Desde a primeira enzima ?-lactamase de espectro estendido (ESBL) detectada, na década de 1980, o número de diferentes enzimas ESBL têm aumentado exponencialmente. Houve também aumento no número de relatos de isolamento de bactérias resistentes presentes em alimentos de origem animal. O objetivo deste estudo foi avaliar enterobactérias de microbiota de frangos comerciais saudáveis, de granjas localizadas no interior do Estado de São Paulo (Brasil), quanto à resistência a antimicrobianos e ao potencial de virulência. Foram avaliadas todas as enterobactérias que apresentaram resistência à cefotaxima e/ou ceftazidima de 200 frangos comerciais para consumo humano. O teste de sensibilidade aos antimicrobianos foi realizado por disco de difusão para diferentes classes de antimicrobianos incluindo ?- lactâmicos e não ?-lactâmicos. Reação em cadeia da polimerase e sequenciamento foram utilizados para a pesquisa de genes codificadores de ESBL, ?-lactamases AmpC e determinantes de resistência às quinolonas mediada por plasmídeos (PMQR). A similaridade genética dos isolados foi caracterizada por eletroforese em campo pulsado (PFGE) e a localização cromossômica ou plasmideal de genes de resistência foi avaliada por I-Ceu IPFGE ou S1-PFGE. Além disso, experimentos de conjugação, tipagem de plasmídeos, investigação de filogenia e de virulência foram realizados. Em todas as amostras de cloaca coletadas foram identificados Enterobacteriaceae, incluindo Escherichia coli, Escherichia fergusonii, Klebsiella oxytoca e Klebsiella pneumoniae resistentes à cefotaxima e/ou ceftazidima. Salmonella sp não foi detectada. Foi encontrada ampla diversidade genômica entre todos os isolados classificados entre diferentes tipos de PFGE. Foram detectados diferentes genes codificadores de ?-lactamases, a maioria em diferentes plasmídeos, de diversos tamanhos, sendo alguns conjugativos, presentes em diferentes populações bacterianas. Foram identificados isolados de E. coli produtores de CTX-M-2, com inserção do gene blaCTX-M-2 no cromossomo bacteriano. Plasmídeo IncI (ST113/ST114) foi identificado carreando o gene blaCTX-M-8. Foram também encontrados os genes codificadores de ?- ii lactamase, blaCTX-M-2 e blaCTX-M-15, sendo carreados por plasmídeos. Foi identificado gene blaCMY-2 disseminado por plasmídeos de diferentes grupos de incompatibilidade, na população comensal de E. coli. Nos isolados que abrigavam gene PMQR, além das resistências às quinolonas, foi observado também resistência a outras importantes classes de antimicrobianos. Genes determinantes de PMQR abrigados em plasmídeos tipo ColE foram encontrados em E. coli, E. fergusonii, K. oxytoca e K. pneumoniae. Todas as aves comerciais de granjas localizadas no interior do Estado de São Paulo, incluídas nesse estudo, apresentaram isolados considerados multirresistentes a antimicrobianos e o trato intestinal destes frangos é reservatório dos genes de resistência em enterobactérias da microbiota normal. Além disso, alguns isolados demonstraram alto potencial de virulência, incluindo a capacidade de adesão e invasão em células epiteliais in vitro. / of commercial poultry in farms located at the countryside of São Paulo State (Brazil). All enterobacteria presenting cefotaxime and/or ceftazidime resistance from 200 commercial broiler chickens for human consumption were evaluated. Antimicrobial susceptibility testing was performed by disc diffusion for different classes of antimicrobials, including ?-lactams and non-?-lactams. The genes encoding ESBL, ampC ?-lactamases and determinants of plasmid mediated quinolone resistance (PMQR) were screened by polymerase chain reaction and sequencing. Genetic similarity of bacterial isolates was characterized by pulsed field gel electrophoresis (PFGE) and the location of the resistance genes in the chromosome or plasmids was evaluated by I-CeuI-PFGE or S1-PFGE. Additionally, experiments of conjugation, plasmid typing, phylogeny and virulence characterization were performed. Enterobacteriaceae were identified in all cloacal swab samples, including Escherichia coli, Escherichia fergusonii, Klebsiella oxytoca and Klebsiella pneumoniae resistant to cefotaxime and/or ceftazidime. Salmonella sp. was not detected. High genetic diversity was detected among all isolates, classified into diferent types of PFGE. Different genes coding for ?-lactamases were detected, harbored in diverse plasmids, of different sizes, some were conjugative and were present in different bacterial populations. E. coli isolates producing CTX-M-2 were identified, harbouring the blaCTX-M-2 gene inserted into the chromosome. IncI (ST113/ST114) plasmid was identified carrying the blaCTX-M-8 gene. The ?-lactamase coding genes, blaCTX-M-2 and blaCTX-M-15 were also found in plamids. The gene blaCMY-2 was found disseminated in different types of plasmid replicons in the commensal E. coli population. In isolates harbouring PMQR genes, in addition to the quinolones resistance, was observed resistance to other important antimicrobials classes was observed. PMQR determinant genes harbored in ColE-like plasmids were found in E. coli, E. fergusonii, K. oxytoca and K. pneumoniae. All commercial poultry from farms located at São Paulo State, evaluated in this study, carried isolates considered multidrug resistant and the intestinal tract of these chickens is reservoir of resistant genes blaCTX-M-2, blaCTX-M-8 and blaCTX-M-15 in enterobacteria from the normal microbiota. Moreover, some have demonstrated a high virulence potential, with adhesion and invasion capacity in epithelial cells cultured in vitro.

Bakgrund: Multiresistenta bakterier är ett globalt växande samhällsproblem och ett utav de största folkhälsoproblemen. Förekomsten av multiresistenta bakterier ökar genom användning av antibiotika, framförallt bred-spektrumantibiotika. Multiresistenta bakterier leder till ökad sjuklighet och dödlighet, längre vårdtider och spridning sker både i samhället samt på sjukhus. MRSA, ESBL, VRE och MDR-TB är de multiresistenta bakterier som litteraturstudien fokuserar på. Syfte: Syftet var att belysa sjuksköterskans erfarenheter av att vårda patienter med multiresistenta bakterier. Metod: En allmän litteraturstudie med kvalitativ metod och induktiv ansats utfördes. Åtta vetenskapliga artiklar granskades och analyserades tills kategorier identifierades. Resultat: Analysen resulterade i att fem kategorier identifierades: sjuksköterskans rädslor, otillräcklig kunskap, sjuksköterskans ansvar, organisatoriska brister och utmaningar med patienter i isolering. Sjuksköterskorna beskrev att det förekom hinder i vårdandet av patienter med multiresistenta bakterier såsom bristande kunskap och ledarskap, rädsla för att smittas och smitta andra, avsaknad av riktlinjer samt isolering av patienter. Konklusion: Sjuksköterskor behöver mer kunskap och goda förutsättningar för att kunna ge patienter med multiresistenta bakterier optimal vård. / Background: Multidrug-resistant bacteria are a globally growing problem in society and one of the largest public health problems. The occurrence of multidrug-resistant bacteria increases through the use of antibiotics, especially broad-spectrum antibiotics. Multidrug-resistant bacteria leads to increased morbidity and mortality as well as longer treatments, and the bacteria are spread in both society and in hospitals. The literature study focuses on the multidrug-resistant bacteria MRSA, ESBL, VRE and MDR-TB. Aim: The aim was to illustrate the nurse''s experiences of caring for patients with multidrug-resistant bacteria. Method: A general literature study with a qualitative method and an inductive approach was carried out. Eight scientific articles were reviewed and analyzed until categories were identified. Results: The analysis resulted in five categories being identified: the nurse''s fears, insufficient knowledge, the nurse''s responsibilities, organizational deficiencies and challenges with patients in isolation. The nurses'' described obstacles in the care of patients with multiresistant bacteria such as lack of knowledge and leadership, fear of being infected and infecting others, lack of guidelines and isolation of patients. Conclusion: Nurses need more knowledge and good conditions to be able to give patients with multidrug-resistant bacteria optimal care.

As infecções em pacientes submetidos a transplantes de órgãos sólidos são importante causa de morbidade, além de serem definidoras da sobrevida desta população. A maioria das infecções que ocorre nos dois primeiros meses pós-transplante é relacionada à assistência à saúde (IRAS). O objetivo deste trabalho é identificar fatores de risco para IRAS por bactérias Gram-negativas (BGN) multi-droga resistentes (MDR) em pacientes submetidos a transplante de fígado (TF), nos dois primeiros meses após o transplante. Os objetivos secundários são: identificar fatores de risco para aquisição por MDR GNB em pacientes submetidos a TF, e determinar o impacto das IRAS por MDR GNB na sobrevida desses pacientes. Foram avaliados os TF consecutivos realizados em pacientes adultos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) no período de novembro de 2009 a novembro de 2011. A vigilância microbiológica foi realizada no dia do TF, e semanalmente até a alta hospitalar ou 60 dias após o transplante. Os sítios de coleta foram swab de orofaringe ou secreção traqueal, swab retal e swab axilar. Foram pesquisadas as seguintes bactérias: A. baumannii. P. aeruginosa e Enterobactérias resistentes a carbapenêmico, e K. pneumoniae e E. coli produtoras de betalactamase de espectro estendido (ESBL). Posteriormente, as amostras clínicas foram comparadas com as cepas da mesma espécie isoladas em culturas de vigilância por tipagem molecular. A análise de fatores de risco foi realizada por tipo de infecção e espécie de bactéria. Na análise estatística utilizou-se o teste qui-quadrado ou teste exato de Fisher para variáveis dicotômicas, e teste de Mann-Whitney para variáveis ordenáveis. A análise multivariada foi realizada por regressão logística. A análise de sobrevida foi realizada por regressão de Cox. O nível de significância de P considerado foi 0,05. Foram realizados, no período, 229 transplantes em 202 pacientes, e analisados 214 transplantes em 195 pacientes. O motivo de indicação do transplante mais frequente foi cirrose pelo vírus C, 33%. Foram identificados no período do estudo 110 pacientes (56,4%) com IRAS pós-TF, e um total de 201 infecções. Em 76,3% dos pacientes com IRAS (84/110) foi isolado MDR GNB em alguma amostra clínica relacionada à infecção. Os dois principais sítios de infecção foram infecção de sitio cirúrgico (32%) e infecção primária de corrente sanguínea (27%). Os dois microrganismos mais frequentemente isolados das IRAS foram A. baumannii e K. pneumoniae, e a proporção de infecções por cepas resistentes a carbapênemico foi, respectivamente, 100% e 48,9%. Os fatores de risco para infecções por MDR GNB pós-TF foram: retransplante precoce, volume de concentrados de hemácias transfundidos no intra-operatório da cirurgia do TF, colonização por MDR GNB no pré-transplante, tempo prolongado de internação em UTI e tempo prolongado de isquemia fria. Cento e cinco pacientes adquiriram algum MDR GNB nos 60 dias pós-TF, e o único fator de risco detectado para aquisição de MDR GMB no pós-TF foi tempo prolongado de sonda vesical de demora. A análise de clonalidade demonstrou que as cepas de MDR identificadas pré-TF eram fortemente relacionadas às cepas isoladas das infecções no pós-TF para A. baumannii e K. pneumoniae resistente a carbapenêmico. As infecções por MDR GNB apresentaram uma tendência a aumentar o risco de óbito nos 60 primeiros dias pós-TF, mas esta / Bacterial infections among patients submitted to liver transplantation (LT) are an important cause of morbidity and have huge impact on patients\' survival. The majority of infections in the first two months after LT are related to healthcare assistance. The aim of this study has been to identify risk factors for healthcare-associated infections (HAI) caused by multidrug-resistant Gram-negative bacteria (MDR GNB) in liver transplant patients in the first two months after LT. The secondary aims have been to identify risk factors for acquisition of MDR BGN among liver transplant patients and analyze the survival rate during the first two months after LT. We analyzed consecutive liver transplantations performed at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) from November 2009 to November 2011. Surveillance cultures were performed on a weekly basis, starting on the day of the LT until the hospital discharge or 60 days after the LT. We collected surveillance cultures through swab from oropharynx (or tracheal secretion), axillary and inguinal rectal sites. We surveyed the following bacteria: carbapenem-resistant A. baumanni, P. aeruginosa, Enterobacteriaceae, ESBL-producing K. pneumoniae, and E. coli. The strains isolated from surveillance culture were compared to strains isolated from clinical cultures through PFGE. The risk factor analysis was performed for each type of MDR bacterium for risk of colonization and infection. The statistical analysis was carried out for dichotomous variables using chi-square tests or Fisher\'s exact tests when appropriate; Mann-Whitney tests were used for continuous variable and step-wise logistic regression was used for multivariate analysis. The survival rate analysis was performed using Cox regression. The significant value of P was 0.05. During the study period, 229 liver transplantations were performed in 202 patients and we analyzed 214 LT performed in 195 patients. The main baseline disease that warranted LT was virus C cirrhosis, 33%. 110 (56.4%) patients developed healthcare-associated infections after the LT and a total of 201 infections were identified; 84 (76.3%) patients had MDR GNB isolated from clinical cultures related to HAI. Surgical wounds (31%) and primary bloodstream (27%) were the most prevalent infection sites. The risk factors for HAI by MDR GNB after the LT were: re-transplantation, volume of blood units transfused during the LT surgery, colonization by MDR GNB before the LT, prolonged time of ICU stay, and prolonged time of cold ischemia. 105 patients acquired MDR GNB during the first 60 days after the LT; the only risk factor identified was the prolonged use of urinary drain. The clonal analysis showed that strains isolated in the period before the LT were closely related to strains isolated from clinical culture after the LT for carbapenem-resistant A. baumannii e K. pneumoniae. The infections by MDR GNB have been shown to increase the risk of death in the first 60 days after LT

As infecções em pacientes submetidos a transplantes de órgãos sólidos são importante causa de morbidade, além de serem definidoras da sobrevida desta população. A maioria das infecções que ocorre nos dois primeiros meses pós-transplante é relacionada à assistência à saúde (IRAS). O objetivo deste trabalho é identificar fatores de risco para IRAS por bactérias Gram-negativas (BGN) multi-droga resistentes (MDR) em pacientes submetidos a transplante de fígado (TF), nos dois primeiros meses após o transplante. Os objetivos secundários são: identificar fatores de risco para aquisição por MDR GNB em pacientes submetidos a TF, e determinar o impacto das IRAS por MDR GNB na sobrevida desses pacientes. Foram avaliados os TF consecutivos realizados em pacientes adultos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) no período de novembro de 2009 a novembro de 2011. A vigilância microbiológica foi realizada no dia do TF, e semanalmente até a alta hospitalar ou 60 dias após o transplante. Os sítios de coleta foram swab de orofaringe ou secreção traqueal, swab retal e swab axilar. Foram pesquisadas as seguintes bactérias: A. baumannii. P. aeruginosa e Enterobactérias resistentes a carbapenêmico, e K. pneumoniae e E. coli produtoras de betalactamase de espectro estendido (ESBL). Posteriormente, as amostras clínicas foram comparadas com as cepas da mesma espécie isoladas em culturas de vigilância por tipagem molecular. A análise de fatores de risco foi realizada por tipo de infecção e espécie de bactéria. Na análise estatística utilizou-se o teste qui-quadrado ou teste exato de Fisher para variáveis dicotômicas, e teste de Mann-Whitney para variáveis ordenáveis. A análise multivariada foi realizada por regressão logística. A análise de sobrevida foi realizada por regressão de Cox. O nível de significância de P considerado foi 0,05. Foram realizados, no período, 229 transplantes em 202 pacientes, e analisados 214 transplantes em 195 pacientes. O motivo de indicação do transplante mais frequente foi cirrose pelo vírus C, 33%. Foram identificados no período do estudo 110 pacientes (56,4%) com IRAS pós-TF, e um total de 201 infecções. Em 76,3% dos pacientes com IRAS (84/110) foi isolado MDR GNB em alguma amostra clínica relacionada à infecção. Os dois principais sítios de infecção foram infecção de sitio cirúrgico (32%) e infecção primária de corrente sanguínea (27%). Os dois microrganismos mais frequentemente isolados das IRAS foram A. baumannii e K. pneumoniae, e a proporção de infecções por cepas resistentes a carbapênemico foi, respectivamente, 100% e 48,9%. Os fatores de risco para infecções por MDR GNB pós-TF foram: retransplante precoce, volume de concentrados de hemácias transfundidos no intra-operatório da cirurgia do TF, colonização por MDR GNB no pré-transplante, tempo prolongado de internação em UTI e tempo prolongado de isquemia fria. Cento e cinco pacientes adquiriram algum MDR GNB nos 60 dias pós-TF, e o único fator de risco detectado para aquisição de MDR GMB no pós-TF foi tempo prolongado de sonda vesical de demora. A análise de clonalidade demonstrou que as cepas de MDR identificadas pré-TF eram fortemente relacionadas às cepas isoladas das infecções no pós-TF para A. baumannii e K. pneumoniae resistente a carbapenêmico. As infecções por MDR GNB apresentaram uma tendência a aumentar o risco de óbito nos 60 primeiros dias pós-TF, mas esta / Bacterial infections among patients submitted to liver transplantation (LT) are an important cause of morbidity and have huge impact on patients\' survival. The majority of infections in the first two months after LT are related to healthcare assistance. The aim of this study has been to identify risk factors for healthcare-associated infections (HAI) caused by multidrug-resistant Gram-negative bacteria (MDR GNB) in liver transplant patients in the first two months after LT. The secondary aims have been to identify risk factors for acquisition of MDR BGN among liver transplant patients and analyze the survival rate during the first two months after LT. We analyzed consecutive liver transplantations performed at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) from November 2009 to November 2011. Surveillance cultures were performed on a weekly basis, starting on the day of the LT until the hospital discharge or 60 days after the LT. We collected surveillance cultures through swab from oropharynx (or tracheal secretion), axillary and inguinal rectal sites. We surveyed the following bacteria: carbapenem-resistant A. baumanni, P. aeruginosa, Enterobacteriaceae, ESBL-producing K. pneumoniae, and E. coli. The strains isolated from surveillance culture were compared to strains isolated from clinical cultures through PFGE. The risk factor analysis was performed for each type of MDR bacterium for risk of colonization and infection. The statistical analysis was carried out for dichotomous variables using chi-square tests or Fisher\'s exact tests when appropriate; Mann-Whitney tests were used for continuous variable and step-wise logistic regression was used for multivariate analysis. The survival rate analysis was performed using Cox regression. The significant value of P was 0.05. During the study period, 229 liver transplantations were performed in 202 patients and we analyzed 214 LT performed in 195 patients. The main baseline disease that warranted LT was virus C cirrhosis, 33%. 110 (56.4%) patients developed healthcare-associated infections after the LT and a total of 201 infections were identified; 84 (76.3%) patients had MDR GNB isolated from clinical cultures related to HAI. Surgical wounds (31%) and primary bloodstream (27%) were the most prevalent infection sites. The risk factors for HAI by MDR GNB after the LT were: re-transplantation, volume of blood units transfused during the LT surgery, colonization by MDR GNB before the LT, prolonged time of ICU stay, and prolonged time of cold ischemia. 105 patients acquired MDR GNB during the first 60 days after the LT; the only risk factor identified was the prolonged use of urinary drain. The clonal analysis showed that strains isolated in the period before the LT were closely related to strains isolated from clinical culture after the LT for carbapenem-resistant A. baumannii e K. pneumoniae. The infections by MDR GNB have been shown to increase the risk of death in the first 60 days after LT

Bakgrund: Kolonisering och spridning av multiresistenta bakterier (MRB) är ett ökande problem både i samhället och i sjukvården idag. MRB smittar genom kontaktsmitta, genom direkt personkontakt eller kontakt av kontaminerade ytor. Frågor rörande patientsäkerhet påverkar alla inom hälso- och sjukvårdens organisationer, men huvudansvaret att utveckla ledningssystem för att ett systematiskt kvalitetsarbete ska kunna bedrivas, ligger på vårdorganisationen- och vårdgivaren. Kunskapsbrist om MRB hos vårdpersonal samt brist på tydliga riktlinjer i vården i det kliniska arbetet kan påverka attityder till och bemötande av patienter med MRB. Syfte: Att belysa vårdorganisationers ansvar, sjuksköterskans kunskaper om MRB samt hens attityder till och bemötande av patienter med MRB- smitta. Metod: Studien gjordes som en litteraturöversikt där tio vetenskapliga artiklar analyserades för att framställa resultatet. Resultat: I resultatet framkom att vårdorganisationen och ledarskapet var av stor vikt för sjuksköterskans förutsättningar att ge god och säker vård till patienter med MRB. Kunskaperna om MRB var oftast låga. Attityder och bemötande visade sig i de flesta fall också påverkas av kunskapsnivån. Dålig kunskap och brist på erfarenhet av patienter med MRB kunde även relateras till ökade rädslor hos sjuksköterskor att smittas av MRB. Diskussion: Resultatet diskuterades mot Travelbee´s teori om mellanmänskliga relationer och konsensusbegreppet vårdande. Vårdorganisationens ansvar och kunskaper hos sjuksköterskor om MRB tycks vara de faktorer som mest påverkade bemötandet gentemot och attityderna till patienter med MRB. / Background: Colonization and transmission of MDRB is an increasing problem today, both in society and in health care settings. MDRB is most commonly transmitted through cross-contamination through personal contact and contact with contaminated surfaces. Patient safety affects everybody within health care settings. Main responsibility lies with healthcare organizations and caregivers, to develop management systems for systematic quality improvement. Knowledge deficiency of MDRB among health care personnel and lack of clear guidelines in health care settings may influence the attitudes and behaviour towards patients with MDRB. Aim: To illustrate healthcare organizations responsibilities, nurses’ knowledge of MDRB and nurses’ attitudes and behaviour towards patients with MDRB. Method: The study was conducted as a literature review and ten scientific papers were analysed to generate the results. Results: The results showed that healthcare organizations and leadership were of great importance for the nurses’ ability to provide good and safe care for patients with MDRB. Knowledge about MDRB was also proved to be low. Deficient knowledge and lack of experience of caring for patients with MDRB among nurses might also influence their own fears of contracting MDRB. Discussions: The results were discussed against Travelbee’s Intrapersonal relationship- theory and the concept of caring. Healthcare organizations responsibility and nurses’ knowledge of MDRB seemed to be the eminent factors that influenced both behaviour and attitudes towards patients with MDRB.

WGS permet d'analyser et de déchiffrer l'étude de résistances de bactéries multirésistantes(MDR), en comprenant les différents mécanismes de résistance, les annuaires génétiques. Au cours de ma thèse de doctorat, j'ai réalisé: 1 revue de la littérature sur l'utilisation de nouveaux outils de diagnostic contemporains et les capacités dans la détection des foyers dans les maladies infectieuses causées par MDR. L'identification et l'analyse de résistances de bactéries multirésistantes Comme étant des Shewanellalgae, normalement de l'environnement marin, dans notre cas une souche clinique isolée du lavage bronchoalvéolaire d'un patient hospitalis avec pneumonie et Chryseobacteriumin dologenes, isolé d'une fibrose kystique du patient. Dans cette analyse, nous pouvons montrer que les bactéries environnementales telles que les S.algae peuvent être un réservoir de gènes de résistance aux antibiotiques. L'analyse exhaustive de ces bactéries a montré leur capacité à s'adapter à leurs écosystèmes, y compris l'acquisition de nouveaux éléments génétiques par transfert latéral de gènes. La détection des gènes impliqués dans la synthèse de peptides synthetasenon ribosomale et de polycétide synthétase peut avoir un rôle dans leur capacité à survivre dans des environnements hostiles tels que le tractus respiratoire des patients atteints de fibrose kystique ou leur présence chez des patients ayant subi plusieurs antibiotiques. Nous avons réalisé une analyse standardisée «insilico» afin de déterminer la résistance de ces bactéries et la présence de métabolites secondaires associés aux bactériocines et aux NRPS/PKS. L'application du NTS pour le séquençage du génome bactérien de nouvelles espèces bactériennes isolées dans le microbiome humain nous a permis de développer une plateforme capable d'analyser ces nouvelles espèces dans les 48heures. Ce travail permet de mieux comprendre la biodiversité des bactéries isolées dans le microbiome humain. / Theuse of WG Sallows to analyze and to decipherthe study of resistome of Multi Drug Resistant bacteria (MDR), understanding the different resistance mechanisms, genetic directories and their dissemination mechanisms at global level. During them y thesis I have achieved: 1. A literature review on the use of new contemporary diagnostic tools and capabilities in detecting out breaksin infectious diseases caused by MDR. 2: The identification and the analysis of resistome of multidrug resistant bacteria from clinical isolates suchasShewanellaalgae, normally marine environmental, in our case clinical strain isolated from the broncho alveolar lavage of a hospitalized patient with pneumonia and Chryseobacteriumin dologenes, isolated from a patient cysticfibrosis. In this analysis, we can show that environment albacteria suchas S.algae can be a reservoir of antibiotic resistance genes. The exhaustive analysis of these bacteria showed their ability to a dapttotheirecosystemsincludingtheacquisitionofnewgeneticelementsbylateralgenetransfer. The detection of genes in volved in the synthesis of nonribosomal peptide synthetase and polyketide synthases may have a role in their ability to survive in hostile environments suchas therespiratorytractofCFpatients or their presence inpatients having suffered multipleofantibiotic. 3:In this work,through theuse of the NTS onnew bacterial species isolated from human microbiome,we have a chieveda standardized analysis"insilico"to determine there sistome of these bacteria and the presence of secondary metabolites associated bacteriocins and the NRPS/PKS. The application of the NTS for sequenc in go bacterial genome of new bacterial species isolated in the human microbiome, allowe dus to develop a platform capable of analyzing the senew species within 48

Bakgrund: Sjukdom kan innebära en påverkan på något mer än det fysiska, sjukdom kan även innebära något annat än ohälsa. Sjuksköterskans kunskap samt relationen mellan sjuksköterska och patient är en viktigdel i skapandet av trygghet i hälsoprocesserna. För somligakan sjukdom ha en positiv effekt på hälsan. Penicillinet kom med stora möjligheter att behandla infektioner, men snabbt började bakterier utveckla resistens. Idag är de vanligaste, anmälningspliktiga multiresistenta bakterierna i Sverige MRSA, ESBL och VRE. Det innebär förhållningsregler för patienter och gör att hälso-och sjukvården behöver genomföra smittskyddsåtgärder för att minska spridning. Sjuksköterskan kan känna osäkerhet och rädsla i omvårdnaden av dessa patienter vilket kan ha en inverkan på den jämlika vård som enligt lagen ska ges. Syfte: Syftet var att belysa patienters upplevelser av att leva med multiresistenta bakterier (MRSA, ESBL eller VRE). Metod: En litteraturöversikt där informationssökning har gjorts i PubMed, CINAHL och SwePub. Artiklar inkluderades om de svarade på syftet, var orginalartiklar, publicerade mellan 2010-2020, skrivna på engelska, hade kvalitativ eller mixad metod, var granskade av referenter och hade ett etiskt godkännande. Den insamlade datan analyserades av författarna och sammanställdes i tre teman och tillhörande underteman. Resultat: Tre teman vilka rubricerades som känslomässig påverkan, upplevelser i mötet med hälso-och sjukvård och förändringar i relationen till andra. Diskussion: Litteraturöversiktens resultat diskuteras gentemot Livsvärldsteorin, bakgrunden, andra referenser och författarnas egna tankar. / Background: Disease can have impact on something more than the physical, disease can be something else than illness. The nurse’s knowledge and the relationship between nurse and patient is an importantpart in creating safety in the health processes. For some, disease can have a positive effecton the health. The penicillin came with great possibilities in treating infections, but the bacteria quickly began to develop resistance. Today, the most common notifiable multidrug-resistant bacteria in Sweden are MRSA, ESBL and VRE. It induces instructions for patients and the health care has to conduct disease control to reduce spread. The nurse can feel uncertainty and fear in the caring of these patients, which can have an impact on the equal care which is to be given according to the law. Aim: The aim was to illustrate patients’ experiences of living with multidrug-resistant bacteria (MRSA, ESBL or VRE). Method: A literature review where the information search has been conducted in PubMed, CINAHL and SwePub. Articles were included if they answered to the aim, was original articles, published between 2010-2020, written in English, had qualitative or mixed method, were peer-reviewed and had an ethical approval. The collected data were analysed by the authors and compiled in to three themes and belonging sub-themes. Results: Three themes who were labelled emotional impact, experiences in the encounter with health care and change in the relationship with others. Discussion: The result of the literaturereview was discussed towards Life World Theory, the background, other references and the authors’ own thoughts.

La résistance bactérienne aux antibiotiques dans les établissements de santé complique la prise en charge thérapeutique et entraîne une surmortalité des patients infectés. L'objectif de ce travail était d'évaluer différentes approches ayant pour finalité la prévention et la maîtrise des infections nosocomiales. Ce travail s'articule autour de trois questions : (i) Existe-t-il une stratégie de promotion d'un juste usage des antibiotiques à privilégier ? (ii) Comment évaluer la performance en matière d'hygiène des mains ? (iii) Quelles mesures pouvons-nous proposer pour limiter la diffusion de P. aeruginosa ?Nous avons d'abord montré que la diffusion de recommandations sous la forme de guides régionaux ou de messages de pharmacovigilance était suivie d'une modification des prescriptions antibiotiques conformes aux recommandations.Ensuite, nous avons évalué le niveau de performance des établissements de santé en matière d'hygiène des mains en étudiant plus particulièrement l'indicateur de consommation de solution hydro-alcoolique (ICSHA). Nous avons ainsi pu montrer que le nombre minimal d'opportunité d'hygiène des mains servant à son calcul, était sous-estime. Dans une autre étude, nous avons été confrontés aux limites liées à sa construction, ces dernières étant en partie responsable de l'absence de relation observée entre cet indicateur et la prévalence des infections associées aux dispositifs invasifs.Enfin, nous avons montré que la charge en soins et la contamination des réseaux d'eau propre des établissements de santé étaient des facteurs de risque contextuels d'acquisition du bacille pyocyanique. Un autre travail a mis en évidence que les réseaux d'eau usée étaient impliqués dans la diffusion extra-hospitalière de souches résistantes. Une étude est actuellement en cours pour évaluer l'intérêt d'une approche globale associant dépistage et précautions complémentaires chez les patients porteurs de P. aeruginosa.En conclusion, si ce travail confirme l'efficacité de certaines actions de prévention tout en mettant en avant les limites d'autres approches, il ne permet pas de privilégier une stratégie particulière. Il apparaît ainsi nécessaire de mettre en place des stratégies globales et transversales allant au-delà des seuls établissements de santé / Bacterial resistance to antibiotics in health care facilities complicates the therapeutic burden and increased mortality of infected patients. The objective of this work was to evaluate different approaches which aim was to prevent and control hospital-acquired infections. This work focuses on three issues: (i) Is there a strategy already in place to promote the appropriate use of antibiotics? (ii) How can we evaluate performance in terms of hand hygiene? (iii) What measures can we implement to limit the spread of P. aeruginosa?We first showed that the distributions of regional guidelines or drug monitoring alerts were followed by a change in the uptake of antibiotic prescriptions in line with such recommandations.Then we evaluated the performance of health care facilities for hand hygiene, focusing especially on the index of consumption of alcohol-base hand-rub solution. We showed that the number of alcohol-based hand-rub is far higher than that defined by the French Ministry of Health. In another study, we were faced with limitations in its construction, the latter being partly responsible for the lack of a relationship between this indicator and the prevalence of invasive devices associated with infections.Finally, we have shown that the burden of care and the contamination of clean water networks of health facilities were contextual risk factors for acquisition of Pseudomonas aeruginosa. Another study showed that wastewater networks were involved in extra-hospital spread of resistant strains. A study is currently underway to assess the value of a global approach combining screening and additional precautions in patients with P. aeruginosa.In conclusion, this study confirms the effectiveness of some preventive measures while underlining the limitations of other approaches. However it does not promote a particular strategy. Because in terms of BMR, it is necessary to define global and cross-sectorial strategies which go beyond the health care facilities

No description available.

L'augmentation et la dissémination de la résistance aux antibiotiques chez les bactéries à gram-negatif, particulièrement les Entérobactéries, les bactéries du genre Pseudomonas et Acinetobacter, représentent un problème majeur de santé publique au niveau mondial. Les infections nosocomiales causées par les bactéries multi-résistantes (BMR) ont conduit non seulement à une augmentation de la mortalité, de la morbidité, et du coût de traitement, mais aussi continuent de mettre en danger la vie des patients surtout immunodéprimés en milieu hospitalier. Bien entendu, l'utilisation abusive et non contrôlée des antibiotiques a grandement contribué à la large diffusion des déterminants de la résistance; cependant, des études récentes ont démontré que ces déterminants de la résistance pouvaient émerger à partir de sources anciennes et/ou environnementales. Ainsi, face à cette préoccupation mondiale, plusieurs études ont été rapportées avec des recommandations importantes de conduire des études épidémiologiques, moléculaires, et génomiques afin de contrôler la diffusion et l'augmentation de la résistance aux antibiotiques. De plus, durant ces 10 dernières années, nous avons assisté à l'emergence et au développement de nouvelles technologies de séquençage à haut débit coïncidant avec une augmentation exponentielle du nombre de genomes bactériens séquencés. / The increase and spread of multidrug-resistant (MDR) 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 not only to an increase in mortality, morbidity, and cost of treatment, but also continue to endanger the life of patients, especially those immunocompromised. Although the frequent misuse of antibiotic drug has greatly contributed to worldwide dissemination and resistance to antibiotics; recent studies have shown that these resistance determinants could emerge from ancient or environmental sources. Front of this worldwide concern, several studies have been reported with significant recommendations to conduct molecular epidemiology, and genomic studies, in order to control the increase and the dissemination of the antibiotic resistance. Moreover, during these last 10 years, we are witnessing the emergence and development of new technologies of high throughput sequencing and coinciding with an exponential increase of number of bacterial genomes sequenced today. Therefore, it is in this context that the project of this thesis was conducted with three essential objectives: (i) the genome sequencing of clinical MDR bacteria, the analysis and the identification of the mechanisms and the genetic determinants of antimicrobial resistance (ii) the achievement of molecular epidemiology studies from clinical MDR bacteria responsible of outbreak (iii) the development and implementation of molecular tools for monitoring and diagnosis of potential MDR bacteria.