The emergence of antimicrobial resistance has become a significant public health burden worldwide. Daptomycin, a cyclic anionic lipopeptide antibiotic, is administered intravenously to treat infections with Gram-positive bacteria such as vancomycin-resistant Enterococcus faecium (VR E. faecium). However, approximately 5-10% of the antibiotic enters the intestines through biliary excretion, which may drive resistance evolution in E. faecium, colonizing the gut and leading to the transmission of antibiotic-resistant bacteria. We have recently found that the oral adjuvant ion exchange resins could remove daptomycin in the intestine of mice without altering plasma concentrations (eLife, 2020, 9:e58147). However, the underlying mechanisms for the antibiotic removal are still unclear. Here, we investigate the resin-mediated daptomycin removal from aqueous media with well-controlled pH and electrolyte environment to uncover the molecular and colloidal mechanisms by which daptomycin is removed from the GI tract. We have identified key resin-antibiotic interaction mechanisms and developed resins that increase the antibiotic removal efficacy.

Uncovering the mechanisms of daptomycin antibiotic removal using engineered ion exchange resins

ACS Spring 2022

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