Comparison of oritavancin versus vancomycin as treatment for clindamycin-induced C. difficile ribotype 027 infection in a human gut model
Abstract number: P540
Baines S., O'Connor R., Saxton K., Freeman J., Wilcox M.
Objectives:C. difficile infection (CDI) is a nosocomial disease of increasing importance. First line treatment is limited currently to metronidazole or vancomycin (VAN). Recent reports have questioned the efficacy of current therapies for CDI, particularly against an apparently hypervirulent C. difficile (CD) strain, PCR ribotype 027 (NAP1/BI). Oritavancin (ORI) is a lipoglycopeptide with activity against Gram-positive bacteria, including drug-resistant pathogens. We evaluated the efficacy of ORI and VAN in treatment of clindamycin-induced CDI in separate experiments in an in vitro human gut model.
Methods: CD PCR ribotype 027 was used in both experiments. Clindamycin instillation was used to achieve human gut concentrations and to induce CD spore germination, proliferation and high-level cytotoxin production. ORI and VAN were instilled at levels equivalent to expected human faecal concentrations. Gut flora and CD (vegetative cells and spores) were recovered and enumerated using selective media and viable counting. CD toxin was detected by cytotoxin assay.
Results: Clindamycin exposure elicited CD proliferation and high-level (5RU) cytotoxin production in both experiments on day 35. ORI and VAN levels peaked at 52 and 1144 mg/L in vessel 3, respectively. VAN instillation reduced vegetative CD counts within 1 day but did not affect CD spore counts. On day 2 of ORI instillation both CD total and spore counts declined by approx 2 logs cfu/mL; on day 3 counts were below the limits of detection and remained so during the rest of ORI instillation. Centrifugation and washing of culture samples, in addition to exposure to activated charcoal (2040g/L) did not enhance recovery of C. difficile. Cytotoxin titres declined to the limits of detection in both experiments but did so 5 days sooner in the VAN experiment. Further CD proliferation and high-level cytotoxin production occurred 12 days after the end of VAN instillation, whereas CD in the ORI experiment was only sporadically isolated at the limits of detection.
Conclusion: Both ORI and VAN were effective in treating clindamycin-induced CDI in a human gut model, but only ORI appeared active against spore forms of CD. Recurrence of toxin production was observed following VAN instillation but not ORI. These results suggest that ORI should be as effective as VAN in treating CDI, and may prevent recrudescence of CD spores.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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