Introduktion: Antibiotikaresistens är ett globalt problem och inkluderar MRSA, meticillinresistenta stafylokocker. Det saknas översiktsstudier som sammanfattar viktiga resultat gällande upplevelser av att bära på antibiotikaresistenta bakterier, främst gällande MRSA-bärare. För att bedriva ett effektivt folkhälso- och smittskyddsarbete är det viktigt att undersöka upplevelser, resurser och strategier kring bärarskapet hos dessa individer. Syfte: Att undersöka hur individer som bär på MRSA upplevde MRSA-bärarskapet ur ett salutogent perspektiv utifrån känsla av sammanhang (KASAM), med avseende på begriplighet, hanterbarhet och meningsfullhet. Metod: En strukturerad litteraturstudie gjordes där 10 vetenskapliga artiklar analyserades genom tematisk analys utifrån ett salutogent perspektiv. Resultat: Elva subteman identifierades och relaterades till tre teman som utgjordes av de främsta komponenterna av KASAM: begriplighet, hanterbarhet och meningsfullhet. Begriplighet beskriver hur individen uppfattar sin situation som MRSA-bärare och utgörs av subtemana ”Pestsmittad, smutsig och invaderad”, ”Chock, rädsla och skam”, ”Utanförskap, ensamhet och stigmatisering”, ”Okunskap, osäkerhet och ett gåtfullt hot” och ”Nuet störs, framtiden påverkas”. Hanterbarhet beskriver hur individen försöker hantera MRSA-bärarskapet och utgörs av subtemana ”Skydda andra från smitta”, ”Söka information” och ”Informera och utbilda vårdpersonal”. Meningsfullhet utgörs av MRSA-bärarnas beskrivningar av vad som ger dem engagemang och motivation och utgörs av subtemana ”Ta kontroll över situationen”, ”Tid, aktivt lärande och reflektion” och ”Goda möten och relationer”. Slutsats: Upplevelsen av MRSA-bärarskapet innebär ofta ett stort lidande för individen med flertalet begränsningar av livet. Att leva med MRSA är att befinna sig på ett kontinuum av salutogenes/patogenes, där möten och relationer med vårdpersonal spelar en avgörande roll för var individens hälsa positioneras. Det finns en outnyttjad salutogen potential i vårdpersonalens möten och interaktioner med MRSA-bärare. / Introduction: Antibiotic resistance is a global problem and includes MRSA, methicillin-resistant Staphylococcus aureus. Reviews summarising important results concerning experiences of being colonised with MRSA are lacking. For efficient public health and infection prevention work, it is important to examine the experiences, resources, and strategies these individuals have regarding colonisation. Aim: To explore how individuals colonised with MRSA experienced this from a salutogenic perspective, based on Sense of Coherence (SOC), with respect to comprehensibility, manageability, and meaningfulness. Methods: A structured literary review was conducted where 10 scientific articles were analysed through thematic analysis from a salutogenic perspective. Results: Eleven subthemes were identified and related to three themes composed from the main components of SOC. “Comprehension” describes how the individual perceives their situation as colonised with MRSA and consists of the subthemes "Plague infected, dirty and invaded", "Shock, fear and shame", "Exclusion, loneliness and stigmatisation", "Ignorance, uncertainty and a mysterious threat" and "The present is disrupted, the future is affected". “Manageability” describes how the individual tries to manage the MRSA colonisation and consists of the subthemes "Protect others from infection", "Seek information" and "Inform and educate healthcare workers". “Meaningfulness” consists of the descriptions of what gives the commitment and motivation and consists of the subthemes "Take control over the situation", "Time, active learning and reflection" and "Good encounters and relationships". Conclusion: The experience of being colonised with MRSA often involves immense suffering for the affected individual. Living with MRSA is to exist on a continuum of salutogenesis/pathogenesis, where encounters and relationships with healthcare professionals play a key role in where the individual's health is positioned. There is an untapped salutogenic potential in healthcare professionals' encounters and interactions with MRSA carriers.

The Gram positive bacterium Staphylococcus aureus is a major cause of human disease in industrialized countries. This multifaceted pathogen is adapted to thrive in a variety of host niches, including the intracellular compartment. S. aureus rapidly develops antibiotic resistance, and infections due to resistant clones pose a global threat, calling for novel therapeutic approaches. The ability to exploit host nutrients and efficiently metabolize these resources for growth is paramount for bacterial pathogenesis. Understanding the nutritional and metabolic determinants that underpin bacterial virulence may lead to the identification of novel antimicrobial targets. This thesis investigates carbon nutrition and metabolism of community-acquired methicillin resistant S. aureus (CA-MRSA) USA300, a widely spread, hyper virulent multi-resistant strain. The dependence of S. aureus on carbohydrates for growth was considered first. In vitro studies in supplemented chemically defined media showed that sugar phosphates, such as hexose phosphates and glycerol phosphates, promote staphylococcal growth more efficiently than glucose. Deletion mutations were introduced to the two putative sugar phosphate transporter genes present in the S. aureus genome, uhpT (hexose phosphate permease) and glpT (glycerol phosphate permease). Phenotypic analysis of USA300 mutants and heterologous expression of the transporters in a previously described Listeria monocytogenes Δhpt mutant, totally unable to use sugar phosphates, confirmed that S. aureus UhpT and GlpT have different substrate specificities. Whilst both can transport glycerol monophosphate (excluding glycerol-2-phosphate) and the organophosphate antibiotic fosfomycin, hexose monophosphates are only imported via UhpT. Since sugar phosphates are only present in significant amounts inside living tissues, particularly the intracellular compartment, the role of S. aureus UhpT and GlpT in pathogenesis was investigated by constructing a double deletion mutant. The ΔuhpTΔglpT USA300 mutant was used to infect several relevant mammalian cell lines. In the conditions tested, it was found that UhpT and GlpT played no role in the intracellular replication of S. aureus. By contrast, Listeria exploits sugar phosphates from the host cell cytosol via the homologous hexose phosphate transporter, Hpt, to maximise replication and enhance virulence. The distinct requirement of sugar phosphates for intracellular proliferation may reflect intrinsic differences in carbon nutrient dependence between the two organisms. It was confirmed that S. aureus can efficiently use other readily available carbon sources for growth, such as amino acids. In contrast, Listeria is strictly dependent upon sugar-derived carbon for growth, due to an incomplete tricarboxylic acid cycle. Whilst the double ∆uhpT∆glpT mutation had no effect in S. aureus, expression of staphylococcal uhpT or glpT restored wild-type intracellular growth in the L. monocytogenes ∆hpt mutant. Taken together, the results illustrate that sugar phosphate permeases have a contextual role in bacterial virulence, where the background in which the genes are expressed determine their contribution as a virulence factor. The intracellular dynamics of S. aureus was also explored using immunofluorescence microscopy. It was observed that, during epithelial cell infection, USA300 remains enclosed in a membrane-bound vacuole. This localisation may form a barrier to cytosolic sugar phosphates and potentially explain the absence of effect of the sugar phosphate permease deletions in intracellular proliferation. Preliminary characterisation of the S. aureus containing vacuole (SACV) was performed and it was found to be positive for the Rab7 late-endosomal GTPase and for trans-Golgi markers. This suggests that SACVs converge at the Golgi apparatus. Interestingly, a USA300 mutant lacking the global regulatory system agr was unable to proliferate intracellularly and did not acquire Rab7 or Golgi markers. Since the Δagr mutation did not cause any impairment in carbon source dependent growth, these preliminary data suggest that modification of the SACV by Agr-regulated effectors may play a key role in modulating cellular processes that control staphylococcal intracellular survival and/or replication. Evidence presented in this thesis provides a platform for further exploration of S. aureus host cell nutrient dependence and the mechanisms that drive replication.

Background: Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) represent the most worrying Gram-negative and Gram-positive nosocomial pathogens of the present age. They are of increasing concern in the clinical environment due to their multi-drug resistance and the dwindling therapeutic options available. A. baumannii is the most frequently isolated clinical species of the genus, and is able to rapidly acquire resistance. Hypermutators, most frequently deficient in mismatch repair (MMR) via defects in the mutS gene, have been associated with antimicrobial resistance in several bacterial populations. To date, however, the potential role of MMR-deficient mutators in the development of resistance in clinical Acinetobacter spp. has not been investigated. Biocides, most notably chlorhexidine (CHX), are increasingly used in the hospital environment to prevent bacterial spread. This has led to concerns about the development of reduced biocide susceptibility and associated antibiotic resistance in hospital bacterial populations, where there is frequent exposure to both of these factors. The effect of CHX upon defined clinical MRSA isolates is examined here. Methods: The mutS gene of clinical Acinetobacter spp. isolates with varying sensitivities was sequenced and compared to establish whether any variations were present. Mutation studies were performed on isolates by challenging them with ciprofloxacin to determine whether different mutS types correlated with any variation in their ability to develop significant fluoroquinolone resistance. The response of clinical MRSA isolates to a range of CHX concentrations was examined with susceptibility testing methods, and effects were compared with standard strains. Determination of post-exposure minimum inhibitory concentrations (MICs) of a range of antibiotics enabled evaluation of whether exposure to CHX had an effect on susceptibility to antibiotics. Results: Variation was observed in the mutS gene of clinical Acinetobacter spp. isolates, with greater homology observed as resistance increased. A highly conserved and previously unreported amino acid sequence was discovered in resistant isolates. Nonresistant isolates with this ‘R-type’ mutS sequence appeared to have a greater ability to develop significant ciprofloxacin resistance. Clinical MRSA isolates had varying susceptibility to CHX, and there were differences in the susceptibility of standard strains compared to clinical isolates. CHX residues exerted a prolonged minimal inhibitory effect, and several increases in antibiotic MICs following CHX exposure were observed. Conclusions: The correlation of the mutS sequence with mutation ability suggests that defects in the mutS gene may have a role to play in the ability of certain Acinetobacter spp. to rapidly acquire resistance. This could have implications for the treatment of Acinetobacter spp. infections, and may enable quick determination of which clinical isolates have the potential to develop clinically significant resistance. Incomplete eradication due to the prolonged minimal effect of CHX residues may act as a selective pressure in the hospital environment, allowing survival of reduced susceptibility MRSA isolates. Increases in antibiotic MICs following CHX exposure is of grave concern for the future of biocide usage.

The gene encoding methicillin resistance in Staphylococcus aureus (MRSA) is carried in the chromosome on a large genomic island called SCCmec and is always inserted at the att site within orfX. SCCmec has been designated a mobile genetic element but a mechanism by which it moves among different strains and species of staphylococci has never been demonstrated. This work shows that bacteriophage 80α is capable of transducing SCCmec into a recipient cell, after which it can integrate into the bacterial chromosome via homologous recombination. More importantly, this work characterizes a conjugative mechanism of SCCmec transfer. Results demonstrate the capture of a 30.8 kb SCCmec element on a conjugative plasmid for the first time, its transfer into both S. aureus and S. epidermidis recipients, and its excision from the plasmid with insertion in the orfX att site in recipients. The element was integrated into the plasmid by recombination between IS elements invariably present on all SCCmec types and pGO1/pSK41-like conjugative plasmids. These data explain the movement of SCCmec from reservoirs in commensal coagulase-negative staphylococci into different Staphylococcus aureus lineages using a ubiquitous conjugative plasmid that can transfer among staphylococci of different species and, thus, describes a mechanism for the environmental dissemination of methicillin resistance in nature.

Staphylococcal pathogenicity island SaPI1 is excised from genomic DNA and extrachromosomal copies are amplified during the vegetative growth of staphylococcal phage 80α. The amplified genetic element is subsequently encapsidated and transduced at very high frequency. Previous studies have demonstrated that the transducing particles have virions with tails that appear identical to those of helper phage 80α but have smaller capsids, commensurate with the smaller genome of the SaPI (Lindsay et.al., 1998). The morphology of the transducing particles, coupled with the observation that the genomic sequence of SaPIl (GenBank U93688) does not reveal any obvious phage structural proteins, has led to the hypothesis that SaPIl is encapsidated in a virion comprised of 80α structural proteins. Analysis of SaPIl transducing particles supports this hypothesis. Further investigation of 80α genes involved in SaPI1 mobilization was accomplished by selection of phage mutants resistant to SaPI1 interference. Two classes of SaPI1 jnterference resistant (sir) mutants were obtained, and point mutations were identified in two adjacent genes. In order to confirm the roles of these genes, an in-frame deletion of each candidate gene was constructed in an 80α prophage. All mutant phage and deletion constructs were evaluated for phage replication, SaPI1 replication, SaPIl transduction and SaPI1 interference. One gene (ORF21) was required for 80α growth and replication, but was not required for SaPIl growth or replication. The second gene (ORF22) was not essential for phage replication, but was required for SaPIl replication and high frequency transduction. The product of this gene was subsequently shown to be required for SaPIl excision.

Background: The proportion of nosocomial Staphylococcus infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has increased from 22% in 1995 to 63% in 2004. Blood stream infections, more commonly referred to as bacteremias, represented the majority (75.5%) of hospital-onset MRSA cases. The economic impact of Staphylococcus aureus bacteremia merits investigation. Methods: This was a retrospective cohort analysis within Cerner HealthFacts data warehouse. Eligible patients were those who had Staphylococcus aureus bacteremia and were discharged between January 1, 2000, and December 31, 2006. Inclusion criteria include age > 18 years old and onset of infection > 48 hours post admission. The crude association was measured by subtracting the total mean hospital charge for MSSA bacteremia from the MRSA charge. A generalized linear model using a gamma distribution and log link were used to determine the adjusted hospital charge and post-infection length of stay for the MRSA and MSSA groups. Path analysis was used to describe the relationships between infection susceptibility status, LOS and total hospital charge. Results: During the study period, 930 patients meet all the inclusion and exclusion criteria. The overall total hospital charge was $111,636 (MRSA = $121,713, MSSA = $97,307.) The crude difference in mean charge was $24,406. The multivariable model included predicted a MRSA patient would have an increased total charge of $22,889. MRSA had a higher total charge but when patients were more severely ill, MRSA charges decreased while MSSA charges increased. The second multivariable model predicted a MRSA patient would have an increased post-infection LOS of 1.3 days. However, the magnitude of increased post-infection LOS based on pre-infection LOS was different for MRSA and MSSA patients. The path analysis model indicated the direct and indirect effects of susceptibility status on both post-infection LOS and total charge were relatively small. Conclusion: This investigation was the first large multi-center investigation to examine the economic impact of MRSA and MSSA bacteremia. MRSA was associated with a higher total charge and longer post-infection LOS than MSSA patients. The path analysis model analyzed suggests the actually role of infection susceptibility status on post-infection LOS and total charge was minor.

Atualmente, S. aureus meticilina resistente (MRSA) é o mais importante patógeno nosocomial, devido à sua multirresistência aos antimicrobianos disponíveis, o que direciona esforços na busca de novas alternativas terapêuticas. Neste estudo foi avaliada a ação antimicrobiana de extratos vegetais contra isolados MRSA do ambiente aéreo, identificados previamente. Os extratos de Annona crassiflora, Bidens pilosa, Eugenia pyriformis, Heliconia rostrata e Plinia cauliflora foram obtidos por maceração em álcool etílico a 70%, submetidos à rota evaporador e liofilizados. Estes foram testados quanto à ação antimicrobiana pela técnica de difusão em ágar. Posteriormente, realizou-se a concentração inibitória mínima (CIM) pela técnica de microdiluição em caldo. Testes de toxicidade em cultura celular e análise fitoquímica dos extratos complementaram a análise, onde a maioria dos extratos apresentou baixa toxicidade, presença de alcalóides, flavonóides, taninos e saponinas. Os extratos da folha, casca do fruto e caule de Plinia cauliflora, caule e folha de Eugenia pyriformis, caule, polpa, casca do fruto e folha de Annona crassiflora e flor, caule e folha de Bidens pilosa foram efetivos contra as amostras multirresistentes analisadas, sendo que o extrato de Bidens pilosa folha apresentou a melhor atividade antibacteriana in vitro por ambos os métodos avaliados. / Currently S. aureus methicillin resistant (MRSA) is the most important nosocomial pathogen due to multidrug resistance to available antimicrobials, which directs efforts in the search for new therapies. In this study we evaluated the in vitro antimicrobial activity of plant extracts against ambient aerial isolates of MRSA previously identified. The hydroethanolic extracts of Annona crassiflora, Bidens pilosa, Eugenia pyriformis, Heliconia rostrata and Plinia cauliflora were obtained by steeping in ethyl alcohol, 70%, evaporated and lyophilized. The antimicrobial activity was evaluated by agar diffusion and determination of minimum inhibitory concentration (MIC) by microdilution broth. Toxicity testing in cell culture and phytochemical analysis complemented the analysis where most of the extracts showed low toxicity, presence of alkaloids, flavonoids, tannins and saponins. The extracts of leaf, stem and fruit rind of Plinia cauliflora, stem and leaf of Eugenia pyriformis, stem, pulp, fruit rind and leaf of Annona crassiflora and flower, stem and leaf of Bidens pilosa were effective against multidrug-resistant samples analyzed being that the leaf extract of Bidens pilosa showed the best in vitro anti-MRSA activity by both methods evaluated. / Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG

Cette thèse recouvre une période de 15 ans de lutte contre la diffusion hospitalière des bactéries multi-résistantes aux antibiotiques (BMR) au sein d’un CHU parisien pilote. Elle intègre plusieurs études axées sur les outils informatiques de surveillance, la maîtrise de la transmission croisée, et le bon usage des antibiotiques. La configuration d'une base de données dédiée, concentrant l'ensemble des données de la résistance, doit intégrer des critères de requêtes épidémiologique précis, normalisés, et reproductibles. Des variations significatives du taux de Staphylococcus aureus résistant à la méticilline (SARM) ont été observées en fonction de la méthode d'élimination des doublons utilisée (de 27,6% à 33,8%), et l’extrapolation des résultats annuels à partir de données colligées sur des unités de temps plus courtes, mésestime la valeur annuelle de l’incidence du SARM (de -42% à +30%). Ces variations peuvent influer sur l'interprétation des indicateurs relatifs au SARM. L'alerte électronique BMR, en avertissant les soignants de la réadmission d'un patient porteur au sein de leur unité, a permis d'optimiser la compliance aux mesures de précautions contact complémentaires (15% avant vs 90,2% après), et de participer à la diminution de l’incidence du SARM (1,07 en 2002 vs 0,37 en 2012). Elle a également mis en évidence la forte pression de colonisation due aux patients SARM réadmis, 46% des patients porteurs étant réadmis au moins une fois dont les 2/3, moins de trois mois après leur sortie. En réanimation, 1/5 des patients sont porteurs d’Entérobactéries productrices de béta-lactamase à spectre étendu (EBLSE) et/ou hyperproductrices de céphalosporinase (HP-CASE), les taux de portage à l’admission étant respectivement de 79,2% et 48,1% rapportés à l’ensemble des patients porteurs. Aucune stratégie de dépistage n’assure une identification de 100% des patients porteurs, la discontinuité de portage au cours du séjour concernant la majorité des patients. Le remplacement de la ceftriaxone par le cefotaxime a permis de ralentir la progression de l'incidence des HP-CASE. Enfin, l’optimisation du dépistage des EBLSE par l'évaluation puis l'utilisation de robots et de milieux de culture dédiés, a permis de gérer l’inflation des échantillons de dépistage / This work describes 15 years of fight against the spread of multi-drug resistant bacteria (MRB) in a tertiary care hospital, and includes several published studies focused on monitoring systems, cross-transmission control, and antibiotics policy. Data processing plays a crucial role in monitoring MRB. The configuration of a dedicated database, concentrating all resistance data, has to include accurate, standardized, and reproducible epidemiological settings. Significant changes in the methicillin-resistant staphylococcus aureus (MRSA) rate were observed, according to the method used to remove duplicates (27.6% to 33.8%), and the extrapolation of annual results from data collected from shorter period length, underestimates the annual value of MRSA incidence (from -42% to + 30%). These variations may affect the interpretation of MRSA official indicators. The MRB electronic alert, used to warn the staff of the readmission of a previously known colonized patient, conducted to increase the compliance for implementation of infection control measures (15% before vs 90.2% after), and participated in reducing the MRSA incidence (1.07 in 2002 vs. 0.37 in 2012). It also highlighted the strong colonization pressure due to readmitted MRSA colonized patients, since 46% of them were readmitted at least once, readmissions occurring less than three months after discharge in 2/3 cases. In intensive care units, 1/5 patient are colonized by Enterobacteriaceae producing broad spectrum beta-lactamase (ESBL) and/or high level cephalosporinase (HL-CASE), rates at admission being respectively 79.2% and 48.1% when considering all colonized patients. No screening strategy is able to detect 100% of colonization situations, the discontinuity of colonization during the hospital stay concerning a majority of patients. A significant inflexion in the slope in the HL-CASE incidence curve occurred after the substitution of ceftriaxone by cefotaxime. Finally, the optimization of ESBL screening by the assessment and then the use of a robot and dedicated culture media, allowed managing the increased number of screening specimens

Meticillinresistenta Stafylokockus aureus (MRSA) är resistenta stammar av den vanliga bakterien Stafylokockus aureus (S. aureus). MRSA upptäcktes första gången 1961 i England och har sedan dess brett ut sig över hela världen. På sjukhus sprids MRSA mellan patienter via sjukvårdspersonalens händer till följd av bristande hygienrutiner och i samhället sprids bakterierna där människor lever och umgås tätt. En av de viktigaste förebyggande åtgärderna är isoleringsvård, vilken ofta upplevs som negativ. Sjuksköterskan har en viktig uppgift i att lindra patientens vårdlidande och främja upplevelsen av hälsa. Det finns mycket medicinsk forskning bedriven kring MRSA men endast några få studier ur ett patientperspektiv. Syftet är att beskriva patienters erfarenhet av att vara smittade med MRSA. Studien är en litteraturstudie enligt Axelssons (2008) modell och bygger på åtta kvalitativa artiklar. Resultatet visar att patienter smittade med MRSA känner sig kränkta och orättvist behandlade inom vården. Vidare upplever de att sjukvårdspersonal saknar adekvat kunskap kring MRSA och smittspridning samt att de slarvar med de basala hygienrutinerna. Isoleringsvård upplevs som traumatiskt för många patienter, särskilt de som fått en oväntad diagnos. Patienter smittade med MRSA känner sig smutsiga och känner ofta rädsla och oro för att smitta andra, de upplever även att omgivningen drar sig undan dem. Medvetenheten i samhället och inom vården om MRSA-problematiken måste ökas, detta för att minska lidandet hos de drabbade patienterna. / Program: Sjuksköterskeutbildning

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O Staphylococcus aureus resistente a meticilina (MRSA) foi inicialmente descrito como um patógeno associado a infecções relacionadas à assistência em saúde; porém, um clone de MRSA, o CA-MRSA emergiu na comunidade e está atualmente incrementando nos hospitais. O objetivo desta tese foi descrever aspectos relacionados com a epidemiologia das infecções por cepas CA-MRSA no Hospital Universitário Pedro Ernesto da Universidade do Estado do Rio de Janeiro (HUPE/UERJ), avaliando especificamente fatores de risco relacionado com as infecções por CA-MRSA. Usando informações das bases de dados do laboratório de microbiologia, da farmácia e da Comissão para Controle da Infecção Hospitalar do HUPE/UERJ foi realizado um estudo retrospectivo de infecções/colonizações por cepas de S. aureus (fevereiro 2005 a Julho 2011). Foi realizado um estudo caso e controle, utilizando como casos os pacientes com infecções por cepas CA-MRSA. Na avaliação da susceptibilidade aos antimicrobianos usados em infecções graves por MRSA (vancomicina, teicoplanina, daptomicina e linezolida), foram determinadas as concentrações inibitórias mínimas (CIM) das amostras por diferentes metodologias (testes de difusão em agar, microdiluição em caldo e E-test). Nas analises das tendências temporais da apresentação dos subtipos de MRSA, usando um critério fenotípico para classificação das cepas MRSA, foi observada uma diminuição do número de cepas de MRSA multirresistente (HA-MRSA) (p<0.05). Também foi observada uma tendência ao aumento de cepas não-multirresistentes (CA-MRSA), mas sem alcançar a significância estatística (p = 0.06) igual que os S. aureus sensíveis a meticilina (MSSA) (p = 0.48). Não houve associação entre o subtipo de MRSA e a mortalidade devida à infecção por cepas MRSA. Uma idade acima de 70 anos (OR: 2.46, IC95%: 0.99 - 6.11), a presença de pneumonia adquirida no hospital (OR: 4.94, IC95%: 1.65 -14.8), a doença pulmonar obstrutiva crônica (OR: 6.09, IC95% 1.16 31.98) e a leucemia (OR: 8.2, IC95%: 1.25 54.7) foram fatores de risco associadas à mortalidade nas infecções por cepas de S. aureus. Usando curvas de Kaplan-Meier, foi observada uma tendência ao aumento da mortalidade em infecções causadas por MSSA na primeira semana, porém sem alcançar significância estatística (p = 0.07). Não foram observadas amostras MRSA com susceptibilidade intermediaria a vancomicina, linezolida, daptomicina ou teicoplanina. A dinâmica das infecções por S. aureus no HUPE/UERJ mudou durante o período de estudo, com menor número de episódios infecciosos causados por cepas de MRSA multirresistentes. Existe uma tendência ao aumento das cepas não-multirresistentes de MRSA entanto que a taxa de infecções por MSSA permaneceu estável no período do estudo. O perfil de resistência dos estafilococos não teve associação com a mortalidade / The methicillin-resistant Staphylococcus aureus (MRSA) was described initially like a health-care associated pathogen. However, an MRSA clone called community-adquired S. aureus emerged with success in the community and now has a worring increasing frequency in hospital settings. The aim of this study was to descript issues related to the epidemiology of infections due tu CA-MRSA isolates at the Pedro Ernesto Universitary Hospital (HUPE/UERJ) in Rio de Janeiro, Brazil from february 2005 to june 2011, analyzing risk factors related to these infections. Thus, using databases of the microbiology laboratory, pharmacia department and the infection control committee of the HUPE-UERJ, was realized an restrospective study of S. aureus isolates obtained from infected/colonizated patients hospitalized from February 2005 to July 2011. To evaluate risk factors related to CA-MRSA infections was conduced a case-control study, using patients with true infections due to MRSA like cases and patients with methicillin susceptible S. aureus (MSSA) like controls. To test the antimicrobial susceptibility of the antibiotics used in MRSA severe infections (Vancomycin, teicoplanin, daptomycin and linezolid), were determinated the minimal inhibitory concentration (MIC) of MRSA isolates using differents methods (disk-difusion test, microdilution in broth and E-test strips). The trend analyses of the MRSA types, using a phenotypic criteria to classificate the MRSA isolates, found a decrease in the infections due to multi-resistant MRSA isolates (HA-MRSA) in our hospital (p<0.05). Also was observed and increase in non-multi-resistant MRSA strains (CA-MRSA), but without reach statistic significancy (p = 0.06), similar to MSSA (p = 0.48). There is not association between the MRSA phenotype and the mortality due to S. aureus infection. In the multivariate analysis, were observed that an older age than 70 years (OR: 2.46, IC95%: 0.99 - 6.11), health-care pneumonia (OR: 4.94, IC95%: 1.65 -14.8), chronic obstructive pulmonary disease (OR: 6.09, IC95% 1.16 31.98) and leucaemia (OR: 8.2, IC95%: 1.25 54.7) were risk factors associated with mortality due to S. aureus infections. The Kaplan-Meier analysis, found a trend to high mortality due to MSSA infections in the first week, but without get statistic significancy (p = 0.07). We dont found any MRSA isolated with resistance or intermediary resistance to vancomycin, linezolid, daptomycin or teicoplanin. There is good correlation between both MICs determinations, with broth microdiluiton and E-Test strips metodhology. Its were concluded that the dynamic of the S. aureus infections at the HUPE/UERJ is changing, with less number of infectious episodes due to multi-resistant MRSA isolates. Moreover, there are an increasing number of infections due to non-multi-resistant MRSA isolate. The prevalence of infections due to MSSA dont have change in the time of period study. The kind of the S. aureus phenotype dont has association with all-causes-mortality