Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial.

BACKGROUND: Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI. METHODS: In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available. RESULTS: The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon. CONCLUSIONS: In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations. CLINICAL TRIALS REGISTRATION: NCT01226992.

A dose-ranging study of a subunit Respiratory Syncytial Virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age.

We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.

Comparison of the safety and immunogenicity of 2 respiratory syncytial virus (rsv) vaccines--nonadjuvanted vaccine or vaccine adjuvanted with alum--given concomitantly with influenza vaccine to high-risk elderly individuals.

BACKGROUND: Respiratory syncytial virus (RSV) has been recognized recently as an important adult pathogen. METHODS: This randomized, double-blind, placebo-controlled study was designed to compare humoral responses to licensed trivalent influenza vaccine given concomitantly with 1 of 2 RSV vaccine formulations in persons > or =65 years old with cardiopulmonary disease. Hemagglutinin-inhibition assays and neutralization assays were used to measure levels of antibody to influenza and RSV, respectively. Subjects with respiratory illnesses during subsequent winters were tested for RSV and influenza by reverse-transcriptase polymerase chain reaction and serologic analysis. RESULTS: Neither RSV vaccine formulation had an effect on the humoral response to influenza vaccination, and both RSV vaccines were well tolerated by 1169 participants. The immunogenicity of the nonadjuvanted vaccine was judged superior on the basis of mean postvaccination neutralizing antibody titers (12.5 vs. 12.1) and the percentage of subjects for whom > or =4-fold increases in neutralizing titer were observed when acute-phase and convalescent-phase serum samples were compared (168 [44%] of 383 vs. 129 [33%] of 400). In year 1, the percentage of illnesses due to RSV was 7% (36 of 492 illnesses) and that due to influenza was 8% (40 of 492), compared with 6% (11 of 189) due to RSV and 11% (20 of 189) due to influenza in year 2. The incidence of RSV infection was not significantly different in the RSV vaccine and placebo groups. CONCLUSIONS: Although the safety and immunogenicity data of these RSV vaccines are encouraging, low rates of infection make it challenging to design efficacy trials.

Respiratory syncytial virus vaccine: Is it coming?

Respiratory syncytial virus (RSV) is recognized as an important cause of childhood morbidity and mortality. Vaccine development has been challenging in young infants and has required the advent of molecular technologies to optimize the safety profile, while maintaining immunogenicity of live-attenuated vaccines. Protein-based vaccines have been evaluated in clinical trials and are promising candidates for RSV-primed populations or for maternal vaccination to provide early life protection. This review provides a summary of the need for an RSV vaccine, as well as the challenges and progress in the vaccine's development.