Introdução: Staphylococcus aureus é um patógeno que causa uma variedade de infecções nosocomiais e comunitárias. Bacteremia por Staphylococcus aureus meticilina resistente (MRSA) está associada com uma elevada morbidade e mortalidade. Alguns autores consideram uma maior taxa de mortalidade em bacteremia por MRSA em comparação aos observados em bacteremia causada por Staphylococcus aureus sensível a meticilina. O uso da vancomicina no tratamento de infecções por MRSA tem estado sobre crescente vigilância nos últimos anos, já que existe uma grande preocupação sobre a redução de sua eficácia no tratamento de pacientes com bacteremia por MRSA. Estudos sugerem que a vancomicina tem atividade reduzida contra infecções por MRSA quando os valores da concentração inibitória mínima (CIM) se aproximam do valor máximo considerável como susceptível. O locus (acessory gene regulator) regula a expressão de vários genes de virulência, de aderência e produção de biofilme, e pode estar envolvido com a diminuição da sensibilidade a vancomicina. O staphylococcal cassette chromosome (SCCmec) carreia o gene mecA que caracteriza o fenótipo clássico de MRSA e confere resistência aos antibióticos β-lactâmicos. Objetivos: Avaliar as CIMs dos antibióticos: vancomicina, por microdiluição em caldo, e daptomicina, linezolida, tigeciclina e quinopristina/dalfopristina e teicoplanina pela metodologia de Etest®; caracterizar o polimorfismo do locus agr e os tipos de SCCmec de isolados de MRSA de pacientes internados em um hospital, terciário e acadêmico, no sul do Brasil. Métodos: Estudo retrospectivo de coorte no qual foram avaliados todos os episódios de bacteremia causada por MRSA nos Centros de Terapia Intensiva (CTIs) durante o período de junho de 2009 a dezembro de 2011. A detecção dos grupos agr (agr tipo I, II, III e IV) e SCCmec (SCCmec I, II, III, IV e V) foi realizada a partir da técnica da reação em cadeia da polimerase (PCR). Resultados: Foram incluídos no total 21 pacientes. Os isolados de MRSA testados se apresentaram sensíveis a todos os antibióticos testados. O locus agr foi determinado em todos os isolados, sendo que onze pertencem ao grupo agr I (52,4%) e dez ao grupo agr II (27,6%). Já a caracterização dos tipos de SCCmec, não foi possível para onze isolados; para o restante, foi encontrado dois isolados SCCmec tipo I, cinco SCCmec tipo III e três SCCmec tipo IV. Conclusão: Apesar do pequeno número de pacientes e da necessidade de maiores estudos em nosso meio, nossos resultados sugerem que a vancomicina continua a ser a primeira opção de escolha para o tratamento de infecções por MRSA, como recomendado pela Infectious Diseases Society of America. No entanto, a publicação de uma série de estudos sugerindo a susceptibilidade reduzida à vancomicina, mesmo com CIMs próximas ou no ponte de corte, a terapia com vancomicina não seria recomendada a estes pacientes, sendo necessário a avaliação de um novo esquema terapêutico. / Background: Staphylococcus aureus is a versatile pathogen that cause a variety of nosocomial and community infections. Bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with high morbidity and mortality. Some authors consider a higher rate of mortality in MRSA bacteremia compared to those observed in bacteremia caused by methicillin-sensitive Staphylococcus aureus. The use of vancomycin to treat infection due to MRSA has been under increased vigilance in recent years, since there is great concern about reducing their effectiveness in treating patients with MRSA bacteremia. Studies suggest that reduced activity against vancomycin has MRSA when the values of the minimum inhibitory concentration (MIC) approach the upper end of the range of susceptibility. The agr locus (acessory regulator gene) and regulates the expression of several virulence genes, adherence and biofilm production and can be involved in reduced sensitivity to vancomycin. The staphylococcal cassette chromosome (SCCmec) carries the mecA gene that characterizes the classic phenotype of MRSA and confers resistance to β-lactam antibiotics. Objectives: Evaluate MICs of antibiotics: vancomycin, by broth microdilution, and daptomycin, linezolid, tigecycline and quinopristina / dalfopristin and teicoplanin by Etest® methodology; characterize the polymorphism of the agr locus and SCCmec types of MRSA isolates from patients in a hospital, tertiary and academic, in southern Brazil. Methods: A retrospective cohort study which evaluated all episodes of bacteremia caused by MRSA in intensive care units (ICUs) during the period June 2009 to December 2011. The detection of agr groups (agr type I, II, III and IV) and SCCmec (SCCmec I, II, III, IV and V) were performed using the technique of polymerase chain reaction (PCR). Results: We included a total twenty one patients. The MRSA isolates tested were susceptible to all antibiotics tested. The agr locus was determined in all isolates, eleven belong to agr group I (52.4%) and ten to agr group II (27.6%). Already characterization of SCCmec types, it was not possible to eleven isolates; for the remaining two isolates found was SCCmec type I, five SCCmec type III and three SCCmec type IV. Conclusions: Despite the small number of patients and the need for further studies in this area, our results suggest that vancomycin remains the first choice option for the treatment of MRSA infections, as recommended by the Infectious Diseases Society of America. However, the publication of a series of studies suggesting reduced susceptibility to vancomycin, even with MICs near or on cut off, with vancomycin therapy would not be recommended for these patients, the evaluation of a new regimen is necessary.

Made available in DSpace on 2014-06-12T18:28:49Z (GMT). No. of bitstreams: 2 arquivo1137_1.pdf: 1321687 bytes, checksum: 253b31bf70dd4ec1654c3742e9f3bb37 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2011 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A resposta imune inata em processos infecciosos é conhecida por sofrer alterações em decorrência de estados de desnutrição. Assim, o objetivo deste estudo foi de comparar a cinética da produção de óxido nítrico (ON) e a viabilidade de macrófagos alveolares (MA), após infecção celular in vitro, com Staphylococcus aureus meticilina-sensível (MSSA), e meticilina-resistente (MRSA) entre grupos de ratos nutridos (N) ou submetidos à desnutrição neonatal (D). Ratos machos Wistar (n=45) foram divididos em dois grupos distintos, de acordo com a dieta utilizada: N (ratos amamentados por mães submetidas à dieta com 17% de caseína) e D (ratos amamentados por mães submetidas à dieta nutricionalmente deficiente com 8% de caseína). Após o período de amamentação, os animais foram submetidos a um longo período de reposição nutricional, com Labina. Os MA foram coletados através da técnica do lavado broncoalveolar, após traqueostomia. O isolamento dos MA foi realizado por adesão em placas, sendo distribuídos na proporção de 106 células/mL de RPMI. Após o isolamento dos MA, foram estabelecidos quatro sistemas: controle negativo (CN), contendo apenas MA; controle positivo (CP), MA mais 10&#956;L de LPS (lipopolissacarídeo); MSSA, MA mais 100&#956;L de suspensão bacteriana (ATCC 29213) (densidade óptica de 0.15, equivalente a 10-6 CFUmL-1) e MRSA, MA mais 100&#956;L de suspensão bacteriana (ATCC 33591). As placas foram incubadas à 37ºC, com atmosfera úmida e 5% de CO2. A cada duas horas, num total de 24 horas de incubação, foram retirados 100&#956;L do sobrenadante das culturas. A quantificação do ON baseou-se na reação de Griess, através da determinação da concentração de nitritos. A leitura foi realizada em leitor de ELISA, filtro-550nm. A viabilidade dos MA foi analisada após 24 horas de incubação dos sistemas, e avaliada pela redução mitocondrial do 3-[4,5-dimetiltiazol-2-il]-2,5- brometo de difenil tetrazólico (MTT) à formazam. A quantificação do formazam solubilizado foi realizada em leitor de ELISA com filtro de 570nm. Utilizou-se teste t- Student e Mann-Whitney, admitindo-se p<0,05. A desnutrição acarretou diminuição do crescimento ponderal dos animais, da liberação de ON nos sobrenadantes das culturas e da viabilidade dos macrófagos. Houve menor produção de ON no MRSA quando comparado com MSSA, entretanto, a partir das 12h, não foi detectada diferença entre os sistemas, permanecendo até 24h. Ao avaliar a viabilidade dos macrófagos entre os sistemas, ocorreu maior redução no MRSA do grupo desnutrido. Pode-se concluir que o modelo de desnutrição neonatal adotado promoveu alteração na função das células fagocitárias, comprometendo o estresse nitrosativo e a viabilidade dos macrófagos alveolares. Além disto, há evidências de diferenças no mecanismo de evasão do sistema imune entre as cepas MSSA e MRSA

Meticillinresistenta staphylococcus aureus, MRSA, är ett ökande problem runt om i världen. Det finns idag personer med MRSA på många vårdinrättningar och i samhället. På grund av kunskaps- och informationsbrist upplever personer med MRSA sig bli stigmatiserade i mötet med vården. De beskrev känslor av att vara pestsmittade, vilket skapade ett vårdlidande. Syftet med studien var att beskriva erfarenheter i mötet med vården utifrån personers med MRSA perspektiv. Resultatet redovisas utifrån tre teman personers erfarenheter av vårdens bemötande, isolering och vårdpersonalens okunskap. Resultatet i litteraturstudien visade att det fanns en okunskap hos vårdpersonalen om MRSA. Okunskapen ledde till att personer med MRSA inte fick information och de upplevde sig bli bemötta på ett ovärdigt sätt. Litteraturstudien visade också att personer med MRSA skapade egna restriktioner och blev socialt isolerade. Personerna upplevde sig som smutsiga och ville undvika smittspridning. I diskussionen lyfter författarna fram att det behövs mer utbildning för vårdpersonalen då författarna har sett en kunskapsbrist om MRSA. Slutsatserna som författarna kom fram till var att ökad kunskap hos vårdpersonal skulle minska vårdlidandet och stigmatiseringen för personer med MRSA. Det krävs ett internationellt samarbete mellan olika länder och myndigheter för att minska antibiotikaresistensen och det behövs ett gemensamt arbete för en hållbar utveckling.

No description available.

Statement of the problem: Methicillin-resistant Staphyloccocus aureus (MRSA) is a pathogen of increasing concern and is associated with higher hospital readmission rates, poorer prognosis, and increased mortality resulting in increasing costs to the Canadian healthcare system.1-13 Institutions have been challenged with developing effective infection control programs to prevent the spread of MRSA. The purpose of this thesis was to examine the clinical and cost-effectiveness of a universal MRSA screening intervention within a large tertiary care facility. Methods of investigation: The retrospective population-based observational study consisted of two periods. In the first period (24 months), patients admitted to the Ottawa Hospital underwent risk factor-based screening. In the second period (20 months), universal MRSA screening was implemented in which all patients were screened for MRSA upon admission. Results: The regression analysis demonstrated that the universal MRSA screening intervention was not effective in reducing the number of nosocomial MRSA cases. The economic analysis estimated that the universal MRSA screening intervention incurred an additional cost of $1.16 million/year with an estimated additional cost per patient screened of $17.76. Conclusions: The universal MRSA screening intervention was not clinically or economically effective. Further research is required to verify/dispute these findings in other settings.

Class of 2017 Abstract / Objectives: To assess the cost-effectiveness of vancomycin, daptomycin, linezolid, oritavancin, and telavancin as empiric treatment for MRSA skin and soft tissue infections in an inpatient setting from a third party perspective. Methods: A decision analytic tree model was constructed using TreeAge Pro and utilizing efficacy data from published clinical trials and costs estimates using HCUPnet.gov and Micromedex’s RedBook. Sensitivity analyses were run on linezolid costs, as well as oritavancin’s costs and efficacy data. Results: Linezolid was the most cost effective medication, dominating all other therapies. In a sensitivity analysis, increasing linezolid’s cost to include 7 days of inpatient therapy did not result in other therapies no longer being dominated. In two other sensitivity analyses, oritavancin was no longer dominated at 91.8% efficacy, but was still dominated with only 3 days of inpatient therapy. Conclusions: Linezolid was the most cost effective therapy for empiric treatment of suspected MRSA skin and soft tissue infections requiring hospitalization from a third party perspective.

Staphylococcus aureus é uma bactéria que pode ser encontrada colonizando diversas partes do corpo humano, entretanto os diversos fatores de virulência que a bactéria possui, ancorados a sua superfície ou excretados para o meio extracelular, tornam essa bactéria um potencial patógeno, causando infecções de pele e tecidos moles, osteomielite, infecções respiratórias, infecções relacionadas a cateteres e outros dispositivos e bacteremia. Um dos fatores de virulência da bactéria, é a habilidade em formar biofilmes. Biofilmes são comunidades bacterianas tridimensionais complexas, que vivem organizadas e aderidas a uma superfície biótica ou abiótica, embebidas em uma matriz exopolimérica. Cerca de 80% das bactérias vivem organizadas na forma de biofilme, pois nestas estruturas são menos sensíveis aos antibióticos e à resposta imune do hospedeiro. A habilidade de S. aureus em formar biofilme é importante pois o torna uma das principais bactérias que infecta dispositivos médicos e implantes, aumentando a morbidade e mortalidade dos pacientes que apresentam esse tipo de infecção. Os medicamentos da classe dos β-lactâmicos eram a principal escolha para o tratamento de S. aureus, entretanto nos últimos anos essa bactéria adquiriu resistência a esses antimicrobianos, através da aquisição do gene mecA, tornando escassa as opções terapêuticas. Como se não bastasse, os biofilmes bacterianos são particularmente mais resistentes a tratamentos com antibióticos, não só devido ao aumento da transmissão de mecanismos de resistência dentro da comunidade, mas também por causa das limitações de difusão da droga colocados pela matriz extracelular, inativação de antibióticos pela alta concentração de íons de metal e baixo pH, entre outros fatores. Combinados, esses atributos tornam o biofilme bacteriano em torno de 1000 vezes mais tolerante e/ou resistente aos antimicrobianos comparado às células planctônicas. A investigação de estudos epidemiológicos para prevenção dessas infecções, bom como de novas estratégias para prevenção e tratamento de infecções por biofilmes, especialmente em isolados clínicos sabidamente multirresistentes, é urgentemente necessária. Dentre estas estratégias estão a pesquisa de diferentes mecanismos ou substâncias capazes de provocar a inibição da formação ou a erradicação do biofilme formado. Neste contexto, 8 os sistemas de bombas de efluxo e inibidores de bombas de efluxo representam uma fonte promissora de erradicação do biofilme formado. O principal objetivo deste estudo é investigar características clínico-epidemiológicas em isolados clínicos que estejam associadas a formação de biofilme, bem como investigar o papel de bombas de efluxo, inibidores dessas bombas e novos genes envolvidos na habilidade de isolados clínicos de S. aureus em formar biofilme. O capítulo 1 associa características clínicas e epidemiológicas com a habilidade de formação de biofilme. O capítulo 2 mostra o papel da adição de antimicrobianos na inibição e erradicação de biofilmes, a associação com inibidores de bomba de efluxo para melhor entender os sistemas de bomba de efluxo na capacidade desses isolados em formar biofilme e por último, novos genes que participam desse processo, em isolados clínicos de MRSA. Este estudo permite planejar ações preventivas para essas infecções relacionadas a biofilmes. Além disso, demonstra que os sistemas de bombas de efluxo parecem ser alvos promissores para erradicar infecções associadas a biofilmes bacterianos. / Staphylococcus aureus can be found colonizing the human body, however its virulence factors anchored to its surface or secreted into the extracellular medium, makes this bacteria as a potential pathogenic, causing skin and soft tissue infections, osteomyelitis, respiratory infections, catheter-related and other devices infections and bacteremia. One of the virulence factors that bacteria produce is the ability to form biofilms. Biofilms are complex three-dimensional bacterial communities, living organized and attached on a biotic or abiotic surface, embedded in a matrix exopolimérica. About 80% of live bacteria are organized in the form of biofilms because in these structures are less sensitive to antibiotic and the host immune response. The ability of S. aureus to form biofilms is important because it makes it one of the main bacteria that infects medical devices and implants, increasing patient morbidity and mortality. The class of β-lactam drugs used to be main choice for the treatment of S. aureus infections, however in recent years the bacteria acquired resistance to these antibiotics by acquiring mecA gene, so therapeutic options becoming scarce. Besides that, bacterial biofilms are particularly resistant to antibiotic treatments, not only due to increased transmission resistance mechanisms within the community, but also because limitations in drug diffusion by extracellular matrix, inactivation of antibiotics due to high concentration of metal ions and low pH, and other factors. Combined, these attributes make the bacterial biofilm around 1000 times more tolerant and / or resistant to antimicrobial compared to planktonic cells. Investigation of epidemiological studies to prevent such infections, as well as new strategies for prevention and treatment of biofilm infections, especially in known multidrug-resistant clinical isolates, is urgently needed. Among these strategies we could list the different search engines or substances capable of causing or inhibiting the formation of biofilm eradication. In this context, system efflux pumps and efflux pump inhibitors represent a promising source of biofilm eradication. The aim of this study is to investigate the clinical and epidemiological characteristics in clinical isolates that are associated with biofilm formation and investigate the role of efflux pumps and inhibitors of these pumps in the ability of S. 10 aureus clinical isoltes to form biofilms. The chapter 1 associates clinical and epidemiological characteristics with biofilm formation ability. Chapter 2 shows the role of the addition of antimicrobials in inhibition and eradication of biofilms, the association with efflux pump inhibitors to better understand the efflux pump systems in the ability of these isolates to form biofilm and, finally, new genes important in MRSA clincal isolates biofilm formation. This study allows planning preventive actions for these biofilm-related infections. In addition, it demonstrates that efflux pump systems appear to be promising targets for eradicating infections associated with bacterial biofilms.

<p>Validerat; 20151127 (global_studentproject_submitter)</p>

Staphylococcus aureus causes an assortment of infections that range from mild skin infections to bacteremia or necrotizing pneumonia. Patients with S. aureus infections may suffer poor outcomes such as extended hospital stay and death. The goal of this study was to improve outcomes of patients with S. aureus infections by examining microbial characteristics of S. aureus associated with poor clinical outcomes, and comparative effectiveness of S. aureus treatment options for patients with S. aureus infections. Additionally, methods to prevent S. aureus infections among hospitalized patients were assessed. We performed a two-hospital retrospective cohort study to identify microbial characteristics, patient characteristics, or antimicrobial treatments that were predictors of mortality or length of stay among patients with methicillin-resistant S. aureus (MRSA) pneumonia. We found increased age (> 54 years) (hazard ratio [HR]: 4.49; 95% confidence interval [CI]: 1.64-12.33), intensive care unit (ICU) admission (HR: 5.25; CI: 1.52-18.21), and having a hospital-onset pneumonia (HR: 0.32; CI: 0.13-0.75) were associated with mortality while admission to the ICU (odds ratio [OR]: 7.34; CI: 3.58-15.04), increased age (> 54 years) (OR: 2.27; CI: 1.19-4.35), having a hospital-onset pneumonia (OR: 3.60; CI: 1.26-10.28), and receiving vancomycin (OR: 10.85; CI: 3.68-32.00) were predictors of increased length of stay. None of the tested microbial characteristics were associated with poor outcomes. We also completed a multicenter retrospective cohort study to compare the effect of beta-lactams versus vancomycin (both empiric and definitive therapy) on mortality for patients with methicillin-susceptible S. aureus (MSSA) bacteremia who were admitted to Veteran Affairs Medical Centers. We found an increased hazard of mortality for patients who received empiric treatment with a beta-lactam compared with vancomycin (HR: 1.19, 95% CI: 1.00-1.42). However, we observed a protective effect among patients who received definitive treatment with a beta-lactam compared with vancomycin (HR: 0.66; CI: 0.50-0.87). In 2007, 2009-2011, we administered surveys that focused on the implementation of the Institute for Healthcare Improvement's (IHI) MRSA bundle to reduce hospital-onset MRSA infections to infection preventionsts who worked in Iowa hospitals. By the end of the study period, most hospitals implemented a hand hygiene program (range: 87%-94%), placed infected (range: 97%-100%) or colonized patients (range: 77%-92%) on contact precautions, performed active surveillance culturing to identify colonized patients, and monitored the effectiveness of environmental cleaning (range: 23%-71%; P < 0.001). To improve patient outcomes, physicians should provide beta-lactams for definitive treatment of patients with MSSA bacteremia. However, the most effective method to improve outcomes is to prevent S. aureus infections from occurring. This study provides benchmark data that infection prevention staff in rural hospitals throughout the U.S. can use to compare their practices with Iowa hospitals.

Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) has been characterized in swine workers and other high-risk groups in the United States, but little is known about non-high risk groups. We intend to determine the prevalence of S. aureus and MRSA colonization in Iowans at baseline, observe incident colonization events during follow-up, and determine the frequency of transmission within family units. We will also assess the oropharynx as a distinct colonization site within our population of healthy community members. A prospective, longitudinal cohort study was conducted, enrolling 263 individuals, comprising 95 family units, from Johnson County and Keokuk County. Participants self-collected swabs weekly, with adults providing nasal and oropharyngeal samples and minors providing nasal samples. S. aureus isolates were confirmed with catalase and coagulase tests, and StaphLatex agglutination assays. Molecular characteristics were determined through mecA and PVL polymerase chain reaction, and spa typing. Demographic and risk factor data were collected via self-report questionnaire at baseline. Of the 263 enrolled individuals, 78 adults (9 with MRSA) and 31 minors (1 with MRSA) were positive for S. aureus at baseline. This gives an overall S. aureus prevalence of 44.1% and 36.1% for adults and children respectively, with 5.1% and 1.2% of these isolates being MRSA respectively. Sensitivity for the nares was 57.7% while sensitivity for the oropharynx was 85.9%. Of adults submitting 14 or more sets of swabs, 13 (8.44%) were colonized in the oropharynx greater than 50% of samples while being colonized in the nares less than 50% of samples, indicating preferential oropharynx colonization. Risk factors identified for preferential oropharynx colonization were the number of positive environmental sites within the participant's home, size of the household, and race of the participant. Transmission events were observed for both adults and minors, with 3.95 events observed per participant year of follow-up for adults and 3.04 events per person year of follow-up for minors. Familial transmission events were observed at a rate of 0.77 events per person year of follow-up for adults, and 1.22 events per person year of follow-up for minors. We hypothesized oropharyngeal colonization would be important in healthy community members. This hypothesis is supported by the greater sensitivity observed at baseline when compared to the nares. The identification of 13 preferential oropharynx carriers also supports the hypothesis. Utilizing the results from this dissertation, our findings of the importance of environmental contamination in colonization of both the oropharynx and the nares support the use of environmental decontamination to prevent familial transmission of S. aureus. The results of this study confirm the oropharynx as a distinct and unique colonization site for S. aureus, but further studies are needed to determine the clinical ramifications.