Ion Exchange Biomaterials to Capture Daptomycin and Prevent Resistance Evolution in Off-Target Bacterial Populations.
ACS Appl Mater Interfaces
; 14(38): 42864-42875, 2022 Sep 28.
Article
in En
| MEDLINE
| ID: mdl-36103577
ABSTRACT
Daptomycin (DAP), a cyclic anionic lipopeptide antibiotic, is among the last resorts to treat multidrug-resistant Gram-positive bacterial infections, caused by vancomycin-resistant Enterococcus faecium or methicillin-resistant Staphylococcus aureus. DAP is administered intravenously, and via biliary excretion, â¼5-10% of the intravenous DAP dose arrives in the gastrointestinal (GI) tract where it drives resistance evolution in the off-target populations of E. faecium bacteria. Previously, we have shown in vivo that the oral administration of cholestyramine, an ion exchange biomaterial (IXB) sorbent, prevents DAP treatment from enriching DAP resistance in the populations of E. faecium shed from mice. Here, we investigate the biomaterial-DAP interfacial interactions to uncover the antibiotic removal mechanisms. The IXB-mediated DAP capture from aqueous media was measured in controlled pH/electrolyte solutions and in the simulated intestinal fluid (SIF) to uncover the molecular and colloidal mechanisms of DAP removal from the GI tract. Our findings show that the IXB electrostatically adsorbs the anionic antibiotic via a time-dependent diffusion-controlled process. Unsteady-state diffusion-adsorption mass balance describes the dynamics of adsorption well, and the maximum removal capacity is beyond the electric charge stoichiometric ratio because of DAP self-assembly. This study may open new opportunities for optimizing cholestyramine adjuvant therapy to prevent DAP resistance, as well as designing novel biomaterials to remove off-target antibiotics from the GI tract.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Daptomycin
/
Methicillin-Resistant Staphylococcus aureus
Limits:
Animals
Language:
En
Journal:
ACS Appl Mater Interfaces
Journal subject:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Year:
2022
Document type:
Article
Affiliation country:
United States