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-01277942] Relationship between Fungal Colonisation of the Respiratory Tract in Lung Transplant Recipients and Fungal Contamination of the Hospital Environment
Date: 23 fév 2016 - 14:05
Desc: Background Aspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention. Method To elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed. Results Forty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27%) had transient aspergillus colonisation, occurring 1–13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6), A. niger (3), A. sydowii (1), A. calidoustus (1) and Aspergillus sp. (1). In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient’s room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases), two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%. Conclusion Taken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients.
[hal-02137949] Tenofovir plasma concentrations related to estimated glomerular filtration rate changes in first-line regimens in African HIV-infected patients: ANRS 12115 DAYANA substudy
Date: 23 mai 2019 - 14:55
Desc: OBJECTIVES: An open-label randomized trial (DAYANA) was conducted in sub-Saharan settings to evaluate four different regimens containing tenofovir disoproxil fumarate as first-line treatment for HIV infection. The objectives of the present substudy were to assess the relationship between trough concentrations of tenofovir in plasma collected after 24 h (C24) and estimated glomerular filtration rates (eGFR) calculated by the different formulae that are available. METHODS: The criteria for eligibility were those of the DAYANA trial, recruiting naive patients. The four tenofovir regimens were: Group 1, tenofovir/emtricitabine/nevirapine; Group 2, tenofovir/lopinavir/ritonavir; Group 3, tenofovir/emtricitabine/zidovudine; and Group 4, tenofovir/emtricitabine/efavirenz. The C24 of tenofovir was determined using LC-MS/MS. The eGFR was calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. RESULTS: The median C24 of tenofovir was 42 ng/mL. The C24 of tenofovir was higher with lopinavir/ritonavir than with the other three regimens: at Week 4, 84 ng/mL versus 25 ng/mL; and at Week 48, 81 ng/mL versus 52 ng/mL. The baseline merged eGFR was 98.2 mL/min/1.73 m(2) with the CKD-EPI equation. Only the mean changes in eGFR in Group 2 differed from the absolute value of zero (-8.2 mL/min/1.73 m(2)) with the CKD-EPI equation between baseline and Week 48. The Cockcroft-Gault formula is inappropriate for these African patients because it underestimated the baseline eGFR and overestimated the changes in eGFR between baseline and Week 48. CONCLUSIONS: In this population of mostly female HIV-1-infected African patients, tenofovir plasma overexposure was associated with PI/ritonavir and a time-dependent decrease in eGFR, probably via an inhibition of MRP2/MRP4 efflux transporters. The close monitoring over time of the eGFR using MDRD or CKD-EPI calculations and by using other biomarkers of renal disorder should be proposed as an alternative to therapeutic drug monitoring in resource-limited countries.
[hal-02407972] Outbreak of Pneumocystis jirovecii Infection Among Heart Transplant Recipients: Molecular Investigation and Management of an Interhuman Transmission
Date: 12 déc 2019 - 17:01
Desc: [...]
[hal-02407034] Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study
Date: 12 déc 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.
[hal-01730461] A Global Declaration on Appropriate Use of Antimicrobial Agents across the Surgical Pathway
Date: 19 Mar 2024 - 12:20
Desc: This declaration, signed by an interdisciplinary task force of 234 experts from 83 different countries with different backgrounds, highlights the threat posed by antimicrobial resistance and the need for appropriate use of antibiotic agents and antifungal agents in hospitals worldwide especially focusing on surgical infections. As such, it is our intent to raise awareness among healthcare workers and improve antimicrobial prescribing. To facilitate its dissemination, the declaration was translated in different languages.
Autres contacts
Hôpital Robert Debré
48, boulevard Sérurier
75935 PARIS CEDEX 19