ArticleScientific reports2016
Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Drug repositioning: Progress and challenges in drug discovery for various diseases.European journal of medicinal chemistry · 2022Pooled it
- Carbadox, a veterinary growth promoter exhibits anticlostridial activity through induction of oxidative stress in Clostridioides difficile.Gut pathogens · 2026Article
- Ionomycin Exhibits Potent and Selective Bactericidal Activity Against Clostridioides difficile Through Calcium-Dependent Membrane Disruption.MicrobiologyOpen · 2026Article
- Repurposing Rafoxanide: From Parasite Killer to Cancer Fighter.Biomedicines · 2025Review
- New functions of pirin proteins and a 2-ketoglutarate: Ferredoxin oxidoreductase ortholog in Bacteroides fragilis metabolism and their impact on antimicrobial susceptibility to metronidazole and amixicile.MicrobiologyOpen · 2024Article
- Current and Ongoing Developments in TargetingMicroorganisms · 2024Review
- Drug Repurposing: Research Progress of Niclosamide and Its Derivatives on Antibacterial Activity.Infection and drug resistance · 2024Review
- Repurposing Anthelmintics: Rafoxanide- and Copper-Functionalized SBA-15 Carriers against Methicillin-ResistantACS applied materials & interfaces · 2023Article
- Investigation of Salicylanilides as Botulinum Toxin Antagonists.ACS infectious diseases · 2022Article
- Double Repositioning: Veterinary Antiparasitic to Human Anticancer.International journal of molecular sciences · 2022Review
- Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics.Colloids and surfaces. B, Biointerfaces · 2022Review
- Irritable Bowel Syndrome Therapeutic Has Broad-Spectrum Antimicrobial Activity.Antimicrobial agents and chemotherapy · 2021Article
- Article
- Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System.International journal of molecular sciences · 2020Review
- Antibiotics in the clinical pipeline in October 2019.The Journal of antibiotics · 2020Review
- Screening for potent and selective anticlostridial leads among FDA-approved drugs.The Journal of antibiotics · 2020Article
- Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases.Antibiotics (Basel, Switzerland) · 2020Review
- Synergistic combinations of anthelmintic salicylanilides oxyclozanide, rafoxanide, and closantel with colistin eradicates multidrug-resistant colistin-resistant Gram-negative bacilli.The Journal of antibiotics · 2019Article
- The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli.Antimicrobial agents and chemotherapy · 2019Article
- Identification of novel triazole inhibitors of Wnt/β-catenin signaling based on the Niclosamide chemotype.Bioorganic & medicinal chemistry letters · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. By broth microdilution techniques, we determined the MIC values of the anthelmintics against 16 C. difficile isolates of defined PCR-ribotype. The anthelmintics broadly inhibited C. difficile growth in vitro via a membrane depolarization mechanism. Interestingly, the salicylanilides were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. The salicylanilides were poorly active against select gut commensals (Bacteroides, Bifidobacterium and Lactobacillus species), and were non-hemolytic and non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable properties for repositioning as anti-C. difficile agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.