title: Probiotics for Clostridium difficile infection in adults (PICO): Study protocol for a double-blind, randomized controlled trial.
abstract: BACKGROUND
  Clostridium difficile is a pathogen of rapidly increasing public health importance. An estimated quarter of a million Clostridium difficile infections (CDI) occur in the United States annually, at a resultant cost of 14,000 deaths and 1 billion dollars. Clostridium difficile related deaths have risen 400% over the last decade, and current standard antibiotic treatments are only 75 to 85% successful. Besides increasing the risk of antibiotic resistance and side effects, these treatments are very expensive. The most vulnerable population for Clostridium difficile is older adults, who make up approximately half of the cases, but account for 90% of the related deaths. Probiotics may have potential as adjunctive therapeutic agents for CDIs, however, current data is limited.
  
  
  METHODS
  This pilot study is a single-site, randomized, placebo-controlled, double-blind, phase two clinical trial. The trial primarily evaluates the effect of four weeks of probiotic therapy in addition to standard of care on Clostridium difficile diarrhea duration and recurrence. Secondary outcomes include effect on fecal cytokines, fecal lactoferrin, and Clostridium difficile toxin density in stool, as well as patient functional status.
  
  
  CONCLUSIONS
  This pilot study will determine the feasibility and effect size to conduct larger randomized controlled trials of probiotic interventions in patients with CDI, to determine the impact of probiotics on the symptoms of CDI. ClinicalTrials.gov Identifier: NCT01680874.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Department of Population Health Sciences, Madison, WI, USA. Electronic address: akbarker@wisc.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Barker
authors.affiliation: University of Wisconsin, Madison, WI, USA. Electronic address: mnd@medicine.wisc.edu.
authors.forename: Megan
authors.initials: M
authors.lastname: Duster
authors.affiliation: Department of Medicine, University of Wisconsin Hospital, Madison, WI, USA. Electronic address: svalentine@medicine.wisc.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Valentine
authors.affiliation: University of Virginia, School of Medicine, Department of Medicine, Division of General, Geriatric, Palliative, and Hospital Medicine, Charlottesville, VA, USA; University of Virginia, School of Medicine, Department of Medicine, Division of Infectious Diseases and International Health, Charlottesville, VA, USA. Electronic address: LA2E@hscmail.mcc.virginia.edu.
authors.forename: Laurie
authors.initials: L
authors.lastname: Archbald-Pannone
authors.affiliation: University of Virginia, School of Medicine, Department of Medicine, Division of Infectious Diseases and International Health, Charlottesville, VA, USA. Electronic address: rlg9a@virginia.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Guerrant
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Wisconsin Hospital, Madison, WI, USA; William S. Middleton Memorial Veterans Affairs Hospital, Madison, WI, USA; Department of Infection Control, University of Wisconsin Hospital and Clinics, Madison, WI, USA. Electronic address: ns2@medicine.wisc.edu.
authors.forename: Nasia
authors.initials: N
authors.lastname: Safdar
keywords: Bifidobacteria; Clinical trial; Clostridium difficile; Diarrhea; Lactobacilli; Probiotics