Effectiveness of a short (4 day) course of oritavancin in the treatment of simulated Clostridium difficile infection using a human gut model.
OBJECTIVE
We previously demonstrated that 7 days of oritavancin instillation effectively treats Clostridium difficile infection (CDI) in a human gut model. Oritavancin may be more effective than vancomycin due to apparently increased activity against spores. We compared the efficacy of shortened dosing duration (4 days) of oritavancin and vancomycin for CDI treatment using the gut model.


METHODS
Clindamycin induced CDI in two triple-stage chemostat gut models primed with pooled human faeces and C. difficile ribotype 027 spores. Oritavancin (64 mg/L twice daily) or vancomycin (125 mg/L four times daily) was instilled for 4 days and the effects on C. difficile proliferation and toxin production, and gut microflora were determined.


RESULTS
Both oritavancin and vancomycin reduced toxin to undetectable levels. Recurrent C. difficile germination occurred 20 days after vancomycin instillation, with high-level toxin production. Oritavancin reduced C. difficile counts to around the detection limit for the remainder of the experiment, with spores undetectable from day 1 of instillation. Toxin production was reduced to below detectable levels, but was sporadically seen later, despite no evidence of germination. Both oritavancin and vancomycin instillation led to only modest effects on gut microflora.


CONCLUSIONS
Shortened courses of oritavancin and vancomycin effectively treated CDI in a human gut model, but evidence of recurrence was observed following vancomycin instillation. Oritavancin exposure inhibited the recovery of C. difficile spores, as previously described. Shortened antibiotic exposure minimizes disruption to the gut microflora. These data indicate the possible value of a 4 day oritavancin dosing regimen for CDI treatment.
Leeds Institute for Molecular Medicine,  University of Leeds, Leeds LS2 9JT,  UK.
C H
CH
Chilton
J
J
Freeman
G S
GS
Crowther
S L
SL
Todhunter
M H
MH
Wilcox
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016360:Clostridioides difficile / Q000187:drug effects*; D003015:Clostridium Infections / Q000188:drug therapy*; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006020:Glycopeptides / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D000077427:Lipoglycopeptides; D008962:Models, Theoretical; D013997:Time Factors; D014640:Vancomycin / Q000031:analogs & derivatives
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin