Orientador: Maria Luiza Moretti / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T02:52:37Z (GMT). No. of bitstreams: 1 Kuboyama_RogerioHakio_D.pdf: 1899697 bytes, checksum: 863826cd141f1e5f89eb90d272c0c330 (MD5) Previous issue date: 2009 / Resumo: Os objetivos do presente estudo, conduzido retrospectivamente, utilizando cepas isoladas de espécimens clínicos obtidos de pacientes internados em dois hospitais brasileiros entre fevereiro de 2001 e junho de 2004 foram descrever: a presença de cepas de Klebsiella pneumoniae produtoras de beta-lactamases de espectro estendido (ESBLs), o melhor método e o substrato preferido para os testes de triagem e de confirmação da produção de ESBLs, a relação epidemiológica das cepas obtidas e analisar os fatores de risco para infecção por cepa produtora de ESBLs. A fim de investigar a relação genética das cepas, foram utilizadas as análises do DNA plasmidial e do DNA cromossômico por eletroforese em campo pulsátil (PFGE). Um total de 89 cepas de K. pneumoniae foram coletadas de diversos sítios anatômicos. Os espécimens clínicos mais comuns dos quais foram isoladas cepas produtoras foram urina (12,4%) e sangue (10,1%). Utilizando os critérios estabelecidos pelo CLSI (testes de triagem), 35 (39,3%) cepas de K. pneumoniae foram consideradas possivelmente produtoras de ESBLs, enquanto que o teste de aproximação de discos (DDAT) revelou distorções características nas zonas de inibição produzidas pela molécula do clavulanato em 96, 62,5, 50, 18,8 e 12,5% das cepas ao redor dos discos contendo aztreonam, cefotaxima, ceftazidima, ceftriaxona e cefpodoxima, respectivamente. Das 89 cepas, 32 (36%) foram consideradas produtoras de ESBLs baseadas no teste confirmatório pelo método Oxoid de discos-combinados. O disco contendo cefotaxima foi capaz de confirmar 100 % dos produtores de ESBLs enquanto que o disco contendo ceftazidima deixou de confirmar 2 cepas produtoras. Dez e 32 diferentes perfis plasmidiais foram observados dentre as cepas de K. pneumoniae produtoras e não produtoras, respectivamente. A PFGE demonstrou melhor poder discriminatório fornecendo 15 e 55 perfis de DNA cromossômico dentre as cepas ESBLs-positivas e ESBLs-negativas, respectivamente. Da análise univariada, as variáveis significativamente associadas com infecção por cepas de K. pneumoniae produtoras de ESBLs foram: uso de cefalosporinas de quarta geração, de lincosamida, de carbapenêmicos, de glicopeptídeos, cirurgia recente, traqueostomia, idade, dias em uso de lincosamida, dias em uso de glicopeptídeos, número total de antibióticos e duração da terapia antimicrobiana. Ao realizar a análise multivariada, utilizando um modelo de regressão logística que incluía as variáveis estatisticamente significantes da análise univariada (P < 0,05), número total de antibióticos permaneceu como única variável independente para infecção por cepa de K. pneumoniae produtora de ESBLs (OR, 1,60; IC95%, 1,194-2,145.; P = 0,0017). Os dados obtidos revelam: uma taxa relativamente alta da produção de ESBLs em cepas de K. pneumoniae obtidas de pacientes das instituições estudadas; a insuficiência da análise plasmidial na elucidação da relação genética dentre as cepas produtoras de ESBLs; aztreonam como melhor substrato indicador da produção presuntiva de ESBLs e cefotaxima como o melhor substrato no teste confirmatório pelo método Oxoid de discoscombinados / Abstract: The objectives of this study conducted restrospectively using strains isolated from clinical specimens obtained from patients hospitalized in two Brazilian hospitals between February 2001 to June 2004 were to describe the presence of extended-spectrum b-lactamase (ESBL)-producing Klebsiella pneumoniae strains, the best method and the preferred substrate for screening and confirming ESBL production and the epidemiological relatedness of ESBL-producing strains and analyse the risk factors for infection due to ESBL-producing K. pneumoniae. To investigate the genetic relatedness of the strains, plasmid analysis and chromosomal DNA analysis by pulsed-field gel electrophoresis were used. A total of 89 K. pneumoniae were collected from diverse body sites. The most commom specimens yielding ESBL-producing strains were urine (12.4%) and blood (10.1%). Using CLSI criteria (ESBL screening breakpoints), 35 K. pneumoniae (39.3%) had presumptive ESBL phenotype, while using the double-disk approximation test (DDAT) characteristic clavulanate-induced distortions of inhibition zones were found in 96, 62.5, 50, 18.8 and 12.5% of the strains around the disks containing aztreonam, cefotaxime, ceftazidime, ceftriaxone and cefpodoxime, respectively. Of 89 isolates, 32 (36%) produced ESBL based on the confirmatory Oxoid combination disk method. The disk containing cefotaxime was able to confirm 100% of the ESBL producers while the disk containing ceftazidime was not able to confirm 2 ESBL-positive strains. Ten and 32 different plasmid profiles were observed among the ESBL-producing K. pneumoniae and non ESBL producers, respectively. Pulsed-field gel electrophoresis showed the best discriminatory power giving 15 and 55 different chromosomal DNA profiles among the ESBL-positive and ESBL-negative K. pneumoniae, respectively. From univariate analysis, variables significantly associated with infection by an ESBL-producing strain of K. pneumoniae included the following: use of 4st-generation cephalosporins, lincosamide, carbapenems, glycopeptides, recent surgery, tracheostomy, age, days in using of lincosamide, days in using of glycopeptides, total number of antibiotics and duration of the antimicrobial therapy. The only variable that remained independent risk factor for acquiring infection due to ESBL-producing K. pneumoniae after multivariable analysis using a logistic regression model, which included the variables associated with acquiring infection by ESBL-producing K. pneumoniae by univariate analysis (P < 0.05), was total number of antibiotics (OR, 1.60; 95%CI, 1.194-2.145; P = 0.0017). In summary, these data indicate that ESBL-producing K. pneumoniae occur at a relatively high incidence at our institutions and the plasmid analysis is not sufficient to identify relationships between ESBL-producing strains of K. pneumoniae. The ESBL screening breakpoints and DDAT with aztreonam appear to be good indicators in presumptive detection of ESBL-producing strains and the cefotaxime used in the Oxoid combination disk method constituted the best substrate in the confirmatory test / Doutorado / Ciencias Basicas / Doutor em Clínica Médica

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / A sepse neonatal à atualmente a infecÃÃo mais freqÃente e importante causa de Ãbito de RN internados nas UTIN de paÃses desenvolvidos. Para conhecer a dimensÃo desse problema em um Hospital UniversitÃrio de atendimento terciÃrio localizado no Nordeste do Brasil, foi realizado um estudo de coorte retrospectivo de todos as crianÃas que nasceram e foram admitidas na UTIN no perÃodo de outubro de 1997 a abril de 1998. Uma coorte de 422 pares de recÃm-nascidos e suas respectivas mÃes foi formada; os RN foram seguidos do nascimento à alta ou Ãbito na UTIN ou atà a idade de 28 dias enquanto internados na UTIN. Ao todo, cerca de 34 variÃveis maternas, do neonato e procedimentos hospitalares foram pesquisadas em cada membro da coorte. Os testes estatÃsticos utilizados foram: Teste do Qui-quadrado e o Teste exato de FISCHER, cÃlculo do risco relativo com os respectivos intervalos de confianÃa. Em seguida procedeu-se a anÃlise multivariada com transformaÃÃo para logÃstica dos fatores mais significativos (p<0,05). Ao final, cinco fatores foram selecionados como preditores independentes da sepse neonatal: cateterizaÃÃo venosa central (OR=8,7, IC95%=2,3 a 32,6), faixa ponderal 1000 a 1499g (OR=4,8, IC95%=2,3 a 9,9), transfusÃo de hemoderivados (OR=3,6, IC95%=1,8 a 7,4), gravidez Ãnica (OR=2,3, IC95%=1,0 a 5,4) e faixa ponderal 1500 a 2499g (OR=2,3, IC95%=1,3 a 4,0). A incidÃncia de sepse na coorte foi de 40,4 para cada 100 RN admitidos (167/413). As bactÃrias mais prevalentes dos casos confirmados foram os bacilos gram-negativos; 67% dos episÃdios surgiram nos seis primeiros dias de vida. A internaÃÃo dos RN com sepse foi 4,3 vezes superior a internaÃÃo dos RN nÃo acometidos. A mortalidade global na UTIN foi de 25,59 para cada 100 RN admitidos, enquanto a letalidade pelo desfecho foi de 41,31%, com risco relativo de morte por sepse de 2,8. Este estudo poderà ser Ãtil para futuras estratÃgias com vistas a diminuir a morbimortalidade por sepse neonatal. / OBJECTIVE: Neonatal sepsis is currently the most frequent infection and an important cause of death among the newborns admitted at NICU. In order to evaluate the extension of this problem in a tertiary care University Hospital of Northeastern Brazil, a retrospective cohort survey was carried out on all inborn and admitted infants at the Assis Chateaubriand NICU from October 1997 to April 1998. METHOD: the survey design was a retrospective cohort carried out on all inborn infants admitted at the Neonatal Intensive Care Unit during seven consecutive months; 422 newborns were enrolled in the study and each one was followed up from birth to discharge from NCIU or death at the NICU. To compare the levels of the risk factors, two groups were formed: one by the all subjects who developed the outcome and another by all those who did not to. Each member of the cohort was investigated for 34 potential predictors variables concerning mothers factors, neonates factors and hospital procedures. In case of presence of sepsis, the variables were measured just up to the outcome. Standard National Nosocomial Infection Surveillance (NNIS-CDC) definitions of sepsis were used. Chi Square and Fischerâs exact tests were applied for comparison of frequencies; relative risk (RR) with their respective confidence interval of 95% (CI95%) was calculated. Subsequently, a multivariate analysis was done using logistic regression of most significant factors (OR). The level of statistical significance considered was p=0,05. RESULTS: The cohort sepsis incidence was 40,4 for each hundred of newborn admitted at NICU. The bacterias more prevalent of the confirmed cases were the gram-negative bacilli. Most sepsis episodes appeared in the first six days of life (67%). The time of NICU hospitalization of the sick newborn was 4,3 times longer compared to that non-sick newborn. Five factors were selected as independent predictors for neonatal sepsis: central venous catheter (OR=8,7, CI95%=2,31 to 32,69, p=0,001), birth weight of 1000-1499g (OR=4,8, CI95%=2,39 to 9,97, p=0,000), blood transfusions (OR=3,6, CI95%=1,81 to 7,45, p=0,003), singular gestation (OR=2,3, CI95%=1,04 to 5,44, p=0,04) and birth weight of 1500<2500g (OR=2,3, CI95%=1,34 to 4,04, p=0,002). Global mortality reached 25,59% of the cohort. Mortality associated to sepsis was 41,31% with Relative Risk for death = 2,8. CONCLUSION: neonatal sepsis incidence and mortality rates found are higher than in developed countries rates. Birth weight under 2500g, singular gestation, central venous catheter and blood transfusions proved be independent predictors related to neonatal sepsis. This study may contribute for the future strategies for reduction of neonatal sepsis rates and its sequels in our hospital.

Made available in DSpace on 2014-07-29T15:04:40Z (GMT). No. of bitstreams: 1 Dulcelene Melo.pdf: 680160 bytes, checksum: 55d8a4c2a66fae3c908abe807d75735e (MD5) Previous issue date: 2005-03-31 / This was a qualitative study done in a big-sized general public hospital in the city of Goiânia Goiás The aims was to analyze nurses´ adherence to standard precautions according to Rosenstock´s health belief model (HBM) (1974) Data were collected using a semi-structured interview guide based on principles of Critical Incidence Technique (CIT) The instrument was validated by judges and was then pre-tested The ethical-legal research principles were observed Among 90 nurses selected to participate in the study 82 agreed to take part in this study Inclusion criteria were nurses who were either in direct contact with patients or in supervisory positions in the hospital cleaning, laundry or sterilization services Data were analyzed in accordance with CIT The analysis categories were constructed using the dimensions of the HBM A total of 139 critical incidents were identified of which 66 were considered positive and 73 negative HBM dimensions were identified within 131 situations: 74 (56,5%) related to perceived susceptibility; 17 (13,0%) to perceived benefits and 40 (30,5%) to perceived barriers The majority of the reported critical incidents related to situations of occupational exposure to biological materials Among the Standard Precautions (SP) use of protective barriers was most frequently utilized Denial of susceptibility was indicated by the lack of use of protective barriers improper management of sharp objects and non-adherence to SP related to patients with multi-resistant pathogens Moderate perceived susceptibility was associated with partial adherence to SP in cases of patients requiring more complex levels of care; in situations following occupational exposure; and when patients needs took priority over personal protection High perceived susceptibility was observed in situations of caring for patients suspected or diagnosed with infections due to pathogens of epidemiological importance and those related to nurses responsibility Perceived seriousness was evident in behaviors and consequences related to critical incidences after occupational exposure in moments when nurses expressed feelings experienced psychosomatic symptoms and were diagnosed with an infection. Perceived benefits emerged above all from positive critical incidente with focus on protective barriers understood as protection strategies which lead to safety while procedures are executed Perceived barriers were: lack of personnel preparation lack of material resources insufficient personnel improper physical structure patient emergencies psychosocial factors lack of personnel policies for cases of exposure to biological material These barriers contribute to lower adherence of SP but they could be addressed by the Health Care Facilities since nurses have demonstrated adequate perception of susceptibility and benefits HBM dimensions were associated with nurses adherence to SP suggesting that plans should be developed to improve the nurses actions and decision-making in day-to-day nursing cars prioritizing the safety of those individuals involved in this process / Estudo qualitativo desenvolvido em um hospital público geral de grande porte de Goiânia-Go Teve como objetivo analisar a adesão dos enfermeiros às precauções padrão (PP) à luz do modelo de crenças em saúde (MCS) de Rosenstock (1974) Os dados foram coletados por meio de entrevista com roteiro semi-estruturado e conforme preconizado pela técnica de incidentes críticos (TIC) O instrumento foi validado por juizes seguido do pré-teste Foram observados os aspectos ético-legais da pesquisa Fizeram parte do estudo 82 enfermeiros dos 90 eleitos que estavam em atividade assistencial direta ao paciente ou atuavam nos setores: de higienização hospitalar reprocessamento de roupas e materiais odonto-médico-hospitalares Procedemos a análise de conteúdo dos dados conforme a TIC As dimensões do MCS foram utilizadas como categorias prévias de análise Obtivemos 139 incidentes críticos sendo que 66 foram positivos e 73 negativos de acordo com a polaridade referida Destes 131 situações remetiam às dimensões do modelo de crenças em saúde: 74 (56,5%) eram relacionadas à suscetibilidade percebida; 17 (13,0%) aos benefícios percebidos e 40 (30,5%) às barreiras percebidas Os incidentes críticos relatados predominantemente relacionavam-se às situações de exposição ocupacional a material biológico O uso de barreiras protetoras foi a PP que obteve maior freqüência de indicação A negação da suscetibilidade foi observada pelo não uso das barreiras protetoras no manuseio inadequado de perfurocortante e não adesão às PP relacionadas ao paciente portador de patógeno multi-resistente A moderada suscetibilidade percebida associou-se à adesão parcial às PP no atendimento a pacientes com maior complexidade nos cuidados assistenciais Estes comportamentos adotados sinalizam limitada percepção da necessidade de intervenção nos cuidados pós-exposição ocupacional priorizando o atendimento às necessidades dos pacientes A alta suscetibilidade percebida foi observada nas situações de atendimento ao paciente sob suspeita ou com diagnóstico de infecção por patógenos de importância epidemiológica e àquelas relacionadas à responsabilidade do enfermeiro nesta particularidade da assistência A severidade percebida foi evidenciada somente nos comportamentos e conseqüências dos incidentes críticos relatados nos momentos de pós-exposição ocupacional expressa em sentimentos alterações psicossomáticas e experiência de infecção Os benefícios percebidos emergiram sobretudo dos incidentes críticos positivos com enfoque no uso das barreiras protetoras que foram compreendidas como estratégia de proteção ratificando a segurança na execução dos procedimentos As barreiras percebidas foram: falta de preparo do profissional falta de material de consumo e permanente número insuficiente de profissionais estrutura física inadequada atendimento a pacientes em situações de urgência/emergência fatores psicossociais e falta de fluxo para o atendimento ao profissional em situação de pós-exposição a material biológico; que poderiam ser minimizadas com a organização do Serviço de Assistência à Saúde pois se constituíram em impedimentos para a adesão às precauções padrão embora os enfermeiros apresentassem adequada percepção da suscetibilidade e benefícios Verificamos que as dimensões do modelo de crenças em saúde elucidaram a adesão dos enfermeiros às PP sugerindo que empreendimentos devam ser feitos para melhor instrumentalizá-los para a tomada e modalidade de ação no cotidiano da assistência que priorize a segurança dos sujeitos envolvidos nesse processo

Die Mehrzahl der jährlich 400.000 bis 600.000 Krankenhausinfektionen in Deutschland wird von Erregern der sog. ESCAPE-Gruppe (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa und verschiedene Enterobacteriaceae, u.a. Klebsiella pneumoniae) verursacht. Besondere Sorge bereitet dabei die Ausbreitung von K. pneumoniae-Stämmen mit enzymvermittelter Resistenz gegenüber Carbapenem-Antibiotika (K. pneumoniae-Carbapenemase, KPC) und die Zunahme von C. difficile-Infektionen (CDI) durch hypervirulente Epidemiestämme (z.B. Ribotyp 027). Die spezifischen Erfahrungen eines prolongierten Ausbruchsgeschehens durch einen KPC-bildenden K. pneumoniae-Stamm (KPC-KP) am Leipziger Universitätsklinikum machen deutlich, dass bei diesem Erregertyp ein hohes Transmissionspotential bei enormer Tenazität (Umweltresistenz) zu berücksichtigen ist, ein Versagen von Standardhygienemaßnahmen in Betracht zu ziehen ist, und Infektionsketten oftmals unklar bleiben. Die Anwendung von Antibiotika ist bei KPC-KP-Infektionen auf einzelne Substanzen (Colistin, Tigecyclin, Gentamicin) beschränkt und vor allem bei immunsupprimierten Patienten (z.B. Lebertransplantierte) mit einem relevanten Risiko des Therapieversagens behaftet. Die Therapie von CDI wird gerade bei Immunsupprimierten durch eine steigende Zahl an Rezidiven erschwert, die teilweise antibiotisch (Vancomycin, Fidaxomicin) nicht beherrschbar sind, so dass alternative Therapieverfahren wie die fäkale Bakterientherapie („Stuhltransplantation“) zur Anwendung kommen. CDI-Rezidive, aber auch eine dauerhafte intestinale Besiedelung mit multiresistenten Enterobakterien wie KPC-KP, scheinen neben wirtsspezifischen Faktoren der Immunantwort durch eine Dysregulation der physiologischen intestinalen Standortflora mit Störung der Kolonisationsresistenz bedingt zu sein. Der Versuch einer Eradikationsbehandlung von Patienten mit persistierender intestinaler Besiedelung durch KPC-KP mittels oraler Applikation der nicht resorbierbaren Antibiotika Colistin und Gentamicin ist mit einem relevanten Risiko der Entstehung von Sekundärresistenzen behaftet. Die Zulassung neuer, besser wirksamer Antibiotika ist für die nächsten Jahre nicht in Sicht, so dass der Infektionsprävention überragende Bedeutung zukommt. Die Erfahrungen der KPC-Ausbruchsbewältigung am Leipziger Universitätsklinikum zeigen, dass nahezu lückenlose Compliance bei der Händedesinfektion, rigoros praktizierte und kontrollierte Barriere- und Isolationsmaßnahmen, Optimierung des Gebrauchs von Breitspektrum-Antibiotika (sog. „Antibiotic Stewardship“) und systematisches mikrobiologisches Erregerscreening dabei unabdingbar sind. Nachhaltige Verbesserungen hinsichtlich der globalen Ausbreitung von multiresistenten Krankenhausbakterien werden sich nur durch grundlegende Umgestaltungen in Umwelt, Landwirtschaft, Tierzucht und Gesundheitswesen mit sparsamer und möglichst gezielter Anwendung von Antibiotika erzielen lassen. Um Risikopopulationen hospitalisierter Patienten vor potentiell lebensbedrohlichen Erregertransmissionen effektiv schützen zu können, sind erweiterte Surveillance und konsequent umgesetzte krankenhaushygienische Maßnahmen erforderlich.

The literature directly comparing the epidemiology of MRSA among adult and pediatric hospitalized patients is strikingly minimal. The objective of this thesis was to identify any differences between these two patient groups. The Canadian Nosocomial Infections Surveillance Program MRSA data (1995 to 2007: n=1,262 pediatric and 35,907 adult cases) were used to compare MRSA clinical and molecular characteristics and rates. Hospital characteristics were modeled using repeated measures Poisson regressions. The molecular and epidemiological characteristics of MRSA differed significantly between adults and children. Compared to children, MRSA in adults was more likely to be healthcare-associated, colonization, SCCmec type II, PVL negative, and resistant to most antibiotics. Rates of MRSA in Canada increased in both populations over time but were significantly higher in adults. The hospital characteristics associated with increased MRSA rates differed in adult and pediatric facilities. Implications for infection prevention and control strategies are discussed.

The literature directly comparing the epidemiology of MRSA among adult and pediatric hospitalized patients is strikingly minimal. The objective of this thesis was to identify any differences between these two patient groups. The Canadian Nosocomial Infections Surveillance Program MRSA data (1995 to 2007: n=1,262 pediatric and 35,907 adult cases) were used to compare MRSA clinical and molecular characteristics and rates. Hospital characteristics were modeled using repeated measures Poisson regressions. The molecular and epidemiological characteristics of MRSA differed significantly between adults and children. Compared to children, MRSA in adults was more likely to be healthcare-associated, colonization, SCCmec type II, PVL negative, and resistant to most antibiotics. Rates of MRSA in Canada increased in both populations over time but were significantly higher in adults. The hospital characteristics associated with increased MRSA rates differed in adult and pediatric facilities. Implications for infection prevention and control strategies are discussed.

Introdução - A crescente resistência antimicrobiana em bactérias responsáveis por infecções hospitalares é um grande desafio à Saúde Pública. as B-lactamases de espectro estendido (ESBL), que hidrolisam a maioria dos compostos B-lactâmicos, são reconhecidas mundialmente como um grande problema para pacientes hospitalizados, devido à localização de seus genes em elementos transferíveis, facilitando sua disseminação. Objetivo - Caracterizar geneticamente cepas de Enterobactérias produtoras de ESBL isoladas de pacientes de um hospital público da cidade de São Paulo. Material e métodos - Todas as cepas de enterobactérias produtoras de ESBL isoladas em um ano foram submetidas a análises moleculares pela PCR, com iniciadores específicos para oito genes bla, e as cepas de Klebsiella pneumoniae ESBL positivas (ESBL-Kp) identificadas nesse período foram comparadas pela técnica de PFGE.Resultados - Os genes, bla(tem), bla(shv), bla(ctx-m), bla(per-2) bla(veb) and bla(ges) foram identificados em 9 espécies: Klebsiella pneumoniae (71,5 por cento), Escherichia coli (13,5 por cento), Morganella morganii (6 por cento), Proteus mirabilis (3 por cento), Klebsiella oxytoca (1,5 por cento), Providencia rettgeri (1,5 por cento), Providencia stuartii (1,5 por cento), Enterobacter aerogenes (0,75 por cento). Os genes bla(per-1) e bla(oxa) não foram detectados. O PFGE revelou 8 perfis moleculares principais em 68,4 por cento das ESBL-Kp, e 31,6 por cento das cepas não estavam relacionadas. Conclusões - Os resultados de PCR revelaram uma grande variedade de grupos de ESBL, e aparentemente este é o primeiro relato de grupos GES e VEB em enterobactérias no Brasil. / Introduction - The increasing antimicrobial resistance in pathogenic bacteria causing nosocomial infections is a major public health challenge. The extended-spectrum &#946;-lactamases (ESBL), which hydrolyze most of &#946;-lactams, are recognized worldwide as a great problem to hospitalized patients, due to the transferable location of their genes, which facilitates their spreading. Objective - Genetically characterize ESBL-producing Enterobacteriaceae strains isolated from patients of a Public Hospital in the city of São Paulo. Material and Methods - All Enterobacteriaceae ESBL-producing strains isolated in an 1-year period were submitted to molecular analysis by PCR with specific primers for eight bla genes, and all ESBL Klebsiella pneumoniae (ESBL-Kp) identified in this period were compared by the PFGE technique. Results - Genes blaTEM, blaSHV, blaCTX-M, blaPER-2, blaVEB and blaGES were identified in 9 species: Klebsiella pneumoniae (71,5%), Escherichia coli (13,5%), Morganella morganii (6%), Proteus mirabilis (3%), Klebsiella oxytoca (1,5%), Providencia rettgeri (1,5%), Providencia stuartii (1,5%), Enterobacter aerogenes (0,75%) and Enterobacter cloacae (0,75%). Genes blaPER-1 and blaOXA were not detected in any strain. PFGE revealed 8 distinct main molecular patterns in 68,4% of ESBL-Kp, and 31,6% of the strains were totally unrelated. Conclusions - PCR results showed a great variety of ESBL groups in the institution, and apparently this is the first report of GES- and VEB-ESBL groups in enterobacteria in Brazil. The results suggest the spread of resistance genes in different strains of ESBL-Kp in some hospital wards, and also that some strongly related clones of these bacteria colonized patients from a neonatal ward in a 3-month period.

Introdução - A crescente resistência antimicrobiana em bactérias responsáveis por infecções hospitalares é um grande desafio à Saúde Pública. as B-lactamases de espectro estendido (ESBL), que hidrolisam a maioria dos compostos B-lactâmicos, são reconhecidas mundialmente como um grande problema para pacientes hospitalizados, devido à localização de seus genes em elementos transferíveis, facilitando sua disseminação. Objetivo - Caracterizar geneticamente cepas de Enterobactérias produtoras de ESBL isoladas de pacientes de um hospital público da cidade de São Paulo. Material e métodos - Todas as cepas de enterobactérias produtoras de ESBL isoladas em um ano foram submetidas a análises moleculares pela PCR, com iniciadores específicos para oito genes bla, e as cepas de Klebsiella pneumoniae ESBL positivas (ESBL-Kp) identificadas nesse período foram comparadas pela técnica de PFGE.Resultados - Os genes, bla(tem), bla(shv), bla(ctx-m), bla(per-2) bla(veb) and bla(ges) foram identificados em 9 espécies: Klebsiella pneumoniae (71,5 por cento), Escherichia coli (13,5 por cento), Morganella morganii (6 por cento), Proteus mirabilis (3 por cento), Klebsiella oxytoca (1,5 por cento), Providencia rettgeri (1,5 por cento), Providencia stuartii (1,5 por cento), Enterobacter aerogenes (0,75 por cento). Os genes bla(per-1) e bla(oxa) não foram detectados. O PFGE revelou 8 perfis moleculares principais em 68,4 por cento das ESBL-Kp, e 31,6 por cento das cepas não estavam relacionadas. Conclusões - Os resultados de PCR revelaram uma grande variedade de grupos de ESBL, e aparentemente este é o primeiro relato de grupos GES e VEB em enterobactérias no Brasil. / Introduction - The increasing antimicrobial resistance in pathogenic bacteria causing nosocomial infections is a major public health challenge. The extended-spectrum &#946;-lactamases (ESBL), which hydrolyze most of &#946;-lactams, are recognized worldwide as a great problem to hospitalized patients, due to the transferable location of their genes, which facilitates their spreading. Objective - Genetically characterize ESBL-producing Enterobacteriaceae strains isolated from patients of a Public Hospital in the city of São Paulo. Material and Methods - All Enterobacteriaceae ESBL-producing strains isolated in an 1-year period were submitted to molecular analysis by PCR with specific primers for eight bla genes, and all ESBL Klebsiella pneumoniae (ESBL-Kp) identified in this period were compared by the PFGE technique. Results - Genes blaTEM, blaSHV, blaCTX-M, blaPER-2, blaVEB and blaGES were identified in 9 species: Klebsiella pneumoniae (71,5%), Escherichia coli (13,5%), Morganella morganii (6%), Proteus mirabilis (3%), Klebsiella oxytoca (1,5%), Providencia rettgeri (1,5%), Providencia stuartii (1,5%), Enterobacter aerogenes (0,75%) and Enterobacter cloacae (0,75%). Genes blaPER-1 and blaOXA were not detected in any strain. PFGE revealed 8 distinct main molecular patterns in 68,4% of ESBL-Kp, and 31,6% of the strains were totally unrelated. Conclusions - PCR results showed a great variety of ESBL groups in the institution, and apparently this is the first report of GES- and VEB-ESBL groups in enterobacteria in Brazil. The results suggest the spread of resistance genes in different strains of ESBL-Kp in some hospital wards, and also that some strongly related clones of these bacteria colonized patients from a neonatal ward in a 3-month period.

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The primary objective of this dissertation is to utilise, adapt and extend current stochastic models and statistical inference techniques to describe the transmission of nosocomial pathogens, i.e. hospital-acquired pathogens, and multiply-resistant organisms within the hospital setting. The emergence of higher levels of antibiotic resistance is threatening the long term viability of current treatment options and placing greater emphasis on the use of infection control procedures. The relative importance and value of various infection control practices is often debated and there is a lack of quantitative evidence concerning their effectiveness. The methods developed in this dissertation are applied to data of methicillin-resistant Staphylococcus aureus occurrence in intensive care units to quantify the effectiveness of infection control procedures. Analysis of infectious disease or carriage data is complicated by dependencies within the data and partial observation of the transmission process. Dependencies within the data are inherent because the risk of colonisation depends on the number of other colonised individuals. The colonisation times, chain and duration are often not visible to the human eye making only partial observation of the transmission process possible. Within a hospital setting, routine surveillance monitoring permits knowledge of interval-censored colonisation times. However, consideration needs to be given to the possibility of false negative outcomes when relying on observations from routine surveillance monitoring. SI (Susceptible, Infected) models are commonly used to describe community epidemic processes and allow for any inherent dependencies. Statistical inference techniques, such as the expectation-maximisation (EM) algorithm and Markov chain Monte Carlo (MCMC) can be used to estimate the model parameters when only partial observation of the epidemic process is possible. These methods appear well suited for the analysis of hospital infectious disease data but need to be adapted for short patient stays through migration. This thesis focuses on the use of Bayesian statistics to explore the posterior distributions of the unknown parameters. MCMC techniques are introduced to overcome analytical intractability caused by partial observation of the epidemic process. Statistical issues such as model adequacy and MCMC convergence assessment are discussed throughout the thesis. The new methodology allows the quantification of the relative importance of different transmission routes and the benefits of hospital practices, in terms of changed transmission rates. Evidence-based decisions can therefore be made on the impact of infection control procedures which is otherwise difficult on the basis of clinical studies alone. The methods are applied to data describing the occurrence of methicillin-resistant Staphylococcus aureus within intensive care units in hospitals in Brisbane and London