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-01792510] Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis
Date: 21 Apr 2020 - 11:05
Desc: Background: Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI).Methods: This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200 mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis. Samples were analysed by an HPLC-tandem MS method. Demographics and SAPS2 and SOFA scores were recorded.Results: Fourteen patients with a median age (IQR) of 62 years (48-70) and with a mean BMI of 30.5 kg/m 2 were included from three centres; 57.1% were women. Their median (IQR) SAPS2 score was 54 (45-67) and their median (IQR) SOFA score was 8 (7-12). Six patients with community-acquired IAI and eight patients with nosocomial-acquired IAI were included. Twelve yeasts were isolated: six Candida albicans , two Candida glabrata , two Candida tropicalis , one Candida parapsilosis and one Candida krusei . Pharmacokinetic parameters were as follows [mean (% coefficient of variation)]: C max (mg/L) = 6.0 (29%); T max (h) = 1.6 (25.8%); C min (mg/L) = 3.2 (36.8%); AUC 0-24 (mg·h/L) = 88.9 (38.6%); t 1/2 (h) = 42.1 (68.2%); CL (L/h) = 1.2 (42.3%); and V (L) = 72.8 (87.8%). A two-compartment model best described the anidulafungin concentrations in the population pharmacokinetic study.Conclusions: The pharmacokinetic parameters of anidulafungin in critically ill ICU patients with complicated IAI are similar to those observed in the literature. However, an increased V and a longer t 1/2 were observed in this study. (EudraCT No. 2010-018695-25).
[hal-03553398] Natural history of Crohn's disease in elderly patients diagnosed over the age of 70 years: a population-based study
Date: 2 Feb 2022 - 17:26
Desc: [...]
[hal-03577876] Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit
Date: 16 Feb 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-01122215] Factors associated with post-seasonal serological titer and risk factors for infection with the pandemic A/H1N1 virus in the French general population.
Date: 5 Jun 2015 - 17:15
Desc: The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.
[hal-02407034] Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study
Date: 12 Dec 2019 - 12:32
Desc: Background: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment. Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome. Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects. Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients.
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