Orientador: Daniela Ponce / Resumo: Introdução: O controle da infecção no ambiente de terapia intensiva por patógenos hospitalares, frequentemente, inclui a utilização de vancomicina. Ressalta-se que profundas alterações ocorrem na farmacocinética dos antimicrobianos prescritos aos pacientes criticamente doentes e que os diferentes métodos dialíticos podem removê-los parcial ou totalmente. Objetivo: Avaliar a redução do antimicrobiano vancomicina por diferentes métodos de diálise em pacientes com lesão renal aguda (LRA) associada à sepse e identificar as variáveis associadas a concentrações terapêuticas. Metodologia: Estudo transversal que avaliou pacientes sépticos com LRA em hemodiálise convencional intermitente (HDI) ou hemodiálise prolongada (HDP) e em tratamento com vancomicina internados em Unidade de Terapia Intensivas (UTI) do Hospital das Clínicas da Faculdade de Medicina de Botucatu-UNESP. Foram colhidas amostras seriadas de sangue no início da terapia dialítica, após 2 e 4 horas do tratamento e ao final da terapia. A concentração sérica de vancomicina foi aferida por cromatografia líquida de alta eficiência (CLAE) ou por Imunoensaio enzimático homogêneo (Enzyme Multiplied Immunoassay Technique - EMIT). A partir desses dados foi realizado avaliação farmacocinética e Modelagem PK/PD. Resultados: De março de 2015 a agosto de 2017 foram incluídos 27 pacientes tratados por HDI, 17 por HDP 6h e 11 por HDP 10h. O volume de distribuição, assim como o tempo de meia vida e clearence dialítico da vancomicina fo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Infection control in the intensive care environment by hospital pathogens often includes the use of vancomycin. It is noteworthy that profound changes occur in the pharmacokinetics of antimicrobials prescribed to critical patients and that different dialytic methods may partially or totally remove them. Objective: To evaluate the reduction of antimicrobial vancomycin by different dialysis methods in patients with AKI associated with sepsis and to identify the variables associated with its therapeutic level. Methodology: A cross-sectional study evaluating septic patients with AKI on intermittent conventional hemodialysis (IHD) and prolonged hemodialysis (PHD) and vancomycin treatment in intensive care unit (ICU) of Clinics Hospital of the Faculty of Medicine of Botucatu - UNESP. Serial blood samples were collected at the start of dialysis therapy after 2 and 4 hours of treatment and at the end of therapy. The serum level of vancomycin was measured by high performance liquid chromatography (HPLC) or by Enzyme Multiplied Immunoassay Technique (EMIT). From these data, pharmacokinetic evaluation and PK / PD modeling were performed. Results: From March 2015 to August 2017, 27 patients treated for IHD, 17 for PHD 6h and 11 for PHD 10h were included. The volume of distribution was higher in the groups PHD 6h and PHD 10h (p <0.001), as well as half-life (p <0.001) and dialytic clearance of vancomycin (p <0.001). The reduction of vancomycin after 2 hours of therapy was 26... (Complete abstract click electronic access below) / Doutor

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Orientador: Julieta Rodini Engrácia Moraes / Coorientador: Flávio Ruas de Moraes / Coorientador: Gustavo da Silva Claudiano / Banca: Rogério Salvador / banca: Laura Satiko Okada Nakaghi / Resumo: Bactérias do gênero Aeromonas causam infecção caracterizada por septicemia, sendo a forma aguda desta afecção a mais prevalente em peixes. Esta bacteriose é responsável por altas taxas de morbidade e mortalidade, ocasionando grandes perdas no setor de produção aquícola. Deste modo, o entendimento de sua fisiopatogenia é de suma importância ao desenvolvimento de estratégias voltadas à intervenção e controle da aeromonose em peixes. Este trabalho visou caracterizar por meio de estudos morfológicos e microbiológicos a fase aguda do processo séptico em diferentes tecidos de pacus (Piaractus mesopotamicus) infectados experimentalmente com Aeromonas hydrophila. Para isso, 160 pacus com peso médio de 250g foram inoculados por via celomática com A. hydrophila (1,78 x 109 UFC/mL) e nos tempos pré-estipulados de 0 (controle), 1, 3, 6 e 9 horas pós-inoculação (hpi) os animais foram anestesiados e o material biológico coletado para realização de exames microbiológicos, histopatológicos e ultraestruturais. Foi evidenciada a presença de necrose, processos degenerativos, alterações vasculares e associação da bactéria a essas lesões nos tecidos estudados, principalmente 6 e 9 horas após a inoculação. / Abstract: Aeromonas bacteria cause infection characterized by septicaemia and acute septicemic form of this disease is the most prevalent in fish. This bacteriosis is responsible for high morbidity and mortality rates, causing considerable losses in the aquaculture sector. Thus, understanding its pathophisiology is crutial to the development of strategies for intervention and control of fish aeromonosis. This study aimed to characterize by morphological and microbiological studies the acute phase of septic process in different tissues of pacu (Piaractus mesopotamicus) experimentally infected with Aeromonas hydrophila. Hence, 160 pacus weighing approximately 250g were inoculated via coelomic route with A. hydrophila (1.78 x 109 CFU / mL) and pre-operative times of 0 (control), 1, 3, 6, and 9 hours post-inoculation (hpi) the animals were anesthetized and the biological material collected for performing microbiological, histopathological and ultrastructural analysis. They showed the presence of necrosis, degenerative processes, vascular damage and close association of the bacteria to these lesions in tissues, mainly 6 and 9 hours after inoculation / Mestre

Orientador: Maria Regina Bentlin / Resumo: Introdução: A sepse tardia (ST) é um grande desafio para neonatologistas por ser frequente e grave. Objetivos: Em prematuros de muito baixo peso (PT MBP): investigar a incidência da ST, clínica e confirmada, e a distribuição dos agentes etiológicos; analisar os fatores de risco; avaliar o prognóstico da sepse em curto prazo. Métodos: Coorte retrospectiva, com coleta prospectiva de dados, aprovado pelo Comitê de Ética, realizado entre 2013-2017 na UTI Neonatal do HC FMB - UNESP. Foram selecionados todos os PT com peso de nascimento (PN) ≤ 1.500 g internados na UTI e incluídos aqueles com idade gestacional (IG) entre 23 e 33 semanas, que sobreviveram por mais de 72h e acompanhados até alta, óbito ou 120 dias de internação. Não incluídos os PT com malformações múltiplas, infecções congênitas sintomáticas. ST foi definida como sinais clínicos e laboratoriais de infecção, confirmada ou não por hemocultura (HMC). Variáveis estudadas: gestacionais, neonatais, procedimentos e agentes etiológicos. Desfechos: óbito, displasia broncopulmonar (DBP), hemorragia peri e intraventricular (HPIV) grave, leucomalácia cística e retinopatia da prematuridade (ROP) ≥ estágio 2. Comparação entre grupos: Sem ST vs ST confirmada (HMC+) vs ST clínica (HMC-). Estatística: ANOVA com comparação múltipla de Tukey ou de Wald (distribuição gama); regressão logística múltipla (stepwise e ajuste para IG). Significância: 5%. Resultados: Foram incluídos 346 PT MBP. A incidência de ST foi de 32% (21% ST confirmad... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Late onset sepsis (LOS) remains a challenge for neonatologists because it is a frequent and severe disease. Aim: In very low birth weight (VLBW) preterm infants (PT): to investigate the incidence of LOS, proven and clinical, and the distribution of etiologic agents; to analyze the risk factors evolved; to evaluate the prognosis in the short term. Methods: Retrospective analysis of cohort, with prospective data collect, approved by the Ethics Committee, performed between 2013-2017 at the Neonatal Intensive Care Unit (NICU) of the Botucatu Medical School - UNESP. All PT with birth weight (BW) ≤ 1.500 g admitted in the NICU were selected. PT with gestational age (GA) between 23 and 33 weeks, admitted for more than 72 hours and followed up until discharge, death or 120 days of NICU stay were included. Not included multiple malformations and symptomatic congenital infections. LOS was defined as clinical and laboratory signs of infection, confirmed or not by blood culture (BC). Variables: gestational, neonatal, procedures and etiological agents. Outcomes: death, bronchopulmonary dysplasia (BPD), severe peri and intraventricular hemorrhage (PIVH), cystic leukomalacia and retinopathy of prematurity (ROP) ≥ stage 2. Comparison among groups: No LOS vs Proven LOS (BC+) vs Clinical LOS (BC-). Statistical analysis: ANOVA with multiple Tukey or Wald comparison (gamma distribution); multiple regression (stepwise), with adjustment for GA. Significance: 5%. Results: 346 PT were ... (Complete abstract click electronic access below) / Mestre

Orientador: Daniela Ponce / Coorientador: André Luis Balbi / Banca: Luís Gustavo Modelli de Andrade / Banca: Ginivaldo Victor Ribeiro do Nascimento / Resumo: Introdução: A mortalidade de pacientes com sepse e lesão renal aguda (LRA) é inaceitavelmente elevada, com necessidade de medidas de prevenção. Faltam estudos brasileiros que mostrem esta incidência em salas de emergências clínicas (SEC) e identifiquem fatores de risco para o seu desenvolvimento, além de marcadores precoces de diagnóstico e prognóstico. Dentre eles, encontra-se o NGAL, que é um biomarcador sérico e urinário (u) promissor de detecção precoce de LRA. Objetivos: Este trabalho teve como objetivo principal avaliar a eficácia do NGALu como preditor diagnóstico e prognóstico da LRA associada à sepse em pacientes admitidos em SEC. Metodologia: Estudo prospectivo de pacientes admitidos na SEC com diagnóstico de sepse durante o período de 01 de fevereiro de 2013 a 31 de maio de 2014. Para cada paciente foi aplicado um protocolo com dados clínicos e laboratoriais. A avaliação da função renal foi realizada por dosagem de creatinina sérica e verificação de débito urinário desde a admissão até o desfecho do quadro (resolução ou óbito). O NGALu foi dosado nas primeiras 24h de admissão (1), entre 24-48h (2) e no momento do diagnóstico de LRA (3). Os resultados foram apresentados por regressão logística e área sob a curva roc para determinar a capacidade do NGALu discriminar o diagnóstico e prognóstico da LRA. Resultados: Foram incluídos 168 pacientes, sendo que 72% tiveram diagnóstico de LRA. Na regressão logística, a idade >65 anos, choque séptico, necessidade de ventilação mecânica (VM) e o NGALu 2 foram identificados como fatores associados à LRA. Quanto à precisão, NGALu 1 e 2, assim como a relação NGAL/Cru 1 e 2 apresentaram área sob a curva ROC para LRA >0,7, com sensibilidade entre 0,63 e 0,75. Os fatores de risco identificados para o óbito foram choque séptico, presença de LRA AKIN 3 e APACHE II > 20. Como preditores de óbito, NGALu 1 e 2 e a relação NGALu/Cru 1 e 2,... / Abstract: Background: The mortality of septic patients and AKI is inaceptable high, showing the need for preventive measures. There are few Brazilian studies showing the incidence of AKI in clinical emergencies rooms (ER) and identify risk factors for its development, and early markers of diagnosis of AKI and prognosis of patients. NGAL is a serum and urinary (u) promising biomarker for early detection of AKI. Objectives: This study aimed to evaluate the efficacy of uNGAL as a diagnostic and prognostic predictor of AKI associated with sepsis in patients admitted to the ER. Methodology: We prospectively studied patients admitted to the ER diagnosed with sepsis during the period of February 1, 2013 to May 31, 2014. For each patient, a protocol was developed containing clinical and laboratory data from the patients admission to the discharge of the hospital (resolution or death). The assessment of renal function was performed daily by serum creatinine, urine output, and dosage of uNGAL within the first 24 hours after admission (1), between 24-48 h (2) and at moment of AKI diagnosis (3). The results were presented using descriptive statistics of the study population and different statistical tests according to the study objectives. Logistic regression and ROC area under curve was used to determine the ability of uNGAL to discriminate the AKI diagnosis and prognosis of septic patients. Results: One hundred eight patients were included, of which 72% were diagnosed with AKI. In logistic regression, age> 65 years, septic shock, need for mechanical ventilation (MV) and the uNGAL 2 were identified as factors associated with AKI. Regarding the accuracy, uNGAL 1 and 2, as well as uNGAL / uCr 1 and 2 showed an area under the ROC curve for AKI> 0.7, with sensibility between 0.63 and 0.75. The risk factors identified in the logistic regression for death were septic shock, presence of AKI AKIN 3 and APACHE II> 20. As predictors of death, the precision of uNGAL1, ... / Mestre

Publicación a texto completo no autorizada por el autor / Determina las características clínicas y epidemiológicas de la sepsis neonatal tardía por Staphylococcus coagulasa negativo en el Hospital Nacional Edgardo Rebagliati Martins durante el año 2016. Se realizó un estudio observacional descriptivo y retrospectivo. Se incluyeron 65 pacientes con diagnóstico de sepsis neonatal tardía confirmada, con evidente predominio de Staphylococcus coagulasa negativo (92%); dentro de éstas, la especie más frecuente fue el Staphylococcus epidermidis (75%), el que causó el total de fallecimientos (10% de la población total). La población estuvo conformada a predominio de varones (63.3%), pretérmino (66.7%), con bajo peso al nacer (66.7%). El signo más predominante fue la dificultad respiratoria (51.8%), el examen auxiliar positivo más frecuente fue el porcentaje de neutrófilos abastonados > 10% (72.5%) y el procedimiento invasivo que se asoció con mayor frecuencia fue el catéter central de inserción periférica (78.2%). El tratamiento más usado fue la combinación imipenem más vancomicina (68.3%). Las principales resistencias a antibióticos encontradas fueron a eritromicina (95.8%) y a oxacilina (93.8%). Se concluye que el Staphylococcus coagulasa negativo es el causante principal de la sepsis neonatal tardía confirmada, con una tasa de 9 por cada 1000 nacidos vivos en el Hospital Nacional Edgardo Rebagliati Martins durante el año 2016. / Tesis

Recently, viral hemorrhagic septicemia virus (VHSV IVb) was associated with several walleye (Sander vitreus) mortality events in the Great Lakes. To examine the effects of route, strain-variation and temperature, walleye were experimentally infected with VHSV IVb using intraperitoneal (i.p.)-injection (102-108 pfu/fish) and immersion (w.; 1.4 x 107 virions mL-1). Walleye were relatively resistant to experimental infection with VHSV IVb, regardless of route or water temperature. High cumulative mortality (64-100%) and severe gross lesions associated with VHSV-IVb infection were only evident in fish i.p.-injected with 108 pfu at 12°C, which had mild to moderate, multifocal necrosis of several tissues including the gill and heart. There were significant differences in mortality between four walleye strains following i.p.-infection. Viral antigen was found in both i.p. and w.-exposed walleye using immunohistochemistry, mostly within the gill and skin epithelium of w.-exposed fish. VHSV IVb was detected in walleye tissues from 6-21 d post-infection using RT-qPCR. / Great Lakes Fisheries Commission and NSERC

Walleye (Sander vitreus M.) are valuable in commercial and recreational fisheries and are affected by bacterial, fungal and viral disease. Pattern recognition receptors (PRRs) are germline-encoded and constitutively expressed and bind non-self or altered-self for immune recognition. Walleye were hypothesised to have circulating PRRs that were capable of binding diverse pathogens. These PRRs were hypothesised to increase with infection, be distributed in immunologically relevant tissues and to be strain and age specific. PRR binding was measured by affinity chromatography, plasma binding assays,SDS-PAGE, Western blots, ELISA, PCR, and immunohistochemistry. ELISA and affinity chromatography assays were developed in rainbow trout (Oncorhynchus mykiss) with known PRRs. Trout ladderlectin was confirmed as a PRR binding viral hemorrhagic septicemia virus (VHSV). These techniques were adapted to walleye using Flavobacterium columnare, chitin, VHSV and Sepharose resin. A 22 kDa protein bound to F. columnare, a 17 kDa protein bound to chitin and a 34 kDa protein bound to VHSV were identified as similar to bass apolipoprotein, carp C3 and rainbow trout intelectin, respectively. PCR and 3'-RACE-PCR were used to generate nucleotide sequence to confirm identity of walleye apolipoprotein and mannose-binding lectin (MBL)-like protein from the intelectin-like sequence. Two rabbit polyclonal antibodies were raised to 34 and 67 kDa MBL amino acid sequences and used to verify MBL-like protein as a PRR for VHSV. Healthy walleye MBL-like protein plasma concentration was 7.5 ng/ml. Significant differences were found between geographically distant strains of walleye. An ELISA demonstrated that MBL-like protein had significant differences in binding affinity between multiple strains of VHSV and different viruses found in Ontario. MBL-like protein plasma levels increased with initial infection of naïve fish with waterborne and IP VHSV (107 pfu) but did not change with IP reinfection. Previous infection with VHSV significantly decreased walleye mortality. IHC of walleye shows MBL-like protein is distributed in epithelial surfaces, primarily skin, oropharynx, gill, gastrointestinal system, renal nephrons, connective tissue of gonads and plasma. There was no qualitative difference in MBL-like protein tissue distribution in healthy and VHSV-infected walleye. This is the first evidence for fish lectins binding viruses.

Thesis (Ph.D.) -- University of Adelaide, School of Medicine, Discipline of Medicine, 2007. / "April 2007" Bibliography: leaves 165-189. Also available in print form.

Thesis (M.A.)--Northern Kentucky University, 2007. / Made available through ProQuest. Publication number: AAT 1441005. ProQuest document ID: 1283974301. Includes bibliographical references (p. 55-56)