Polymeric Anti-Antibiotic Microparticles to Prevent Antibiotic Resistance Evolution

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Vancomycin (VAN) and daptomycin (DAP) are critical last-resort antibiotics for multidrug-resistant Gram-positive infections.
• Biliary excretion of VAN and DAP into the gastrointestinal (GI) tract promotes resistance in commensal Enterococcus faecium (E. faecium).

Purpose of the Study:

• To investigate sevelamer's (SEV) potential to mitigate antibiotic resistance driven by GI drug excretion.
• To evaluate SEV's efficacy in preventing VAN resistance enrichment in vivo.

Main Methods:

• In vitro assessment of SEV's binding kinetics and inactivation of VAN and DAP.
• In vivo study using E. faecium-colonized mice treated with VAN and oral SEV.
• Analysis of VAN resistance emergence in the E. faecium population.

Main Results:

• Sevelamer (SEV) demonstrated rapid capture of DAP and slower capture of VAN in vitro, consistent with a diffusion-adsorption model.
• Oral SEV administration effectively prevented the enrichment of VAN resistance in E. faecium populations in mice treated with VAN.
• SEV inactivated the antibacterial efficacy of both VAN and DAP.

Conclusions:

• Sevelamer (SEV) acts as an effective adjuvant therapy to prevent antimicrobial resistance by sequestering off-target antibiotics in the GI tract.
• SEV holds promise for preserving the efficacy of last-resort antibiotics like VAN and DAP against nosocomial pathogens.
• This study presents a novel strategy to combat antimicrobial resistance by managing antibiotic excretion and its downstream effects.