O conhecimento científico da doença meningocócica cresceu significativamente desde que a natureza epidêmica da enfermidade foi pioneiramente descrita por Vieusseux no começo do século dezenove. De fato, dois séculos depois, houve avanços revolucionários nas esferas de saúde pública, técnicas diagnósticas, antibioticoterapia, assim como nas terapias adjuvantes envolvendo modulação das cascatas de coagulação e inflamação. Além disso, terapia de suporte para manter a homeostase via monitorização do status hemodinâmico, empregos de vasopressores, transfusão de plasma e suporte respiratório. Contudo, as taxas de letalidade e morbidade desta infecção não se alteraram significativamente nas últimas três décadas. Anualmente, a Organização Mundial de Saúde estima que ocorram 1.2 milhões de novos casos da doença, resultando em 135.000 mortes. No Brasil, anualmente, há 3500 casos da doença com uma taxa de incidência igual a 2 casos por 100.000 habitantes e uma taxa de letalidade igual a 20%. No Instituto de Infectologia Emílio Ribas (IIER) há 100 casos por ano. Assim, nós observamos um amplo espectro clínico da infecção, incluindo manifestações dramáticas como purpura fulminans e complicações atípicas como peritonite. O propósito deste estudo foi avaliar as características clínicas e laboratoriais, assim como a severidade da doença nos pacientes hospitalizados no IIER entre 2003 e 2004. Assim, pacientes previamente hígidos com diagnóstico de infecção meningocócica foram incluídos neste estudo prospectivo. Durante o período de estudo um total de 91 (53 homens e 38 mulheres) pacientes foram identificados como casos confirmados de infecção meningocócica como previamente descrito em materiais e métodos. Culturas de sangue, líquor, ou biópsia de pele de 39 pacientes (43%) foram positivas para N. meningitidis. Todos pacientes tiveram o exame de contraimunoeletroforese ou teste de aglutinação do látex positivo. A idade mediana dos pacientes foi igual a 6 anos (variação, 2 a 16 anos). A letalidade foi igual a 14% (13/91) e seqüelas ou complicações clínicas ocorreram em 63% (49/78) dos sobreviventes. Todos pacientes morreram de choque séptico e o tempo mediano entre hospitalização e óbito foi igual a 24 horas (variação, 18-72 horas). Concluindo, os resultados deste estudo prospectivo criam um elo entre infecção meningocócica e uma constelação de fenômenos fisiopatológicos: hipocalemia, hipomagnesemia, hipocalcemia, hiponatremia, hipoglicemia, hiperglicemia, leucopenia, coagulopatia e plaquetopenia. Os níveis de IL-6 e IL-10 corresponderam bem com a classificação baseada em parâmetros clínicos. A letalidade foi igual a 14% (13/91) e seqüelas ou complicações clínicas ocorreram em 63% (49/78) dos sobreviventes. Uma complexa interação entre mediadores é responsável por determinar a severidade da infecção e tais observações podem ser utilizadas para identificar fatores associados com a gravidade na fase aguda da infecção meningococócica / Scientific knowledge of meningococcal infection has increased greatly since the epidemic nature of the illness was first described by Vieusseux at the dawn of the nineteenth century. In fact, two centuries later, revolutionary advances have been made in public health measures, diagnostic procedures, antimicrobial therapy, and adjunctive therapies involving modulation of the inflammatory and coagulation cascades. In addition, supportive care facilities can maintain homeostasis by monitoring hemodynamic status, administering vasoactive agents and/or plasma exchange, and providing respiratory support. However, the prognosis of and case fatality rate among patients affected by meningococcal disease have not changed significantly over the past 3 decades. The World Health Organization estimates that there are 1.2 million cases of meningococcal disease and 135,000 related deaths annually. In Brazil, 3500 cases are reported annually, with a median incidence of 2 cases per 100,000 population and a case-fatality rate of 20%. At the Emílio Ribas Institute of Infectology (ERII), the incidence of meningococcal disease is approximately 100 cases per year. Therefore, we have observed a broad range of clinical presentations of N. meningitidis infection, including dramatic manifestations as purpura fulminans and atypical complications such as peritonitis. The purpose of this study was to evaluate the clinical features, laboratory features, and the severity of meningococcal disease in patients admitted to the ERII between 2003 and 2004. Therefore, consecutive previously healthy patients with a diagnosis of meningococcal disease were included in a prospective cohort study. During the study period a total of 91 (53 males and 38 females) patients were identified as confirmed cases of meningococcal infection as previously described in material and methods. Cultures of blood, CSF, or skin biopsy specimens from 39 patients (43%) yielded N. meningitidis. All patients had positive counterimmunoelectrophoresis or latex agglutination test in blood or CSF. The median age of the patients was 6 years (range, 2 years to 16 years). The case fatality rate was 14% (13/91) and sequelae or clinical complications occurred in 63% (49/78) of the survivors. All patients died of irreversible septic shock and the median duration from the hospitalization until death was 24 hours (range, 18-72 hours). In conclusion, results from this prospective cohort study support a link between meningococcal infection and a constellation of pathophysiological phenomena: hypokalemia, hypomagnesemia, hypocalcemia, hyponatremia, hypoglycemia, hyperglycemia, leukopenia, coagulopathy, and thrombocytopenia. Both pro-inflammatory IL-6 and anti-inflammatory IL-10 corresponded well with a classification based on clinical parameters. The case fatality rate was 14% (13/91) and sequelae or clinical complications occurred in 63% (49/78) of the survivors. A complex interplay of mediators is responsible for determining severity of disease and these observations can be used to identify factors associated with severity in the acute phase of meningococcal infection

A sepse é uma resposta inflamatória sistêmica resultante da inabilidade do sistema imune em controlar uma infecção, onde a taxa de sobrevida está associada ao recrutamento de neutrófilos para o local da infecção. Tem sido demonstrado que a expressão de receptores quimiotáticos pode ser alterada durante a sepse. Neutrófilos de animais naives respondem às quimiocinas CXC, mas são irresponsivos às quimiocinas CC. Entretanto, dados do nosso laboratório mostram que a expressão de CXCR2 é reduzida na sepse, prejudicando a migração de neutrófilos para o foco da infecção. Além disso, ocorre o aparecimento do receptor CCR2 nos neutrófilos, levando à infiltração dessas células no pulmão e outros órgãos. Nesse contexto, o nosso objetivo foi investigar a possível expressão do receptor CCR5 em neutrófilos e seu papel na evolução da sepse. Demostramos que animais sham-operados expressam baixos níveis de CCR5 e altos níveis de CXCR2. Entretanto, sob a condição de sepse experimental induzida por ligação e perfuração do ceco (CLP), neutrófilos circulantes e que migraram para a cavidade peritoneal expressam altos níveis de CCR5 em paralelo com a internalização de CXCR2. Além disso, animais deficientes para CCR5 (CCR5-/-), submetidos à CLP, apresentam diminuição na taxa de sobrevida, redução na migração de neutrófilos para o foco da infecção, aumento da disseminação bacteriana, aumento no infiltrado de neutrófilos no pulmão e aumento nos níveis de marcadores de lesão do coração e rim, quando comparados com animais selvagens (WT). Adicionalmente, a incubação de neutrófilos isolados da medula óssea com LPS aumentou a expressão de CCR5 e os tornou responsivos à MIP-1? (ligante de CCR5), induzindo quimiotaxia. Também demonstramos que o receptor CCR5 possui importante papel durante a adesão de neutrófilos ao endotélio vascular para posterior migração. Em conjunto, esses resultados indicam que durante a CLP, o aumento da expressão de CCR5 em neutrófilos tem um papel protetor, visto que animais CCR5-/- sépticos apresentam reduzida migração de neutrófilos para o foco infeccioso, inflamação sistêmica acentuada e baixa taxa de sobrevivência. / Sepsis is a systemic inflammatory response resulted from the inability of the innate immune system to control infections, being the survival rate associated to the recruitment of neutrophils to the infection site. It has been demonstrated that chemokine receptors expression profile can be altered under sepsis conditions. Neutrophils from naïve mice respond to CXC chemokines, but are usually unresponsive to CC chemokines. However, data from our laboratory show that CXCR2 expression is down regulated, impairing the neutrophil migration to infection focus. In addition, CCR2 appears on the surface of neutrophils, mediating the accumulation of these cells in the lung and other organs. In this context, we aimed to investigate the possible expression of CCR5 receptor on neutrophils and its role on sepsis evolution. We showed that neutrophils from sham mice express high levels of CXCR2 and low levels of CCR5. However, during experimental sepsis, induced by cecal ligation and puncture (CLP), in parallel with CXCR2 internalization, neutrophils from the circulation or from the peritoneal cavity express higher levels of CCR5. Interestingly, deficient mice for the CCR5 receptor (CCR5-/-), undergone to CLP show decreased survival rate, reduction in the neutrophil migration to the site of infection, increase in the numbers of bacteria, increase in the neutrophil infiltration in lung and heart and increase in the levels of markers of injuries in heart and kidney, when compared to wild type mice (WT).In addition, the incubation of bone marrow derivedneutrophils with LPS enhances the expression of CCR5 and renders them responsive to CCL4 (a ligant of CCR5)-induced chemotaxis. Moreover, we demonstrated that CCR5 receptor has an important role during neutrophil adhesion to the vascular endothelium before transmigration. Together, these results indicate that during CLP-induced sepsis, the increase of the expression of CCR5 on neutrophils plays a host protective role, since CCR5-/- mice under sepsis present reduced neutrophil migration to infection focus, high systemic inflammation and low survival rate.

Sepse bacteriana é a maior causa de morbimortalidade na faixa etária pediátrica e neonatal. A detecção precoce do quadro séptico é difícil, devido os sinais iniciais da doença serem inespecíficos. A possibilidade da existência de exame laboratorial capaz de identificar precocemente quadros sépticos melhoraria o prognóstico desses pacientes. Várias proteínas de fase aguda foram estudadas como marcadores de infecção sendo a proteína C reativa (PCR) a mais utilizada. A procalcitonina (PCT), um pró-hormônio, encontra-se elevado precocemente em quadros sépticos em crianças e adultos. Estudo prospectivo com 14 crianças submetidas à cirurgia cardíaca com circulação extra-corpórea (CEC), com dosagens seriadas de procalcitonina e proteína C reativa, serviram como modelo de resposta inflamatória sistêmica sem infecção com dosagens antes da CEC, após a CEC no primeiro, segundo e terceiro dia após cirurgia, enquanto 14 crianças com sepse/choque séptico dosagens seriadas de PCT e PCR foram obtidas sequencialmente antes do tratamento antibioticoterápico e a cada dia até o terceiro dia. Em crianças sépticas a PCT demonstrou ser superior a PCR como marcador de sepse assim como para diferenciar quadros inflamatórios sistêmicos. / Bacterial sepsis is a major cause of morbidity and mortality in neonates and children. Early detection of bacterial sepsis is difficult because the first signs of this disease may be minimal or nonspecific. The availability of a laboratory test to accurately and rapidly identify septic neonates and children would be of great value in improving the outcome of these patients. Several acute-phase proteins have been used for the diagnosis of bacterial sepsis and C reactive protein (CRP) is the usual marker. It has been reported that the concentration of procalcitonin (PCT), a pro-hormone, is markedly higher in children and adults with sepsis. In a prospective study, 14 children were enrolled after cardiac surgery with cardiopulmonary bypass (CPB), these group represent the non infected children with inflammatory response. Blood samples were obtained before CPB, after CPB, on the first, second and third day after surgery. Another group with 14 children with sepsis or septic shock were enrolled, and blood samples were obtained before antibiotic start, on the first, second and third days. In septic children PCT concentration is a better diagnostic marker of sepsis and to differentiate inflammatory response than CRP.

A sepse é uma síndrome de resposta inflamatória sistêmica decorrente de um processo infeccioso, a qual acarreta alta taxa de mortalidade. Relatos da literatura tem demonstrado que pacientes e animais de experimentação que sobrevivem à sepse desenvolvem quadro de imunossupressão tardia, o qual contribui com a maior sucetibilidade destes a infecções secundárias. Nosso grupo demonstrou que as células T reguladoras (Tregs) participam ativamente do desenvolvimento desta imunossupressão. O Fator de Necrose Tumoral (TNF) é uma citocina pleotrópica responsável por diversas funções durante a resposta inflamatória, apresentando dois receptores responsáveis pelas suas atividades: o TNFR1 e o TNFR2. Foi demonstrando que o TNF exerce um importante papel na atividade de Tregs, induzindo a proliferação, estabilização do fenótipo e aumentando sua atividade imunossupressora, sugerindo que tais atividades sejam atribuidas ao TNFR2. Desta forma, nosso objetivo foi avaliar a participação dos receptores de TNF no desenvolvimento da imunossupressão pós-sepse. Para isso animais WT, TNFR1-/- e TNFR1/2 -/- foram submetidos à sepse grave, induzida por CLP e tratados com um suporte básico (reposição hidríca e antibioticoterapia). Inicialmente avaliamos a participação dos receptores de TNF na fase aguda da sepse. Demonstramos que nesta fase os receptores de TNF, principalmente TNFR1, apresentam um papel prejudicial na migração de neutrófilos, no controle do processo infeccioso e nas lesões de orgãos decorrentes da sepse. Posteriormente, os animais sobreviventes foram infectados com um dose subletal de L. pneumophila i.n 15 dias após a CLP. Avaliamos a participação dos receptores TNF na sucetibilidade à infecção secundária induzida por L. pneumophila em animais sobreviventes à sepse. Observamos que animais TNFR1-/- sobreviventes à sepse são mais suscetíveis, ao passo que animais TNFR1/2-/- sobreviventes à sepse são resitentes à infecção secundária em relação aos animais WT sobreviventes à sepse. Avaliamos então, a expansão de Tregs no baço destes animais sobreviventes à sepse e, observamos que animais TNFR1-/- apresentam aumento da expansão de Tregs, ao passo que os animais TNFR1/2-/- não apresentaram expansão de Tregs comparados ao WT. Observamos também que as Tregs apresentam maior densidade de receptores de TNF do que as células T convencionais e, que durante a sepse ocorre aumento da densidade destes receptores nas Tregs. Sugerimos então que possivelmente o TNFR1 seja um regulador negativo, enquanto o TNFR2 possa assumir um papel na regulação positiva na expansão de Tregs após a sepse, durante o desenvolvimento da imunossupressão. / Sepsis is a systemic inflammatory response syndrome resulting from infectious process, resulting in high mortality rate. It has been shown that septic mice and patients that survived from sepsis develop a late immunosuppression, which contributes to greater susceptibility to these secondary infections. Our group has shown that regulatory T cells (Tregs) actively participate in the development of this immunosuppression. The Tumor Necrosis Factor (TNF) is pleiotropic cytokine responsible for several processes in the inflammatory response. Two receptors are responsible for the various activities of TNF: TNFR1 and TNFR2. It have shown that TNF plays an important role in the activity of Tregs, inducing proliferation, stabilization of phenotype and increasing their immunosuppressive activity. The authors also suggested that these activities are TNFR2-mediated. Thus, our objective was to evaluate the role of TNF receptors in the acute phase of sepsis and also in the development of immunosuppression post-sepsis. For that, TNFR1-/ -, TNFR1/2 -/ - and WT mice were underwent to severe sepsis induced by CLP and treatment with basic support (hydration and antibiotics). Initially we evaluated the participation of TNF receptors in the acute phase of sepsis. We suggest that at this stage the TNF receptor, TNFR1 mainly exert a deleterious role in the migration of neutrophils in control of the infectious process and the tissue damage resulting from sepsis. In addition, the survivors from the septic event were intranasaly infected with L. pneumophila in the 15th day after sepsis induction. We evaluated the participation of these receptors in susceptibility to secondary infection induced by L. pneumophila in survivors from sepsis. Comparing the animals that survived from sepsis, we observed that TNFR1/2-/- , like WT mice, are not susceptible to the secondary infection, while TNFR1-/- survivors are more susceptible to it. We also observed that TNFR1-/ - animals show increased expansion of Tregs in the spleen, different of TNFR1/2-/- mice, that did not show expansion of Tregs compared to WT. We also observed Tregs have a higher density of receptors for TNF than conventional T cells, whereas during sepsis occurs increased expression of this receptor in Tregs. Altogether, the results suggest that TNFR1 is a negative regulator, whereas TNFR2 may play a role in the upregulation during expansion of Tregs, in development of sepsis-induced imunossupression.

A piometra canina é uma infecção bacteriana que acomete o útero de cadelas sexualmente maduras e gera a síndrome clínica conhecida como sepse e síndrome da resposta inflamatória sistêmica. Quando não tratada adequadamente ocorre a progressão da doença para estágios mais graves como a sepse grave e o choque séptico. Embora as alterações ocasionadas pela infecção serem conhecidas, o correto estadiamento da gravidade do quadro ainda é um obstáculo. O processo de inflamação sistêmica é complexo, o fator de necrose tumoral (TNF-α e a interleucina 1β (IL-1&#946) aparecem como mediadores inflamatórios centrais nos casos de sepse. Estudos recentes do DNA de pacientes em choque séptico têm demonstrado a presença de mutações ou polimorfismos que exercem grande influência na produção do TNF-α e da IL-1&#946. Com exceção da avaliação sérica de lactato, a proteína C reativa (CRP) é o biomarcador mais utilizado em testes clínicos para o diagnóstico e tratamento da sepse. Os objetivos principais do estudo foram avaliar a gravidade do caso; as alterações sistêmicas e metabólicas do paciente no período pré-operatório; as concentrações plasmáticas do TNF-α, IL-1β, IL-6 e CRP no momento do diagnóstico; a presença de polimorfismos na região decodificadora do TNF-α e da IL-1&#946. Foram incluídas 9 cadelas sem piometra e 85 com piometra, afecção diagnosticada a partir do histórico e dos sinais clínicos identificados por meio do exame físico e ultrassonografia abdominal; e foram estratificadas para a gravidade do caso em sepse, sepse grave ou choque séptico. As variáveis clinicas e laboratoriais foram coletadas no momento do diagnóstico e confrontadas estatisticamente pelo método de comparações múltiplas. Os resultados mostraram 23 (24,4%) animais em sepse, 60 (63,82%) em sepse grave e dois (2,12%) em choque séptico. As alterações mais significativas foram observadas nos animais com sepse grave e em choque séptico e pode-se destacar a variação no tempo de preenchimento capilar, na pressão arterial, na contagem leucocitária, na albuminemia, na fosfatase alcalina, na creatinina, no pH, na CRP e na IL-6. O exame do gene da IL-1β demonstrou que os animais em sepse com o alelo GG apresentam níveis séricos de IL-1β mais elevados. Foi possível concluir que a estratificação da gravidade do caso para os animais em sepse grave é muito branda e não distingue os animais em estado mais grave dos menos grave dentro do mesmo grupo; que o estadiamento da gravidade poder ser realizado com avaliações corriqueiras e empregadas de forma rotineira no atendimento dos pacientes; que a proteína C reativa e a IL-6 apresentam correlação direta com a gravidade do caso; e que o polimorfismo do gene da IL-1β e o tempo decorrido entre o inicio dos sintomas até que os proprietários procurassem ajuda médica foram os de maior influência sobre a gravidade do caso / Canine pyometra is a bacterial infection that affects the uterus of sexually mature bitches and generates the clinical syndrome known as sepsis and systemic inflammatory response syndrome. When not treated properly the disease progression to more severe stages as severe sepsis and septic shock occurs. Although the changes caused by the infection are known, the correct staging of the severity of the condition is still an obstacle. The process of systemic inflammation is complex, tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) appear as central inflammatory markers in sepsis. Recent studies of DNA from patients in septic shock have shown the presence of mutations or polymorphisms that exert great influence on the production of TNF-α and IL-1β. Except the assessment of serum lactate, C-reactive protein (CRP) is the most widely used biomarker in clinical trials for the diagnosis and treatment of sepsis. The main objectives of the study were to evaluate the severity of the case, systemics and metabolics changes in the patient preoperatively, plasma concentrations of TNF-α, IL-1β, IL-6 and CRP at the time of diagnosis; the presence of polymorphisms in the decoding region of the TNF-α and IL-1β. In the study was included 9 bitches without pyometra and 85 bitches with pyometra, disease was diagnosed from the history and clinical signs identified through physical examination and abdominal ultrasonography; and were stratified according to the severity of the case in sepsis, severe sepsis or septic shock. The clinical and laboratory variables were collected at diagnosis and compared statistically by the method of multiple comparisons. The results showed 23 (24.4%) animals with sepsis, 60 (63.82%) in two and severe sepsis (2.12%) in septic shock. The most significant changes were observed in animals with severe sepsis and septic shock and can highlight the variation in capillary refill time, blood pressure, leukocyte count, the albumin, alkaline phosphatase, creatinine, pH, CRP and IL-6. Examination of the IL-1β gene showed that animals with sepsis with GG allele have higher levels of seric IL-1β. It was concluded that the stratification of the severity of the case for animals in severe sepsis is very bland and does not distinguish the animals in a more severe state of less severe within the same group; the staging of gravity can be done with ordinary ratings and employed routinely in patient care; the C reactive protein and IL-6 show a direct correlation with the severity of the case; and the polymorphism of the IL-1β and the time elapsed between the onset of symptoms until the owners sought medical help were the most influence on the severity of the case

Electronic Health Record (EHR) systems could make healthcare delivery safer by providing benefits such as timely access to accurate and complete patient information, advances in diagnosis and coordination of care, and enhancements for monitoring patient vitals. This study explored the nature of EHR adoption in U.S. hospitals and their patient safety performance in relation to one hospital acquired condition: postoperative sepsis – a condition that complicates hospitalizations, increases lengths of stay, and leads to higher mortality rates. Administrative data from several sources were utilized in order to obtain comprehensive information about the patient, organizational, and market characteristics of hospitals, their EHR adoption patterns, and the occurrence of postoperative sepsis among their patients. The study sample consisted of 404 general, short-term, acute care, non-federal, and urban hospitals based in six states, which provided longitudinal data from 2005 to 2009. Hospital EHR and the EHR’s sophistication level were measured by the presence of eight clinical applications. Econometric techniques were used to test six hypotheses that were derived from macro-organizational theories and frameworks. After controlling for potential confounders, the study’s key findings suggested that hospitals had a significant increase in the probability of having EHR as the percent of other hospitals having the most sophisticated EHR (i.e., EHRS3) in the market increased. Conversely, hospitals had a significant decrease in the probability of having EHR when the percent of Medicaid patients increased within a hospital or when the hospital belonged to centralized or moderately centralized systems. Also, the study findings suggested that EHR was associated with a higher rate of postoperative sepsis. Specifically, the intermediate EHR sophistication level (i.e., EHRS2) and the most sophisticated EHR level (i.e., EHRS3) were associated with a significantly higher rate of postoperative sepsis when compared to hospitals that did not have such EHR sophistication. The study results, however, did not support the hypotheses that higher degrees of fit between hospitals’ EHR sophistication level and specific structural dimensions were associated with greater reductions in postoperative sepsis outcomes vis-à-vis hospitals that did not have these types of fit.

Sepsis is the leading cause of death among hospitalized patients in the United States, is responsible for more than 200,000 deaths annually, and has as high as a 50% mortality rate. Sepsis requires prompt identification so that early goal-directed therapy can be instituted to lead to better outcomes. The purpose of this quality improvement project was to determine if implementing an evidence-based identification and intervention program, Project Code Sepsis, in the emergency department can increase the number of patients who receive antibiotics within the first hour of triage and decrease the length of hospital stay. Specifically, the primary project goals were: (a) to administer initial antibiotic treatments within 1 hour of triage to more than 75% of patients, and (b) to reduce length of hospital stay to an average of less than 7 days. The project was developed from the Donabedian Healthcare Quality Triad and guided by the Six Sigma DMAIC method. A total of 306 patients were included in this project conducted from May to October 2015. The sepsis-screening tool was fully implemented during August when more than 75% of patients received their initial antibiotic within one hour of triage time. However, this accomplishment was not sustained during the next two months. Interestingly, August was also the month with the highest length of hospital stay (7.49 days) among sepsis patients. This quality improvement project did not show that the provision of antibiotic therapy within the first hour of triage time decreases the length of hospital stay among sepsis patients. Multiple factors including administration of intravenous fluids and vasopressors for hypotension, nurse and physician experiences, patient acuity, and local sepsis bacteria profile should be considered together in future studies and quality improvement projects.

Sepsis is life-threatening organ dysfunction caused by a response to infection that causes multiorgan failure. This condition causes high mortality and morbidity rates and leaves permanent disabilities. The purpose of this project was to create a sepsis protocol and an education training program for clinical staff in a hospital setting where no sepsis protocol was in place. The practice-focused question examined whether an educational program would improve clinical staff perception of their knowledge of the early recognition and management of sepsis. A literature review was conducted to identify an evidence-based practice protocol; the results were used to develop the education program for the clinical staff at the site. Malcolm Knowles'€™s theory of adult learning framed the project that included a team of 9 content experts consisting of physicians, physician assistants, and an educator who reviewed and approved the protocol and education program prior to implementation. The education program was then presented to 45 staff members including physicians, licensed vocational nurses, registered nurses, physician assistants, and nurse practitioners. Results of a 14-item knowledge test before and after the education program were examined for percent correct; results were compared using a paired-samples t test. Participant knowledge increased significantly (p <.05) from 20% correctly answering 10 of the 14 questions on the pretest to 87% answering all of the posttest questions correctly. The results of this project may promote positive social change by supporting clinical staff in early recognition and treatment of sepsis thereby reducing the morbidity and mortality that accompanies sepsis.

Le choc septique reste grévé d'une mortalité importante malgré les efforts de recherche expérimentale et clinique. Certains protocoles thérapeutiques cependant, ont permis ces dernières années de diminuer cette mortalité. Les mécanismes précis d'amélioration de ce pronostic sont inconnus. Il est possible que ce gain de survie soit du à une atténuation du Syndrome de Défaillance Microcirculatoire et Mitochondriale du Sepsis. Les travaux réunis dans une première partie de ce volume ont permis de mieux caractériser l'effet de différentes thérapeutiques sur la microcirculation, la vasoréactivité. Thérapeutique annexe comme la sédation qui est utilisée en pratique clinique dans nos services de réanimation ou dans nos laboratoires chez nos animaux, qui perturbe la microcirculation. Thérapeutique directe comme la protéine C activée qui est déjà connue pour être bénéfique sur la microcirculation. La protéine C activée dans notre modèle de choc au LPS chez le rat a notamment un effet bénéfique microcirculatoire possiblement par une dégradation moindre du glycocalyx, le manteau endothélial. Ce produit a également un effet bénéfique sur la réponse vasculaire à la noradrénaline, restaurant cette réponse par rapport à des rats septiques. Une amélioration de la fonction vasculaire et cardiaque est constatée avec ce traitement, sans que l'on puisse affirmer que cette amélioration soit le fait d'une action directe bénéfique sur la microcirculation, la cellule musculaire lisse etc ou une amélioration globale de la réponse de l'organisme au choc : baisse concommittante de médiateurs comme le TNF-α, les dérivés nitrés, ou baisse concommitante du stress oxydatif. Dans une deuxième partie du travail, l'implication de la mitochondrie par le biais de la modulation de facteurs proapoptotiques et de la dissipation du potentiel de membrane ouvre des perspectives pour mieux caractériser cette atteinte chez l'homme dans le futur. En effet moduler la dissipation du potentiel membranaire mitochondriale module chez l'animal la mortalité dans notre modèle. Nous proposons pour l'avenir d'essayer de mieux caractériser ces anomalies chez l'homme.

Objetivo: Determinar el perfil microbiológico y la susceptibilidad antibiótica de los aislamientos bacterianos obtenidos en hemocultivos de pacientes con sepsis neonatal en el Hospital Nacional Ramiro Prialé Prialé de Huancayo, durante los años 2009-2011. Metodología: Se realizó un estudio descriptivo, retrospectivo y transversal; en base a reportes de hemocultivos de pacientes con sepsis neonatal durante los años 2009-2011. Resultados: La incidencia de sepsis neonatal fue de 47,66 x 1000 NV. Los gérmenes gram positivos fueron los agentes etiológicos más frecuentes, SCN se halló en el 70,63%; seguido de S. aureus en el 11,11% y B. cepacia en un 4,76% de casos. En los episodios de sepsis neonatal por gram positivos en el 100% de los casos el antibiograma reportó ser sensible a Vancomicina, Tigeciclina, Linezolid. Así mismo se encontró en su gran mayoría resistencia a Ampicilina, Oxacilina y Eritromicina. En el 100% de los casos el antibiograma reportó ser sensible a Ciprofloxacino para los gram negativos. Conclusiones: El tratamiento antibiótico empírico para los casos de sepsis neonatal debe basarse en las estadísticas microbiológicas de cada hospital.