Dissertations / Theses on the topic 'Nosocomial Sepsis'

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El presente trabajo estuvo orientado a determinar los factores asociados a sepsis nosocomial en los recién nacidos en el servicio de neonatología de Hospital Militar Central, para ello se realizó un estudio, descriptivo, retrospectivo, de casos y controles. La muestra seleccionada estuvo comprendida por 136 neonatos que desarrollaron sepsis intrahospitalaria clínica atendidos en el periodo que corresponde al estudio. Los instrumentos empleados estuvieron conformados por una ficha de recolección de datos convenientemente elaborados para los fines de estudio.
Trabajo académico

Le sepsis est à l’origine d’une dysfonction immunitaire prolongée responsable d’infections nosocomiales et d’une mortalité tardive élevée. Sa physiologie complexe demeure mal connue et il n’existe aucun traitement spécifique en dehors de l’antibiothérapie et des thérapeutiques de suppléance d’organes. Nous nous sommes intéressés au rôle des cellules myéloïdes dans cette dysfonction immunitaire. Nous avons pu montrer qu’il existe chez les patients atteints de sepsis une augmentation du nombre de cellules suppressives d’origine myéloïde monocytaires (M-MDSC) CD14+HLA-DRlow/- et granulocytaires (G-MDSC) identifiées comme des granulocytes de faible densité CD14-CD15+. Ces cellules sont responsables d’une activité Indoléamine 2,3-dioxygénase (IDO) et arginase 1, et leur déplétion permet de restaurer la prolifération des lymphocytes T in vitro. L’augmentation précoce des G-MDSC prédit la survenue ultérieure d’infections nosocomiales. De même, l’augmentation de l’activité IDO et de l’arginase 1 plasmatique sont associées à un mauvais pronostic. Au total, nous avons pu démontrer que les cellules myéloïdes acquièrent un phénotype suppresseur en partie responsable de l’immunodépression acquise et du pronostic péjoratif chez les patients septiques. Afin de restaurer les capacités immunitaires des patients, les MDSC pourraient devenir une future cible thérapeutique
Sepsis results in a sustained immune dysfunction responsible for poor prognosis and nosocomial infections. Sepsis physiology remains poorly understood and no treatment exists currently, excepted from antibiotherapy and life-support techniques. We asked if myeloid cells could play a role in this sustained immune dysfunction. We demonstrated that Peripheral CD14+HLA-DRlow/- monocytic-myeloid-derived suppressor cells (MDSCs) and CD14-CD15+ low-density granulocytes identified as granulocytic- (G-)MDSCs were increased in septic patients. In vitro, arginase and IDO activities relied on MDSCs and depletion of both subsets restored T-cell proliferation. The initial proportion of G-MDSC predicted occurrence of nosocomial infections. Similarly, high plasma Indoleamine 2,3-dioxygenase (IDO) activity and arginase 1 level were associated with poor outcome. Altogether, our results demonstrate that myeloid cells acquire suppressive functions during sepsis, partially responsible for the sustained immune dysfunction and poor outcome. MDSCs may become a future therapeutic target to restore the immune capacities of septic patients

Les infections néonatales tardives (INT, survenant après 3 jours de vie) sont fréquentes et sont associées à une mortalité et une morbidité importantes chez les nouveau-nés prématurés. Dans ce contexte, il a été récemment décrit un clone de Staphylococcus capitis, appelé NRCS-A, impliqué spécifiquement dans ces INT dans différents services de réanimation néonatale (RN) à travers la France, et présentant un profil multirésistant atypique chez cette espèce, incluant notamment une sensibilité diminuée à la vancomycine, qui est pourtant l'antibiotique de première ligne en cas de suspicion d'INT. Dans le cadre de ce travail, nous avons démontré la distribution endémique du clone NRCS-A dans au moins 17 pays à travers le monde, spécifiquement dans les services de RN. De plus des données épidémiologiques issues des services de RN français ont identifié une prévalence élevée du clone dans certains services, illustrant sa capacité à s'implanter puis à persister dans ces services. Une caractérisation génétique du clone NRCS-A a été réalisée afin de mettre en évidence d'éventuels facteurs génétiques pouvant favoriser son implantation dans les services de RN. Cette analyse a démontré le rôle des éléments génétiques mobiles dans l'émergence du phénotype multirésistant du clone NRCS-A. En revanche aucun gène de virulence spécifique du clone n'a pu être mis en évidence. L'analyse des gènes spécifiques du clone a toutefois permis d'identifier le gène nsr codant pour la résistance à la nisine, bactériocine active sur de nombreuses bactéries à Gram positif et sécrétée par les bactéries de la flore commensale digestive. Ce gène pourrait donc conférer un avantage sélectif au clone NRCS-A pour s'implanter dans le microbiote des nouveau-nés prématurés. La persistance du clone dans les services de RN évoque la présence de réservoirs inertes ou humains au sein de ces services. Grâce à la mise au point d'une technique d'identification de S. capitis par gélose chromogénique sélective, nous avons pu démontrer la diffusion et la persistance de S. capitis dans un service de RN, sans toutefois identifier un réservoir unique responsable de cette colonisation. Nous avons également observé une inefficacité partielle des mesures de décontamination. Il n'existe en revanche pas de portage chronique chez le personnel soignant, ni de colonisation vaginale chez les femmes enceintes. Par ailleurs, nous avons pu mettre en évidence par repiquages successifs in vitro une capacité particulière du clone NRCS-A à acquérir de façon rapide et stable une résistance à la vancomycine sous pression de sélection par cet antibiotique. Cette capacité constitue un avantage sélectif majeur pour ce clone et pourrait avoir favorisé son implantation et sa persistance dans les services de RN où la pression de sélection par la vancomycine est élevée. Pour compléter ces résultats, une étude de cohorte prospective menée en RN a permis de démontrer que l'administration de vancomycine constituait un facteur de risque indépendant de survenue d'INT à S. capitis. Au-delà de la problématique spécifique des INT à S. capitis en RN, nos travaux illustrent plus largement un des enjeux majeurs de santé publique qui est l'impact écologique potentiel de l'utilisation des antibiothérapies probabilistes à large spectre sur l'émergence et la sélection de bactéries multirésistantes impliquées secondairement dans des infections nosocomiales. Ces travaux ouvrent de nouveaux axes de recherche concernant d'une part la meilleure compréhension de la physiopathologie des INT à S. capitis, et d'autre part plus largement les modalités de prévention des INT en RN et d'amélioration du diagnostic précoce des INT
Pas de résumé en anglais

The purpose of this thesis is to develop an educational sheet that could be kept on-hand in the Neonatal Intensive Care Unit (NICU) as a reference for a group of evidence-based recommendations designed to reduce the rates of neonatal sepsis. This handout includes information regarding primary and secondary interventions, as well as signs and symptoms of sepsis. The primary interventions include healthcare worker hygiene and evidence-based practice for caring for patients with central venous catheters. The secondary interventions include antibiotic treatment information.

En dépit de nombreux essais thérapeutiques, les syndromes septiques sont la première cause de mortalité en service de soins intensifs. La population septique étant très hétérogène, une meilleure caractérisation des patients serait essentielle afin de mieux individualiser et cibler les thérapeutiques potentiellement bénéfiques. Une approche multiparamétrique de l'utilisation des biomarqueurs est une alternative qui viserait à appréhender la situation de manière plus globale. Notre travail s'inscrit dans ce contexte au travers de l'étude plus spécifique de la défaillance des systèmes cardio-vasculaire et immunitaire. Au-delà de la confirmation de l'intérêt des biomarqueurs présentement étudiés (prohormones cardio-vasculaires et PD-1) dans la prédiction de la mortalité et du risque d'infections nosocomiales, nos résultats apportent des éléments nouveaux. Nous avons montré que (1) la sur-expression des molécules PD-1 est associée à l'énergie leucocytaire, (2) un même biomarqueur peut apporter une information différente au cours du temps, (3) l'information apportée par l'analyse simultanée de deux biomarqueurs est supérieure à celle de la somme de leurs valeurs individuelles, et (4) l'expression dynamique d'un biomarqueur est meilleure que son expression à un temps donné. Au total, notre travail illustre l'intérêt potentiel d'un panel de biomarqueurs pour mieux appréhender la complexité des états septiques et leur rapide évolution. Il reste néanmoins à développer des outils biostatistiques capables de donner au clinicien une vision globale en temps réel des processus en cours. Cela constituera une étape clé pour mieux stratifier et cibler les prochains essais cliniques dans le domaine.

Las definiciones de sepsis y los procesos relacionados con ̩sta se introdujeron inicialmente en los adultos. En 1992 se reúne el consenso de la American College of Critical Care Medicine y Society of Critical Care Medicine (por sus siglas en ingles: ACCM-SCCM) y se mencionan por primera vez términos como: síndrome de respuesta inflamatoria sist̩émica (SIRS), sepsis severa, shock s̩ptico y síndrome de disfunción multiorgánica. En 2001, durante la segunda Conferencia Internacional se propone que la definición de sepsis se haga con base en marcadores biológicos, pero no se obtiene el impacto esperado. En 2004 se reúne el Foro Internacional de Sepsis, el cual crea un consenso para definir parámetros de sepsis en pacientes pediátricos y neonatales. 1

Skin related injuries are some of the most dangerous forms of wounds. In addition to treating the wound itself, health care providers must be cautious of microbial infections. In this study, we evaluate a novel all-natural antimicrobial gel compound (AMG) designed to kill planktonic bacteria, penetrate bacterial biofilms, and accelerate wound healing. In -vitro experiments demonstrate that AMG is effective in inhibiting planktonic growth and biofilm development of eight common pathogens. LIVE/DEAD staining and confocal microscopy reveal that planktonic growth and three-dimensional structure of biofilms were significantly reduced. Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) was used to investigate a small panel of genes (PrsA, Sprx) and showed potential targets for future study. A physiologically relevant wound model was created for treating S. aureus infections by using AMG alone or in combination with a common topical antibiotic, Mupirocin. AMG is a safe and effective treatment option for skin related infection.

Con el fin evaluar el MEDS score, en pacientes con sepsis o sospecha de sepsis en el servicio de Emergencia adultos del HNERM. y determinar la validez de dicho score en nuestro medio, se realiza el presente estudio en 240 pacientes que cumplieron los criterios de inclusión establecidos. Objetivos: a) Estratificar mediante el MEDS score , pacientes con sepsis o sospecha de sepsis en diferentes niveles de riesgo. b) Conocer la frecuencia de mortalidad.por sepsis c) Determinar el grado de correlación entre los diferentes niveles de riesgo y sus índices de mortalidad. d) Proponer la aplicación de guías de atención ajustadas al riesgo que permitan mejorar el pronóstico de los pacientes sépticos en el servicio de emergencia. Tipo de estudio: Descriptivo, prospectivo, longitudinal. Lugar: Servicio de Emergencia Adultos del HNERM. Métodos y Resultados: Los pacientes fueron estratificados mediante MEDS score según niveles de riesgo de mortalidad: obteniéndose los siguientes resultados : Muy Bajo (10,00%), Bajo ( 19,17% ), Moderado ( 29,58%); Alto (17,92%) y Muy Alto ( 23,33 % ). La tasa de mortalidad global fue de 39,58 % ( 95/240 ), siendo mayor en los niveles de riesgo: Muy Alto 22,5% y Alto 13,8%. El análisis proporcional de riesgo de Cox mostró que la presencia en el momento de ingreso de Comorbilidad mayor (p=0,000), Transtorno del sensorio (p=0.000) y Shock séptico (p=0,000) se correlacionaron con una menor supervivencia y por tanto un mayor riesgo de mortalidad por sepsis. Finalmente se construyó la curva ROC, para el Meds Score total, observándose que en el presente estudio la prueba mantiene una buena capacidad discriminativa ( área bajo la curva ROC = 0.73), y por tanto el Meds score es una prueba válida en los pacientes estudiados. Conclusiones: El MEDS Score es una regla de alto valor predictivo de mortalidad por sepsis : que mantiene su nivel de validez en los pacientes del servicio de emergencia adultos del HNERM y que podría ser aplicado en los mismos
With the end to evaluate the MEDS score, in patient with sepsis or sepsis suspicion in the mature service of Emergency of the HNERM. and to determine the validity of this score in our means, we intended to be carried out the present study in 240 patients that completed the established inclusion approaches. Objectives: a) to Stratify by means of MEDS score, patient with sepsis or sepsis suspicion in different levels of risk. b) Conocer the frequency of mortalidad.por sepsis c) Determinar the correlation grade between the different levels of risk and their indexes of mortality. d) Proponer the application of adjusted guides of attention to the risk that you/they allow to improve the presage of the septic patients in the emergency service. Study type: Descriptive, prospective, longitudinal. Place: Mature service of Emergency of the HNERM. Methods and Results: The patients were stratified by means of MEDS score according to levels of risk of mortality: being obtained the following results: Very Low (10,00%), Lower (19,17%), Moderate (29,58%); High (17,92%) and Very High (23,33%). The rate of global mortality was of 39,58% (95 / 240); being bigger in the levels Very High 22,5% and High 13,8%. The proportional analysis of risk of Cox showed that the presence in the moment of entrance of more Comorbilidad (p=0,000), Transtorno of the sensory one (p=0.000) and septic Shock( p=0.00 ) was correlated with a smaller survival and therefore a bigger risk of mortality for sepsis. Finally the curve ROC was built, for the Meds total Score, being observed that presently study the test it maintains a good discriminatory capacity (area under the curve ROC = 0.73), and therefore the Meds score is a valid test in the studied patients. Conclusions: The MEDS Score is a rule of high value predictive of mortality for sepsis: that it maintains their level of validity in the patients of the mature emergency service of the HNERM and that it could be applied in the same ones

OBJETIVO: Determinar la valoración del Índice de Disfunción Orgánica Múltiple de Marshall en pacientes con sepsis en el Hospital Nacional 2 de Mayo. DISEÑO: Estudio prospectivo observacional con un diseño descriptivo longitudinal. LUGAR: Servicio de emergencia del Hospital Nacional 2 de Mayo. PACIENTES: Se evaluaron a 71 pacientes adultos con sepsis admitidos entre el 1 de julio al 31 de octubre del 2004 en el servicio de emergencia del Hospital Nacional 2 de Mayo. MEDIDAS Y RESULTADOS: Se encontró que de los 71 pacientes; 39 (54.9 %) fueron mujeres y 32 (45.1 %) fueron hombres; el foco séptico que más predominó fue el pulmonar con 42 casos que representa el 59.16 %, seguido por el foco dérmico con 11 casos. En cuanto al Índice de Disfunción Orgánica Múltiple (IDOM) se encontró que a partir del tercer día la elevación del mismo se correlacionó directamente con la mortalidad en forma altamente significativa (p<0.05), observándose un RR de 44.25, con una sensibilidad y especificidad del 90 % y 95 % respectivamente. CONCLUSIONES: Se evidenció que el poco difundido y poco aplicado Índice de Disfunción Orgánica Múltiple (IDOM) de Marshall sí tiene utilidad como instrumento de valoración, seguimiento y predicción de eventos adversos (fallecimiento) en pacientes sépticos (críticos), en relación a los demás scores (APACHE II, SOFA), por ser estos últimos de mayor complejidad en su aplicación y de necesitar mayor apoyo logístico.

Con el fin evaluar el MEDS score, en pacientes con sepsis o sospecha de sepsis en el servicio de Emergencia adultos del HNERM. y determinar la validez de dicho score en nuestro medio, se realiza el presente estudio en 240 pacientes que cumplieron los criterios de inclusión establecidos. Objetivos: a) Estratificar mediante el MEDS score , pacientes con sepsis o sospecha de sepsis en diferentes niveles de riesgo. b) Conocer la frecuencia de mortalidad.por sepsis c) Determinar el grado de correlación entre los diferentes niveles de riesgo y sus índices de mortalidad. d) Proponer la aplicación de guías de atención ajustadas al riesgo que permitan mejorar el pronóstico de los pacientes sépticos en el servicio de emergencia. Tipo de estudio: Descriptivo, prospectivo, longitudinal. Lugar: Servicio de Emergencia Adultos del HNERM. Métodos y Resultados: Los pacientes fueron estratificados mediante MEDS score según niveles de riesgo de mortalidad: obteniéndose los siguientes resultados : Muy Bajo (10,00%), Bajo ( 19,17% ), Moderado ( 29,58%); Alto (17,92%) y Muy Alto ( 23,33 % ). La tasa de mortalidad global fue de 39,58 % ( 95/240 ), siendo mayor en los niveles de riesgo: Muy Alto 22,5% y Alto 13,8%. El análisis proporcional de riesgo de Cox mostró que la presencia en el momento de ingreso de Comorbilidad mayor (p=0,000), Transtorno del sensorio (p=0.000) y Shock séptico (p=0,000) se correlacionaron con una menor supervivencia y por tanto un mayor riesgo de mortalidad por sepsis. Finalmente se construyó la curva ROC, para el Meds Score total, observándose que en el presente estudio la prueba mantiene una buena capacidad discriminativa ( área bajo la curva ROC = 0.73), y por tanto el Meds score es una prueba válida en los pacientes estudiados. Conclusiones: El MEDS Score es una regla de alto valor predictivo de mortalidad por sepsis : que mantiene su nivel de validez en los pacientes del servicio de emergencia adultos del HNERM y que podría ser aplicado en los mismos.
--- With the end to evaluate the MEDS score, in patient with sepsis or sepsis suspicion in the mature service of Emergency of the HNERM. and to determine the validity of this score in our means, we intended to be carried out the present study in 240 patients that completed the established inclusion approaches. Objectives: a) to Stratify by means of MEDS score, patient with sepsis or sepsis suspicion in different levels of risk. b) Conocer the frequency of mortalidad.por sepsis c) Determinar the correlation grade between the different levels of risk and their indexes of mortality. d) Proponer the application of adjusted guides of attention to the risk that you/they allow to improve the presage of the septic patients in the emergency service. Study type: Descriptive, prospective, longitudinal. Place: Mature service of Emergency of the HNERM. Methods and Results: The patients were stratified by means of MEDS score according to levels of risk of mortality: being obtained the following results: Very Low (10,00%), Lower (19,17%), Moderate (29,58%); High (17,92%) and Very High (23,33%). The rate of global mortality was of 39,58% (95 / 240); being bigger in the levels Very High 22,5% and High 13,8%. The proportional analysis of risk of Cox showed that the presence in the moment of entrance of more Comorbilidad (p=0,000), Transtorno of the sensory one (p=0.000) and septic Shock( p=0.00 ) was correlated with a smaller survival and therefore a bigger risk of mortality for sepsis. Finally the curve ROC was built, for the Meds total Score, being observed that presently study the test it maintains a good discriminatory capacity (area under the curve ROC = 0.73), and therefore the Meds score is a valid test in the studied patients. Conclusions: The MEDS Score is a rule of high value predictive of mortality for sepsis: that it maintains their level of validity in the patients of the mature emergency service of the HNERM and that it could be applied in the same ones.
Tesis de segunda especialidad

OBJETIVO: Determinar la valoración del Índice de Disfunción Orgánica Múltiple de Marshall en pacientes con sepsis en el Hospital Nacional 2 de Mayo. DISEÑO: Estudio prospectivo observacional con un diseño descriptivo longitudinal. LUGAR: Servicio de emergencia del Hospital Nacional 2 de Mayo. PACIENTES: Se evaluaron a 71 pacientes adultos con sepsis admitidos entre el 1 de julio al 31 de octubre del 2004 en el servicio de emergencia del Hospital Nacional 2 de Mayo. MEDIDAS Y RESULTADOS: Se encontró que de los 71 pacientes; 39 (54.9 %) fueron mujeres y 32 (45.1 %) fueron hombres; el foco séptico que más predominó fue el pulmonar con 42 casos que representa el 59.16 %, seguido por el foco dérmico con 11 casos. En cuanto al Índice de Disfunción Orgánica Múltiple (IDOM) se encontró que a partir del tercer día la elevación del mismo se correlacionó directamente con la mortalidad en forma altamente significativa (p<0.05), observándose un RR de 44.25, con una sensibilidad y especificidad del 90 % y 95 % respectivamente. CONCLUSIONES: Se evidenció que el poco difundido y poco aplicado Índice de Disfunción Orgánica Múltiple (IDOM) de Marshall sí tiene utilidad como instrumento de valoración, seguimiento y predicción de eventos adversos (fallecimiento) en pacientes sépticos (críticos), en relación a los demás scores (APACHE II, SOFA), por ser estos últimos de mayor complejidad en su aplicación y de necesitar mayor apoyo logístico.
Tesis de segunda especialidad

Le choc septique reste une pathologie grave, associée à des taux de mortalité et d'infections nosocomiales (IN) secondaires élevés. La prédiction du pronostic est de la plus haute importance pour sélectionner les patients qui pourraient bénéficier de traitements visant à moduler la réponse immunitaire. Le système immunitaire, classiquement active par des agents externes, peut également être activé par des médiateurs endogènes exprimés à la suite d'une agression d'origine septique ou non. Les protéines S100 font partie de ces signaux de danger endogènes (ou alarmines). Le but de ce travail est d'évaluer la capacité de l'ARNm de S100A9 mesuré dans le sang total de patients en choc septique à prédire la survie et la survenue d'IN. Nous avons également étudié la régulation de l'expression des ARN messagers de S100A8 et S100A9 dans un modèle ex vivo de tolérance à l'endotoxine qui reproduit partiellement les dysfonctions de l'immunité innée induites par le sepsis. L'ARNm de S100A9 est surexprimé dans le sang des patients en choc septique. Un taux élevé entre le 7eme et le 10eme jour du début du choc septique est associé à la survenue d'IN secondaires. Ex vivo, l'expression des ARNm de S100A8 et S100A9 est augmentée durant le phénomène de tolérance à l'endotoxine. Le blocage de l IL-10 et l'administration d'IFN-γ réduisent l'augmentation de ces ARNm dans ce modèle. Apres confirmation dans des études cliniques, ces résultats préliminaires suggèrent que l'expression des ARNm de S100A8 et S100A9 puisse être utilisée comme marqueur du phénomène de tolérance à l'endotoxine et comme outils pour évaluer la dysfonction immunitaire des patients en choc septique. Ces patients pourraient alors bénéficier de thérapies visant à restaurer leurs fonctions immunitaires
Septic shock remains a serious disease with high mortality and increased risk of hospital-acquired infection. The prediction of outcome is of the utmost importance for selecting patients for therapeutic strategies aiming to modify the immune response. Immune system, typically activated by external agents, can also be activated by endogenous mediators induced by various types of stress (trauma, infection, burns). S100 proteins are part of the alarmins family. The aim of this study was to assess the capability of S100A9 messenger RNA in whole blood from patients with septic shock to predict survival and the occurrence of hospital-acquired infection. We also investigate the regulation of S100A8 and S100A9 mRNA expressions in an ex vivo model of endotoxin tolerance which partially reproduces sepsis-induced innate immune alterations. S100A9 messenger RNA is increased in septic shock and its delayed overexpression is associated with the occurrence of secondary hospital-acquired infection. Ex vivo, S100A8 and S100A9 mRNA expressions are increased during endotoxin tolerance. IL-10 blockade and rIFN-γ treatment partially abrogated S100A8/A9 mRNA increases in this model. Pending confirmation in larger, independent clinical studies, these preliminary results suggest that S100A8 and S100A9 mRNA levels might be used as surrogate markers of endotoxin tolerance and as evaluation tools for immune dysfunctions in septic shock patients. These patients could be selected for therapeutic aiming to restore immune functions

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.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Paediatrics and Child Health 29 May 2017
Introduction Sepsis, and in particular, severe sepsis, remains a major cause of death in children worldwide. One of the areas where the burden of sepsis is keenly felt is in the paediatric intensive care unit (PICU) setting, contributing significantly to childhood mortality. Fungal organisms have emerged as a major organism contributing to nosocomial sepsis in PICU. No local data regarding nosocomial fungal sepsis in the non-neonatal, PICU population exists regarding this matter. This study describes the characteristics of patients with nosocomial fungal sepsis in the PICU at South Africa’s largest hospital Chris Hani Baragwanath Academic Hospital (CHBAH). Methods This study was a retrospective review of patient records. All patients aged 0-16 years admitted to the PICU at Chris Hani Baragwanath Academic Hospital (CHBAH) from January 2008 through December 2011 were assessed. A total of seventeen patients who developed nosocomial fungal sepsis were included in this study. Results The incidence of candidaemia was reported to be 3.2 per 100 cases. The major age group affected by nosocomial fungal sepsis was the under one age group. The most common diagnoses on admission were lower respiratory tract infection (LRTI) followed by haematology-oncology and acute gastroenteritis cases. ICU factors found to commonly co-­‐exist with proven nosocomial fungal sepsis were presence of a central venous catheter (100%), mechanical ventilation (82%), arterial line (70%), and systemic corticosteroid use (47%). The penicillin class was the most common antimicrobial that patients were found to be on at the time of nosocomial sepsis. The most common fungal organism as a cause for nosocomial sepsis was C. parapsilosis rather than C. albicans. Furthermore, the majority of this study’s isolates were susceptible to voriconazole rather the current empiric antifungal of choice, namely fluconazole. Conclusion The presence of central venous catheters, arterial lines, mechanical ventilation and systemic corticosteroid use is common in paediatric patients with nosocomial fungal sepsis. However, this study was unable to determine statistically significant factors associated with fungal sepsis in a tertiary PICU due to the surprisingly small number of cases (n=35) detected over a four-year period. This perhaps represents the most striking finding of the study together with a concerning pattern of fluconazole resistance (14%) among isolated organisms.
MT2017

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
As infeções nosocomiais são um dos eventos mais temíveis nas Unidades de Cuidados Intensivos Neonatais (UCIN), sendo responsáveis pelo aumento significativo da morbimortalidade, do tempo de hospitalização e dos gastos hospitalares. A sua incidência mantém-se elevada, ocorrendo em cerca de 20% dos recém-nascidos de muito baixo peso (RNMBP) e 50% nos de extremo baixo peso (RNEBP). Estes recém-nascidos (RN) são sujeitos a inúmeras manipulações e procedimentos invasivos, tais como, intubação endotraqueal, colocação de cateteres venosos centrais (CVC), punções periféricas, entre outros. Os CVCs, apesar de desempenharem um papel fulcral nas UCINs, constituem por sua vez, um dos grandes fatores de risco para o desenvolvimento de sepsis nosocomial.Os micro-organismos responsáveis pelas infeções nosocomiais podem ser bactérias, fungos e raramente vírus. Tal como as infeções nosocomiais, as septicémias associadas com os CVCs cursam, mais frequentemente, com o isolamento de bactérias gram positivas, em particular Staphylococcus coagulase negativa (SCN), seguido pelas bactérias gram negativo. Torna-se, assim, necessário que muitos RNs pré-termo façam vários ciclos de antibioterapia, iniciando-a muitas vezes no primeiro dia de vida por risco infecioso, podendo ocasionar um aumento das resistências bacterianas e a emergência de espécies multirresistentes. A implementação integrada de cuidados rigorosos de assepsia na colocação, manutenção e remoção dos CVCs é de extrema importância, principalmente nos pré-termo, uma vez que a sépsis terá maior impacto na vida do RN quanto maior for a sua prematuridade.O objetivo deste trabalho prende-se com a definição e caracterização da epidemiologia da sépsis nas UCINs, abordagem dos factores de risco associados, nomeadamente com o CVC, avaliação das principais espécies microbianas envolvidas e do seu perfil de resistências aos antimicrobianos e dos métodos de prevenção necessários em todas as UCINs.
Nosocomial infections are one of the most fearsome events in the Neonatal Intensive Care Units (NICU) and are responsible for a significant increase in morbidity, mortality, length of stay and costs. Its incidence remains high, occurring in about 20% of the very low birth weight and 50% of the extremely low birth weight infants. These newborns are subject to numerous manipulations and invasive procedures, such as endotracheal intubation, placement of central venous catheters (CVC), peripheral punctures, among others. Although CVCs play a central role in NICUs, they are, in turn, one of the major risk factors for the development of nosocomial sepsis.The microorganisms responsible for nosocomial infections can be bacteria, fungi and rarely virus. Like nosocomial infections, septicemia associated with CVC more frequently leads to the isolation of gram positive bacteria, in particular coagulase-negative Staphylococcus, followed by gram negative bacteria. It is therefore necessary that many preterm infants undergo several cycles of antibiotherapy, starting on the first day of life due to infectious risk, which may lead to an increase in bacterial resistance and the emergence of multidrug resistant species.The integrated implementation of rigorous aseptic care in the placement, maintenance and removal of CVCs is extremely important, especially in the preterm, since sepsis will have a greater impact on the life of the newborn when the prematurity is greater.The main goal of this article is to define and characterize epidemiology of sepsis in the NICUs, approach the associated risk factors, namely with the CVC, evaluation of the main microbial species involved and their profile of antimicrobial resistance and prevention methods required in all NICUs.

Indiana University-Purdue University Indianapolis (IUPUI)
Sepsis is a clinical syndrome due to a systemic inflammatory response to severe microbial infection. Little is known about the changes in the bone marrow (BM) and how they affect the hematopoietic response to bacterial infection. Using an animal model of severe sepsis induced by Pseudomonas aeruginosa, we have previously reported that hematopoietic stem cells (HSC) undergo a significant expansion in the BM accompanied with myeloid suppression. This bone marrow response was Toll-like Receptor 4 (TLR4)-dependent. TLR4 is activated by bacterial lipopolysaccharide (LPS) and signals through two major independent downstream molecules: TRIF and MyD88. In the present study, I found that the TLR4/TRIF and the TLR4/MyD88 pathways contribute in a distinct manner to the BM response to P. aeruginosa's LPS. TRIF plays a major role in the expansion of the HSC pool, whereas MyD88 is required for myeloid suppression. Following LPS stimulation, HSCs enter in the cell cycle, expand and exhaust when transplanted in healthy mice. Loss of TRIF rescued completely the long-term engraftment and multilineage reconstitution potential of septic HSCs, but did not affect myeloid differentiation. Conversely, MyD88 deficiency prevented completely the myeloid suppression in the myeloid progenitors, but conferred limited protective effects on the HSC function. It is of great therapeutic value to identify the downstream molecules involved in TLR4/MyD88 dependent myeloid suppression. I found miR-21, a microRNA that is involved in inflammation, was up-regulated upon LPS challenge in a MyD88-dependent manner. However, deletion of miR-21 in the BM did not rescue LPS-induced bone marrow dysfunction, demonstrating that miR-21 is not a critical regulator in these processes. Further studies are warranted to determine the precise molecular mechanisms involved in the complex pathogenesis of BM response to sepsis. Taken together, my results show for the first time that the TLR4/TRIF signaling as a key mediator of HSC damage during acute LPS exposure and that activation of the TLR4/MyD88 signaling pathway play a dominant role in myeloid suppression. These results provide novel insights into our understanding of the molecular mechanisms underlying bone marrow injury during severe sepsis and may lead to the development of new therapeutic approaches in this disease.

Sepsis represents a serious medical, but also social problem. Hundreds of thousands of patients die from serious sepsis and septic shock every year. Patients with serious sepsis are treated at intensive care units and their treatment is long, costly and low efficient. These are the reasons why prevention of sepsis focused on prevention and effective treatment of nosocomial infections or timely solution of another problem, e.g. a shock is so much stressed. Nosocomial infections affect about 30 per cent of patients at intensive care units and may cause serious diseases, sepsis or even death. This thesis deals with the possibilities nurses have to influence sepsis, particularly by adherence to aseptic procedures and prevention of nosocomial infection, which might consequently develop in nosocomial sepsis. Combination of quantitative and qualitative methods was used for the research. There were two goals set for the quantitative research. 1. To find whether obstacles occur in adherence to proper aseptic procedures in nursing work as prevention of nosocomial infection occurrence and subsequent septic conditions in patients hospitalized at intensive medicine workplaces. 2. To map the weak points in adherence to proper aseptic procedures in nursing work in intensive care. The goals led to hypotheses H1 Obstacles obstructing thorough adherence to proper aseptic procedures in nursing work exist in intensive care. H2 Non-adherence to aseptic procedures occurs in nursing work at intensive medicine workplaces as a consequence of lack of time for particular interventions. The research sample consisted of nurses from the intensive care workplaces ARD and ICU from 8 hospitals. Questioning method through the questionnaire technique was used for data collection. 342 questionnaires were distributed in total. Hypothesis 1 was refuted, hypothesis 2 was refuted. We found that no obstacles obstructing adherence to proper aseptic methods occur, we mapped the weak points in adherence to proper aseptic procedures in nursing work in intensive care. There were two goals set for the qualitative research. GOAL 3 To find what measures preventing occurrence of nosocomial infection and subsequent septic conditions in patients hospitalized at intensive medicine workplaces are taken by department managements. GOAL 4 To find out how department management deals with possible occurrence of nosocomial infection and subsequent septic conditions in patients hospitalized at intensive medicine workplaces. The following research questions were set. 1. What are the measures preventing occurrence of nosocomial infection and subsequent septic conditions in patients hospitalized at intensive medicine workplaces taken by department managements? 2. How does department management solve possible occurrence of nosocomial infection and subsequent septic conditions in patients hospitalized at intensive medicine workplaces? The research sample consisted of 5 departmental nurses and 5 head nurses from intensive care workplaces from the same hospitals where the quantitative research took place. The research was performed by semi-standardized interview. The research questions were answered. A manual for nurses called ?Recommendation for nurses in prevention of nosocomial infection and nosocomial sepsis not only at intensive care units? was elaborated upon study of these issues and the performed research. A thought map for department management illustrating prevention and solution of nosocomial infection and nosocomial sepsis was also elaborated. Both the document and the research results will be provided particularly to the managements of the hospitals that took part in our research. The thesis may also be helpful to nurses, students and other interested people to gain overall insight into the issue.