Susan Valentine

Impact of Probiotics for Reducing Infections in Veterans (IMPROVE): Study protocol for a double-blind, randomized controlled trial to reduce carriage of Staphylococcus aureus

BACKGROUND Staphylococcus aureus (S. aureus) is an organism of great public health importance, causing 20,000 deaths annually. Decolonization of patients with S. aureus may prevent infections, yet current options are limited to antimicrobials that promote antibiotic resistance and can cause adverse side effects. Probiotics have potential to reduce colonization of pathogenic bacteria, representing a promising alternative for S. aureus decolonization, but thus far lack rigorous evaluation. METHODS Potential subjects were recruited from inpatient and outpatient settings within a VA medical center and screened for S. aureus gastrointestinal (GI) or extra-GI colonization using swabs at multiple body sites. Positive, eligible, consenting participants were stratified by colonization site and randomized in a 1:1 ratio to 4-weeks of daily placebo or Lactobacillus rhamnosus (L. rhamnosus) HN001 probiotic treatment. Blood and stool samples, and treatment adherence reports were collected from each subject throughout the study, along with a final set of swabs at study completion to detect S. aureus carriage. The outcomes of this study are GI or extra-GI carriage by S. aureus at the end of 4weeks of therapy, change in phagocytic activity of polymorphonuclear cells from pre-intervention to post-intervention, and symptomatic S. aureus infection at any site during the study period. CONCLUSION 114 participants have been recruited for this study. Analysis of outcomes is underway. This is the first clinical trial to examine the efficacy of L. rhamnosus HN001 for decolonization of S. aureus, and investigates the mechanism by which L. rhamnosus HN001 mediates its effect on S. aureus colonization. ClinicalTrials.govIdentifier NCT01321606.

Probiotics for Clostridium difficile infection in adults (PICO): Study protocol for a double-blind, randomized controlled trial.

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. DISCUSSION 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.

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

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.

Vancomycin-resistant Enterococcus co-colonization rates with methicillin-resistant Staphylococcus aureus and Clostridium difficile in critically ill veterans

A prospective study was conducted to identify risk factors for vancomycin-resistant Enterococcus, including co-colonization with methicillin-resistant Staphylococcus aureus and Clostridium difficile infection in patients admitted to the intensive care unit in 2 Veterans Affairs facilities. Methicillin-resistant Staphylococcus aureus and Clostridium difficile infection co-colonization were significant risk factors for vancomycin-resistant Enterococcus colonization. Further studies are needed to identify measures for preventing co-colonization of these major organisms in veterans.

Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study

BackgroundInfection by Staphylococcus aureus (S. aureus) is a major cause of morbidity and mortality. Colonization by S. aureus increases the risk of infection. Little is known about decolonization strategies for S. aureus beyond antibiotics, however probiotics represent a promising alternative. A randomized controlled trial was conducted to determine the efficacy of Lactobacillus rhamnosus (L. rhamnosus) HN001 in reducing carriage of S. aureus at multiple body sites.MethodsOne hundred thirteen subjects, positive for S. aureus carriage, were recruited from the William S. Middleton Memorial Medical Center, Madison, WI, USA, and randomized by initial site of colonization, either gastrointestinal (GI) or extra-GI, to 4-weeks of oral L. rhamnosus HN001 probiotic, or placebo. Nasal, oropharyngeal, and axillary/groin swabs were obtained, and serial blood and fecal samples were collected. Differences in prevalence of S. aureus carriage at the end of the 4-weeks of treatment were assessed.ResultsThe probiotic and placebo groups were similar in age, gender, and health history at baseline. S. aureus colonization within the stool samples of the extra-GI group was 15% lower in the probiotic than placebo group at the endpoint of the trial. Those in the probiotic group compared to the placebo group had 73% reduced odds (OR 0.27, 95% CI 0.07–0.98) of methicillin-susceptible S. aureus presence, and 83% reduced odds (OR 0.17, 95% CI 0.04–0.73) of any S. aureus presence in the stool sample at endpoint.ConclusionUse of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites.Trial registrationClinicalTrials.gov Identifier: NCT01321606. Registered March 21, 2011.

On the hands of patients with Clostridium difficile: A study of spore prevalence and the effect of hand hygiene on C difficile removal

HighlightsClostridium difficile may remain on a high proportion of patient hands after typical soap and water use.New C difficile contamination can occur immediately after patient hand hygiene.Prevalence of C difficile on patient hands may be low while on treatment. &NA; The prevalence of Clostridium difficile spores was assessed in 48 observations of infected inpatients. Participants were randomized to hand hygiene with either alcohol‐based handrub or soap and water. C difficile was recovered in 14.6% of pre‐hand hygiene observations. It was still present on 5 of these 7 participants after hand hygiene (3/3 using alcohol‐based handrub; 2/4 using soap and water).

Regional differences in vancomycin-resistant Enterococcus colonization rates in critically ill veterans

Screening for vancomycin-resistant Enterococcus (VRE) has not been universally implemented within the Department of Veterans Affairs (VA). A prospective study was conducted to identify the admission prevalence rate of VRE in patients admitted to the intensive care unit in 2 VA facilities. Significant regional differences were found between the 2 facilities. Further studies are needed to account for regional differences in VRE admission prevalence, to optimize infection control interventions.