Abstract
In this journal's recent review of Clostridium difficile-associated disease (CDAD) management, McFarland (2005) emphasized the need for definitive efficacy trials to test recurrent CDAD (RCDAD) therapies. To address this recommendation, we report results and feasibility issues learned from a pilot trial of adjunctive Lactobacillus rhamnosus GG (LGG) for prevention of RCDAD.
Adults presenting with RCDAD (i.e. diarrhoea, enzyme immunoassay detection of stool C. difficile toxin A or B, and history of CDAD in the preceding year) were recruited from two hospitals and an extended care facility in St. Louis, Missouri, USA, over 9 months. Exclusion criteria included critical or terminal illness, compromised immunity, prosthetic heart valves, >5 days of anti-C. difficile antibiotic therapy, recent probiotic use and confounding diarrhoeal illness. Informed consent was obtained from all participants or their proxies, and the study was approved by the institutional review board of each institution.
Participants were randomized to receive one LGG capsule (40 mg lyophilized LGG and 320 mg inulin) or one placebo capsule (360 mg inulin) orally twice daily, adjunctively with anti-C. difficile antibiotics as chosen by the primary clinician, for the duration of antibiotic therapy and for an additional 21 days. The LGG and placebo capsules were donated by CAG Functional Foods, Omaha, Nebraska, USA. Investigators and participants were blinded to the treatment assignment. Randomly selected LGG capsules were analysed and contained 2.8 × 1011 c.f.u. per capsule of Gram-positive bacilli with uniform colony morphology at study initiation and 4.0 × 1010 c.f.u. after 8 months stored at 4 °C. The primary outcome was subsequent RCDAD within 60 days of completing anti-C. difficile antibiotic therapy. Participants were analysed within their assigned treatment arm in an intention-to-treat analysis, using t-tests and Mann-Whitney U tests for continuous variables and Fisher's Exact tests for categorical variables in Statistical Package for the Social Sciences version 12.0.