Behaviour of Saccharomyces boulardii in recurrent Clostridium difficile disease patients

Background: Despite recent interest in therapeutic microorganisms taken ora lly, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool c oncentrations of Saccharomyces boulardii in a patient population with Clost ridium difficile disease (CDD) and correlates stool concentrations with eff icacy. Methods: Patients with recurrent CDD all received a 10-day standard antibio tic regimen together with 28 days of S. boulardii or placebo. Stool samples were collected from patients at various time points and assayed for S. bou lardii. Results: The mean concentration of S. boulardii of patients who recurred wa s 2.5 x 10(4) CFU/g compared to 1 x 10(6) CFU/g in patients that did not re cur (P=0.02). Patients with low yeast concentrations in their stools (< 10( 4)/g) recurred more often (14/15, 93%) compared with patients with higher l evels (19/35, 54%, P=0.007). Clearance of S. boulardii was rapid; only 4% h ad positive stools 3 days after stopping dosing. Conclusions: After chronic dosing of S. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentr ations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not gi ve a true reflection of the disturbed microecology in the disease state.