Дисертації з теми "Infections à Acinetobacter – Chimiothérapie"
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1
Antraygues, Kévin. "Conception, synthèse et évaluation biologique de nouveaux ansamacrolides dans le traitement d'infections bactériennes." Electronic Thesis or Diss., Université de Lille (2022-....), 2022. http://www.theses.fr/2022ULILS027.
Анотація:
L'antibiorésistance est un problème de santé publique majeur à l'heure actuelle et ceci sera d'autant plus vrai dans les prochaines décennies. Parmi les bactéries impliquées dans ce phénomène alarmant, Acinetobacter baumannii et Mycobacterium abscessus ont développé toutes deux des résistantes à de nombreux antibiotiques actuellement disponibles sur le marché. La recherche et le développement de nouveaux antibiotiques est donc nécessaire afin de lutter contre ces pathogènes.La rifabutine, un macrocycle hémisynthétique de la classe des rifamycines, a récemment montré des activités intéressantes in vitro contre A. baumannii et M. abscessus, ce qui s'est traduit ensuite par une efficacité in vivo de la molécule. La rifabutine semble donc prometteuse dans la lutte contre ces bactéries, cependant l'emploi de cet antibiotique est à ce jour limité. Afin de traiter une infection causée par A. baumannii, la rifabutine doit être injectée par voie intraveineuse, ce qui n'est pas chose simple au vue de la faible solubilité aqueuse de la molécule. Concernant la lutte contre M. abscessus, la rifabutine, bien qu'efficace in vivo, présente une activité limitée contre cette mycobactérie, ce qui peut conduire à un échappement thérapeutique.Les travaux présentés dans ce manuscrit de thèse cherchent donc à pallier les limitations de la rifabutine mentionnées ci-dessus.Dans une première partie, des prodrogues hydrosolubles de la rifabutine ont été synthétisées dans le but de permettre une administration par voie intraveineuse et ainsi de lutter efficacement contre des infections à A. baumannii en clinique. Afin de conduire à la libération de rifabutine après clivage enzymatique dans le plasma, une stratégie de cyclisation intramoléculaire a été employée. Après l'évaluation des composés lors de tests de stabilité plasmatique, des études de relations structure-stabilité ont été réalisées, menant à l'identification de trois prodrogues prometteuses. Des études in vitro supplémentaires ont ensuite été conduites telles que la mesure de la solubilité aqueuse et de l'inhibition de la croissance bactérienne, puis une étude in vivo de pharmacocinétique a finalement été réalisée afin d'identifier un candidat pour le développement.Dans une seconde partie, des analogues de la rifabutine modifiée en position C25 ont été synthétisés afin d'identifier des composés plus puissants. En se basant sur une stratégie de chimie en parallèle, un grand nombre de dérivés a pu rapidement être obtenu, puis ceux-ci ont été évalués contre M. abscessus dans le but de mener des études de relations structure-activitéAntimicrobial resistance is a major public health issue nowadays and this will be even more true in the coming decades. Among the bacteria involved in this alarming phenomenon, Acinetobacter baumannii and Mycobacterium abscessus are both resistant to many antibiotics currently available on the market. Research and development of new antibiotics is therefore necessary to fight these pathogens.Rifabutin, a semi-synthetic macrocyle of the rifamycin class, has recently shown interesting in vitro activities against A. baumannii and M. abscessus, which then translated into in vivo efficacy. Rifabutin therefore seems to be promising to the fight against these bacteria, but the use of this antibiotic is currently limited. In order to treat an infection caused by A. baumannii, rifabutin requires to be injected by intravenous route, which is not so easy because of the low water solubility of the molecule. Concerning the treatment of M. abscessus infections, rifabutin, although effective in vivo, has moderate activity against this mycobacterium, which could lead to therapeutic escape.Therefore, the work presented in this thesis manuscript seeks to address the limitations of rifabutin mentioned above.In a first part, water-soluble prodrugs of rifabutin have been synthesized in order to allow an intravenous injection and thus fight effectively against A. baumannii infections. To achieve the release of rifabutin after enzymatic cleavage in plasma, an intramolecular cyclization strategy was employed. After evaluation of the compounds in plasma stability assays, structure-stability relationship studies were performed, leading to the identification of three promising prodrugs. Additional in vitro studies were then conducted such as the measurement of aqueous solubility and bacterial growth inhibition, and finally an in vivo pharmacokinetic study was performed to be able to select for a preclinical candidate.In a second part, analogues of rifabutin modified at the C25 position were synthesized to identify more potent compounds. Based on a parallel chemistry strategy, a large number of derivatives were rapidly obtained and then evaluated against M. abscessus in order to conduct structure-activity relationship studies
2
Henein, Alexandra Elisabeth. "The potential of bacteriophage therapy in Acinetobacter spp. infections." Thesis, University of Brighton, 2009. https://research.brighton.ac.uk/en/studentTheses/9726f331-e5dc-4b67-a282-44cac1fe978f.
Анотація:
Bacteria resistant to multiple antibiotics pose a number of therapeutic problems. This situation is likely to worsen in the future, as the development of new classes of antibiotics has declined sharply in recent years. Acinetobacter species are an example of antibiotic-resistant bacterial pathogens with increasing clinical significance, particularly with respect to infections in high-risk patients such as those with severe burns. The treatment options for these patients are severely limited, and they often can only be treated with highly toxic antibiotics such as colistin. It is therefore evident that there is a need to investigate alternative approaches to therapy in these cases. This thesis represents some preliminary investigations into the use of bacteriophages for the treatment of Acinetobacter infections of severe burns patients. Bacteriophages are viruses that have bacteria as their host. They cannot attack human cells and indeed they are highly specific for given species of bacteria. The aim of this thesis was to investigate the potential use of bacteriophages in these infections and their possible toxic effects on mammalian (including human skin) cells. Since bacteriophages lytic against Acinetobacter species were not available through conventional culture collections it was necessary to identify other sources. Clinical isolates of Acinetobacter species were obtained from Sussex hospitals and characterised. Several unsuccessful attempts were made to isolate corresponding bacteriophages from the environment and ultimately 10 isolates of Acinetobacter spp. and their corresponding phage were obtained from Laval University, Canada. These bacterial strains were identified and host matched to each phage using a refined screening technique and purified phage preparations were produced for those potentially therapeutic phages. The results of this study formed the basis for the selection of a small number of phage to take forward for cytotoxicity studies. Very little scientific evidence has been published on the cytotoxic potential of bacteriophage or their bacterial lysis products, although phages have been routinely used for therapeutic purposes over many years. The establishment of phages as a mainstream treatment choice for bacterial infections in the West will require stringent testing and proof that phage preparations are not harmful. Human dermal fibroblast (HDF) and keratinocytes (HDK) were isolated from human biopsies. A 3T3 mouse fibroblast cell line, HDF and HDK with 3T3 feeder layers were exposed to dilutions of purified phage. The cytotoxic impact and effect on cell proliferation was measured using a range of assays. No statistically significant difference could be detected between controls and phage with the Trypan blue method (3T3 cells). Hoechst propidium iodide stain experiments remained inconclusive (3T3 cells). Lactate dehydrogenase (LDH) and MTS tetrazolium compound reduction (MTS) results showed no evidence of statistically significant cytotoxic effect of phage on 3T3 cells, HDF or HDK. Some data suggested phage may have some beneficial effect on cell survival of HDK and proliferation of HDF and 3T3 cells compared to controls. Endotoxin levels present in phage lysates and purified phage preparations were compared to those found in bacterial suspensions subjected to lysis by other methods including autoclaving, bead beating, sonication and high concentrations of antibiotics. There was no evidence to suggest that bacteria lysed by phage liberated significantly more endotoxins than the other methods of cell disruption. A variety of endotoxin preparations and phage lysates were incubated with HDF and cytotoxicity together with cell proliferation were measured using LDH and MTS assays. Changes in interleukin levels of the same samples were monitored, measuring IL-1β, IL-6, IL-8 and TNF-α levels. IL-1β or TNF-α could not be detected in any samples. Highly concentrated phage gave rise to significantly higher IL-6 outputs than any other samples. Ten-fold dilutions of the same phage preparation were not statistically different to any other samples, including controls. This suggested components introduced during the phage purification process, rather than the phage itself may have contributed to higher IL-6 readings. Purified and crude phage lysate gave rise to significantly higher IL-8 outputs than all other samples. Colony formation assays utilising a V79 hamster cell line were used to indicate the cytotoxicity of purified phage in different diluents and provided comparison with endotoxin containing preparations used in other experiments. There was no statistically significant difference in terms of colony numbers or colony size (where measured) between phage samples and controls. This thesis has therefore demonstrated that because of the lack of cytotoxic effect of phage on mammalian cells in culture, there is potential for therapeutic applications of bacteriophage.
3
Diallo, Bruno Salla. "Études des acinetobacter : à propos de 98 souches isolées en milieu hospitalier." Bordeaux 2, 1990. http://www.theses.fr/1990BOR23091.
4
Gagné, Stéphanie. "Étude des mécanismes de virulence du pathogène nosocomial Acinetobacter baumannii." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1045/document.
Анотація:
Acinetobacter baumannii est un pathogène nosocomial qui induit principalement des infections du système respiratoire ou urinaire, et des septicémies chez les patients immunodéprimés. L'émergence de souches multi résistantes aux antibiotiques et l'augmentation de nombreuses d'infections par A. baumannii fait de ce pathogène un enjeu majeur de santé publique. De plus aujourd'hui émerge des souches hypervirulentes. Nous nous sommes intéressés à différentes souches afin de caractériser le phénotype hypervirulent de ces souches. L'étude du système de sécrétion de type VI montre la complexité des mécanismes de virulence d'A. baumannii et sa régulation dépendante des souches. Dans un second temps l'étude des souches cliniques hypervirulentes et nous avons mis en évidence deux nouveaux potentiels mécanismes de virulence : une phase de réplication intracellulaire et une limitation de la réponse immunitaire. Ces mécanismes peuvent expliquer la virulence accrue de ces souches chez l'homme. L'étude nous montre également qu'A. baumannii est un pathogène complexe et qu'on son étude à l'heure actuelle nécessité l'emploi de souche représentative des souches infectant les patientsA. baumannii is an hospital acquired pathogen which causes mainly ventilator associated infection, urinary tract infection and bacteraemia. Last years Multi Drug Resistant strains increase and nosocomial infection cause by A. baumannii also which led him as a serious health care problem. We compare different strains in propose to find phenotype that can explain hypervirulent strain emergence. We studied type six secretion and showed that the complexity of A. baumannii virulence mechanism. Indeed type six secretion system regulation is strain dependant. Secondary we study hypervirulent strain and showed that intracellular stage exists and there is intracellular replication. Also hypervirulent strain induces less immune response. Those two mechanisms can explain A. baumannii hypervirulent phenotype
5
Fabre, David. "Approche pharmacocinétique de l'antibiothérapie dans les infections pulmonaires." Montpellier 1, 1995. http://www.theses.fr/1995MON13504.
6
Hauret, Sylvie. "Epidémiologie moléculaire d'infections nosocomiales à Acinetobacter Baumannii dans un service de réanimation." Bordeaux 2, 1996. http://www.theses.fr/1996BOR2P039.
7
Webster, Carol Ann. "The use of molecular typing systems for studying the epidemiology of Acinetobacter infections." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388315.
8
Chou, So-ha, and 周素霞. "Molecular epidemiology of carbapenem-resistant acinetobacter baumanniiin patients and their surrounding environment." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48333669.
Анотація:
Background
There has been an increasing awareness of the role of the hospital environment as a reservoir of Acinetobacter baumannii. A. baumannii is an important nosocomial pathogen and is difficult to control due to the increasing cases of resistance to carbapenem.
Objectives
The objectives of this study areto examine carbapenem-resistant Acinetobacter baumannii (CRAB) positive patients according to their environmental sample to determine how frequently the environment surrounding the patient becomes contaminated and which environmental surfaces are most commonly contaminated.
Methodology
During June 2011 to December 2011, data regarding 30 hospitalized patients with at least one positive CRAB clinical sample were collected from hospital X in Kowloon of Hong Kong. For 30 case patients, one patient in the ICU ward had been isolated in a single room and the other 29 patients stayed in a multi-room. Fifteen surfaces in the patient cubicle and nine surfaces in health care worker stations were evaluated for the presence of CRAB. 29 control environmental samples were obtained from the surroundings of patients without CRAB in the same cubicle and one control environmental sample was obtained from the surroundings of patients without CRAB in the other room of ICU. Pulsed-field gel electrophoresis was performed on all environmental isolates and clinical samples.
Results
Of the 30casepatients, 26 patients (86.7%) were found to have CRAB contamination in their surrounding environment and 6negative control patients (20%) were found to have CRAB in their environmental samples. The percentage of positive CRAB cultures in the case environment, control and health care worker stations was 28.9% (117/405), 3.4% (14/406) and 1.9% (5/265)respectively. In the surrounding case patient area, pillows (60% 18/30) and bed sheets on which the patients sleep on (60% 18/30), bed sheets covering the patients (50% 15/30) and bedside table tops (40% 12/30) were the most commonly contaminated. For 26casepatientswere found to have CRAB contamination in their surrounding environment, 23 (88.5%) of these patients were found to have the clone of isolates in the case environment related to the patients.
Conclusion
For patients with CRAB, the surrounding environment is frequently contaminated.
Surfaces often touched by the patients are commonly contaminated. CRAB was also found on surfaces that were not closely related to the patient which are frequently touched by healthcare workers during patient care.published_or_final_version
Microbiology
Master
Master of Medical Sciences
9
Brandely, Marie-Laure. "Nouvelles prises en charge des principales infections fongiques hospitalières : évaluation pharmaco-économique." Paris 5, 1999. http://www.theses.fr/1999PA05P183.
10
Adegoke, Anthony Ayodeji. "Commensal bacteria belonging to the Staphylococcus Acinetobacter and Stenotrophomonas genera as reservoirs of antibiotic resistance determinants in the environment of Nkonkobe Municipality, Eastern Cape Province , South Africa." Thesis, University of Fort Hare, 2012. http://hdl.handle.net/10353/6539.
Анотація:
A study to assess the potentials of some commensal bacteria that belong to Staphylococcus, Acinetobacter and Stenotrophomonas genera as reservoirs of antibiotic resistance determinants in the environment of Nkonkobe Municipality of the Eastern Cape Province, South Africa, was carried out using standard microbiological and molecular techniques. A total of 120 Staphylococcus isolates which consisted of Staphylococcus haemolyticus (30%), Staphylococcus aureus (23.3%) from pig; Staphylococcus capitis (15%) from goat; Staphylococcus heamolyticus (5%) and Staphylococcus xylosus (15%) from cattle and other Staphylococci (11%) from dead chicken and pigs were isolated. About 23.3% of these isolates were coagulase positive and 76.7% were coagulase negative. This difference in prevalence along coagulase production divide was statistically significant (p < 0.05). Eighty-six Acinetobacter species (Acinetobacter baumannii/calcoaceticus and Acinetobacter haemolyticus) were also isolated from Alice and Fort Beaufort towns samples, while 125 Stenotrophomonas maltophilia isolates were from grass root rhizosphere (96%) and soil butternut root rhizosphere (4%). Between 75-100% of the Staphylococccus species were resistant to Penicillin G, tetracycline, sulphamethaxole and nalidixic acid; about 38 % were methicillin resistant, consisting of 12.6% methicillin resistant Staphylococcus aureus (MRSA) from pig and a total of 12% vancomycin resistant were observed. Also, 12% of the isolates were erythromycin resistant while 40.2 % were resistant to the third generation cephalosporin, ceftazidime. The antibiotic resistance genes vanA, VanB, eryA, eryB, eryC were not detected in all the phenotypically resistant Staphylococccus species, but mec A gene and mph genes were detected. In the Acinetobacter species, a wide range of 30-100% resistance to penicillin G, ceftriazone, nitrofurantoin, erythromycin, and augmentin was observed. Polymerase chain reaction (PCR) revealed the presence of Tet(B) and Tet(39) genes in these species, while Tet (A), Tet(M) and Tet(H) were absent. Also, 9.3% of the Acinetobacter species showed phenotypic production of extended spectrum beta lactamases (ESBLs) while 3.5% were positive for the presence of blaCTX-M-1 genes. The Stenotrophomonas maltophilia isolates showed varying resistance to meropenem (8.9%), cefuroxime (95.6 %), ampicillin-sulbactam (53.9%), ceftazidime (10.7%), cefepime (29.3 %), minocycline (2.2%), kanamycin (56.9%), ofloxacin (2.9%), levofloxacin (1.3%), moxifloxacin (2.8%), ciprofloxacin (24.3%), gatifloxacin (1.3%), polymyxin B (2.9 %), cotrimoxazole (26.1%), trimethoprim (98.6%), aztreonam(58%) and Polymyxin B (2.9 %). The isolates exhibited significant susceptibility to the fluoroquinolones (74.3-94.7 %), polymycin (97.1%) and meropenem (88.1%). Only sul3 genes were the only sulphonamide resistance gene detected among the trimethoprim-sulphamethoxazole resistant isolates. The observed multiple antibiotic resistance indeces (MARI) of >2 for Staphylococcus species, Acinetobacter species and Stenotrophomonas maltophilia suggest that they have arisen from high-risk sources where antibiotics are in constant arbitrary use resulting in high selective pressure. The presence of tetracycline resistance genes in Acinetobacter species justifies the observed phenotypic resistance to oxytetracycline and intermediate resistance to minocycline. High phenotypic resistance and the presence of some resistance genes in Staphylococcus species is a possible threat to public health and suggests animals to be important reservoirs of antibiotic resistance determinants in the environment. Indiscriminate use of antibiotics induces this kind of antibiotic resistance and should be discouraged. Personal hygiene is encouraged as it reduces the load of Acinetobacter species contacted from the environment that may be difficult to control. Commensal Stenotrophomonas maltophilia are as important as their clinical counterparts due to their roles in opportunistic infection, antibiotic resistance and their associated genes, especially sul gene. Personal hygiene is hereby advocated especially when in contact with soil, plants and plants’ rhizospheric soil
11
Zupanc, Kauss Tina. "Intérêt thérapeutique et formulation galénique des polyphénols dans le traitement des infections et inflammations." Bordeaux 2, 2007. http://www.theses.fr/2007BOR21501.
Анотація:
La réponse immune pro-inflammatoire peut parfois entraîner des processus pathologiques, comme la destruction de la matrice articulaire dans le cas de la polyarthrite rhumatoide ou une cachexie mortelle dans le cas de la trypanosomose africaine. Dans ces deux pathologies, des nouveaux traitements sont nécessaires pour une meilleure prise en charge des malades. Les flavonols, des molécules naturelles végétales peu toxiques, pourraient apporter cette alternative thérapeutique, mais leurs effets anti-inflammatoires et anti-parasitaires doivent être démontrés et/ou caractérisés. Notre travail consistait à évaluer le potentiel thérapeutique de deux flavonols : la quercétine et la rutine. Nous avons étudié leurs effets à des doses non toxiques pour les cellules humaines sur les médiateurs d'inflammation macrophagiques au niveau génomique et protéique. L'inhibition duTNFα, de l'IL1β et du NO a pu être mise en évidence in vitro. L'effet anti-inflammatoire a été confirmé in vivo sur un modèle d'arthrite chez le rat (un modèle proche de la polyarthrite rhumatoide humaine) où l'amélioration des scores cliniques et de la cachexie était corrélée à la diminution des marqueurs inflammatoires sériques. Par ailleurs, l'effet trypanocide de la rutine et de la quercétine a été démontré et étudié in vitro pour déterminer sa cinétque et les relations dose-réponse. De plus, l'effet trypanocide de la vitamine C a pu être démontré in vitro. Les études in vivo devront vonfirmer l'efficacité de ces molécules dans le cas de la trypanosomose africaine. Une première approche de développement galénique a été réalisée pour améliorer la biodisponibilité et donc les effets thérapeutiques des flavonolsImmune response can become a pathological process, leading to a joint matrix destruction in rheumatoid arthritis or to a chronic cachexia in African trypanosomosis. In both pathologies, new therapeutics are needed for a better patients care. Flavonols, non toxic vegetal compounds, could bring a therapeutic alternative in these diseases, but their anti-inflammatory and anti-parasitic effects should be proved and/or characterized. We evaluated therefore the therapeutic potential of two flavonols, quercetin and rutin, in view of their use in human medicine. The effects of non toxic doses of flavonols on macrophage inflammatory mediators' gene transcription and protein expression were studied. In vitro inhibition of TNFα? il1β and NO was also confirmed on rat adjuvant-induced arthritis model, showing a correlation between clinical signs of inflammation (clinical scores and cachexia) and serum inflammatory mediators. In addition, quercetin and rutin trypanocidal effects were demonstrated and the kinetics and dose-response relationship studied. Furthermore, the in vitro trypanocydal effect of vitamin C was highlighted. In vivo studies should confirm the effectiveness of these molecules in African trupanosomosis. A first galenic approach was also conducted in order to improve the bioavailability and consequent therapeutic effects of flavonols
12
Gounden, Ronald. "Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections." Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3282.
Анотація:
Includes bibliographical references (leaves 42-47).Background: Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and effectiveness with other antimicrobials, particularly the aminoglycosides. Metbods: A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital was performed. Colistin was used for A baumannii isolates which were resistant to all other available antimicrobials. Tobramycin was used when the organism was susceptible to this antimicrobial. We assessed and compared ICU mortality, nephrotoxicity and time to the first negative culture in the colistin and tobramycin groups.
13
Reddy, Deveshnee. "Acinetobacter baumannii infections in the paediatric intensive care unit of a tertiary hospital in South Africa." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/13974.
Анотація:
Acinetobacter baumannii (A. baumannii) is now increasingly recognised as an important cause of nosocomial infections in paediatric intensive care unit (PICU) patients, particularly in developing countries, where it contributes significantly to morbidity and mortality. Furthermore, it has been documented that emerging antimicrobial resistance patterns complicate antibiotic choice in these patients. At present, more paediatric data is needed regarding these infections. This is a retrospective case-control study that aims to document the demographic data and relevant clinical details of patients in whom A. baumannii was cultured, either from blood or respiratory specimens (thus including both infections and colonisation), in the PICU at Red Cross War Memorial Children's Hospital (RCWMCH) during 2010. Secondary objectives include comparing these patients with those in whom A. baumannii was not cultured and determining which isolates were causing infection and which were colonisers. In addition; of the isolates regarded as infections, documenting the antimicrobial sensitivities and resistance of the organisms cultured, determining whether infections were late or early onset and determining whether specific bed numbers were consistently involved.
14
Oung, Nguon Pumngear. "Infections nosocomiales : intérêt du suivi des consommations d'antibiotiques." Paris 5, 1999. http://www.theses.fr/1999PA05P061.
15
Oliveira, Maura Salaroli de. "Tratamento de infecções causadas por Acinetobacter spp. resistente a carbapenem." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-29052008-102737/.
Анотація:
O gênero Acinetobacter tem sido implicado em grande variedade de infecções hospitalares, principalmente em Unidades de Terapia Intensiva. O tratamento de infecções por Acinetobacter spp. é geralmente realizado com imipenem embora não haja ensaios clínicos randomizados que embasem esta recomendação. No caso de resistência a esta classe, situação cada vez mais freqüente, as opções mais estudadas são as polimixinas e ampicilinasulbactam. Diante da escassez de dados sobre o assunto, estudos que avaliem o tratamento de infecções por Acinetobacter spp resistente a carbapenem são necessários. Realizou-se um estudo de coorte retrospectivo de pacientes com infecção causada por Acinetobacter spp. resistente a carbapenem, internados no Instituto Central do Hospital das Clínicas (HC-FMUSP) e no Hospital do Servidor Público Estadual (HSPE) no período de 1996 a 2004. Foram considerados como casos os pacientes com diagnóstico de infecção hospitalar baseado em critérios estabelecido pelo Centers for Disease Control and Prevention (CDC) somado ao isolamento de Acinetobacter spp. resistente a carbapenem obtidos de materiais estéreis ou lavado bronco-alveolar.Não foram incluídos casos de infecção do trato urinário. Foi realizada a análise dos prontuários dos pacientes e foram coletadas informações clínico-demográficas, tratamento utilizado, sinais, sintomas e exames auxiliares no diagnóstico da infecção e no decorrer do tratamento. Foram avaliados três desfechos: mortalidade até o final do tratamento, mortalidade até o final da internação e evolução clínica. Oitenta e dois pacientes (30%) receberam polimixina B ou E, oitenta e cinco (31%) foram tratados com ampicilina-sulbactam, 99 (36%) não receberam tratamento específico. As características clínico-demográficas dos grupos foram semelhantes. A mortalidade durante a internação foi de 78% e boa resposta clínica foi observada em 50% dos pacientes tratados. Na análise multivariada de fatores associados à má evolução clínica, início do tratamento após 72 horas do isolamento e piora da função renal durante o tratamento foram estatisticamente significativos. Pontuação de Apache II >= 15, início do tratamento após 72 horas do isolamento; piora da função renal durante o tratamento; presença de choque séptico e uso de polimixina foram variáveis associadas com óbito até o final do tratamento. As variáveis independentemente associadas com óbito durante a internação foram: idade >= 58 anos, presença de choque séptico no dia do início do tratamento e pontuação de Apache II >=15. Concluiu-se que para o tratamento de infecções causadas por Acinetobacter spp. resistente a carbapenem, ampicilinasulbactam foi superior a polimixinas considerando mortalidade durante o tratamento.Acinetobacter spp. is a cause of a number of infections, mainly in the ICU setting. Antimicrobials drugs frequently reported as active against Acinetobacter spp include carbapenems, colistin, ampicillin/sulbactam, amikacin, rifampin and tetracyclines and currently carbapenens are considered the main antimicrobial treatment. Unfortunately, over the past years there has been a worldwide increase in infections caused by carbapenem-resistant Acinetobacter. This poses a therapeutic challenge as few treatment options are avaible. We performed a retrospective review of the case records of patients from 1996 to 2004 who had nosocomial infections caused by carbapenem-resistant Acinetobacter spp. from 2 large teaching hospitals. Diagnosis of infection was based on CDC criteria plus the isolation of Acinetobacter from a usually sterile site or from broncoalvelolar lavage. Urinary tract infections were not included. We collected data on demographic and clinical features, treatment, signs and symptoms from medical records. We evaluate 3 outcomes: mortality until the end of treatment, in-hospital mortality and clinical outcome. Eighty two patients received polymyxins (30%), 85 were treated with ampicilin-sulbactam (31%) and 99 (36%) did not receive any of these antibiotics. The demographic and clinical characteristics of the groups were similar. Multivariate analysis showed that treatment with polymyxins, Apache II score >= 15; septic shock; treatment delay and renal failure were independent predictors of mortality. On multivariate analysis, age >= 58 years, presence of septic shock and Apache II score >=15 were prognosis factors for mortality during hospitalization. Multiple logistic regression analysis revealed that Apache II >=15 and renal failure during treatment were associated with treatment failure. In conclusion, ampicillin-sulbactam was superior to polymyxin considering mortality during treatment.
16
Couturier, Sarah. "Synthèse et étude de 3'-desoxy-3'-C-methylnucléosides pyrimidiques." Montpellier 2, 2004. http://www.theses.fr/2004MON20183.
17
Péguy, Agnès. "Acinetobacter baumannii : antibiotype, sensibilité aux beta-lactamines et résistance à l'Imipenem." Bordeaux 2, 1995. http://www.theses.fr/1995BOR23081.
18
Le, Moing Vincent. "Réponse virologique et immunologique aux traitements avec inhibiteurs de protéase chez les patients infectés par le VIH." Bordeaux 2, 2001. http://www.theses.fr/2001BOR28872.
Анотація:
Les traitements antirétroviraux avec inhibiteurs de protéase ont été largement prescrits avant d'avoir été complètement évalués. Cette thèse a pour principal but, grâce à l'étude dans une cohorte de patients traités de mesures répétées de marqueurs biologiques, la charge virale plasmatique (CV) et le taux de lymphocytes CD4, de montrer comment les études d'observation peuvent contribuer à répondre à deux questions en suspens concernant ces traitements : quand faut-il les débuter ? comment mesurer leur effet à court et moyen terme ? La réponse immuno-virologique semblait plus importante et durable chez les patients débutant le traitement à CV basse et lymphocytes CD4 élevés ce qui était en faveur d'une initiation précoce des traitements au cours de la maladie. Cependant, pour la question de l'indication des traitements, les études d'observation sont possiblement limitées par la présence de biais, seul un essai contrôlé permettrait d'y répondre de façon valide. L'analyse des relations entre réponse virologique et évolution des lymphocytes CD4 a permis d'introduire la notion de réponse virologique partielle, définie par une CV basse mais détectable, par opposition à la CV indétectable, habituellement considérée comme l'objectif du traitement : le taux de lymphocytes CD4 continuait d'augmenter après la survenue d'un échec virologique avec une CV < 5000 copies/ml. Une analyse préliminaire de la progression vers le SIDA durant les deux premières années de suivi semblait confirmer ce résultat : la progression était associée à une CV > 10000 copies-ml 4 mois après le début du traitement. Sous réserve de confirmation à plus long terme sur un plus grand nombre d'événements, ces résultats sont en faveur d'un objectif plus modeste des traitements antirétroviraux. En prenant en compte des variables socio-comportementales, l'adhérence au traitement ou la précarité, ces travaux ont également permis de souligner leur importance tant en épidémiologie qu'en pratique quotidienneProtease inhibitor-containing antiretroviral regimens have been largely prescribed before a complete evaluation. The main objective of this thesis is to analyse repeated measures of two biological markers : plasma HIV RNA (VL) and CD4+cell counts (CD4) in a cohort of treated patients in order to show how observational studies may contribute to the answering to two pending questions concerning these treatments : when to start them ? how to measure their short and longer term efficacy ? The analyses of immunological and virological response yielded results favouring early initiation of therapy in the course of the disease : response was more frequent and more sustained when patients initiated therapy at low VL and high CD4. Due to the observational nature of the data, there are many potential biases however and only a controlled trial may answer to the question of the moment of initiation of therapy. The analyses of the relationships between virological response and further increase of CD4 suggested a potential role for partial virological response, i. E. Low but detectable VL as opposed to the complete virological response, undetectable VL, which is usually considered as the goal of therapy. In patients having virological failure with a VL < 5,000 copies/ml, a continuous increase of CD4 was observed. Preliminary analyses of progression to AIDS tended to confirm this result : progression was associated with a VL > 10,000 copies/ml 4 months after the initiation of therapy. If these results were confirmed with a longer follow-up and a higher number of events, they would be in favour of a more modest goal of therapy. Studies presented in this thesis also took into account sociological and behavioural measures, like adherence to therapy and social support and emphasised their important role, in epidemiology as well as in routine clinical practice
19
Jarrige, Jean Marc. "La pharmacochimie de l'acyclovir et de ses analogues." Paris 5, 1989. http://www.theses.fr/1989PA05P005.
20
Dupin, Valérie. "Chimiothérapie des infections à VIH et à Herpesviridae : modes d'action : mécanismes de résistances : revue de la littérature." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2P017.
21
Magen, Isabelle. "Helicobacter pylori : un nouveau regard dans le traitement de la maladie ulcéreuse gastroduodénale." Bordeaux 2, 1997. http://www.theses.fr/1997BOR2P090.
22
Lepère, Armelle. "Diagnostic et traitement des infections génitales basses à "Chlamydia trachomatis"." Paris 5, 1991. http://www.theses.fr/1991PA05P123.
23
Paradis-Bleau, Catherine. "Développement accéléré de nouveaux inhibiteurs contre les protéines de division cellulaire FtsZ et FtsA de Pseudomonas aeruginosa." Thesis, Université Laval, 2003. http://www.theses.ulaval.ca/2003/21334/21334.pdf.
Анотація:
L’impact des infections bactériennes couplé à l’émergence des mécanismes de résistance aux antibiotiques suscite un besoin urgent de nouvelles classes d’agents antibactériens. D’ailleurs, la résistance du pathogène opportuniste P. aeruginosa diminue l’efficacité de traitement et met en danger la vie des personnes infectées. Dans le but d’identifier de nouveaux antimicrobiens, nous exploitons la machinerie de division cellulaire bactérienne en tant que cible. Ainsi, les protéines de division cellulaire FtsZ et FtsA de P. aeruginosa ont été utilisées afin d’identifier des inhibiteurs protéiques spécifiques à l’aide de la technique de présentation phagique. Nous avons identifié des peptides détenant une affinité pour les enzymes FtsZ et FtsA puis nous avons caractérisé 3 peptides inhibiteurs de l’activité GTPase de FtsZ. Le peptidomimétisme devrait permettre le développement d’une nouvelle classe d’agents antimicrobiens à partir de ces peptides.The impact of bacterial infections and emergence of antibiotic resistance led to a serious need to develop new class of antibacterials. The acute resistance of the opportunistic pathogen Pseudomonas aeruginosa lowers the treatment efficiency of infected cystic fibrosis patients and immuno-compromised individuals. In the perspective of finding new antimicrobial agents, we are using the bacterial cell division machinery of as a new target. Thus, P. aeruginosa cell division proteins FtsZ and FtsA have been used to identify inhibitory peptides with the phage-display technique. We identified FtsZ and FtsA tight binding peptides and we characterized three inhibitory peptides of FtsZ GTPase activity. Peptidomimetism will allow the development of new antimicrobial agents with these leader peptides.
24
Robigo, Christel. "Deux pathologies virales : le zona et l'herpès génital. Leur traitement par deux agents antiviraux : l'aciclovir commercialisé sous le nom de zovirax et le famciclovir en développement clinique." Bordeaux 2, 1995. http://www.theses.fr/1995BOR2P095.
25
Marimoutou, Catherine. "Evolution de la prise en charge de l'infection par le VIH à l'ère des multithérapies : expériences des Cohortes Aquitaine et MANIF 2000 : et du département de recherche clinique du CISIH-Sud de Marseille." Bordeaux 2, 2003. http://www.theses.fr/2003BOR21085.
Анотація:
Ce travail présente l'impact des multithérapies sur la prise en charge hospitalière du VIH au travers des données des cohortes Aquitaine et MANIF 2000 et celles des patients coinfectés VIH-VHC suivis au CISIH-Sud de Marseille. Nous avons ainsi pu observer l'amélioration de l'état clinique et biologique des patients parallèlement à la diffusion des HAART, ainsi qu'une modification qualitative des causes de décès, due à la baisse des décès Sida. Parmi les causes de décès on retrouve la place prépondérante des causes hépatiques. La prise en charge nécessaire de la coinfection par le VHC est cependant ralentie par la difficulté d'obtenir un bilan pré-thérapeutique complet. Ainsi, dans notre étude, seul un patient sur deux porteurs chroniques du VHC a pu avoir une biopsie hépatique et un patient coinfecté sur cinq a été traité. Le rôle péjoratif d'une HAART avec antiprotéase sur la réponse au traitement anti-VHC, soulève le problème des interactions médicamenteuses chez ces patientsThis work presents the results observed through three different cohorts of HIV infected patients and focused on changes in morbidity and mortality of HIV infected patients since HAART era. First, we observed the decraese in deaths and AIDS cases following the large diffusion of HAART in 1996 and persisting nowadays. Non AIDS deaths were mainly due to liver or heart failures and neoplasia. In patients infected through injecting drug use, deaths due to liver failure were as frequent as AIDS deaths. These results underlined the necessity to manage the hepatitis C virus (HCV) coinfection. The main barrier to this management seemed to be the complete realization of the HCV screening, particularly the performance of liver biopsy. However, 1/2 HIV-VHC coinfected patients had a biopsy performed and 1/5 were treated for HCV. Among treated patients, the pejorative role of HAART with PI on HCV therapeutic response underlined the problem of therapeutic interaction in such coinfected patients
26
Hombrouck, Cécile. "Haemophilus influenzae, B-lactamase négative - "ampicilline résistants" : détection et étude de la résistance." Paris 5, 1999. http://www.theses.fr/1999PA05P172.
27
Figueiredo, Samy. "Acinetobacter spp. et réservoir de gènes de carbapénèmases." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00743039.
Анотація:
Acinetobacter baumannii, microorganisme responsable d'infections nosocomiales survenant le plus souvent par épidémies, pose un problème émergent de multi-résistance aux antibiotiques, notamment aux carbapénèmes. Cette résistance aux carbapénèmes est le plus souvent liée à l'acquisition et à l'expression de gènes codant pour des b-lactamases de classe D à activité de carbapénèmase (CHDLs). Le réservoir de ces gènes de résistance est inconnu.Nous avons montré que l'espèce bactérienne Acinetobacter radioresistens, espèce proche de A. baumannii, est le progéniteur du déterminant de résistance aux carbapénèmes le plus prévalent dans le monde chez A. baumannii : le gène blaOXA-23. Nous avons identifié l'espèce Acinetobacter lwoffii comme progéniteur d'un gène codant pour une nouvelle CHDL : OXA-134. Nous avons identifié les CHDLs naturelles des espèces Acinetobacter johnsonii, Acinetobacter calcoaceticus et Acinetobacter haemolyticus, dénommées respectivement OXA-211, OXA-213 et OXA-214. Nous avons ensuite étudié l'expression des gènes codant pour ces CHDLs naturelles en prenant l'exemple du gène naturel blaOXA-51/-66 de A. baumannii et nous avons démontré que ce gène était impliqué dans la réduction de sensibilité aux carbapénèmes chez A. baumannii, notamment lorsque la séquence d'insertion (IS) ISAba1 était présente en amont de ce gène. Nous avons ensuite identifié une nouvelle IS, ISAba9, à l'origine de la surexpression du gène blaOXA-51 naturel de A. baumannii. Enfin, nous avons identifié VIM-4, b-lactamase de classe B capable d'hydrolyser les carbapénèmes, dans une souche de Acinetobacter non-baumannii, Acinetobacter genomic species 16.
28
Jelena, Đekić Malbaša. "Faktori rizika i javnozdravstveni značaj infekcije krvi izazvane multirezistentnim bakterijama Acinetobacter spp." Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2017. https://www.cris.uns.ac.rs/record.jsf?recordId=104676&source=NDLTD&language=en.
Анотація:
Uvod: Infekcija krvi izazvana multirezistentnim bakterijama roda Acinetobacter (MDRA) je praćena značajnim letalitetom i visokim troškovima bolničkog lečenja. Ciljevi istraživanja: Ustanoviti učešće izolata Acinetobacter spp. u strukturi pozitivnih hemokultura i kretanje procenta rezistencije na antibiotike u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa na teritoriji AP Vojvodine u periodu 2013-2015. godina; Utvrditi kod kojih pacijenata se najčešće javljaju infekcije krvi izazvane MDRA; Utvrditi faktore rizika za nastanak bolničke infekcije (BI) krvi izazvane MDRA i uticaj BI krvi izazvane ovim uzročnicima na dužinu trajanja hospitalizacije i na ishod lečenja pacijenata hospitalizovanih u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa u AP Vojvodini. Materijal i metode: Podaci iz protokola mikrobiološke laboratorije Centra za mikrobiologiju Instituta za javno zdravlje Vojvodine su korišteni za retrospektivnu analizu učestalosti izolata Acinetobacter spp. u strukturi hemokultura i za praćenje kretanja procenta rezistentnih izolata Acinetobacter spp. na posmatrane vrste antibiotika u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa u AP Vojvodini u periodu od 01.01.2013. do 31.12.2015. godine. Utvrđivanje faktora rizika za nastanak infekcije krvi izazvane MDRA je sprovedeno kao prospektivna kohortna studija u jedinicama intenzivnih nega (JIN) u zdravstvenim ustanovama u AP Vojvodini u periodu od 01.01.2013. do 31.03.2016. godine. Grupu 1 (n=164), studijsku grupu kohortne studije su činili ispitanici sa BI krvi izazvanom MDRA. Grupu 2 (n=328), kontrolnu grupu kohortne studije, sačinjavali su pacijenti JIN bez izolata Acinetobacter spp. u hemokulturi. Kontrole su bile uključene u istraživanje samo ako je dužina njihovog boravka u JIN (dužina trajanja hospitalizacije do otpusta) bila ista ili duža od dužine boravka para iz studijske grupe do izolacije MDRA iz hemokulture. Kontrole su bile uparene sa slučajem iz studijske grupe u odnosu (1:2) prema: uzrastu (+/-5 godine), vrsti JIN i vremenu (isti kalendarski mesec u kojem je kod para iz studijske grupe izolovana pozitivna hemokultura). U cilju utvrđivanja predisponirajućih faktora za letalni ishod (14-dnevni letalitet) pacijenata u JIN sa infekcijom krvi izazvanom MDRA sprovedena je anamnestička studija. Rezultati: Učešće izolata Acinetobacter spp. u strukturi hemokultura pacijenata uzrasta 18 i više godina hospitalizovanih u zdravstvenim ustanovama u AP Vojvodini u periodu 2013-2015. godina iznosilo je 13,9%. Primoizolati Acinetobacter spp. iz uzoraka hemokultura pacijenata su u 96,1% (198/204) bili multirezistentni. Analizom kretanja rezistencije izolata Acinetobacter spp. na ispitivane antibiotike jedino je na cefepim ustanovljeno statistički značajno smanjenje učešća rezistentnih izolata (od 98,5% u 2014. godini do 83,3% u 2015. godini), (p=0,025). Izolati Acinetobacter spp. su najčešće registrovani kod pacijenata hospitalizovanih u JIN (71,1% (145/204)). Multivarijantnom analizom izdvojili su se nezavisni prediktori za nastanak infekcije krvi izazvane MDRA: prijem iz drugog odeljenja/bolnice, prijemne dijagnoze politrauma i opekotina, prethodna kolonizacija gornjeg respiratornog trakta MDRA, prisustvo dva i više komorbiditeta, prethodna primena mehaničke ventilacije, viši indeks invazivnih procedura, prethodna primena derivata imidazola i prethodna primena četiri i više klasa antibiotika. Pacijenti sa infekcijom krvi izazvanom MDRA su statistički značajno duže boravili u JIN (24.5±17,5) u odnosu na neinficirane kontrole (19,7±12,6), (p=0,001) i statistički značajno češće su imali letalan ishod (51,2% (84/164) u odnosu na pacijente bez infekcije krvi izazvane ovim mikroorganizmom (25,0% (82/328), (p<0,0001). Multivarijantnom analizom, kao nezavisni prediktori letalnog ishoda pacijenata, izdvojili su se: starija životna dob, prijemnom dijagnoza akutne respiratorne insuficijencije i primena neadekvatne antimikrobne terapije nakon izolacije uzročnika iz hemokulture. Zaključak: Učestalost i struktura faktora rizika je ukazala da je snižavanje prevalencije i snižavanje letaliteta moguće ostvariti kombinovanom primenom mera koje obuhvataju racionalnu upotrebu antibiotika širokog spektra u empirijskoj antimikrobnoj terapiji i striktno poštovanje procedura vezanih za primenu invazivnih nastavaka.Aim: Establish the participation of Acinetobacter spp. isolates in the structure of positive hemocultures and the percentage range of resistance to antibiotics in the health institutions of secondary and tertiary level on the territory of AP of Vojvodina in the period from 2013 to 2015; determine which patients most commonly get BSI caused by MDRA; determine risk factors for the occurrence of healthcare-associated infection (HAI) of blood caused by MDRA and the impact of HAI of blood caused by these pathogens to the duration of hospitalization, and the treatment outcome of patients admitted to the health care institutions of secondary and tertiary levels in the AP of Vojvodina. Material and Methods: Data from the protocol of the microbiological laboratory of the Center for Microbiology, Institute of Public Health of Vojvodina were used for retrospective analysis of the frequency of isolates of Acinetobacter spp. in the structure of positive hemocultures and for monitoring the percentage isolates of Acinetobacter spp. resistant to the observed type of antibiotics in health institutions of secondary and tertiary levels in AP of Vojvodina in the period from January 1, 2013 to December 31, 2015. Determining the risk factor for the occurrence of BSI induced by MDRA was conducted as a prospective cohort study in intensive care units (ICU) in the health institutions in AP of Vojvodina in the period from January 1, 2013 to March 31, 2016. Group 1 (n=164), study group of the cohort study included the patients with HAI of blood induced by MDRA. Group 2 (n=328), control group of the cohort study consisted of ICU patients without isolates of Acinetobacter spp. in the hemoculture. Controls were included in the study only if the length of their stay in the ICU (duration of hospitalization until discharge) was the same or longer than the length of the stay of their study group counterparts until the isolation of MDRA from blood culture. Controls were matched with the cases of the study group in the ratio (1: 2) according to: age (+/- 5 years), type of ICU and time (the same calendar month in which positive hemoculture was isolated in the the study group pair). In order to determine the predisposing factors of lethal outcome (14-day lethality) of patients in the ICU with the BSI caused by MDRA, anamnestic study was conducted. Results: Participation of Acinetobacter spp. isolates in the structure of hemocultures of patients, aged 18 and older, hospitalized in medical institutions in AP of Vojvodina in the period from 2013 to 2015 amounted to 13.9%. Acinetobacter spp. primoisolates from the patients' hemoculture samples were in 96.1% (198/204) multi-drug resistant. Analysing the Acinetobacter spp. isolates resistance to the tested antibiotics, Cefepime was the only to prove to cause statistically significant decrease in the share of resistant isolates (from 98.5% in the year 2014 to 83.3% in 2015), (p=0.025). Isolates of Acinetobacter spp. are most frequently registered in patients hospitalized in ICU (71.1% (145/204)). Multivariate analyses separated independent predictors for the occurrence of blood infection caused by the MDRA: patient transfers from another ward/hospital, admission diagnoses of polytrauma and burns, previous colonization of the upper respiratory tract MDRA, the presence of two or more co-morbidity, previous use of mechanical ventilation, higher index of invasive procedures, previous use of Imidazole derivates and the previous use of four or more classes of antibiotics. Patients with BSI caused by MDRA stayed statistically much longer in the ICU (24.5±17.5) as compared to uninfected controls (19.7±12.6), (p=0.001) and significantly more likely to have the lethal outcome (51.2% (84/164)) compared to patients without bloodsteram infections caused by this micro-organism (25.0% (82/328) (p<0.0001). Using multivariate analysis, independent predictors of death of patients, were found to be: advanced age, admission diagnosis of acute respiratory insufficiency and the application of inadequate antibiotic therapy after the isolation of pathogens from the hemoculture. Conclusion: The frequency and the structure of the risk factors suggested that the reduction of the prevalence and lowering of lethality can be achieved by combined administration of measures that include the rational use of broad spectrum antibiotics in the empirical antimicrobial treatment and strict compliance with the procedures related to the use of invasive follow-ups.
29
Dauchot, Jean-Marc. "Passage en ville des antirétroviraux : rapports d'enquête en milieu hospitalier et associatif avant et après la mise en place du dispositif." Paris 5, 1999. http://www.theses.fr/1999PA05P040.
30
Gozalo, Claire. "Nouvelles approches thérapeutiques des maladies à prions." Paris 5, 2006. http://www.theses.fr/2006PA05P619.
Анотація:
L’objectif de ce projet était de jeter les bases de nouvelles approches thérapeutiques pour le traitement des maladies à prions, à travers l’étude de molécules originales appartenant à deux classes de produits décrits aujourd’hui parmi les plus efficaces. Suite aux études d’efficacité réalisées en modèle cellulaire par comparaison avec la molécule de référence, le Pentosane Polysulfate, le CR36 a été sélectionné parmi les héparanes-mimétiques. Les profils très différents d’efficacité et de toxicité observés ensuite entre ces deux molécules dans plusieurs modèles animaux nous ont conduit à étudier leur mécanisme d’action et à proposer différentes hypothèses : leur degré de sulfatation jouerait ainsi un rôle central dans leur différence d'affinité pour la PrP et influerait également sur leur interaction avec les héparanes sulfates endogènes. Les porphyrines sélectionnées, quant à elles, n'ont permis d'obtenir qu'une diminution modérée d'accumulation splénique de PrPres. Leurs propriétés oxydatives ne semblent pas intervenir dans leur activité anti-prion et nos résultats favorisent plutôt l’hypothèse d’une intervention du métal coordinant en terme de structure et de capacité à déstabiliser les agrégats de PrPresThe purpose of this project was to map out new therapeutical approaches for the treatment of prion diseases through the study of original molecules belonging to two of the most efficient therapeutical classes described to date. Following efficacy studies on cellular models in comparison with Pentosan Polysulfate, the reference molecule, CR36 was selected within the heparan-mimetic class. The very different efficiency and toxicity profiles observed on various animal models led us to investigate on their respective mechanism of action and to propose different hypothesis : a central role in their affinity for PrP and in their interaction with endogenous heparan sulfates would therefore be played by the sulfation degree of these molecules. The selected porphyrins only induced a mild decrease of splenic PrPres after administration to mice. Their oxidative properties were not found to be involved in their anti-prion activity and our results favor the hypothesis of a structural and destabilizing role of the cooordinating metal for PrP aggregates
31
Gug, Fabienne. "Nouveaux dérivés à activité anti-prion : synthèse d'outils moléculaires permettant l'étude de leur mécanisme d'action." Paris 5, 2006. http://www.theses.fr/2006PA05P631.
Анотація:
Les encéphalopathies spongiformes transmissibles sont des maladies neurodégénératives caractérisées par l’accumulation d’une forme anormale de la protéine PrP dans le cerveau et contre lesquelles il n’existe pas de traitement. Récemment, un test de criblage haut débit utilisant le prion de levure à été mis au point par l’équipe du Pr M. Blondel. Son utilisation a permis la découverte de deux composés actifs : La 6-aminophénanthridine (6-AP) et le 2,6-benzylidène aminoguanidine (2,6-DBAG). Ce travail est divisé en deux parties. Dans la première, deux méthodes de synthèse innovantes de la 6-AP sont proposées ; de nombreuses séries dérivées de la 6-AP et du 2,6-DBAG sont décrites, et leurs relations structure-activité étudiées. La seconde partie concerne la synthèse d’outils moléculaires dérivés de ces composés. Les uns appliqués à la chromatographie d’affinité et les autres au photomarquage permettent l’étude de leurs mécanismes d’actionTransmissible spongiform encephalopathies are a group of fatal neurodegenerative disorders characterized by the accumulation of an abnormal form of prion protein into aggregates in brain. There is currently no treatment available for these disorders. Recently a simple, safe and rapid yeast-based method to screen for anti-prion drugs had been developed by Pr M Blondel et al. Thanks to this method, two interesting compounds have been identified: 6-aminophenanthridine ( 6-AP) and 2,6-dichlorobenzylidene aminoguanidine (2,6-DBAG). This work is divided in two parts. In the first one, two original synthesis of 6-AP are presented and numerous series derived from 6-AP and 2,6-DBAG are described. Structure-activity relationships are discussed. In the second one, two types of new molecular tools derived from these two compounds are synthetised. Based on affinity chromatography and photoaffinity labelling these tools allowed the identification of the molecular targets of the active products
32
Trabelsi, Mohamed. "Synthèse d'une nouvelle série de spiroarsoranes à ligands catécholamide. Activités antifilarienne et trypanocide." Toulouse 3, 1992. http://www.theses.fr/1992TOU30113.
Анотація:
Les travaux qui font l'objet de cette these sont consacres a la mise au point d'une nouvelle serie de spiroarsoranes a ligands catecholamide, inclus ou non dans des structures macrocycliques. La presence d'une fonction amide et d'une molecule d'eau dans ces structures leur confere des caracteristiques physicochimiques particulieres. Une etude en resonance magnetique nucleaire dynamique de ces composes pentacoordines a permis la mise en evidence d'une labilite structurale qui se traduit par la mise en jeu de plusieurs formes en equilibre. Ceci est lie a l'intervention de plusieurs phenomenes dont la stereomutation, propre aux structures pentacoordines, l'isomerie cis/trans, imposee par la substitution du noyau phenyle des ligands, et le caractere de double liaison de la fonction carbone-azote amide. Du point de vue biologique, les spiroarsoranes ont deja montre de bonnes activites antiparasitaire, antifongique et antitoxoplasmique. Cette nouvelle serie, dont le but est d'ameliorer leurs performances, a permis de reveler une activite antifilarienne, in vitro, tres interessante, meilleure que celle des spiroarsoranes de premiere generation et celle du mel w pris comme reference lors des tests biologiques. Les tests de cytotoxicite, in vitro, realises sur des cellules buccale et hepatique, montrent que les produits les plus actifs restent peu toxiques comparativement au meme produit de reference
33
Godoy, Cássia Silva de Miranda. "Infecções por Acinetobacter baumannii em adultos admitidos em unidades de terapia intensiva (UTIs) de Goiânia e Aparecida de Goiânia." Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tede/3395.
Анотація:
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Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG
Acinetobacter baumannii (Ab), has an important role in healthcare-associated infections, present a rapid global and emerging multidrug-resistant (MDR) strains, affecting many countries. In Brazil, Ab is responsible for outbreaks infections in intensive care units (ICUs) since 1996, with high rates of antimicrobial resistance. This was a descriptive cohort study of adult infected with Ab during the period of June to December of 2010, that evaluated the clinical and epidemiological profile of infections caused by Ab and analyzed genetically, by pulsed field gel electrophoresis (PFGE), clinical isolates from patients admitted in five ICUs of the Municipality of Goiania. We identified 64 cases of patient infected or colonized with Ab during the study period, 84 samples culture positive for Ab with a global infection rate of 4.8%. Infection incidence at each hospital was as follows: 10 % in ICU-1, 4.3% in ICU-2, 7.8% in ICU-3, 1.3% in ICU-4, and 7.5 % in ICU-5. The mean age of patients was 53.2 years (sd=19) and 59.4% (38) were male. Symptomatic infections occurred in 90.6% of the cases. The most frequent site of infection was pulmonary (53.1%), followed by surgical site (10.9%), and urinary tract (7.8%). The most common underlying diseases were neoplasia (34.4%) and AIDS (17.2%). Most of the patients infected with Ab (98.4%) had received antimicrobial therapy previously. The most frequently used drugs were cephalosporins (71.4%), carbapenems (50.8%), glycopeptides (46.0%), and fluoroquinolones (33.3%). Among the invasive procedures realized prior to Ab infection, intravascular catheters and vesical catheters where the most frequent (93.7%). The culture results from the isolate of each patient revealed that carbapenems resistance was 73.4%, ampicillin-sulbactam 60.9%, amikacin 20.3%, polymyxins 6.2%, tigecycline 3.1%. The overall mortality rate was 79.7% and related mortality rate to Ab infection was 67.2%. PFGE analysis of the isolates from 56 patients demonstrated the dissemination of genetically related clones within the ICU and between the different ICUs, and the identification of a major outbreak of MDR Ab in four out of the five analyzed ICUs involving 12 patients. In conclusion a high rate of antimicrobial resistance was detected as well as a high mortality rate among ICU patients infected with Ab, requiring stronger and more efficient measures to control this agent, as well as urgent measures are needed for the rational utilization of antibiotics in ICUs.
O Acinetobacter baumannii (Ab) tem importante papel nas infecções relacionadas à assistência à saúde e apresenta emergência rápida e global de cepas multidrogarresistentes (MDR), atingindo vários países. No Brasil, o Ab é responsável por surtos de infecções em unidades de terapia intensiva (UTIs) desde 1996, com elevadas taxas de resistência aos antimicrobianos. Esse estudo foi delineado como uma coorte descritiva de pacientes adultos infectados por Ab no período de junho a dezembro de 2010. Avaliou o perfil clínico e epidemiológico das infecções causadas por Ab e analisou geneticamente, por eletroforese em gel de campo pulsado (PFGE), os isolados clínicos destes pacientes em cinco UTIs de Goiânia e Aparecida de Goiânia. Foram identificados 64 casos de pacientes infectados ou colonizados por Ab no período do estudo, 84 amostras de cultura positivas para Ab e taxa global de infecção de 4,8 %. A frequência de infecções por UTIs foi de: 10% na UTI-1; 4,3% na UTI-2; 7,8% na UTI-3 e 1,3% na UTI-4 e 7,5% na UTI-5. A média de idade dos pacientes foi de 53,2 anos (dp=19) sendo 59,4% (38) do sexo masculino. Infecção sintomática ocorreu em 90,6% dos casos. O sítio de infecção mais frequente foi o pulmonar com 53,1%, seguido de infecção do sítio cirúrgico 10,9% e trato urinário 7,8%. As doenças de base mais comuns foram neoplasia (34,4%) e AIDS (17,2%). Dos pacientes com infecção pelo Ab, 98,4% receberam antibacteriano prévio. Os antibacterianos mais usados foram: cefalosporinas 71,4% (45); carbapenêmicos 50,8% (32), glicopeptídeos 46,0% (29) e fluorquinolonas 33,3% (21). Dos procedimentos invasivos realizados previamente à infecção pelo Ab, cateter vascular central e sondagem vesical de demora (93,7%) foram os mais comuns. A letalidade global foi de 79,7% (51/64), e a relacionada às infecções pelo Ab foi de 67,2% (39/58). Avaliando os resultados de cultura positiva, a resistência aos carbapenêmicos foi de 73,4%, à ampicilina/sulbactam de 60,9% (39/64), amicacina de 20,3% (13/64), polimixinas de 6,2% (4/64) e tigeciclina de 3,1% (2/64). A análise por PFGE das isolados bacterianos dos pacientes (56), demonstrou a disseminação clonal de Ab dentro das UTIs, e entre as diferentes UTIs, com identificação de um surto por Ab MDR entre quatro das cinco UTIs investigadas no período do estudo, envolvendo 12 pacientes. Constatamos alto índice de Ab MDR e alta letalidade nas UTIs avaliadas, com necessidade de intensificar o controle deste agente, além de racionalização do uso de antimicrobianos nas UTIs.
34
Dulin, Jacqueline. "Traitement des infections urinaires chez la personne agée : élaboration et évaluation d'un protocole d'antibiothérapie." Bordeaux 2, 1994. http://www.theses.fr/1994BOR2P002.
35
Oliveira, Maria Manuela Pereira de. "Optimisation des paramètres biopharmaceutiques de l'indinavir." Poitiers, 2005. http://www.theses.fr/2005POIT1801.
36
Cayla, Rémy. "Traitement des ulcères duodénaux associés à Hélicobacter pylori : résultats et suivi à long terme d'un essai randomisé associant une biantibiothérapie à un anti-sécrétoire (Ranitidine vs Omeprazole)." Bordeaux 2, 1992. http://www.theses.fr/1992BOR23090.
37
Jebbari, Mostafa. "Les inhibiteurs de la pompe à protons, l'ulcère gastroduodénal à l'heure de l'Helicobacter Pylori." Bordeaux 2, 1998. http://www.theses.fr/1998BOR2P025.
38
Bottalico, Fabrice. "Antibiothérapie de première ligne du sujet adulte fébrile en aplasie prolongée : évaluation de l'association empirique céfépime-tobramycine en hématologie maligne, à propos de 140 cas." Bordeaux 2, 1999. http://www.theses.fr/1999BOR2M030.
39
Fattal, Elias. "Mise au point de nanoparticules et de liposomes chargés en ampicilline pour le traitement des infections intracellulaires." Paris 11, 1990. http://www.theses.fr/1990PA114807.
40
Andron, Pascal. "Les infections à "Streptococcus pneumoniae" de 1984 à 1990 à l''hôpital Louis Mourier de Colombes : aspect épidémiologique et évolution de la résistance à la pénicilline." Paris 5, 1992. http://www.theses.fr/1992PA05P006.
41
Casas, Christiane. "Synthèse de métalloporphyrines-vecteurs : cas des oligonucléotides." Toulouse 3, 1992. http://www.theses.fr/1992TOU30236.
Анотація:
Ce travail concerne la synthese de metalloporphyrines cationiques monofonctionnalisees et leur vectorisation a l'aide d'oligonucleotides. Une premiere partie presente la mise au point de voies de synthese permettant d'obtenir des precurseurs porphyriniques portant une fonction acide, alcool ou amine libre, un metal central et quaternarisees sur les substituants pyridines. Dans une deuxieme partie est decrite la synthese et la fonctionnalisation des oligonucleotides. Une troisieme partie concerne les essais de couplage entre ces deux molecules. La preparation de la molecule mixte fait intervenir une etape d'activation de la fonction acide du bras de la porphyrine par du carbonyldiimidazole et de l'hydroxy-benzotriazole. La reaction sur la fonction amine de l'oligonucleotide est rapide et le couplage est effectue avec de bons rendements (25 a 50%). Cette strategie est applicable aux porphyrines hydrophobes ou cationiques, metallees ou libres et quelle que soit la sequence de l'oligonucleotide. Une derniere partie presentera l'utilisation de ces molecules hybrides comme agent de coupure specifique de l'adn: l'activite nuclease de la molecule hybride metalloporphyrine cationique de manganese-19 mer est observee a partir d'une concentration de 10 nm et pour un rapport agent de coupure/cible de l'ordre de 2,6. Le 19 mer est dans ce cas un oligonucleotide complementaire de la zone du codon d'initiation du gene tat du virus vih-1
42
Lobo, Caroline Zapater. "Características microbiológicas e clínicas das infecções por Acinetobacter spp. e Pseudomonas aeruginosa em Unidade de Terapia Intensiva Cardíaca de um Hospital Universitário do Rio de Janeiro." Universidade do Estado do Rio de Janeiro, 2012. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=7590.
Анотація:
As infecções em cirurgia cardíaca ainda apresentam um cenário importante nas infecções associadas à assistência a saúde (IAAS), favorecendo ao paciente à aquisição de infecções por micro-organimos multirreristentes. Este trabalho teve como objetivo avaliar o perfil de resistência a antimicrobianos, verificar a presença de genes que codificam as enzimas dos tipos oxacilinases e metalo-beta-lactamases e descrever as características demográficas e clínicas dos pacientes colonziados/infectados por Acinetobacter spp. e P.aeruginosa internados no Centro de Terapia Intensiva Cardíaca do HUPE no período de 2005 a 2010. A maioria das 46 amostras de Acinetobacter spp e das 35 de P.aeruginosa foram de origem respiratória seguido de sangue. A maioria das amostras de A. baumannii apresentou altos percentuais de resistência a: ceftazidina, cefepime, piperacilina-sulbactam, ciprofloxacin, ceftriaxona e CIM ≥32 μg/mL para os carbapenêmicos. Uma amostra foi resistente a Polimixina B. O gene blaOXA-23 foi detectado em 65% das amostras e uma amostra apresentou o gene blaOXA-24. Não foram detectados os genes blaOXA-58-like e blaOXA-143. Para P. aeruginosa os percentuais de resistência para todos os antimicrobianos foram inferiores a 32%. Quatro amostras apresentaram resistência intermediária a polimixina B e nenhum gene de resistência foi detectado. Os prontuários dos pacientes foram analisados a fim de associar as características clínicas com os processos infecciosos identificados e seu desfecho clínico. Na análise por tipo de micro-organismo associado ao processo infeccioso à idade acima de 70 anos, DM e uso da ventilação mecânica por tempo prolongado foi maior no grupo dos pacientes que apresentaram infecção por P.aeruginosa. O IAM, a ICC em internações anteriores e suas complicações (choque cardiogênico e arritmia) tiveram impacto na mortalidade na série de pacientes (p<0,05). A insuficiência renal entre todas as comorbidades foi à única que teve associação com a mortalidade (OR= 8,3). Não houve associação entre a mortalidade e o micro-organismo que causou a infecção (Acinetobacter spp. p=0,3 e P.aeruginosa p=0,2) ou a resistência a carbapenêmicos (p=0,5). Foram observados dois casos de mediastinte por Acinetobacter spp. e dois por P. aeruginosa sendo um achado inédito no Brasil até o momento.Infections in cardiac surgery still have an important scenario infections associated with health assistance(IAHA), favoring acquisition of the patients to infection by microrganisms multiresistants. This work aimed to avaluate the profile of the resistance antimicrobial, to verify the presence of genes encoding enzymes of types oxacilinases and metallo-beta-lactamases and describe demographic and clinical caracteristics of inpatients colonized/infected by Acinetobacter spp. and P. aeruginosa in Cardiac Care Center the Pedro Ernesto University Hospital during the period 2005 to 2010. Most of 46 samples of Acinetobacter spp. and 35 the P. aeruginosa were the respiratory origen and and blood. Most sample A.baumannii showed higher percentages of resistance to: ceftazidime, piperacilin-sulbactam, ciprofloxacin, ceftriaxone and CIM ≥32 μg/mL for carbapenems. A sample was resistant a polymyxin B. The gene blaOXA-23 was detected in 65% of the samples and a sample showed gene blaOXA-24.The genes blaOXA-58-like e blaOXA-143 not were detected. For P. aeruginosa the percentage of resistance to all antimicrobials was less than 32%. Four samples showed intermediate resistance to polymyxin B and no gene the resistance was detected.The charts of all patients were analyzed in order to associated the clinical caracteristics with infections processes identified and the clinical outcome. The analyses by type of microrganism associated with infections process over the age of 70 years, DM and use mechanical ventilation for prolonged was higer in the patients with infection by P. aeruginosa. The IAM and the ICC of previous hospitalizations and complications (cardiogenic shock and arrhythmia) had an impact on mortality in series of patients (p<0,05). The renal failure among all comorbitidies was the only one that was associated with mortality (OR=8,3). There was no association between mortality and the organism causing the infection (Acinetobacter spp. p=0,3 and P.aeruginosa p=0,2). Two cases of mediastinitis of Acinetobacter spp. and two cases of P. aeruginosa was observed. It was an umprecedented finding in Brazil at that moment.
43
Meyer-Madelaine-Dupuich, Christine. "Nouvelle voie de synthèse de dérivés aromatiques d'acides disulfoniques : Etude de leurs propriétés physico-chimiques en relation avec leur activité anti-V.I.H." Toulouse 3, 1994. http://www.theses.fr/1994TOU30161.
Анотація:
Dans ce memoire, nous proposons une methode de synthese originale et peu couteuse de derives monocatenaires d'acides naphthalene et stilbene disulfoniques. Cette methode consistant a faire reagir un derive de 3-acyl-2-thiazolidinethione avec un acide amino-naphtalenedisulfonique ou amino-stilbenedisulfonique dans le d. M. F. Conduit a des rendements (15-60%) superieurs a ceux de la litterature. L'etude physicochimique des derives synthetises montre que les derives monocatenaires se micellisent et penetrent au cur des membranes biologiques. Les derives bolaformes forment des vesicules d'un diametre moyen de 20 nm. Les tests anti-v. I. H. Menes sur cellules cem-ss ont permis de mettre a jour une nouvelle famille de derives d'acides 1,3-naphtalene disulfonique a potentiel anti-v. I. H. Dont les ic50 varient de 35 a 190 nm
44
Bildstein, Sophie. "Évaluation de l'antibiothérapie dans le traitement des pneumopathies nosocomiales en réanimation : étude prospective sur une population de 45 patients." Bordeaux 2, 1995. http://www.theses.fr/1995BOR2P093.
45
Toure, Abdoulaye II. "Impact de la nutrition parentérale associée à la chimiothérapie intraveineuse sur l'incidence des infections aux cathéters veineux chez les patients ayant un cancer digestif." Phd thesis, Université Claude Bernard - Lyon I, 2012. http://tel.archives-ouvertes.fr/tel-00976860.
Анотація:
Les cathéters veineux centraux sont utilisés pour des traitements dont la chimiothérapie, l'hydratation, l'antibiothérapie et la nutrition parentérale chez les patients ayant un cancer. Cependant, ces cathéters sont responsables de graves complications dont les infections. Elles peuvent entraîner la suspension ou l'arrêt des traitements et peuvent engager le pronostic vital des patients. Le taux d'incidence et les facteurs de risque des infections liées aux cathéters veineux centraux (ILCVC) en oncologie restent mal connus. Une étude prospective menée pendant 5 ans à l'hôpital Edouard Herriot et à l'hôpital de la Croix Rousse nous a permis de décrire les ILCVC chez 425 patients ayant un cancer digestif. Nous avons d'abord estimé le taux d'incidence des ILCVC selon la localisation du cancer primitif. Ensuite, nous avons analysé les facteurs de risque. Pour mieux estimer l'impact de la nutrition parentérale sur le risque d'ILCVC, nous avons utilisé le score de propension pour imiter certaines caractéristiques d'un essai randomisé. Enfin, nous avons analysé la mortalité dans les 30 jours qui ont suivi l'ILCVC. Les résultats ont montré que le taux d'incidence des ILCVC était plus élevé chez les patients ayant un cancer pancréas ou un cancer de l'œsophage que ceux qui ont un cancer colorectal. Les facteurs de risque indépendamment associés à une ILCVC étaient le performance status, les journées d'utilisation du cathéter, le cancer du pancréas et la nutrition parentérale. Le risque d'ILCVC était supérieur à 5 chez les patients qui recevaient de la nutrition parentérale associée à la chimiothérapie intraveineuse. Le diabète était un facteur de risque indépendamment associé à la mortalité dans les 30 jours qui suivent la survenue l'ILCVC.
46
Maruejouls, Christophe. "Etat actuel de la sensibilité aux antibiotiques des "Pasteurella" et bactéries apparentées isolées d'infections humaines." Paris 5, 1995. http://www.theses.fr/1995PA05P194.
47
Ndonga, Lutumba. "Antibiothérapie en milieu hospitalier (enquête du 1 février au 15 avril 1992)." Paris 5, 1998. http://www.theses.fr/1998PA05P004.
48
Thibon, Jacques. "Synthèse d'analogues acycliques organosiliciés de nucléosides." Bordeaux 2, 1997. http://www.theses.fr/1997BOR28494.
49
Montagu, Angélique. "Composants aromatiques nano-encapsulés : une alternative face à la résistance aux antibiotiques : Démonstration des effets biologiques seuls ou nano-encapsulés de l’in vitro à l’in vivo Prevention of Bacterial Infections Using Encapsulated Phytophenolic Actives Aromatic and terpenic compounds loaded in lipidic nanocapsules: activity against multi-drug resisant Acinobacter baumannii assessed in vitro and in a murine model of sepsis Demonstration of the interactions between aromatic compound-loaded lipid nanocapsules and Acinetobacter baumannii bacterial membrane." Thesis, Angers, 2016. http://www.theses.fr/2016ANGE0072.
Анотація:
Face à la montée en puissance des bactéries multi-résistantes, la découverte de nouvelles stratégies antibactériennes s’impose. Une alternative est l’utilisation de substances actives antibactériennes issues d’huiles essentielles. Ces actifs de nature lipophile, ont été encapsulés via les nanocapsules lipidiques (NCL) pour une utilisation par voie systémique. L’efficacité de ces NCL chargées en actifs a été montrée dans un modèle de sepsis à Acinetobacter baumannii avec un taux de survie de 45% à 55%. Notre étude a montré le pouvoir d’attraction et de pénétration du carvacrol (Car) encapsulé via les fonctions hydroxyles vis-à-vis de la membrane bactérienne. Les effets biologiques de ces actifs ont été caractérisés par une dégradation de l’ARNr et une surexpression des gènes codant pour des heat shock protein. Une surexpression de la catalase due au Car est également observée, en lien avec le stress oxydatif (rôle de détoxification). Nos travaux ont montré que les bactéries pourraient utiliser dans ce processus une stratégie de défense contre le Car en utilisant les ROS endogènes lors d’une réponse au stress environnemental. Ces effets biologiques sont conservés après l’encapsulation des actifs par les NCL. Dans un modèle in vivo de pneumopathie, aucune survie animale n’a été constatée, malgré la post-insertion des NCL, qui est censée augmenter leur furtivité dans le sang. L’infection pulmonaire n’a pas favorisé d’accumulation des NCL dans les poumons. Ce phénomène pourrait s’expliquer par la métabolisation du Cin en acide cinnamique dans le sang, forme oxydée de l’actif qui réduirait drastiquement l’activité antibactérienne des NCL chargées en Car-CinFaced with the rise of multidrug-resistant bacteria, the discovery of new antibacterial strategies is imperative. An alternative is the use of antibacterial active substances from essential oils. These lipophilic compounds were encapsulated via lipidic nanocapsules(LNC) allowing a use by systemic way. The efficacy of actives loaded LNC has been showed in a murine model of sepsis against Acinetobacter baumannii with a survival rate of 45% to 55%. Our study showed the power of attraction and penetration of the encapsulated carvacrol (Car) via the hydroxyl functions. The biological effects of these compounds were characterized by a degradation of rRNA, an over expression of genes encoding heat shock proteins. A catalase overexpression was also observed which is related to an oxidative stress (role of detoxification). Our works showed that bacteria could use in this process, a defense strategy against Car using the endogenous reactive oxygen species in response to environmental stress. These biological effects are preserved after encapsulation by LNC. In an in vivo model of pneumonia, no animal survival has been observed, despite the use of pegylated LNC, which is supposed to increase their stealth in the blood. Pulmonary infection did not promote the LNC accumulation in the lungs. This phenomenon could be explained by the metabolization of Cin in cinnamic acid in the blood, the oxidized form ofthe compound which would drastically reduce the antibacterial activity of Car-Cin loaded LNC
50
Célestin, Hanitranirina Michel. "Influence du ritonavir sur le taux sanguin de polynucléaires neutrophiles chez les patients infectés par le VIH." Bordeaux 2, 1998. http://www.theses.fr/1998BOR2P045.