Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention. OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada. INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%. RESULTS: A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups. CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.

Large community outbreak of Streptococcus pneumoniae serotype 5 invasive infection in an impoverished, urban population.

BACKGROUND: Streptococcus pneumoniae is a common cause of sporadic invasive infections, but outbreaks of invasive pneumococcal disease are infrequent. In August 2006, a sudden increase in the number of patients presenting with invasive pneumococcal disease was noted at St. Paul's Hospital (Vancouver, Canada). Most patients with severe disease resided in an area referred to as the Downtown Eastside, a neighborhood known for its high rates of poverty and illicit drug use. METHODS: Prospective, laboratory-based surveillance for invasive pneumococcal disease was initiated, including on-site serotyping of S. pneumoniae isolates. A vaccination campaign using 23-valent polysaccharide pneumococcal vaccine was launched in the Downtown Eastside. Multiple logistic regression was used to examine the association of sociodemographic variables and medical risk factors with S. pneumoniae serotype status. RESULTS: A single S. pneumoniae serotype (serotype 5) was responsible for 78% of invasive pneumococcal disease cases (137 of 175 cases) during the outbreak period of August 2006-July 2007. The outbreak strain, although fully susceptible to penicillin, caused significant morbidity and placed considerable strain on the acute care system within the Vancouver Coastal Health region. Crack cocaine use was found to be the main independent risk factor associated with invasive pneumococcal disease due to S. pneumoniae serotype 5 (odds ratio, 12.4; 95% confidence interval, 2.22-69.5). CONCLUSIONS: A targeted vaccination campaign using polysaccharide pneumococcal vaccine appeared to help control this outbreak. In urban centers with high rates of illicit drug use, vaccination strategies for preventing invasive pneumococcal disease may need to be refined to include individuals who use crack cocaine.

Antimicrobial activities of sesquiterpene lactones and inositol derivatives from Hymenoxys robusta.

Six compounds from the aerial parts of the Argentinean plant Hymenoxys robusta (Rusby) Parker were isolated and their structures elucidated using extensive spectroscopic analyses. These compounds comprise two inositol derivatives and four 3,4-seco-pseudoguaianolides, including vermeerin. Bioactivity assays of these compounds against bacterial and fungal pathogens showed that only vermeerin possessed antimicrobial activity specific against Staphylococcus aureus, and showed no toxicity when exposed to human-derived macrophages.