title: Co-amoxiclav induces proliferation and cytotoxin production of Clostridium difficile ribotype 027 in a human gut model.
abstract: OBJECTIVE
  Co-amoxiclav is widely prescribed in hospitals. Although reports have suggested it may be linked to onset of Clostridium difficile infection (CDI), data on the risk of CDI associated with specific antibiotics is difficult to obtain, due to confounding clinical factors. We have examined the propensity of co-amoxiclav to induce CDI using a human gut model.
  
  
  METHODS
  We used a triple-stage chemostat human gut model to study the effects of co-amoxiclav on indigenous gut microorganisms and C. difficile PCR ribotype 027. C. difficile viable counts and spores were evaluated, and cytotoxin titres were assayed. Co-amoxiclav concentrations were measured using a large plate bioassay.
  
  
  RESULTS
  Co-amoxiclav induced rapid C. difficile germination and high toxin production in the gut model, from 5 days after commencement of instillation. Cell proliferation and toxin production were prolonged and continued throughout the duration of the experiment. Only very low levels of co-amoxiclav antimicrobial activity could be detected within the gut model, despite having a marked effect on gut flora microorganisms.
  
  
  CONCLUSIONS
  Co-amoxiclav induced CDI within the gut model, supporting clinical observations linking co-amoxiclav treatment with CDI onset. This reinforces the value of the gut model as a clinically relevant means of studying CDI. Caution should be exercised in the prescription of co-amoxiclav to patients in high CDI risk settings.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Chilton
authors.forename: Jane
authors.initials: J
authors.lastname: Freeman
authors.forename: Grace S
authors.initials: GS
authors.lastname: Crowther
authors.forename: Sharie L
authors.initials: SL
authors.lastname: Todhunter
authors.forename: Scott
authors.initials: S
authors.lastname: Nicholson
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wilcox
mesh_terms: D000368:Aged; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000096:biosynthesis*; D001427:Bacterial Toxins / Q000096:biosynthesis*; D016360:Clostridioides difficile / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D008962:Models, Theoretical; D021521:Ribotyping; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile; D019980:Amoxicillin-Potassium Clavulanate Combination