An adjunctive therapy approach prevents antibiotic resistance emergence in opportunistic pathogens colonizing the gut

BioRxiv : the Preprint Server for Biology
Valerie J MorleyA. F. Read

Abstract

Therapeutic antibiotic use drives the spread of antibiotic resistance, a major threat to public health. Ideally, clinicians could treat infections with antibiotics without fueling transmission of resistant pathogens. Here, we show proof of concept for an adjunctive therapy approach that allows treatment of target pathogens without the emergence and onward transmission of resistance. Like many of the bacterial species responsible for the antimicrobial resistance crisis, vancomycin-resistant Enterococcus (VRE) is a colonizing opportunistic pathogen and an important cause of drug-resistant healthcare-associated infections. VRE causes life-threatening infections in the bloodstream, but spreads via fecal-oral transmission because it asymptomatically colonizes the gastrointestinal (GI) tract. Thus, there is a physical separation between the VRE targeted by treatment (those in the blood) and the VRE contributing to onward transmission (those in the GI tract). An oral adjuvant that can bind or inactivate antibiotic in the GI tract would make possible intravenous patient treatment without promoting transmissible resistance. We tested this idea in a mouse model of VRE GI tract colonization using cholestyramine, which we show binds daptom...Continue Reading

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