Infection, anti-microbien, modélisation, évolution
Présentation
Rattaché à Paris Diderot, à l'INSERM ainsi qu'à l'université Paris 13, IAME est une unité multidisciplinaire (approche expérimentale, épidémiologie, modélisation statistique et mathématique) afin d’identifier les paramètres écologiques et évolutifs de l’adaptation des micro-organismes, en particulier ceux impliqués dans la virulence et la résistance aux antibiotiques. Le laboratoire dépend de deux départements de l'Alliance pour les sciences de la vie et de la santé (AVIESAN) : Maladies Infectieuses et Santé Publique. Situé sur le campus de Paris Diderot à la Faculté de médecine de l'Hôpital Bichat dans le nord de Paris, et relié à plusieurs hôpitaux universitaires à proximité, il offre une occasion unique de mélanger les scientifiques et cliniciens impliqués dans la recherche sur les maladies infectieuses. L'équipe consacrée à l'épidémiologie de la diversité écologique de Escherichia coli travaille sur le site Xavier Bichat (Université Paris 7) et aux laboratoires de Bactériologie des hôpitaux Avicenne et Jean Verdier.
Thèmes de recherche
Malgré un siècle d'efforts de prévention et de contrôle souvent fructueux, les maladies infectieuses restent un problème majeur de santé publique causant 13 millions de morts chaque année. De nouvelles maladies émergent, d'autres quasiment disparues ressurgissent, et l'on assiste au développement de la résistance aux agents antimicrobiens.
Deux types de causes expliquent ces données : les changements démographiques, comportementaux et technologiques des sociétés humaines associés aux modifications écologiques de la planète apparus durant le XXème siècle, et la capacité constante des microorganismes à évoluer et s'adapter. L'adaptation des populations repose sur la création de diversité génétique et l'action de la sélection naturelle. Parmi les mutants créés aléatoirement, la sélection naturelle ne retient que les individus les plus adaptés, soit les plus à même de survivre et de se reproduire dans leur environnement. Si de nombreux travaux ont très largement éclairci les aspects moléculaires de la virulence microbienne, peu d'études en revanche se sont appliquées à détailler les origines et conséquences évolutives de cette virulence.
Le but de notre recherche est de mieux détailler les paramètres écologiques et évolutifs qui permettent l'adaptation des microorganismes commensaux et pathogènes, et notamment ceux qui sont impliqués dans la transition d'un état à l'autre. Deux aspects sont essentiels pour comprendre l'évolution des microorganismes : l'adéquation entre leur génome et leur environnement d'une part et les contraintes agissant sur leur mode d'adaptation d'autre part.
Pour étudier ces deux aspects, nous avons choisi l'espèce Escherichia coli/Shigella, qui comprend des souches commensales du tube digestif mais aussi responsables de nombreuses pathologies intestinales et extra-intestinales, ainsi que les bactériophages phiX174 and phi6. A l'aide d'une approche mêlant (i) analyse de données génomiques (séquences de génomes complets, séquences de quelques gènes chez de nombreux isolats, présence/absence et expression de gènes) et (ii) analyse de nombreux phénotypes (croissance, activité métabolique, résistance aux stress divers dont les antimicrobiens, colonisation et virulence dans divers modèles animaux, circonstances cliniques d'isolement) sur des panels d'isolats naturels, nous souhaitons comprendre comment les génomes des microorganismes ont évolué et le lien avec l'émergence de la virulence.
Equipements
Structures L2, Automates incubateur/lecteur de DO
[hal-04487805] Elective distribution of resistance to beta-lactams among Enterobacter cloacae genetic clusters
Date: 4 Mar 2024 - 10:10
Desc: Objectives: The Enterobacter cloacae complex (Ecc), routinely referred to as "E. cloacae" in clinical microbiology, encompasses several species with 12 genetic clusters and one sequence crowd that can be identified based on hsp60 sequencing. Little is known about the pathogenicity and distribution of resistance to antibiotics among the Ecc. Methods and results: In this prospective multicentre study, a total of 193 Ecc clinical isolates were collected from 10 academic hospitals distributed nationally across France and identified at the genetic cluster level on the basis of hsp60 sequencing. E. hormaechei isolates, which belong to clusters VI-VIII, were the largest group (53%), followed by cluster III that accounted for 28% of clinical isolates. All other Ecc clusters were present except cluster VII (E. hormaechei subsp. hormaechei). Cephalosporinase overproduction and ESBL were significantly more present in E. hormaechei (33% and 20%) than in other clusters (19% and 3%, respectively). Conclusions: These results suggest that rapid identification of "E. cloacae" at the genetic cluster level could improve adequacy of empirical antibiotic treatment and reduce the unnecessary use of broad spectrum antibiotics.
[hal-01490237] Discussing HIV Status: Is It Easier After 10 Years of Antiretroviral Treatment? The ANRS CO8 APROCO-COPILOTE Cohort
Date: 15 Mar 2017 - 10:01
Desc: This study's objective was to explore the factors associated with the belief (or not) by people living with HIV that it is easier to talk about their seropositivity 10 years after initiating a protease inhibitor-containing ART. All patients in the ANRS CO8 APROCO-COPILOTE cohort who completed a self-administered questionnaire at 10 years of follow-up were included in this study. Forty-four percent of patients declared that discussing their seropositivity with their family was easier 10 years later, while 28 % declared this was true for discussing their status with a new sexual partner. Having a low socioeconomic status, not receiving social support from a steady partner and declaring a low number of discomforting symptoms 12 months after PI initiation were all independently associated with less difficulty in discussing seropositivity. This study highlights the difficulties in disclosing HIV 10 years after PI initiation, and the important influence of psychosocial factors and patients' daily-life experience on disclosure.
[hal-01394021] Ethanol Lock and Risk of Hemodialysis Catheter Infection in Critically Ill Patients. A Randomized Controlled Trial
Date: 8 nov 2016 - 14:51
Desc: RATIONALE: Ethanol rapidly eradicated experimental biofilm. Clinical studies of ethanol lock to prevent catheter-related infections (CRIs) suggest preventive efficacy. No such studies have been done in intensive care units (ICU). OBJECTIVES: To determine whether ethanol lock decreases the risk of major CRI in patients with short-term dialysis catheters (DCs). METHODS: A randomized, double-blind, placebo-controlled trial was performed in 16 ICUs in seven university hospitals and one general hospital in France between June 2009 and December 2011. Adults with insertion of a nontunneled, nonantimicrobial-impregnated double-lumen DC for an expected duration greater than 48 hours, to perform renal-replacement therapy or plasma exchange, were randomly allocated (1:1) to receive a 2-minute catheter lock with either 60% wt/wt ethanol solution (ethanol group) or 0.9% saline solution (control group) at the end of DC insertion and after each renal-replacement therapy or plasma exchange session. The main outcome was major CRI defined as either catheter-related clinical sepsis without bloodstream infection or catheter-related bloodstream infection during the ICU stay. MEASUREMENTS AND MAIN RESULTS: The intent-to-treat analysis included 1,460 patients (2,172 catheters, 12,944 catheter-days, and 8,442 study locks). Median DC duration was 4 days (interquartile range, 2-8) and was similar in both groups. Major CRI incidence did not differ between the ethanol and control groups (3.83 vs. 2.64 per 1,000 catheter-days, respectively; hazard ratio, 1.55; 95% confidence interval, 0.83-2.87; P = 0.17). No significant differences occurred for catheter colonization (P = 0.57) or catheter-related bloodstream infection (P = 0.99). CONCLUSIONS: A 2-minute ethanol lock does not decrease the frequency of infection of DCs in ICU patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00875069).
[hal-03577876] Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit
Date: 16 fév 2022 - 18:58
Desc: BACKGROUND The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. METHODS In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60. RESULTS A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P = 0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P = 0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001). CONCLUSIONS In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients.
[hal-01729758] Initial nutritional management during noninvasive ventilation and outcomes: a retrospective cohort study
Date: 24 avr 2018 - 16:14
Desc: Background: Patients starting noninvasive ventilation (NIV) to treat acute respiratory failure are often unable to eat and therefore remain in the fasting state or receive nutritional support. Maintaining a good nutritional status has been reported to improve patient outcomes. In the present study, our primary objective was to describe the nutritional management of patients starting first-line NIV, and our secondary objectives were to assess potential associations between nutritional management and outcomes. Methods: Observational retrospective cohort study of a prospective database fed by 20 French intensive care units. Adult medical patients receiving NIV for more than 2 consecutive days were included and divided into four groups on the basis of nutritional support received during the first 2 days of NIV: no nutrition, enteral nutrition, parenteral nutrition only, and oral nutrition only. Results: Of the 16,594 patients admitted during the study period, 1075 met the inclusion criteria; of these, 622 (57.9%) received no nutrition, 28 (2.6%) received enteral nutrition, 74 (6.9%) received parenteral nutrition only, and 351 (32.7%) received oral nutrition only. After adjustment for confounders, enteral nutrition (vs. no nutrition) was associated with higher 28-day mortality (adjusted HR, 2.3; 95% CI, 1.2-4.4) and invasive mechanical ventilation needs (adjusted HR, 2.1; 95% CI, 1.1-4.2), as well as with fewer ventilator-free days by day 28 (adjusted relative risk, 0.7; 95% CI, 0.5-0.9). Conclusions: Nearly three-fifths of patients receiving NIV fasted for the first 2 days. Lack of feeding or underfeeding was not associated with mortality. The optimal route of nutrition for these patients needs to be investigated.
Autres contacts
Hôpital Robert Debré
48, boulevard Sérurier
75935 PARIS CEDEX 19