title: Evaluation of the effect of oritavancin on Clostridium difficile spore germination, outgrowth and recovery.
abstract: OBJECTIVE
  Previous work suggests oritavancin may be inhibitory to Clostridium difficile spores. We have evaluated the effects of oritavancin exposure on C. difficile spore germination, outgrowth and recovery.
  
  
  METHODS
  Germination and outgrowth of C. difficile spores exposed to different concentrations of oritavancin, vancomycin, or metronidazole (0.1-10 mg/L) were monitored at 0, 2, 4, 6, 24 and 48 h using phase-contrast microscopy. Recovery of antimicrobial-exposed spores was determined by viable counting on Brazier's modified CCEYL agar. Persistence of oritavancin activity on spores after washing was determined by measuring activity against a Staphylococcus aureus lawn.
  
  
  RESULTS
  Oritavancin, vancomycin and metronidazole exposure did not prevent germination of phase-bright spores to phase-dark spores, but did inhibit further outgrowth into vegetative cells. The inhibitory effect of oritavancin persisted after washing, whereas the inhibitory effects of vancomycin and metronidazole did not. Oritavancin exposure affected spore recovery; fewer spores were recovered after washing following oritavancin exposure than vancomycin exposure. The extent of this effect was dependent on PCR ribotype, with recovery of ribotype 078 spores completely prevented, but recovery of ribotype 001 spores only slightly affected. Spores exposed to oritavancin, but not vancomycin, retained antimicrobial activity after washing, indicating adherence of oritavancin, but not vancomycin, to the spore surface
  
  
  CONCLUSIONS
  Oritavancin may adhere to spores, potentially causing early inhibition of germinated cells, preventing subsequent vegetative outgrowth and spore recovery. This may prevent some recurrences of symptomatic C. difficile infection that are due to germination of residual spores following antibiotic therapy.
authors.affiliation: Leeds Institute for Molecular Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Chilton
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.forename: S D
authors.initials: SD
authors.lastname: Baines
authors.forename: G S
authors.initials: GS
authors.lastname: Crowther
authors.forename: S
authors.initials: S
authors.lastname: Nicholson
authors.forename: M H
authors.initials: MH
authors.lastname: Wilcox
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000254:growth & development*; D015169:Colony Count, Microbial; D006020:Glycopeptides / Q000494:pharmacology*; D000077427:Lipoglycopeptides; D050296:Microbial Viability / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D013171:Spores, Bacterial / Q000187:drug effects* / Q000254:growth & development*; D013997:Time Factors; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin
keywords: adherence; outgrowth inhibition; recurrence