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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Bacterial viruses targeting multi-resistant Klebsiella pneumoniae and Escherichia coli

Eriksson, Harald January 2015 (has links)
The global increase in antibiotic resistance levels in bacteria is a growing concern to our society and highlights the need for alternative strategies to combat bacterial infections. Bacterial viruses (phages) are the natural predators of bacteria and are as diverse as their hosts, but our understanding of them is limited. The current levels of knowledge regarding the role that phage play in the control of bacterial populations are poor, despite the use of phage therapy as a clinical therapy in Eastern Europe. The aim of this doctoral thesis is to increase knowledge of the diversity and characteristics of bacterial viruses and to assess their potential as therapeutic agents towards multi-resistant bacteria. Paper I is the product of de novo sequencing of newly isolated phages that infect and kill multi-resistant Klebsiella pneumoniae. Based on similarities in gene arrangement, lysis cassette type and conserved RNA polymerase, the creation of a new phage genus within Autographivirinae is proposed. Paper II describes the genomic and proteomic analysis of a phage of the rare C3 morphotype, a Podoviridae phage with an elongated head that uses multi-resistant Escherichia coli as its host. Paper III describes the study of a pre-made phage cocktail against 125 clinical K. pneumoniae isolates. The phage cocktail inhibited the growth of 99 (79 %) of the bacterial isolates tested. This study also demonstrates the need for common methodologies in the scientific community to determine how to assess phages that infect multiple serotypes to avoid false positive results. Paper IV studies the effects of phage predation on bacterial virulence: phages were first allowed to prey on a clinical K. pneumoniae isolate, followed by the isolation of phage-resistant bacteria. The phage resistant bacteria were then assessed for their growth rate, biofilm production in vitro. The virulence of the phage resistant bacteria was then assessed in Galleria mellonella. In the single phage treatments, two out of four phages showed an increased virulence in the in G. mellonella, which was also linked to an increased growth rate of the phage resistant bacteria. In multi-phage treatments however, three out of five phage cocktails decreased the bacterial virulence in G. mellonella compared to an untreated control. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>
2

Patienter med multiresistenta bakterier : En litteraturbaserad studie om upplevelser av mötet med vården / Patients with multi-resistant bacteria : A literature-based study regarding experiences of the encounter with healthcare

von Brömsen, Caroline, Björkbacke , Maria January 2020 (has links)
Multi-resistant bacteria are a growing problem worldwide. In relation to the bacteria spreading, the proportion of patients with multi-resistant bacteria also increase. In nursing, the encounter is described as a central part and works to ensure that the patient can express their feelings. How the meeting takes place has a great impact on whether the patient experiences suffering or not. A professional approach and knowledge regarding patients experience of the encounter as well as communication, forms a basis for the nurse to be able to meet the patient's unique needs in the encounter. The aim of this study is to describe how patients with multi-resistant bacteria experience the encounter with healthcare. This is a literature study is based on analysis of qualitative studies. The ten articles that make up the work have been analysed using a fivestep model. This resulted in two main themes and five sub-themes, which describe the experience of the meeting. The results describe how the staff's hygiene routines, attitudes and knowledge affect how patients experience the encounter. It also highlights the impact of the isolation in which patients are cared for and the stigmatization that was experienced during the encounter. In summary, it showed that patients with multi-resistant bacteria are at risk of experiencing an encounter that is stigmatizing. Patients experienced feelings such as guilt and shame due to the healthcare staff´s routines and attitudes in the meeting.
3

Problematika tuberkulózy v Zambii / The problem of Tuberculosis in Zambia

LUBASI, Sundano Kutoma January 2013 (has links)
Tuberculosis is one of the worlds? deadliest infectious diseases, and is one of the major causes of morbidity and mortality especially in poor countries. In Zambia, Tuberculosis remains a major health problem and is among the top ten causes of morbidity and mortality. Tuberculosis notifications have increased 5- fold in the last 20 years, mainly due to HIV/AIDS, it is estimated that approximately 70 % of all detected tuberculosis cases are also co-infected with HIV. The interaction of tuberculosis with the human immunodeficiency virus (HIV) infection has complicated and made difficult the Tuberculosis control program. Tuberculosis has become the leading cause of death among people living with HIV/AIDS. The management of tuberculosis in Zambia is faced with many challenges, such as lack of compliance to treatment by patients, poverty as well as lack of adequate finance for diagnosis, treatment and follow-up care. The main aim of my thesis was monitoring the problem of tuberculosis in Zambia, other accompanying aims were to find out how well informed the Zambian population is, about tuberculosis, monitor the diagnostic procedure for tuberculosis, analyse the tuberculosis treatment regime and lastly to analyse the preventive measures that have been implemented and how effective they have been. In this thesis, both qualitative and quantitative types of research were used. With the qualitative research, secondary analysis of data was used. Data from different sources of information like books, publications and research findings of various surveys and researches that were done not only by the Zambian Ministry of Health but also by other organizations was used. With the quantitative research, a questionnaire was formulated whose main aim was to find out about how well informed the Zambian people are about tuberculosis. This was done only in the capital city of Zambia which is Lusaka, and the number of respondents was 100. From the results obtained, the tuberculosis burden in Zambia still remains high and tuberculosis continues to be a serious public health problem. The implementation of the various preventive measures, though still facing difficulties, has however yielded positive results. There have been improvements in the treatment success rates from 77 % in the year 2000 to the current 86 %, the incidence rate per 100 000 population has also reduced from 504 in the year 2000 to the current 365 per 100 000 population. This reduction in incidence rates can be attributed to the preventive measures like the expansion of directly observed therapy treatment ? shortcourse (DOTS)strategy to all the districts in the country, the strengthening of the National Tuberculosis Control program and many others. This work can be used as a source of reference for future research in relation to the topic of tuberculosis in Zambia.
4

Alternativas farmacológicas para a resistência parasitária múltipla em rebanhos de ruminantes: uma nova abordagem / Pharmacological alternatives for multiple parasitic resistance in ruminant livestock: a new approach

Cezar, Alfredo Skrebsky 10 March 2010 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Infections by gastrointestinal nematodes are among the main diseases of the ruminants around the world. These infections cause - in their clinical or subclinical courses a decrease of the productivity of the herds, thus, the economic viability of the ruminant farms is directly related to an adequate control of these parasites. Although the benefits of the use of several practices of alternative control of parasites are proven and, despite of that these practices have been improved through the years, in general, the use of efficacious antiparasitic drugs is imperative to control satisfactorily the helminths of the ruminants. However, the development of parasite resistance to these drugs has become common and, in some cases, parasitic populations are multiple resistant to several classes of anthelmintics and endectocides, and it makes very difficult to control the helminthosis adequately. In this study are shown some experiments conducted with the aim of to find ways to restore the efficacy of the treatments, for recovering the usefulness of active ingredients for which the gastrointestinal nematodes of ruminants became resistant. Efficacy tests of the drugs were made using Fecal Egg Count Reduction Tests (FECRT) and larvae cultures, for the identification of the genus of nematodes existing, before and after the treatments. We evaluated the anthelmintic action of high concentrated (long acting) drugs, overdoses (high dosages), commercial combinations of drugs and combinations of chemicals, formulated with basis in previous efficacy tests for each active ingredient alone. These combinations, done from drugs sold separately, gave us the best results. Based in these observations, we are proposing a new approach regarding helminth control in multi-resistant populations, by using combinations of drugs with different mechanisms of action on the parasites, and taking advantage of the efficacy tests, performed before the choose of drugs, and then, to prove the results obtained with the combinations done particularly for each herd. / As infecções por nematódeos do trato gastrintestinal estão entre as principais enfermidades de ruminantes ao redor do mundo. Essas infecções, clínicas ou subclínicas, impactam negativamente a produtividade dos rebanhos, e a viabilidade econômica dos mesmos está diretamente relacionada a um controle adequado desses parasitas. Embora estejam comprovados os benefícios de utilizarem-se diversas práticas de controle alternativo de parasitas, as quais vêm sendo aprimoradas ao longo dos anos, em geral, a utilização de fármacos antiparasitários eficazes sobre os helmintos que infectam os ruminantes ainda é essencial para que se obtenham resultados satisfatórios. No entanto, o desenvolvimento de resistência parasitária a tais fármacos tem se tornado cada vez mais comum e, em alguns casos, as populações de parasitas já apresentam resistência múltipla a várias classes de anti-helmínticos e endectocidas, comprometendo o adequado controle das helmintoses. Neste estudo apresentam-se experimentos que foram conduzidos com o objetivo de encontrarem-se meios de restabelecer a eficácia dos tratamentos, recuperando-se a utilidade de princípios ativos para os quais os nematódeos gastrintestinais de rebanhos de ruminantes já tenham desenvolvido resistência. Foram utilizados testes de eficácia com base na redução da contagem de ovos nas fezes dos animais após os tratamentos (FECRT), e em culturas de larvas para a identificação dos gêneros de nematódeos presentes nessas amostras. Avaliaram-se os efeitos anti-helmínticos de fármacos de alta concentração (longa ação), de superdosagens, de combinações comerciais e de combinações de drogas elaboradas com base em estudos prévios de eficácia das mesmas (isoladamente), utilizando-se para isso, fármacos comercializados separadamente. Os melhores resultados foram obtidos, justamente, com estas últimas. Propõe-se, a partir destas constatações, uma nova abordagem em relação ao controle antiparasitário em populações de helmintos multi-resistentes, utilizando-se a combinação de diferentes fármacos (com princípios ativos e mecanismos de ação distintos), e valendo-se de testes de eficácia para a escolha dos fármacos e para a comprovação dos resultados obtidos com suas combinações especificamente em cada rebanho.
5

Patienters upplevelser av att bära på multiresistenta bakterier - en litteraturöversikt / Patients' experiences of carrying on multi-resistant bacteria -  a literature review

Israelsson, Sandra, Mickelsson, Therese January 2020 (has links)
Bakgrund:  Multiresistenta bakterier (MRB) förekommer i hela världen och klassas  som ett globalt folkhälsoproblem. Kunskapen om multiresistenta bakterier är låg både hos  patienter och sjukvårdspersonal. För att minska risken för spridning behövs mer kunskap och om vikten av följsamhet till basala hygienrutiner. Överdriven användning av antibiotika är en  bidragande orsak till den ökade antibiotikaresistensen i världen.  Sjukvårdspersonal upplever svårigheter med att vårda patienter med MRB och bristande kunskap hos kan ses som bidragande faktor till detta. Att undvika smittspridning är en stor del i hur patienterna ska hanteras inom vården.  Syfte: Att sammanställa patienters upplevelser av att leva med multiresistenta bakterier såsom Meticillinresistenta Staphylococcus aureus (MRSA), Vancomycinresistenta enterokocker (VRE) och Extended Spectrum Beta-Lactamase (ESBL).  Metod: Studien har genomförts som en litteraturöversikt baserat på 15 vetenskapliga artiklar. Artiklarna är av kvalitativ, kvantitativ och mixad ansats. Databaser som använts är CINAHL, PubMed och Scopus.  Resultat: Resultatet presenteras i fyra olika kategorier: Upplevelser av MRB i vardagen, Upplevelser av att få bristande information, Upplevelser av bemötande från sjukvårdspersonal och Upplevelser av stigmatisering. Konklusion: Stigmatisering, oro och ångest genomsyrade resultatet av denna litteraturöversi kt. Sjukvårdspersonalens bemötande spelar en viktig roll i hur patienten hanterar att bli diagnostiserad med multiresistenta bakterier och sen att leva med multiresistenta bakterier.  Okunnig sjukvårdspersonal gav upphov till ökat lidande för patienterna. / Background: Multi-resistant bacteria (MRB) occur worldwide and are classified as a global public health problem. Knowledge of multi-resistant bacteria is low in both patients and healthcare professionals. To reduce the risk of spreading, more knowledge and the importance of adherence to basic hygiene routines are needed. Excessive use of antibiotics is a contributing cause of the increased antibiotic resistance in the world. Healthcare professionals experience difficulties in caring for patients with MRB and lack of knowledge can be seen as a contributing factor. Avoiding the spread of infection is a major part of how patients should be managed in healthcare situations.  Aim: To compile patients' experiences of living with multi-resistant bacteria such as Multiresistant staphylococcus aureus, Vancomycin-resistant enteroccal and Extended-spectrum betalactamase  Method: The study has been conducted as a literature review based on 15 scientific articles.  The articles are of qualitative, quantitative, and mixed method. Databases used in the search  are CINAHL, PubMed and Scopus.  Results: The results are presented in four different categories: Experiences of multi-resistant bacteria in everyday life, Experiences of lack of information, Experiences of treatment from healthcare professionals and Experiences of stigmatization. Conclusion: Stigmatization, anxiety and concern permeated the results of this literature review. The care of healthcare personnel plays an important role in how the patient handles being diagnosed with and then living with multidrug resistant bacteria. Unskilled healthcare  professionals caused increased suffering for patients.
6

Infections péri prothétiques et bactéries multi résistantes : un challenge médico-chirurgical / Peri prosthetic infections and multi-resistant bacteria : a medical- surgical challenge

Gatin, Laure 29 September 2017 (has links)
La survenue d’une infection péri prothétique (IPP) est la principale complication de la chirurgie prothétique articulaire, depuis son invention par Robert et Jean Judet en 1947. Comme le nombre de prothèses articulaires posées chaque année augmente de façon importante, ces infections sont de plus en plus fréquentes et l’optimisation de leur prise en charge est un enjeu important sur le plan médical et économique.Les modèles animaux d’IPP permettent de comprendre les mécanismes éthio-pathogéniques et tester de nouvelles thérapeutiques. Une analyse critique de la littérature a été effectuée en évaluant chaque modèle selon son type d’inoculation qui influence les taux et la sévérité de l’infection expérimentale obtenue.Un modèle expérimental d’IPP chez le lapin obtenu par remplacement partiel du genou et inoculation locale a été utilisé pour tester l’efficacité de nouvelles thérapeutiques au cours d’infections à deux bactéries multi résistantes qui posent des problèmes en thérapeutique humaine.Dans un 1er temps nous avons évalué l’efficacité de la ceftaroline (CPT) céphalosporine bactéricide in vivo contre le Staphylococcus aureus résistant à la méticilline (SARM) en la comparant à la vancomycine en association ou non à la rifampicine. 5.107UFC (Unités Formant Colonies) de SARM (Concentration Minimale Inhibitrice (CMI) de 0,38, 0,006, et 1 mg/l pour CPT, RIF, et VAN, respectivement) était injecté dans le genou. Les animaux infectés ont été randomisés et recevaient : aucun traitement (contrôles), CPT (60 mg/kg im), VAN (60 mg/kg im), CPT plus RIF (10 mg/kg im), ou VAN plus RIF débutant 7 jours après l'inoculation et durant 7 jours. L’efficacité des traitements a été évaluée sur la quantité de bactéries persistantes dans l’os (tibia proximal) après traitement. Ce travail a montré que la CPT et la VAN étaient efficace en monothérapie mais que seule l’association avec la rifampicine permettait de stériliser la quasi totalité des animaux. La CPT apparaît donc comme un traitement potentiellement efficace dans cette infection.Dans un 2ème temps nous avons étudié l'efficacité de la colistine (COL) dans le ciment, seule ou en combinaison avec des injections intramusculaires (im) de COL et/ou de méropénème (MRP) dans des infections à Klebsiella pneumoniae résistantes aux carbapénèmes (KPC). Un modèle proche de celui décrit pour le SARM a été utilisé. La souche KPC99YC est une souche clinique, résistante à la gentamicine (CMI 8mg/l) intermédiaire à l'imipénème (CMI 4mg/l), et sensible à la COL (CMI 0,25mg/l). L’inoculum était de 1.109UFC. Sept jours après l'infection, les prothèses étaient remplacées par espaceur sans antibiotique (contrôle), ou par espaceur imprégné de COL (3 MUI de COL/40g de ciment), ou par espaceur sans antibiotique et injections de COL (12 mg/kg im), ou l’association des deux, ou injections de COL avec espaceur en ciment imprégné de COL associé ou non à des injections de MRP (80 mg/kg im). Le traitement durait 7 jours. Tous les lapins témoins étaient infectés à J15, avec une moyenne de densité bactérienne de 6,17 [5,69, 7,04] CFU/g d'os. Contrairement à la COL locale, la COL systémique seule ou combinée avec le MRP était plus efficace que le contrôle sur le nombre de bactéries dans l'os à la fin du traitement. L’association COL locale + systémique était significativement plus efficace que le groupe témoin sur le dénombrement bactérien. D’ailleurs, c'était le seul schéma efficace sur le nombre de lapins avec un os stérile et à la limite de significativité par rapport au traitement systémique seul. Une souche résistante à la COL a été détectée dans le traitement local seul mais pas avec l’association de COL locale et systémique.Les modes d’inoculation directs sont les plus efficaces pour reproduire une IPP aigue. Les études expérimentales permettent de tester des traitements innovants en particulier pour les infections à bactéries multi résistantes. / The occurrence of prosthetic joint infection (PJI) is the main complication of joint prosthetic surgery since its invention by Robert and Jean Judet in 1947. Since the number of articular prostheses placed each year increases significantly, these infections are more and more frequent and the optimization of their management is an important medical and economic stake.The animal models of PJI make it possible to understand the ethiopathogenic mechanisms and to test new therapeutics. A critical analysis of the literature was carried out by evaluating each model according to its type of inoculation which influences the rates and the severity of the experimental infection obtained.An experimental model of PJI in rabbits obtained by partial replacement of the knee and local inoculation was used to test the efficacy of new therapeutics during infections with two multi-resistant bacteria which pose problems in human therapeutics.In a first step we evaluated the efficacy of ceftaroline (CPT) cephalosporin bactericidal in vivo against methicillin-resistant Staphylococcus aureus (MRSA) by comparing it with vancomycin (VAN) in combination with or without rifampin (RIF). 5.107UFC MRSA (Minimum Inhibitory Concentration (MIC) of 0.38, 0.006, and 1 mg/l for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomized to receive no treatment (control), CPT (60 mg/kg im), VAN (60 mg/kg im), CPT plus RIF (10 mg/kg im) or VAN plus RIF, 7 days after inoculation and for 7 days. The efficacy of treatments was evaluated on the amount of persistent bacteria in the bone (proximal tibia) after treatment. This work has shown that CPT and VAN were effective as monotherapy, but only the combination with RIF allowed the sterilization of almost all animals. CPT appears to be a potentially effective treatment in this infection.In a second step we studied the efficacy of colistin (COL) in cement, alone or in combination with intramuscular (im) injections of COL and/or meropenem (MRP) in carbapenem-resistant Klebsiella pneumoniae infections (KPC). A model close to that used for MRSA was used. The strain KPC99YC is a clinical strain, resistant to gentamicin (MIC 8mg/L) intermediate to imipenem (MIC 4mg/l), and sensitive to COL (MIC 0,25mg/l). The inoculum was 1,109UFC. Seven days after the infection, the prosthesis were replaced by antibiotic-free spacer (control), or by COL-impregnated spacer (3 MIU of COL/40g of cement), or by antibiotic-free spacer and COL injections (12 mg/kg im), or the combination of the two, or COL injections with COL-impregnated cement spacer associated or not with MRP injections (80 mg/kg im). The treatment lasted 7 days. All control rabbits were infected at D15, with median and interquartile range (IQR) bone bacterial count of 6.17 [5.69, 7.04] CFU/g of bones. In contrast to local COL, systemic COL alone or combined with MRP was more effective than control on bacterial counts in bone at the end of treatment. The combination of COL local + systemic was significantly more effective than control group on bacterial counts. Interestingly it was the only effective regimen on the number of rabbits with sterile bone and at the limit of significance vs systemic treatment alone. One COL-resistant strain was detected in the COL local treatment alone but not with the combination of local and systemic COL.Direct inoculation modes are most effective in reproducing an acute PJI. The experimental studies allow testing innovative treatments in particular for the infections with multi-resistant bacteria.
7

Art och resistensmönster hos acinetobacterstammar i blodprover från patienter i skånsk sjukvård 2011-2019 / Species Identification and Resistance Patterns of Acinetobacter Strains in Blood Samples from Patients in Medical Care in Skåne 2011-2019

Nafaa, Fatima January 2021 (has links)
Acinetobacter är gramnegativa bakterier som orsakar svåra nosokomiala infektioner hos immunkomprometterade och neutropena patienter. Det har rapporterats att den vanligaste smittkällan är sjukhusutrustning såsom andningsinstrument, där kolonisation av acinetobacter observerats. Av den anledningen att acinetobacter är multiresistenta mot olika antibiotikum medför det att en acinetobact infektioner blir svåra att behandla. Syftet med studien var att undersöka vilka acinetobactarter som orsakat bakteremi i Skåne från 2011-2019 samt undersöka vilka antibiotika de är resistenta för. Dessutom undersöktes hur stor andel av bakteremifynden som är resistenta mot betalaktamantibiotika, och vilka arter som är mest resistenta. För att artidentifiera acinetobacterna användes MALDI-TOF som analysinstrumentet. Resistensbestämningen bestämdes med E-test och diskdiffusionsmetoden, där tolv olika antibiotika testades. Resultatet visade att bland de 107 stammarna var A. Iwoffii störst då den utgjorde 31 st. Dessutom visade resultatet att majoriteten av stammarna var känsliga mot de tolv antibiotikasorterna. Bland de resistenta stammarna var de flesta av arten A. Baumannii som tidigare är kända för att vara multidrug-resistant (MDR). / Acinetobacter are gram-negative bacteria that cause severe nosocomial infections in immunocompromised and neutropenic patients. It has been reported that the most common source of infection is hospital equipment such as respiratory instruments, where colonization of acinetobacter has been observed. Due to the fact that acinetobacter is multi-resistant to various antibiotics, it makes an acinetobact infection difficult to treat. The aim of the study is to investigate which acinetobact species caused bacteremia in Skåne from 2011-2019 and to investigate which antibiotics they are resistant to. In addition, the proportion of bacteremia findings that are resistant to beta-lactam antibiotics was examined, and which species are most resistant. MALDI-TOF was used to identify the species of acientobacter. Twelve different antibiotics were tested with E-test and the disc diffusion method. The results showed that among the 107 strains was A. iwoffii the largest acinetobacter species, which corresponds to 31. In addition, the results obtained showed that the majority of the strains were sensitive to the twelve types of antibiotics. Among the resistant strains were the majority of the species A. Baumannii, which are known to be multidrug resistant (MDR).
8

Infecções por Klebsiella pneumoniae resistente aos carbapenêmicos em hospital de nível terciário: epidemiologia e caracterização

Almeida, Vivieni Vieira Prado 14 February 2013 (has links)
Introduction: The carbapenem resistance among bacteria of the family Enterobacteriaceae, particularly Klebsiella pneumoniae, is becoming a serious problem in hospitals through different mechanisms that may act alone or combined, such as changes in outer membrane permeability with the porin loss associated with the overproduction of &#946;-lactamases ESBL and AmpC or the specific production of KPC. These infections by Klebsiella pneumoniae resistant to carbapenems (CRKP) are associated with high morbidity, mortality, and costs. Objectives: In our study, we describe the epidemiology and clinical outcomes associated with CRKP infections as well as the risk factors associated with 30 days hospital mortality among these patients and characterize resistance mechanisms: AmpC, ESBL, MBL and KPC. Methods: Case study (patients with infections CRKP) vs. control (uninfected by KPRC) at a ratio of 1:2, detected by laboratory surveillance and collecting demographics dates, co-morbidities, use of invasive procedures and antimicrobial use and patient outcome by checking medical records, between November / 2007 to May/2011. Characterization of phenotypic AmpC, KPC and ESBL performed with the test boronic acid as neutralizing enzyme test and synergism with imipenem-EDTA for MBL. The presence of genotype blaKPC was performed by PCR. Results: In total, 63 patients were included, with 22 patients infected by CRKP in different anatomical sites, predominantly bloodstream infections (40%). Resistance to ertapenem, meropenem and imipenem was 100%, 68.2% and 45.4%, respectively. Statistical analysis by logistic regression of risk factors for infection by CRKP showed the following as independent variables: malignancy (P = 0.025, OR = 63.74, 95% CI 1.69 to 2409.05), Charlson co-morbidity index &#8805; 3 (P = 0.033, OR = 7.90, 95% CI, 1.18 to 52.80) and use of fluoroquinolones (P = 0.005, OR = 18.92, 95% CI, 2.42 - 147.81). The ESBL phenotype was most frequent (90.9%), followed by AmpC (63.6%) and blaKPC (14%), and usually combined. The presence of co morbidities &#8805; 3 (P = 0.027, OR = 7.65 95% CI, 1.26 to 46.53) and KPRC infection (P = 0.026, OR = 4.91 95% CI, 1, 21 to 20.05) were associated with 30-day hospital mortality, and there was significant mortality in infected patients 54.5% (P = 0.026, OR = 3.72, 95% CI, 1.24 to 11.19) with an attributed mortality rate of 25.2%. Conclusion: The mortality rate associated with CRKP infection and the limited antimicrobial options for treatment highlight the need for improved laboratory detection, mainly KPC producing isolates, points out that it s crucial to implement efficient infection control measures to limit the spread of these pathogens in hospitals from countries with limited resources as Brazil. / Introdução: A resistência aos carbapenêmicos entre as amostras de Enterobacteriaceae, especialmente Klebsiella pneumoniae, está se tornando um grave problema nos hospitais e pode resultar da aquisição de diferentes mecanismos que atuam isolados ou combinados, destacando-se diminuição na permeabilidade da membrana externa pela perda de porina associada com hiperprodução de &#946;-lactamases ESBL, AmpC ou produção específica de carbapenemases. As infecções por Klebsiella pneumoniae resistente aos carbapenêmicos (KPRC) estão associadas com altas taxas de morbidade, mortalidade e custos. Objetivos: No nosso estudo, descrevemos a epidemiologia e a evolução clínica associadas com a infecção por KPRC, bem como os fatores de risco associados com a mortalidade hospitalar no prazo de 30 dias entre estes pacientes e caracterizamos os mecanismos de resistência: AmpC, ESBL, MBL e KPC. Métodos: Estudo modelo caso (pacientes com infecções por KPRC) vs. controle (pacientes não infectados por KPRC) na proporção de 1:2, detectados por vigilância laboratorial e coleta de dados demográficos, das co-morbidades, dos procedimentos invasivos e uso de antimicrobianos, bem como evolução nos respectivos prontuários, realizado entre novembro/2007 e maio/2011. A caracterização fenotípica de AmpC, ESBL e KPC foi realizada pelo teste do ácido borônico como neutralizante de enzima e o de sinergismo com imipenem-EDTA para MBL. A pesquisa de presença de genótipo blaKPC foi realizada pela reação de PCR. Resultados: No total, foram incluídos 63 pacientes, com 22 pacientes infectados por KPRC em diferentes sítios anatômicos, com predomínio de corrente sangüínea (40%). A resistência ao ertapenem, meropenem e imipenem foi de 100%, 68,2% e 45,4%, respectivamente. A análise estatística dos fatores de risco para infecção por KPRC por regressão logística mostrou as seguintes variáveis como independentes: neoplasia (P=0,025; OR=63,74, 95% IC, 1,69-2409,05), índice de co-morbidade Charlson &#8805; 3 (P=0,033; OR=7,90, 95% IC, 1,18-52,80) e uso da fluorquinolona (P=0,005; OR=18,92, 95% IC, 2,42-147,81). O fenótipo de resistência mais freqüente foi o ESBL (90,9%), seguido de AmpC (63,6%) e blaKPC (14%), usualmente combinados. A presença de &#8805; 3 co-morbidades (P=0,027; OR=7,65 95% IC, 1,26-46,53) e infecção por KPRC (P=0,026; OR=4,91 95% IC, 1,21-20,05) foram associadas à mortalidade total hospitalar no prazo de trinta dias, esta foi significativa nos pacientes infectados 54,5% (P=0,026; OR=3,72, 95% IC, 1,24-11,19) e com freqüência de mortalidade atribuída de 25,2%. Conclusão: A taxa de mortalidade associada com infecção por KPRC e a limitação das opções terapêuticas enfatizam a necessidade da melhoria na detecção laboratorial, principalmente dos produtores de KPC, assim como implementar medidas de controle de infecção eficientes para limitar a disseminação desses patógenos em hospitais de países com recursos limitados como o Brasil. / Mestre em Ciências da Saúde
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Déterminisme du support moléculaire et de l'épidémiologie de la résistance aux β-lactamines chez des bacilles à Gram négatif isolés dans des hôpitaux tunisiens et libyens / Determinism of molecular support and epidemiology of resistance to b-lactamines in clinical isolates of gram-negative bacilli in tunisian and libyan hospitals

Mathlouthi, Najla 08 April 2017 (has links)
L’augmentation et la dissémination de la résistance aux β-lactamines chez les bacilles à Gram négatif, particulièrement les Entérobactéries, les bactéries du genre Pseudomonas et Acinetobacter, représentent un problème majeur de santé publique. Les infections nosocomiales causées par ces bactéries multi-résistantes (BMR) ont conduit à une augmentation de la mortalité, de la morbidité et du coût de traitement. L’utilisation abusive et non contrôlée de ces antibiotiques a grandement contribué à la large diffusion de cette résistance. Ainsi, face à cette préoccupation mondiale et suite à de nombreuses recommandations, plusieurs études épidémiologiques et moléculaires ont été rapportées afin de contrôler et de surveiller la diffusion et la dissémination des BMR. Contrairement à de nombreuses régions dans le monde, il existe peu d’informations concernant la caractérisation moléculaire des gènes de résistance aux β-lactamines des bacilles à Gram négatif isolés en Tunisie et surtout en Libye. C’est dans cette optique que ce projet de Thèse de Doctorat s’articule avec comme objectifs: (i) mettre en évidence la prévalence des bacilles à Gram négatifs multi-résistants isolés aux niveaux des hôpitaux tunisiens et libyens (ii) identifier le support génétique de la résistance aux β-lactamines de ces souches cliniques (iii) étudier la diversité clonale des souches multi-résistantes par typage moléculaire. / The increase and spread of β-lactam resistance in gram negative bacteria especially Enterobacteriaceae, Pseudomonas and Acinetobacter (E.P.A) species have become a major concern worldwide. The hospital-acquired infections caused by MDR bacteria have led to an increase in mortality, morbidity and cost of treatment. The frequent misuse of antibiotic drug has greatly contributed to worldwide dissemination of antibiotics resistance. Front of this worldwide concern, and various recommendations, several epidemiological and molecular studies have been reported in order to control the spread and the dissemination of these MDR. Unlike many parts of the world, there is little information concerning the molecular characterization of the β-lactam resistance genes of Gram-negative bacilli isolated in Tunisia and especially in Libya. Therefore, it is in this context that the project of this thesis was conducted with essential objectives: (i) highlight the prevalence of multi-resistant Gram negative bacilli isolated in Tunisian and Libyan hospitals (ii) identify the genetic support of resistance to β-lactams of these clinical strains (iii) study the clonal diversity of the multi-resistant strains by molecular typing (iii) study the molecular epidemiology of these BMRs in these countries in order to control the decision-making process of the treatment and the rapid identification of epidemics by implementing appropriate control measures for the spread of infections and especially developing new tools and software for the diagnosis and monitoring of potential MDR bacteria in Mediterranean countries.

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