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An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen

Citation

Morley, Valerie; Kinnear, Clare (2020), An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen , Dryad, Dataset, https://doi.org/10.5061/dryad.qrfj6q5c2

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 could eliminate 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 daptomycin, one of the few remaining front-line antibiotics against VRE. Adjunctive cholestyramine therapy reduced the fecal shedding of daptomycin-resistant VRE by up to 80-fold in mice treated with daptomycin. These results provide proof-of-concept for an approach that could reduce the spread of antibiotic resistance for many important hospital pathogens.

Funding

Eberly College of Science, Penn State University

Eberly Family Trust

Eberly College of Science, Penn State University

Eberly Family Trust