In vitro and in vivo activities of the carbonic anhydrase inhibitor, dorzolamide, against vancomycin-resistant enterococci

Vancomycin-resistant enterococci (VRE) are a serious public health threat and leading cause of healthcare-associated infections. Bacterial resistance to antibiotics recommended for the treatment enterococcal infections complicates management these Hence, there is critical need discovery new anti-VRE agents. We previously reported carbonic anhydrase inhibitors (CAIs) as potent VRE inhibitors. In present study, activity CAI, dorzolamide was evaluated against both in vitro vivo. Dorzolamide exhibited panel clinical isolates, with minimum inhibitory concentration (MIC) values ranging from 1 µg/mL 8 µg/mL. A killing kinetics experiment determined that bacteriostatic effect VRE, which similar drug choice (linezolid). interacted synergistically gentamicin four strains an additive interaction six strains, reducing gentamicin’s MIC by several folds. Moreover, outperformed linezolid vivo colonization reduction mouse model. significantly reduced burden fecal samples mice 2.9-log 10 (99.9%) 3.86-log (99.99%) after 3 5 days treatment, respectively. Furthermore, count cecal (1.74-log (98.2%) reduction) ileal contents (1.5-log (96.3%)) mice, superior linezolid. Collectively, results indicate represents promising option warrants consideration supplement current therapeutics used