Behaviour of Saccharomyces boulardii in recurrent Clostridium difficile disease patients.
BACKGROUND
Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations of Saccharomyces boulardii in a patient population with Clostridium difficile disease (CDD) and correlates stool concentrations with efficacy.


METHODS
Patients with recurrent CDD all received a 10-day standard antibiotic regimen together with 28 days of S. boulardii or placebo. Stool samples were collected from patients at various time points and assayed for S. boulardii.


RESULTS
The mean concentration of S. boulardii of patients who recurred was 2.5 x 104 CFU/g compared to 1 x 106 CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%, P=0.007). Clearance of S. boulardii was rapid; only 4% had 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 concentrations 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 give a true reflection of the disturbed microecology in the disease state.
Elmer
G W
GW
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle 98195, USA. elmer@u.washington.edu
McFarland
L V
LV
Surawicz
C M
CM
Danko
L
L
Greenberg
R N
RN
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003015:Clostridium Infections / Q000628:therapy*; D005243:Feces / Q000382:microbiology*; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D010919:Placebos; D012008:Recurrence; D012440:Saccharomyces / Q000302:isolation & purification*; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010919:Placebos; D008795:Metronidazole; D014640:Vancomycin