Polymeric Anti-Antibiotic Microparticles to Prevent Antibiotic Resistance Evolution

Vancomycin (VAN) and daptomycin (DAP) are among the last-resort antibiotics for treating multidrug-resistant Gram-positive bacterial infections. They are administered intravenously (IV); however, ≈5 - 10% of the total IV dose is released in the gastrointestinal (GI) tract via biliary excretion, driving resistance emergence in commensal Enterococcus faecium (E. faecium) populations. Here, it is reported that sevelamer (SEV), a Food and Drug Administration (FDA)-approved anion-exchange polymeric microparticle, captures anionic DAP within minutes and cationic VAN within hours, inactivating the antibacterial efficacy of DAP and VAN. In vitro SEV-mediated VAN or DAP transient removal is successfully described by a diffusion-adsorption mechanism. In vivo oral SEV treatment effectively prevented VAN resistance enrichment following the VAN treatment of E. faecium-colonized mice. This work shows, for the first time, that the adjuvant SEV therapy prevents antimicrobial resistance in nosocomial pathogens by eliminating off-target antibiotics. It is envisioned that SEV may protect DAP and VAN from resistance development, potentially addressing the long-lasting antimicrobial resistance.