Analyse pharmacocinétique et impact écologique du traitement par linézolide

PARIS-BIUP (751062107) / SudocSudocFranceF

Evaluation des antibiothérapies dans un service de maladies infectieuses et tropicales

PARIS-BIUP (751062107) / SudocSudocFranceF

INFECTION A BORDETELLA PERTUSIS (DIAGNOSTIC ET EPIDEMIOLOGIE CLINIQUE ET MOLECULAIRE (DES BIOL.MED.))

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Emergence de la résistance aux antibiotiques chez les entérocoques au sein de l'écosystème intestinal

L objectif de cette étude est de quantifier et de préciser au niveau moléculaire les conditions d émergence et/ou de transfert de la résistance aux antibiotiques chez les entérocoques dans le tube digestif de souris gnotoxéniques. Tout d abord nous avons étudié le transfert du gène vanA entre diverses espèces d entérocoques. Nous avons montré que ce transfert de souches animales vers des souches humaines est possible et a lieu rapidement, suggérant que le transit même bref d entérocoques résistants aux glycopeptides peut permettre aux entérocoques de la flore résidente d acquérir ce gène. Ensuite nous avons modélisé l effet de différentes doses de linézolide sur l émergence de mutants résistants au linézolide. La sélection de mutants est possible mais la fréquence, la concentration et le type de mutants dépend de la concentration de linézolide présente dans le tube digestif. Nos résultats montrent que la dose administrée est un paramètre critique dans la dynamique de la résistance et devraient aider à définir les meilleures stratégies thérapeutiques pour réduire au minimum l'apparition de la résistance en clinique.The objective of this study is to quantify and specify at the molecular level the conditions of emergence and/or transfer of resistance to antibiotics at enterococci in the digestive tract of gnotobiotic mice. First is represented by the study of the transfer of the gene vanA between various species of enterococci in the digestive tract of gnotobiotic mice. We showed that the horizontal transfer of the gene vanA between animal strain and human strain is possible. Early transfer of this gene suggests that even a brief transit of enterococi of animal origin would allow resident human bacteria to acquire glycopeptide resistance genes. Second, we modelled the effect of different regimens of linezolid on Enterococcus faecalis in gnotobiotic mice. The selection of mutants resistant to the linezolid is possible but the frequency; the concentration and the type of mutants depend on the concentration of linezolid present in the digestive tract. Our results show that antibiotic dose appears to be critical in the dynamics of resistance and its molecular basis and should help to define the best therapeutic strategies to the minimum to reduce the appearance of resistance in clinic.PARIS-BIUP (751062107) / SudocSudocFranceF

Histoire naturelle de la résistance transférable aux glycopeptides chez les entérocoques

La résistance bactérienne aux glycopeptides existait dans la nature préalablement à l'utilisation humaine des glycopeptides. Toutefois, u n solide faisceau d'arguments suggère que c'est l'utilisation massive des antibiotiques de cette famille, en médecine et en élevage, qui en a permis l'émergence chez l'homme et chez l'animal. Ensuite, l'utilisation d'autres antibiotiques, notamment les céphalosporines de troisième génération, a concouru à l'amplification et à la dissémination du phénomène. La dissémination de la résistance aux glycopeptides est encore limitée à des entérocoques peu pathogènes mais qui peuvent être responsables d'infections graves chez des patients qui bénéficient par ailleurs de techniques sophistiquées de soins. Toutefois, le risque majeur associé aux entérocoques résistants aux glycopeptides (ERG) est celui de la dissémination des gènes de résistance à des espèces plus pathogènes et potentiellement épidémiques, notamment S. aureus. Ce transfert est possible et pourrait aboutir à la survenue d'épidémies difficiles à contrôler alors que l'on assiste à l'assèchement des filières de découvertes de nouvelles molécules antibiotiques. Ce risque justifie les efforts de contrôle de la dissémination des ERG en tant qu'objectif intégré à la politique d'antibiothérapie

Evaluation of the Cepheid Xpert GBS Assay for Rapid Detection of Group B Streptococci in Amniotic Fluids from Pregnant Women with Premature Rupture of Membranes

International audienceThe Xpert GBS real-time PCR assay for the detection of group B streptococci (GBS) in antepartum screening samples was evaluated on amniotic fluid samples collected from 139 women with premature rupture of membrane at term. When any intrapartum positive result from the Xpert GBS or culture was considered a true positive, the sensitivities of the Xpert GBS and culture were 92.3% and 84.6%, respectively. This assay could enhance exact identification of candidates for intrapartum antibiotic prophylaxis

Activation of class 1 integron integrase is promoted in the intestinal environment.

Class 1 integrons are widespread genetic elements playing a major role in the dissemination of antibiotic resistance. They allow bacteria to capture, express and exchange antibiotic resistance genes embedded within gene cassettes. Acquisition of gene cassettes is catalysed by the class 1 integron integrase, a site-specific recombinase playing a key role in the integron system. In in vitro planktonic culture, expression of intI1 is controlled by the SOS response, a regulatory network which mediates the repair of DNA damage caused by a wide range of bacterial stress, including antibiotics. However, in vitro experimental conditions are far from the real lifestyle of bacteria in natural environments such as the intestinal tract which is known to be a reservoir of integrons. In this study, we developed an in vivo model of intestinal colonization in gnotobiotic mice and used a recombination assay and quantitative real-time PCR, to investigate the induction of the SOS response and expression and activity of the class 1 integron integrase, IntI1. We found that the basal activity of IntI1 was higher in vivo than in vitro. In addition, we demonstrated that administration of a subinhibitory concentration of ciprofloxacin rapidly induced both the SOS response and intI1 expression that was correlated with an increase of the activity of IntI1. Our findings show that the gut is an environment in which the class 1 integron integrase is induced and active, and they highlight the potential role of integrons in the acquisition and/or expression of resistance genes in the gut, particularly during antibiotic therapy

Susceptibility trends including emergence of linezolid resistance among coagulase-negative staphylococci and meticillin-resistant Staphylococcus aureus from invasive infections

International audienceMultiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC\textgreater4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern

Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France.

BackgroundTo fight the COVID-19 pandemic, lockdown has been decreed in many countries worldwide. The impact of pregnancy as a severity risk factor is still debated, but strict lockdown measures have been recommended for pregnant women.ObjectivesTo evaluate the impact of the COVID-19 pandemic and lockdown on the seroprevalence and circulation of SARS-CoV-2 in a maternity ward in an area that has been significantly affected by the virus.Study designProspective study at the Antoine Béclère Hospital maternity ward (Paris area, France) from May 4 (one week before the end of lockdown) to May 31, 2020 (three weeks after the end of lockdown). All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well concomitant SARS-CoV-2 RT-PCR on one nasopharyngeal sample.ResultsA total of 249 women were included. Seroprevalence of SARS-CoV-2 was 8%. The RT-PCR positive rate was 0.5%. 47.4% of the SARS-CoV-2-IgG-positive pregnant women never experienced any symptoms. A history of symptoms during the epidemic, such as fever (15.8%), myalgia (36.8%) and anosmia (31.6%), was suggestive of previous infection.ConclusionsThree weeks after the end of French lockdown, SARS-CoV-2 infections were scarce in our region. A very high proportion of SARS-CoV-2-IgG-negative pregnant women, which is comparable to that of the general population, must be taken into consideration in the event of a resurgence of the pandemic. The traces of a past active circulation of the virus in this fragile population during the spring wave should encourage public health authorities to take specific measures for this independent at-risk group, in order to reduce viral circulation in pregnant patients