Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

In vitro propagation and germplasm conservation of wild orchids from South America

Orchids are an important part of plant biodiversity on this planet due to their high variability among species and their habitats. South America represents more than thirty percent of all known orchid species, Colombia, Ecuador, Brazil, Peru, and Bolivia being among the richest countries in the world in terms of orchid biodiversity. Nevertheless, concerning the orchid conservation status, in Colombia precisely orchids occupy the unlucky first place as the plant family with the highest number of threatened species. There is a similar situation in the rest of the South American countries. The two main threats to orchid survival are both anthropogenic: the first one is deforestation, and the second largest threat to orchids is collection from the wild. One desirable action to safeguard these endangered species is to develop procedures that make possible their massive propagation, which would provide material for both environmental restoration and commercial purposes avoiding extractions from nature. Likewise, the development of systems that allow the ex situ conservation of orchid germplasm is imperative. This chapter reviews the progresses of different in vitro approaches for orchid propagation and germplasm conservation, safeguarding the genetic biodiversity of these species. Several study cases are presented and described to exemplify the protocols developed in the Botanical Institute of Northeast (UNNE-CONICET) for propagating and long-term storing the germplasm of wild orchids from Argentina (Cattleya lundii, Cohniella cepula, C. jonesiana, Gomesa bifolia, Aa achalensis, Cyrtopodium brandonianum, C. hatschbachii, Habenaria bractescens). Moreover, it has been attempted to put together most of the available literature on in vitro propagation and germplasm conservation for South American orchids using different explants and procedures. There are researches of good scientific quality that even cover critical insights into the physiology and factors affecting growth and development as well as storage of several orchid materials. Moreover, studies are still necessary to cover a major number of South American species as well as the use of selected material (clonal) for both propagation and conservation approaches.Fil: Dolce, Natalia Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Medina, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Terada, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: González Arnao, María Teresa. Universidad Veracruzana; MéxicoFil: Flachsland, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentin