Evaluation of 1,3,4-Thiadiazole Carbonic Anhydrase Inhibitors for Gut Decolonization of Vancomycin-Resistant Enterococci.

ACS Med Chem Lett

Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.

Published: April 2023

Vancomycin-resistant enterococci (VRE), and , are high-priority drug-resistant pathogens in need of new therapeutic approaches. VRE originate in the gastrointestinal tract of carriers and can lead to more problematic downstream infections in the healthcare setting. Having a carrier of VRE admitted into a healthcare setting increases the risk to other patients for acquiring an infection. One strategy to eliminate the downstream infections is decolonization of VRE from carriers. Here, we report the activity of a set of carbonic anhydrase inhibitors in the VRE gastrointestinal decolonization mouse model. The molecules encompass a range of antimicrobial potency and intestinal permeability, and these factors were shown to influence the efficacy for VRE gut decolonization. Overall, carbonic anhydrase inhibitors exhibited superior VRE decolonization efficacy compared to the current drug of choice, linezolid.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108396PMC
http://dx.doi.org/10.1021/acsmedchemlett.3c00032DOI Listing

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