Dataset Information

A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO).

ABSTRACT: Background:Clostridium difficile is the most common cause of hospital-acquired infections, responsible for >450000 infections annually in the USA. Probiotics provide a promising, well-tolerated adjunct therapy to standard C. difficile infection (CDI) treatment regimens, but there is a paucity of data regarding their effectiveness for the treatment of an initial CDI. Objectives:We conducted a pilot randomized controlled trial of 33 participants from February 2013 to February 2015 to determine the feasibility and health outcomes of adjunct probiotic use in patients with an initial mild to moderate CDI. Methods:The intervention was a 28?day, once-daily course of a four-strain oral probiotic capsule containing Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bi-07 and B. lactis Bl-04. The control placebo was identical in taste and appearance. Registered at clinicaltrials.gov: trial registration number?=?NCT01680874. Results:Probiotic adjunct therapy was associated with a significant improvement in diarrhoea outcomes. The primary duration of diarrhoea outcome (0.0 versus 1.0?days; P?=?0.039) and two exploratory outcomes, total diarrhoea days (3.5 versus 12.0?days; P?=?0.005) and rate of diarrhoea (0.1 versus 0.3?days of diarrhoea/stool diary days submitted; P?=?0.009), all decreased in participants with probiotic use compared with placebo. There was no significant difference in the rate of CDI recurrence or functional improvement over time between treatment groups. Conclusions:Probiotics are a promising adjunct therapy for treatment of an initial CDI and should be further explored in a larger randomized controlled trial.

SUBMITTER: Barker AK

PROVIDER: S-EPMC5890711 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO).

Barker Anna K AK Duster Megan M Valentine Susan S Hess Timothy T Archbald-Pannone Laurie L Guerrant Richard R Safdar Nasia N

The Journal of antimicrobial chemotherapy 20171101 11

<h4>Background</h4>Clostridium difficile is the most common cause of hospital-acquired infections, responsible for >450000 infections annually in the USA. Probiotics provide a promising, well-tolerated adjunct therapy to standard C. difficile infection (CDI) treatment regimens, but there is a paucity of data regarding their effectiveness for the treatment of an initial CDI.<h4>Objectives</h4>We conducted a pilot randomized controlled trial of 33 participants from February 2013 to February 2015 t ...[more]

PMID: 28961980

Similar Datasets

Project description:BackgroundTo date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials.ObjectiveTo determine the efficacy and safety of FMT for treatment of recurrent CDI.DesignRandomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494).SettingTwo academic medical centers.Patients46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode.InterventionFecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy.MeasurementsThe primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on donors' stool.ResultsIn the intention-to-treat analysis, 20 of 22 patients (90.9%) in the donor FMT group achieved clinical cure compared with 15 of 24 (62.5%) in the autologous FMT group (P = 0.042). Resolution after autologous FMT differed by site (9 of 10 vs. 6 of 14 [P = 0.033]). All 9 patients who developed recurrent CDI after autologous FMT were free of further CDI after subsequent donor FMT. There were no SAEs related to FMT. Donor FMT restored gut bacterial community diversity and composition to resemble that of healthy donors.LimitationThe study included only patients who had 3 or more recurrences and excluded those who were immunocompromised and aged 75 years or older.ConclusionDonor stool administered via colonoscopy seemed safe and was more efficacious than autologous FMT in preventing further CDI episodes.Primary funding sourceNational Institute of Diabetes and Digestive and Kidney Diseases.

Project description:Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials.

Dataset Information

A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO).

Publications

A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets