Evaluation of 1,3,4-Thiadiazole Carbonic Anhydrase Inhibitors for Gut Decolonization of Vancomycin-Resistant Enterococci
Nader S. Abutaleb, Annadka Shrinidhi, Aloka B. Bandara, Mohamed N. Seleem, Daniel P. Flaherty
Abstract
Vancomycin-resistant enterococci (VRE), Enterococcus faecium and Enterococcus faecalis, 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 in vivo VRE gastrointestinal decolonization mouse model. The molecules encompass a range of antimicrobial potency and intestinal permeability, and these factors were shown to influence the in vivo efficacy for VRE gut decolonization. Overall, carbonic anhydrase inhibitors exhibited superior VRE decolonization efficacy compared to the current drug of choice, linezolid.