Ion Exchange Biomaterials to Capture Daptomycin and Prevent Resistance Evolution in Off-Target Bacterial Populations

Area of Science:

• Biomaterials Science
• Pharmacology
• Microbiology

Background:

• Daptomycin (DAP) is a critical antibiotic for multidrug-resistant Gram-positive infections.
• DAP's biliary excretion leads to gastrointestinal (GI) presence, promoting resistance in off-target bacteria like Enterococcus faecium.
• Previous studies showed cholestyramine prevents DAP resistance enrichment in mice.

Purpose of the Study:

• To investigate the interfacial interactions between ion exchange biomaterials (IXB) and daptomycin (DAP).
• To elucidate the molecular and colloidal mechanisms of DAP removal from the GI tract by IXB.
• To explore optimizing cholestyramine therapy for preventing DAP resistance.

Main Methods:

• Measured IXB-mediated DAP capture in controlled pH/electrolyte solutions.
• Assessed DAP removal in simulated intestinal fluid (SIF).
• Analyzed adsorption dynamics using unsteady-state diffusion-adsorption mass balance.

Main Results:

• IXB electrostatically adsorbs anionic DAP via a time-dependent, diffusion-controlled process.
• Adsorption dynamics are accurately described by unsteady-state diffusion-adsorption mass balance.
• Maximum DAP removal capacity exceeds stoichiometric ratios due to DAP self-assembly.

Conclusions:

• The study reveals the electrostatic adsorption mechanism of DAP by IXB.
• Findings support optimizing cholestyramine as an adjuvant therapy to prevent DAP resistance.
• This research may guide the design of novel biomaterials for targeted antibiotic removal.