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.

The Effect of Aeration for 6-Pentyl-alpha-pyrone, Conidia and Lytic Enzymes Production by Trichoderma asperellum Strains Grown in Solid-State Fermentation

International audienceIn recent years, the production of biopesticides has gained great attention in the scientific word because it is an important alternative to replace the much debated chemical pesticides used on the field crops. Fungal lytic enzymes, conidia and secondary metabolites like 6 pentyl-alpha-pyrone (6-PP) play a very important role in the biological control of pests. On the present study, the influence of application of air through a solid-state fermentation using three Trichoderma asperellum strains to produce conidia, 6-PP and essential enzymes were evaluated. A mix of vine shoots, potatoes flour, jatropha, olive pomace and olive oil as substrates was used. T. asperellum TV104 showed the best 6-PP production (3.06 ± 0.15 mg g DM−1), cellulases activities (34.3 ± 0.4 U g−1), and amylase activity (46.3 ± 0.6 U g−1) however, T. asperellum TF1 produced the higher levels of lipase (30.6 ± 0.3 U g−1), under air conditions. The production of these same enzymes was less efficient without the application of forced aeration. The forced aeration increased the conidia production, the best value was observed with T. asperellum TF1 (2.23 ± 0.07 × 109 g DM−1)

Aroma compounds production by solid state fermentation, importance of in situ gas-phase recovery systems

International audienceFlavour and fragrance compounds are extremely important for food, feed, cosmetic and pharmaceutical industries. In the last decades, due to the consumer's increased trend towards natural products, a great interest in natural aroma compounds has arisen to the detriment of chemically synthesised ones. Recently, solid state fermentation (SSF) has been applied in the production of many metabolites. Aroma compounds can be produced by SSF with a higher yield compared to submerged fermentation (SmF). In SSF processes, aroma compounds can be produced in the solid matrix or in the headspace, but they can be lost or stripped when aeration is required. This review focuses on the production of aroma compounds by SSF processes with a special highlight on in situ systems to recover the volatiles released in the gaseous phase and stripped due to aeration. Following a brief presentation of specificities of SSF processes concerning the choice of microorganisms and the solid matrix used for the production of aroma compounds, bioreactor aspects, factors affecting production of aroma compounds and in situ gas phase aroma recovery systems in aerated SSF bioreactors are discussed