Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

[Organization for the coverage of the transfusional needs of patients with hemoglobinopathy at the Établissement français du sang Bretagne]. / Organisation de la prise en charge des besoins transfusionnels des patients atteints d'hémoglobinopathie à l'Établissement français du sang Bretagne.

UNLABELLED: Brittany is a low prevalence region for hemoglobinopathies. Despite of that, the number of patients is increasing each year. In 2013, 140 patients were known at the EFS Bretagne, and medical consultations are growing for 50% each year since 2011. The consequence is an increase of needs of 22% of compatible packed red blood cells. To anticipate the announced progress, various actions were implemented as study groups, creation of a new informatic prescription for red blood cells phenotyping, promotion of donation, transfusion organisation. RESULTS: Fifthty-nine percent of the 400 ABO RH-KELL, FY, JK, MNS 3, 4, red blood cells were realised on the basis of this new informatic prescription, as the 99% of the packed red blood cells identified Fy (a- b-). So, 92% of the compatible transfused packed red blood cells were already in stock when the patients needed them. CONCLUSIONS: In Brittany, that organisation leads to assume qualitative and quantitative transfusion for sickle cell disease in more than 90% of cases, with fast distribution. In the same time promotion of donation is done to increase the diversity of donors.

Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis - current evidence and potential clinical applications.

BACKGROUND: Gastrointestinal mucositis is defined as inflammation and/or ulcers of the gastrointestinal tract occurring as a complication of chemotherapy and radiation therapy, and affects about 50% of all cancer patients. AIM: To assess the role of gut microbiota in the pathogenesis of gastrointestinal mucositis and the potential for manipulations of the microbiota to prevent and to treat mucositis. METHODS: Search of the literature published in English using Medline, Scopus and the Cochrane Library, with main search terms 'intestinal microbiota', 'bacteremia', 'mucositis', 'chemotherapy-induced diarrhoea', 'chemotherapy-induced mucositis', 'radiotherapy-induced mucositis'. RESULTS: The gut microbiota plays a major role in the maintenance of intestinal homoeostasis and integrity. Patients receiving cytotoxic and radiation therapy exhibit marked changes in intestinal microbiota, with most frequently, decrease in Bifidobacterium, Clostridium cluster XIVa, Faecalibacterium prausnitzii, and increase in Enterobacteriaceae and Bacteroides. These modifications may contribute to the development of mucositis, particularly diarrhoea and bacteraemia. The prevention of cancer therapy-induced mucositis by probiotics has been investigated in randomised clinical trials with some promising results. Three of six trials reported a significantly decreased incidence of diarrhoea. One trial reported a decrease in infectious complications. CONCLUSIONS: The gut microbiota may play a major role in the pathogenesis of mucositis through the modification of intestinal barrier function, innate immunity and intestinal repair mechanisms. Better knowledge of these effects may lead to new therapeutic approaches and to the identification of predictive markers of mucositis.

Beneficial effects of probiotics in upper respiratory tract infections and their mechanical actions to antagonize pathogens.

Probiotics are live micro-organisms with beneficial effects on human health, which have the ability to counteract infections at different locations of the body. Clinical trials have shown that probiotics can be used as preventive and therapeutic agents in upper respiratory tract infections (URTIs) and otitis. Their mechanical properties allow them to aggregate and to compete with pathogens for nutrients, space and attachment to host cells. Consequently, they can directly antagonize pathogens and thus exert beneficial effects without directly affecting the metabolism of the host. An overview of the probiotics with such traits, tested up to date in clinical trials for the prevention or treatment of URTIs and otitis, is presented in this review. Their mechanical properties in the respiratory tract as well as at other locations are also cited. Species with interesting in vitro properties towards pharyngeal cells or against common respiratory pathogens have also been included. The potential safety risks of the cited species are then discussed. This review could be of help in the screening of probiotic strains with specific mechanical properties susceptible to have positive effects in clinical trials against URTIs.

[Study of four kits used for titration of tetanus antibody for selection of plasma donors intended to fractionation]. / Etude de quatre trousses de titrage des anticorps antitétaniques pour la sélection des plasmas destinés au fractionnement (LFB).

UNLABELLED: Antitetanus antibodies titration is carried out by French National Blood Services (FNBSs) with the aim of seeking donors whose title of antibodies are greater or equal to 8 IU/ml. Different kits are used: ELISA antitetanus toxoid IgG (The Binding Site), ELISAT (Diagast), tetanus toxoid IgG ELISA (Diamed), ELISA IgG tetanus (Ingen). As the results obtained using these different reagents show some discrepancies with the control results carried out by the Laboratoire Français des Biotechnologies (LFB), it appeared necessary to harmonize the selection practices. With this intention a study of the different kits was initiated. METHOD: Different samples were used during this evaluation: (1) the Reference Control (RC) used by the FNBS; (2) a serum sample of high title; (3) a range of dilution of national standard. The following tests were carried out: (1) robustness with the evaluation of the contamination and the board effect; (2) linearity and repeatability (eight deposits of each standard, RC and points of national standard dilutions); (3) reproducibility; (4) homogeneity. After automatic dilution of the samples, the plates were then processed according to the protocol of the manufacturer. RESULTS: The study gives the CV in percentage of repeatability and reproducibility, the values of the standards provided as well as the bias compared to the RC and the uncertainty of measurements. CONCLUSION: This study gave the possibility to rank each kit compared to RC and to specify the variations which surround each result. This variation can explain the discrepancy of conformity of plasma when title is close to the threshold of selection.

[Equipment qualification]. / Qualification des matériels.

The qualification of the equipment is a particularly important stage in the transfusional process. On the one hand, of many standards such as those of certification or that of accreditation require it, just as the good transfusional practices; in addition, the practices of steps of quality assurance develop this aspect. Indeed, the absence of the realization of this qualification of material having an influence on the finished product, can lead to an error in the product. This qualification passes by various stages of which some are major such as the drafting of the schedule of conditions, the drafting of the operational protocol of qualification, the decision made for the setting in routine. Finally so that this qualification takes all its dimensions it is necessary to carry out methods linked to the international system of measurement. Moreover certain questions after reflexions must find response such as which unit to check, and only this one, the equipment is - it a complex one, is there a maintenance contract? Once all these elements taken into account, the questions having found their answer, the operational protocol will then well be built, the decisions of settings in routine could be done and the sets of the finalized stages.

Relationships between susceptibility to LAK cell-mediated lysis, conjugate formation and expression of adhesion molecules in B-cell derived non-Hodgkin's lymphomas.

Adoptive immunotherapy with LAK cells has been investigated for the treatment of B-cell-derived lymphomas, but only a few significant tumor regressions were obtained. In order to explain this refractory state, the sensitivity to normal LAK-mediated lysis of 30 non-Hodgkin's lymphoma (NHL) malignant B-cells was determined using flow cytofluorimetry. A large heterogeneity was found, and we report a close correlation (p < 0.001) between the extent of lysis of malignant B-cells and their ability to form conjugates with LAK cells; which is the first step in LAK-mediated cytolysis. The levels of expression of HLA class I molecules, LFA-1 (CD11a/CD18), CD54 and CD58 were also studied and found to be expressed very heterogeneously. CD54 expression on malignant B-cells plays a major role in the initial conjugate formation with LAK cells (p < 0.001), and this was confirmed by inhibition experiments. Our results suggest that a weak expression of CD54 could constitute one mechanism by which NHL tumor B-cells escape natural immune surveillance and resist LAK cells immunotherapies.

Autotumour reactive T-cell clones among tumour-infiltrating T lymphocytes in B-cell non-Hodgkin's lymphomas.

Seventy-three T-cell clones (TCC) were established from tumour-infiltrating lymphocytes-T (TIL-T) derived from lymph nodes involved by B-cell non-Hodgkin's lymphomas (B-NHL) in nine patients with different histological subtypes and clinical stages. 40 TCC (55%) expressed the CD25 Ag and were also able to proliferate in the presence of irradiated autologous B-NHL cells. Among them, 23 autotumour (AuTu) proliferative TCC were found not to proliferate to autologous EBV-transformed B-cell lines, indicating that the proliferative reactivity of these TCC was preferentially directed at autologous B-NHL cells. Tested against autologous B-NHL cells, only three AuTu proliferative TCC (CD8+) showed a significant level of cytotoxicity (specific lysis > 15%). In blocking experiments, the AuTu proliferative reactivity of three TCC from one patient was strongly inhibited by anti-DR and anti-DQ mAbs, whereas that of three TCC from another patient was not affected by either anti-MHC class I or class II (DR, DP, DQ) mAbs. These findings suggest that the recognition of autologous B-NHL cells by AuTu proliferative TCC may occur through MHC-restricted as well as MHC-unrestricted mechanisms.