Repurposing the Antiamoebic Drug Diiodohydroxyquinoline for Treatment of Clostridioides difficile Infections
| Autor: | Mohamed N. Seleem, Nader S. Abutaleb |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug medicine.medical_treatment media_common.quotation_subject 030106 microbiology Virulence Microbiology 03 medical and health sciences Clostridioides Lactobacillus Iodoquinol medicine Humans Experimental Therapeutics Pharmacology (medical) media_common Bifidobacterium Pharmacology biology Clostridioides difficile business.industry Drug Repositioning biology.organism_classification Anti-Bacterial Agents Metronidazole 030104 developmental biology Infectious Diseases Pharmaceutical Preparations Clostridium Infections Vancomycin Diiodohydroxyquinoline Bacteroides business medicine.drug |
| Zdroj: | Antimicrob Agents Chemother |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.02115-19 |
| Popis: | Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for the treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at concentrations of 0.5 μg/ml and 2 μg/ml, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3 log(10) within 6 h. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit the growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium, and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs. |
| Databáze: | OpenAIRE |
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