ArticleInfectious diseases and therapy2021
Global Landscape of Clostridioides Difficile Phylogeography, Antibiotic Susceptibility, and Toxin Polymorphisms by Post-Hoc Whole-Genome Sequencing from the MODIFY I/II Studies.
Article in Infectious diseases and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 21 papers.
What it found
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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.
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium Difficile Toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and Toxin B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY I)
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of a Single Infusion of MK-6072 (Human Monoclonal Antibody to Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY II)
Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Whole-Genome Sequencing Analysis of ST1, ST11, ST17, and ST37Microorganisms · 2026Article
- Pooled analyses of Clostridioides difficile vaccine trials identify baseline predictors for vaccine response.Scientific reports · 2026Article
- Comparative genomic analysis of Clostridioides difficile strains in Mexico: insights into virulence and resistance.Access microbiology · 2026Article
- Characterization of Adult and Pediatric Healthcare-Associated and Community-Associated Clostridioides difficile Infections, Canada, 2015-2022.Emerging infectious diseases · 2025Article
- Newly emerging metronidazole-resistantEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025Article
- Abundant geographical divergence of Clostridioides difficile infection in China: a prospective multicenter cross-sectional study.BMC infectious diseases · 2025Article
- Whole-Genome Sequencing-Based Characterization ofMicroorganisms · 2024Article
- Gut Microbiota and New Microbiome-Targeted Drugs forAntibiotics (Basel, Switzerland) · 2024Review
- Genomic study of EuropeanMicrobial genomics · 2024Article
- Review
- Antimicrobial Resistance ofInfection and drug resistance · 2024Article
- Clostridioides difficile Sporulation.Advances in experimental medicine and biology · 2024Review
- Decoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile.Nature communications · 2023Article
- Update on Commonly Used Molecular Typing Methods forMicroorganisms · 2023Review
- Article
- Non-ToxigenicAntibiotics (Basel, Switzerland) · 2023Article
- Novel ribotype/sequence type associations and diverse CRISPR-Cas systems in environmental Clostridioides difficile strains from northern Iraq.FEMS microbiology letters · 2023Article
- Make It LessGenes · 2022Review
- Capturing the environment of the Clostridioides difficile infection cycle.Nature reviews. Gastroenterology & hepatology · 2022Review
- Mechanisms and impact of antimicrobial resistance in Clostridioides difficile.Current opinion in microbiology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
introductionClostridioides (Clostridium) difficile infection, the leading cause of healthcare-associated diarrhea, represents a significant burden on global healthcare systems. Despite being a global issue, information on C. difficile from a global perspective is lacking. The aim of this study is to model the global phylogeography of clinical C. difficile.
methodsUsing samples collected from the MODIFY I and II studies (NCT01241552, NCT01513239), we performed whole-genome sequencing of 1501 clinical isolates including 37 novel sequence types (STs), representing the largest worldwide collection to date.
resultsOur data showed ribotypes, multi-locus sequence typing clades, and whole-genome phylogeny were in good accordance. The clinical C. difficile genome was found to be more conserved than previously reported (61% core genes), and modest recombination rates of 1.4-5.0 were observed across clades. We observed a significant continent distribution preference among five C. difficile clades (Benjamini-Hochberg corrected Fisher's exact test P < 0.01); moreover, weak association between geographic and genetic distance among ribotypes suggested sources beyond healthcare-related transmission. Markedly different trends of antibiotic susceptibility among lineages and regions were identified, and three novel mutations (in pyridoxamine 5'-phosphate oxidase family protein: Tyr130Ser, Tyr130Cys, and a promoter SNP) associated with metronidazole-reduced susceptibility were discovered on a nim-related gene and its promotor by genome-wide association study. Toxin gene polymorphisms were shown to vary within and between prevalent ribotypes, and novel severe mutations were found on the tcdC toxin regulator protein.
conclusionOur systematic characterization of a global set of clinical trial C. difficile isolates from infected individuals demonstrated the complexity of the genetic makeup of this pathogenic organism. The geographic variability of clades, variability in toxin genes, and mutations associated with antibiotic susceptibility indicate a highly complex interaction of C. difficile between host and environment. This dataset will provide a useful resource for validation of findings and future research of C. difficile.
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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.