Methods: Adult patients with first episode of CDI, less than 24 h of prior CDI therapy, and provided consent were included. Patients were randomized to oral VAN 125mg q6h or FDX 200mg q12h for 10 days. Stool samples were collected on the following days: 0, 3-5, 10-13 (end-of-therapy [EOT]), and 19-29 (follow-up [F/U]) to assess C. difficile (vegetative cells and spores) burden. The primary endpoint was the percentage of patients who achieved ≥ 2log10CFU/g reductions of spores from baseline by the EOT. Secondary endpoints were CFU reductions at day 3-5, EOT, and F/U for total cells (spores plus vegetative) and the rate of clinical cure, defined as <3 loose stools daily at EOT and F/U. Sustained clinical response (SCR) was continued cure at end-of-study (day 38).
Results: Thirty-four patients were enrolled, 18 randomized to FDX and 16 to VAN. However, 12 patients in each group (n=24 total) provided data at all end-points and were included in final analyses. Total baseline C. difficile burden (vegetative cells plus spores) was 5.41 ± 1.72 and 4.96 ± 1.81 log10CFU/g in the FDX and VAN groups, respectively (p= 0.51). At D3-5, a ≥ 2 log10CFU/g reductions of vegetative cells was observed for 71% of patients in both groups. Vegetative reductions over other time points were similar (p>0.12). At D3-5 and EOT, reductions in spore burden were similar (p= 0.08) with 67% VAN patients observed to have a ≥ 2 log10CFU/g spore reduction compared with 92% FDX patients. Significantly more FDX patients (67%) achieved ≥ 2 log10CFU/g reduction in spores at F/U compared with VAN patients (14%, p=0.02). Clinical cure was 100% and 80% in the FDX and VAN groups, respectively. Recurrence was observed in two patients in each group. SCR was achieved in 80% of FDX patients compared with 62% of VAN patients.
Conclusion: Both FDX and VAN resulted in rapid reductions of vegetative cells throughout therapy. FDX resulted in significantly greater reductions in spore counts.
S. T. Housman,
J. Kuti, Cubist Pharmaceuticals: Research Contractor and Scientific Advisor , Consulting fee and Research support
R. Quintiliani, None
D. P. Nicolau, Cubist Pharmaceuticals: Consultant , Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Grant recipient , Research grant , Research support and Speaker honorarium