Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses. METHODS: In this prospective cohort study, all consenting eligible CPE carriers received oral capsulized FMT for 2 days. Primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by polymerase chain reaction. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed. RESULTS: Fifteen CPE carriers received FMT, 13 of whom completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants who achieved CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes. CONCLUSIONS: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication. CLINICAL TRIALS REGISTRATION: NCT03167398.

Does early corticosteroid therapy affect prognosis in IBD patients hospitalized with Clostridioides difficile infection?

BACKGROUND: Corticosteroids (CS) therapy to Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) flares may worsen CDI outcomes. AIM: Assess the impact of early CS exposure on outcomes of IBD patients diagnosed with CDI. METHODS: Retrospective study of IBD patients admitted with first-time CDI between 2002 and 2018. Comparisons were made based on CS exposure 48 h from admission. Patients were further subdivided to 5 groups based on CS-antibiotics temporal exposure. The primary outcome was all-cause mortality or colectomy within 3 months. Secondary outcomes were colectomy and mortality rates at 1 year, length of stay, readmissions, bacteremia, and diarrhea improvement by day 7/discharge. Cox proportional hazard model and Kaplan-Meier curves were used to assess the effects on survival. Logistic and ordinal regressions were used to assess primary and secondary outcomes. RESULTS: One hundred thirteen patients (64 CD, 46 UC, and 3 IBDU) were included, 82 (72.5%) received early CS. At baseline, CRP was significantly lower and albumin was higher in the group not exposed to early CS. At 3 months, 4 (4.8%) patients required colectomy and 6 (5.8%) died (p = NS). Length of stay was significantly reduced among patients not exposed to early CS. All other endpoints were not associated with CS exposure. In subgroup analysis, the primary outcome was not significantly different among the sub-groups. Mortality rate at 1 year was significantly lower in patients who did not receive antibiotics for CDI. CONCLUSION: Early CS therapy in IBD patients hospitalized with CDI is not associated with worse clinical outcomes. However, additional prospective research is required.

Tensile Behavior and Evolution of the Phases in the Al10Co25Cr8Fe15Ni36Ti6 Compositionally Complex/High Entropy Alloy.

Compositionally complex alloys, or high entropy alloys, are good candidates for applications at higher temperatures in gas turbines. After their introduction, the equiatomic Al17Co17Cr17Cu17Fe17Ni17 (at.%) served as a starting material and a long optimization road finally led to the recently optimized Al10Co25Cr8Fe15Ni36Ti6 (at.%) alloy, which shows promising mechanical properties. Investigations of the as-cast state and after different heat treatments focus on the evolution of the microstructure and provide an overview of some mechanical properties. The dendritic solidification provides two phases in the dendritic cores and two different ones in the interdendritic regions. Three of the four phases remain after heat treatments. Homogenization and subsequent annealing produce a γ-γ' based microstructure, similar to Ni-based superalloys. The γ phase is Co-Cr-Fe rich and the γ' phase is Al-Ni-Ti rich. The understanding of the mechanical behavior of the investigated alloy is supported and enhanced by the study of the different phases and their nanohardness measurements. The observations are compared with mechanical and microstructural data from commercial Ni-based superalloys, Co-based alloys, and Co-Ni-based alloys at the desired application temperature of ~800 °C.

Influence of W, Mo and Ti trace elements on the phase separation in Al8Co17Cr17Cu8Fe17Ni33 based high entropy alloy.

Compositionally complex alloys, also called high entropy alloys, have been investigated for over a decade in view of different applications, but so far only a small number of alloys can be considered as presenting good enough properties for industrial application. The most common family of elements is Al-Co-Cr-Cu-Fe-Ni. The equiatomic alloy having 5 phases and being too brittle, the composition has been modified in order to improve the mechanical properties. Different compositions have been tested and as a first result ductile Al8Co17Cr17Cu8Fe17Ni33 has been chosen for deeper investigation. It shows a dendritic segregation into Co-Cr-Fe rich cores and Al-Cu-Ni rich interdendritic sites. The as-cast state is characterized mainly by two phases, namely Al-Cu-Ni rich precipitates of L12 structure inside a solid solution matrix. After homogenization both alloys consists of a single solid solution phase. Results are compared to calculations by ThermoCalc. In order to further improve the properties of the alloy the Cr content has been decreased and replaced by trace elements W, Mo and Ti, which, according to ThermoCalc, increase the melting point and the phase transition temperature which leads to the formation of the L12 phase. As-cast and heat treated samples of the base and the modified alloy have been investigated by transmission electron microscopy and three dimensional atom probe. Results of the investigations will be discussed in terms of microstructure, hardness and coherence with Thermo Calc predictions.