Impact of vancomycin faecal concentrations on clinical and microbiological outcomes in Clostridium difficile infection

Abstract

To assess the impact of faecal vancomycin concentrations on clinical and microbiological outcomes in patients with Clostridium difficile infection (CDI) and whether these concentrations vary with stool consistency and frequency, faecal concentrations of vancomycin were measured in stools collected at various times from patients initiated on 125mg every 6h (q6h) for 10 days. Stool consistency and frequency were determined over the course of therapy. Clinical and microbiological outcomes were assessed during therapy, at the end of therapy (EOT) and during a 19-38-day follow-up visit. Faecal vancomycin concentrations in 55 stool samples from 15 patients ranged from 175-6299μg/g at Days 3-5 of therapy (midpoint), 17-5277μg/g at EOT and 0-70μg/g at follow-up. Clinical cure or failure at EOT and at follow-up was not dependent on vancomycin concentrations measured at the midpoint (P=0.72) or at EOT (P=0.76). Likewise, concentrations at EOT and at follow-up did not predict colonisation at follow-up (P=0.85 and 0.71, respectively). Faecal vancomycin concentrations during the course of therapy (Days 3-5) did not differ with either stool consistency or frequency (P=0.94 and 0.16, respectively). However, after completion of therapy, patients with more frequent stools showed higher concentrations than patients with less frequent stools (P=0.04). Oral vancomycin 125mg q6h led to faecal concentrations that did not predict clinical outcomes of CDI in terms of cure or gut colonisation and did not vary with stool consistency and frequency.

Keywords: Clostridium difficile; Colonisation; Faecal concentration; Pharmacokinetics; Vancomycin.