ArticleThe Journal of antimicrobial chemotherapy2016
Impact on toxin production and cell morphology in Clostridium difficile by ridinilazole (SMT19969), a novel treatment for C. difficile infection.
Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 54 citations in OpenAlex.
- Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin.The Journal of antimicrobial chemotherapy · 2018Trial
- Ionomycin Exhibits Potent and Selective Bactericidal Activity Against Clostridioides difficile Through Calcium-Dependent Membrane Disruption.MicrobiologyOpen · 2026Article
- Recent advances in fecal microbiota transplantation forFrontiers in microbiomes · 2024Review
- Antibiotics in the clinical pipeline as of December 2022.The Journal of antibiotics · 2023Review
- Ridinilazole: a novel, narrow-spectrum antimicrobial agent targeting Clostridium (Clostridioides) difficile.Letters in applied microbiology · 2022Review
- Practical observations on the use of fluorescent reporter systems in Clostridioides difficile.Antonie van Leeuwenhoek · 2022Article
- Frontiers in antibiotic alternatives forWorld journal of gastroenterology · 2021Article
- Article
- Immunotherapy and vaccination against infectious diseases.Wiener klinische Wochenschrift · 2021Review
- Antibiotics in the clinical pipeline in October 2019.The Journal of antibiotics · 2020Review
- Investigational Treatment Agents for RecurrentJournal of experimental pharmacology · 2020Review
- Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections.Annals of the New York Academy of Sciences · 2019Review
- Management of Primary and RecurrentAntibiotics (Basel, Switzerland) · 2018Review
- Advances in the diagnosis and treatment of Clostridium difficile infections.Emerging microbes & infections · 2018Review
- Protective Effects of Bifidobacterial Strains Against ToxigenicFrontiers in microbiology · 2018Article
- A Small Molecule-Screening Pipeline to Evaluate the Therapeutic Potential of 2-Aminoimidazole Molecules AgainstFrontiers in microbiology · 2018Article
- Novel Antimicrobials for the Treatment ofFrontiers in medicine · 2018Review
- Ridinilazole-a novel antibiotic for treatment of Clostridium difficile infection.Journal of thoracic disease · 2018Article
- A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment.Journal of visualized experiments : JoVE · 2017Article
- A Review of Experimental and Off-Label Therapies for Clostridium difficile Infection.Infectious diseases and therapy · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesRidinilazole (SMT19969) is a narrow-spectrum, non-absorbable antimicrobial with activity against Clostridium difficile undergoing clinical trials. The purpose of this study was to assess the pharmacological activity of ridinilazole and assess the effects on cell morphology.
methodsAntibiotic killing curves were performed using the epidemic C. difficile ribotype 027 strain, R20291, using supra-MIC (4× and 40×) and sub-MIC (0.125×, 0.25× and 0.5×) concentrations of ridinilazole. Following exposure, C. difficile cells were collected for cfu counts, toxin A and B production, and morphological changes using scanning electron and fluorescence microscopy. Human intestinal cells (Caco-2) were co-incubated with ridinilazole-treated C. difficile growth medium to determine the effects on host inflammatory response (IL-8).
resultsTreatment at supra-MIC concentrations (4× and 40× MIC) of ridinilazole resulted in a significant reduction in vegetative cells over 72 h (4 log difference, P < 0.01) compared with controls without inducing spore formation. These results correlated with a 75% decrease in toxin A production (P < 0.05) and a 96% decrease in toxin B production (P < 0.05). At sub-MIC levels (0.5× MIC), toxin A production was reduced by 91% (P < 0.01) and toxin B production was reduced by 100% (P < 0.001), which resulted in a 74% reduction in IL-8 release compared with controls (P < 0.05). Sub-MIC (0.5×)-treated cells formed filamentous structures ∼10-fold longer than control cells. Following fluorescence labelling, the cell septum was not forming in sub-MIC-treated cells, yet the DNA was dividing.
conclusionsRidinilazole had robust killing effects on C. difficile that significantly reduced toxin production and attenuated the inflammatory response. Ridinilazole also elicited significant cell division effects suggesting a potential mechanism of action.
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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.