Bartonella gabonensis sp. nov., a new bartonella species from savannah rodent Lophuromys sp. in Franceville, Gabon.

We describe a new strain named Bartonella gabonensis sp. nov. strain 669T (CSURB1083). The entire genome of this strain is described here. It was isolated from a savannah rodent, a brush-furred rat (Lophuromys sp.), trapped the city of Franceville in Gabon, in Central Africa. B. gabonensis is an aerobic, rod-shaped and Gram-negative bacterium. On the basis of the organism's features, and following a taxonogenomic approach, we propose the creation of the species Bartonella gabonensis sp. nov.

Taxonogenomics description of Bacillus dakarensis sp. nov., Bacillus sinesaloumensis sp. nov. and Bacillus massiliogabonensis sp. nov., three new species isolated from human stools.

Using microbial culturomics, three Bacillus strains were isolated, identified and characterized following the taxonogenomics strategy. Bacillus dakarensis strain Marseille-P3515T (=CSURP3515), Bacillus sinesaloumensis strain Marseille-P3516T (=CSURP3516), and Bacillus massiliogabonensis strain Marseille-P2639T (=CSURP2639) were isolated from human stool samples. The phylogenetic analysis, phenotypic characteristics and genotypic data presented here prove that these three bacteria are different from previously known bacterial species with standing in nomenclature and represent new Bacillus species.

Description of Clostridium cagae sp. nov., Clostridium rectalis sp. nov. and Hathewaya massiliensis sp. nov., new anaerobic bacteria isolated from human stool samples.

Using culturomics methods, three strains were isolated, identified and characterized following the taxonogenomics concept. Clostridium cagae strain Marseille-P4344T (=CSURP4344), Clostridium rectalis strain Marseille-P4200T (=CSURP4200) and Hathewaya massiliensis strain Marseille-P3545T (=CSURP3545) were isolated from human stool samples. The phylogenetic reconstruction, phenotypic criteria and genomic analyses were carried out and demonstrated that these three bacteria are different from previously known bacterial species with standing in nomenclature and were classified as new members of the Clostridiaceae family.

Genome sequence and description of Urinicoccus timonensis gen. nov., sp. nov., a new bacterium isolated from a human stool sample.

Urinicoccus timonensis gen. nov., sp. nov. strain Marseille-P3926T is a new species from the phylum Firmicutes and the family Peptoniphilaceae that was isolated from a human faeces sample. Genome was 1 978 908 bp long with a 41.1 G + C content. The closest species based on 16S ribosomal RNA was Peptoniphilus ivorii DSM 10022 with 90.8% sequence similarity. Considering phenotypic features, 16S rRNA sequence and comparative genome studies, we proposed Marseille- P3926T as the strain type of Urinicoccus timonensis gen. nov., sp. nov.

Massilistercora timonensis gen. nov., sp. nov., a new bacterium isolated from the human microbiota.

Massilistercora timonensis gen. nov., sp. nov. strain Marseille-P3756T is a new species of the phylum Firmicutes; it was isolated from the human gut microbiota and has a genome of 2 769 591 bp (51.2% G + C). The closest species based on 16S rRNA sequence was Merdimonas faecis strain BR31 with 95.2 % sequence similarity. Considering phenotypic features and comparative genome studies, we proposed the strain Marseille-P3756T as the type strain of Massilistercora timonensis sp. nov., a new species within the genus Massilistercora.

Anaerococcus marasmi sp. nov., a new bacterium isolated from human gut microbiota.

Anaerococcus marasmi sp. nov. strain Marseille-P3557T is a new species isolated from a stool of a Nigerian child with marasmus. The genome of Marseille-P3557T was 2 130 060 bp long (35.4% G + C content). The closest species based on 16S ribosomal RNA sequence was Anaerococcus prevotii strain 20548, with 97.6% sequence similarity. Considering phenotypic features and comparative genome studies, we propose the strain Marseille-P3557T as the type strain of Anaerococcus marasmi sp. nov., a new species within the genus Anaerococcus.

Parabacteroides bouchesdurhonensis sp. nov., a new bacterium isolated from the stool of a healthy adult.

Parabacteroides bouchesdurhonensis strain Marseille-P3763T (= CSURP3763) is a new species isolated from the stool of a heathy adult.

Clostridium transplantifaecale sp. nov., a new bacterium isolated from patient with recurrent Clostridium difficile infection.

Clostridium transplantifaecale strain Marseille-P8228T (= CSURP8228) is a new species isolated from a patient with recurrent Clostridium difficile infection.

Olsenella timonensis sp. nov., a new bacteria species isolated from the human gut microbiota.

Olsenella timonensis sp. nov., strain Marseille-P2300T (= CSUR P2300; =DSM102072), is a new bacterial species from the phylum Firmicutes in the family Atopobiaceae.This bacteria species was isolated from the human gut microbiota.

Massilicoli timonensis sp. nov., a new bacterium isolated from the human microbiota.

Massilicoli timonensis sp. nov., strain Marseille-P3755T (= CSUR P3755 = DSM 103513) is a new bacterial species from the phylum Firmicutes and the family Clostridiales which was isolated from the human gut microbiota.

Genome sequence and description of Bacteroides bouchesdurhonensis sp. nov., a new anaerobic bacterium isolated from the human gut.

Bacteroides bouchesdurhonensis sp. nov., strain Marseille-P2653T (= CSUR; P2653=DSM103120) is a new bacterial species belonging to the Firmicutes phylum in the family Bacteroidaceae that was isolated from the human gut microbiota.

Massilimicrobiota timonensis gen. nov., sp. nov., a new bacterium isolated from the human gut microbiota.

Massilimicrobiota timonensis gen. nov., sp. nov. strain Marseille-P2264 is a new species from Firmicutes phylum isolated from the human gut. Its genome was 2,849,574 bp-long with a 31.8% G+C content. The closest species based on 16S rRNA sequence was Longibaculum muris with 95.6% sequence similarity. Considering phenotypic features, 16S rRNA sequence and comparative genome studies, we proposed Marseille-P2264 as the type strain of Massilimicrobiota timonensis gen. nov., sp. nov.

[Aseptic process validation and stability study of an injectable preparation of fructose (5%)-glycerol (10%) as part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract]. / Validation du procédé aseptique et étude de stabilité d'une préparation injectable de fructose (5 %)-glycérol (10 %) dans le cadre d'un programme hospitalier de recherche clinique portant sur le traitement curatif endoscopique des lésions néoplasiques épithéliales précoces du tube digestif.

INTRODUCTION: As part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract, a new hospital sterile and non-pyrogenic preparation of fructose (5%)-glycerol (10%) was realized. Under pharmaceutical legislation, the provision of this hospital preparation involves of aseptic process validation and achieve a stability study. MATERIALS AND METHODS: After the aseptic process validation with Mediafill Test, the preparation was made under aseptic conditions associated with a sterilizing filtration according to the good practices preparation. Prepared flexible bags (100mL of solution) were stored for one year in a climatic chamber (25±2°C). To assess stability, the physicochemical controls (fructose concentration, glycerol concentration, hydroxy-methyl-5 furfural [5-HMF] concentration, sodium concentration, pH measure, osmolality and sub-visible particles count) and microbiological (bioburden, bacterial endotoxin and sterility) were performed at regular intervals for one year. RESULTS: Neither significant decrease of fructose concentration, glycerol concentration and sodium concentration nor pH, 5-HMF, osmolality variations out of specifications were observed for one year. The sub-visible particles count, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The hospital preparation was stable over one year at 25±2°C, ensuring safe administration in humans within the framework of this clinical research.

[Advantages and special features of hospital preparations of parenteral nutrition in neonatalogy]. / Avantages et spécificités des préparations hospitalières de nutrition parentérale en néonatalogie.

INTRODUCTION: The care of premature infants requires specific, suitable parenteral nutrition, in which the dosage must be frequently adjusted. METHOD: A comparative analysis of four industrial standard parenteral nutrition formulations NP 100®, Pediaven AP-HP Nouveau-né 1®, Pediaven AP-HP Nouveau-né 2® and Numetah G13% E® and of two hospital preparations made specifically in hospital pharmacies produced by two separate university hospitals (Nutrine® HCL and Formule standardisée début de nutrition) was conducted. The comparison between the formulations focused on electrolytic compositions and protein/energy ratio. RESULTS: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are free from (i) sodium and potassium, (ii) potassium respectively. Almost equivalent sodium concentration (19-27 mM) and more variable potassium concentration (∼9-26 mM) characterize the other formulations. Protein/energy ratio of Numetah G13% E®, Nutrine® HCL and Formule standardisée début de nutrition is 58% higher than that of NP 100®, Pediaven AP-HP Nouveau-né 1® and Pediaven AP-HP Nouveau-né 2®. DISCUSSION: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are in accordance with the recommendations about hydro-electrolytic supplies during transition phase. Nutrine® HCL complies best to the recommendations about hydro-electrolytic account during stabilization phase. CONCLUSION: Hydro-electrolytic composition and protein/energy ratio of standard hospital parenteral nutrition formulations comply best to nutritional needs of premature infants.

[Injectable hospital preparation of valine labeled with the carbon 13 and nitrogen 15 (5 mg/mL) for a clinical trial on the brain tumor metabolism: Pharmaceutical control of active pharmaceutical ingredient and stability study of the finished product]. / Préparation hospitalière injectable de valine marquée au carbone 13 et à l'azote 15 (5mg/mL) pour un essai clinique sur le métabolisme tumoral cérébral : contrôle pharmaceutique de la substance active et étude de stabilité du produit fini.

INTRODUCTION: The L-Valine labeled (L-[U-(13)C,(15)N] Val) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the brain tumor metabolism. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of active pharmaceutical ingredient followed by stability study of hospital preparation were realised. MATERIALS AND METHODS: After the pharmaceutical control of the L-[U-(13)C,(15)N] Val, the hospital preparation was prepared according to the good manufacturing preparation. Prepared bottles were stored at 5°C±3°C and 25°C±2°C for six months. The stability of the preparation was determined by physico-chemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C,(15)N] Val concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility). RESULTS: Concentrations of L-[U-(13)C, (15)N] Val and sodium does not significantly decrease during the stability study. In parallel, no change in pH and osmolality were highlighted. Isotopic enrichment higher than 99.9% reflected the stability of labeling of L-valine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European Pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The stability of this hospital preparation of L-[U-(13)C, (15)N] Val has been demonstrated for six months at 5°C±3°C and 25°C±2°C, ensuring a parenteral administration as part of the clinical trial.

[Pharmaceutical involvement in academic clinical trials: Quality assessment of pharmaceutical manufacturing operations]. / Implication pharmaceutique dans le cadre d'essais cliniques institutionnels : évaluation de la qualité des opérations de mise sous forme pharmaceutique.

INTRODUCTION: For academic clinical trials, the hospital pharmacy may be required to perform the specific activity of preparing investigational drugs. MATERIAL AND METHODS: With regards to such activity, and in light of the recent changes in the regulatory environment, the main objective of this study was to evaluate whether quality levels and traceability were in compliance with the applicable regulatory standards. In order to do so, two internal audits have been conducted, the first on the compliance of operations with existing regulatory standards and the second on the quality of traceability of the operations. RESULTS: The proportion of academic clinical trials is constantly growing and currently represents 41% of the total clinical trials in the establishment. An average of 29,000 therapeutic units of investigational drugs are prepared each year (84% under the form of capsules). An overall conformity level of 75% and 88% has been identified in the aforementioned audits, respectively. Such audits have also allowed for the identification of weaknesses in current practices as well as potential improvement areas to achieve better compliance. DISCUSSION: The hospital pharmacy can provide expertise for the preparation of specific dosage or drugs that are not available on the market. It also can be involved for the conception of appropriated packaging function of the study design. CONCLUSION: Results of audits encourage us to continue this activity with a satisfactory level of quality in accordance with the necessary requirements to ensure the safety of patients and the quality of clinical trials conducted.

[Injectable preparation of labeled leucine with the carbon 13 for a clinical research program on the Alzheimer disease: pharmaceutical control of raw materials and the finished product and stability study]. / Préparation injectable de leucine marquée au carbone 13 pour un programme de recherche clinique sur la maladie d'Alzheimer : contrôle pharmaceutique des matières premières et du produit fini et étude de stabilité

INTRODUCTION: The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the diagnosis of the Alzheimer's disease. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of raw materials and the finished product followed by a stability study were realised. MATERIALS AND METHOD: After the pharmaceutical control of raw materials, the solution of L-[U-(13)C] Leu was prepared according to the good practices preparation. Prepared bottles were stored for 1 year of a share in a climatic chamber (25 °C±2 °C) and the other in a refrigerator (5 °C±3 °C). To assess stability, the physicochemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1 year. RESULTS: Neither significant decrease of L-[U-(13)C] Leu concentration and sodium concentration nor pH and osmolality variation were observed for 1 year. Isotopic enrichment higher than 99.9% reflected the stability of labelling of L-leucine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The injectable preparation of L-[U-(13)C] Leu was stable after 1 year for two preservation conditions, ensuring to safety for administration for human within the framework of this clinical research.

[Depyrogenation test regarding inox and glass containers in the preparation of parenteral nutrition mixtures]. / Test de dépyrogénation des conteneurs en inox et en verre pour la préparation des mélanges pour nutrition parentérale.

INTRODUCTION: The preparation of parenteral nutrition mixture (PNM) in an open chamber requires the use of intermediate containers sterile and non-pyrogenic. A sterilization of containers by moist heat in large autoclaves is the suitable method. However, sterilization by moist heat is not a depyrogenation method. In our study, we report the validation of a sterilization and depyrogenation method for containers by dry heat using a convection oven. MATERIALS AND METHODS: Sterilization and depyrogenation of material by dry heat have been audited by the reduction of at least three logarithms of original endotoxin rate. The containers were initially artificially contaminated with a suspension of endotoxin for 16 hours. Contaminated containers were placed in an oven with revolving heat at 250 °C for 1 hour. After treatment with dry heat, the residual endotoxin levels in the containers were determined by a kinetic chromogenic method. RESULTS: After treatment with dry heat, the average log reductions of endotoxin levels were respectively, for glass and steel containers, 4.78 ± 0.07 and 4.87 ± 0.03. DISCUSSION AND CONCLUSION: The present validation study confirms the effectiveness of treatment with dry heat for sterilization and depyrogenation of glass and steel containers. This method of sterilization and depyrogenation meets the microbiological quality requirements for the preparation of MNP.

[Validation of pharmaceutical quality of a [6,6-(2)H(2)]-glucose parenteral solution used for insulin-resistance measurement during human clinical trials]. / Validation de la qualité pharmaceutique de préparations de [6,6-(2)H(2)]-glucose en solution aqueuse administrées par voie parentérale pour la mesure de l'insulino-résistance dans le cadre d'essais cliniques.

INTRODUCTION: Deuterated glucose ([6,6-(2)H(2)]-glucose) is a stable isotopic tracer administered parenterally in healthy volunteers, obese or diabetic patients in clinical trial to study glucose metabolism during euglycemic hyperinsulinemic clamps. In accordance with the Health Authorities on drug safety, we evaluated the pharmaceutical quality of this preparation for biomedical research with a stability study. METHODS: After pharmaceutical qualification of the raw material, the [6,6-(2)H(2)]-glucose was dissolved in water for injection, then sterile, filtered under positive pressure of nitrogen and then autoclaved. Two batch products (500mg/10mL and 2g/15mL) were sampled to evaluate glucose alteration, isotope shift, limpidity, apyrogenicity and sterility at regular intervals for 2 years. Deuterated glucose solutions were stored in the dark, at +2°C+8°C, in type II glass bottles. RESULTS: Neither significant decrease of glucose concentration nor pH variation were observed for 2 years. The 5-hydroxymethylfurfural concentration was below the human harmful levels, attesting a non-generation of metabolites during autoclaving. Isotopic enrichment higher than 99% reflected the stability of deuterated label on the 6-carbon of glucose molecules. The non-visible particle concentration below the minimal permissible concentration tolerated by the European Pharmacopoeia and the absence of bacterial endotoxin and bacterial growth attested limpidity, apyrogenicity and sterility of the [6,6-(2)H(2)]-glucose solutions. CONCLUSION: After the 2-year study, 500mg/10mL and 2g/15mL deuterated glucose solutions stored in the dark at +2°C+8°C were stable in aqueous solution, allowing to ensure safety administration for human clinical trials using euglycemic hyperinsulinemic clamps.