treatment effectively prevented VAN resistance enrichment following the VAN treatment of <jats:italic>E. faecium<\/jats:italic>\u2010colonized mice. This work shows, for the first time, that the adjuvant SEV therapy prevents antimicrobial resistance in nosocomial pathogens by eliminating off\u2010target antibiotics. It is envisioned that SEV may protect DAP and VAN from resistance development, potentially addressing the long\u2010lasting antimicrobial resistance.<\/jats:p>","DOI":"10.1002\/smll.202407549","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T03:31:57Z","timestamp":1737343917000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Polymeric Anti\u2010Antibiotic Microparticles to Prevent Antibiotic Resistance Evolution"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-3963","authenticated-orcid":false,"given":"Roya","family":"Koshani","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering The Pennsylvania State University  University Park PA 16802 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang\u2010Lin","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Chemical 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