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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
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Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci
Haroon Mohammad1, Ahmed AbdelKhalek1, Nader S Abutaleb1
1Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
International Journal of Antimicrobial Agents
|February 13, 2018
Summary
Niclosamide shows potent antibacterial activity against vancomycin-resistant Enterococci (VRE). This anthelmintic drug effectively reduced VRE colonization in mice, outperforming linezolid and warranting further investigation as a decolonizing agent.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterococci are common gut microbes, but vancomycin-resistant Enterococci (VRE) cause severe infections in immunocompromised individuals.
- Effective VRE decolonization is crucial for infection control, yet few clinical agents are available.
- Current treatment options for VRE infections have limitations.
Purpose of the Study:
- To investigate the antibacterial potential of niclosamide against clinical VRE isolates.
- To evaluate niclosamide's efficacy in reducing VRE colonization in a murine model.
- To compare niclosamide's performance against established VRE treatments like linezolid.
Main Methods:
- In vitro susceptibility testing of niclosamide against clinical VRE isolates.
- Assessment of VRE resistance development through serial passage experiments.
- In vivo evaluation of niclosamide in a VRE colonization-reduction murine model, comparing it with linezolid and ramoplanin.
Main Results:
- Niclosamide demonstrated potent in vitro activity against VRE (MIC 1-8 µg/mL).
- No VRE resistance to niclosamide was observed after 10 serial passages.
- In vivo, niclosamide significantly reduced VRE burden in mice, outperforming linezolid and matching ramoplanin's efficacy.
Conclusions:
- Niclosamide exhibits significant antibacterial properties against VRE.
- Its efficacy in a murine model suggests potential as a novel VRE decolonizing agent.
- Further research into niclosamide for VRE suppression is warranted.
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