title: Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection.
abstract: OBJECTIVE
  First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model.
  
  
  METHODS
  We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C. difficile total viable counts, spores and toxin levels were monitored throughout.
  
  
  RESULTS
  Ceftriaxone instillation promoted C. difficile germination and high-level toxin production. Commencement of NVB302 and vancomycin instillation reduced C. difficile total viable counts rapidly with only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302 instillation commenced in vessel 2 and 3, respectively, and remained undetectable for the remainder of the experiments. C. difficile spores were unaffected by the presence of vancomycin or NVB302. NVB302 treatment was associated with faster resolution of Bacteroides fragilis group.
  
  
  CONCLUSIONS
  Both NVB302 and vancomycin were effective in treating simulated CDI in an in vitro gut model. C. difficile spore recrudescence was not observed following successful treatment with either NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the treatment of simulated CDI, and had less deleterious effects against B. fragilis group. NVB302 warrants further clinical investigation as a potentially novel antimicrobial agent for the treatment of CDI.
authors.affiliation: Leeds Institute of Molecular Medicine, Faculty of Medicine and Health,  University of Leeds, Leeds LS2 9JT,  UK.
authors.forename: Grace S
authors.initials: GS
authors.lastname: Crowther
authors.forename: Simon D
authors.initials: SD
authors.lastname: Baines
authors.forename: Sharie L
authors.initials: SL
authors.lastname: Todhunter
authors.forename: Jane
authors.initials: J
authors.lastname: Freeman
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Chilton
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wilcox
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001430:Bacteriocins / Q000494:pharmacology* / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000187:drug effects*; D003015:Clostridium Infections / Q000188:drug therapy* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D014640:Vancomycin