Abstract
Enterococci represent one of the microbial world’s most challenging enigmas. Colonization of the gastrointestinal tract (GIT) of high-risk/immunocompromised patients by enterococci exhibiting resistance to vancomycin (VRE) can lead to life-threating infections, including bloodstream infections and endocarditis. Decolonization of VRE from the GIT of high-risk patients represents an alternative method to suppress the risk of the infection. It could be considered as a preventative measure to protect against VRE infections in high-risk individuals. Though multiple agents (ramoplanin and bacitracin) have been evaluated clinically, no drugs are currently approved for use in VRE decolonization of the GIT. The present study evaluates ebselen, a clinical molecule, for use as a decolonizing agent against VRE. When evaluated against a broad array of enterococcal isolates in vitro, ebselen was found to be as potent as linezolid (minimum inhibitory concentration against 90% of clinical isolates tested was 2 μg/ml). Though VRE has a remarkable ability to develop resistance to antibacterial agents, no resistance to ebselen emerged after a clinical isolate of vancomycin-resistant E. faecium was serially-passaged with ebselen for 14 days. Against VRE biofilm, a virulence factor that enables the bacteria to colonize the gut, ebselen demonstrated the ability to both inhibit biofilm formation and disrupt mature biofilm. Furthermore, in a murine VRE colonization reduction model, ebselen proved as effective as ramoplanin in reducing the bacterial shedding and burden of VRE present in the fecal content (by > 99.99%), cecum, and ileum of mice. Based on the promising results obtained, ebselen warrants further investigation as a novel decolonizing agent to quell VRE infection.
Highlights
Enterococcal infections represent one of the major challenges facing healthcare providers worldwide, in part because of the uncanny ability of enterococci to acquire or develop resistance to antibiotics
The challenge of multidrug-resistant enterococcal infection continues to pose a threat to patients in healthcare facilities
Treatment of enterococcal infections has become increasingly challenging given the remarkable ability of enterococci to develop resistance to antibacterial agents [3,25]
Summary
Enterococcal infections represent one of the major challenges facing healthcare providers worldwide, in part because of the uncanny ability of enterococci to acquire or develop resistance to antibiotics. VRE decolonization by ebselen isolates exhibiting resistance to vancomycin (termed vancomycin-resistant enterococci or VRE) has been troubling as these isolates are often co-resistant to other classes of antibiotics including β-lactams [2] Though newer antibiotics such as linezolid, daptomycin, tigecycline and quinupristin/dalfopristin remain effective treatment options clinically, several cases of enterococcal resistance against all the aforementioned drugs have been reported [4,5,6,7,8,9]. One novel strategy that warrants further investigation is identifying agents capable of decolonizing VRE from the gastrointestinal tract (GIT) of high-risk patients susceptible to infection [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
