Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

Made available in DSpace on 2016-12-23T13:56:00Z (GMT). No. of bitstreams: 1 Bermudes.pdf: 1280638 bytes, checksum: cf675a18fbda30bc9b61e74a1921a53e (MD5) Previous issue date: 2007-07-06 / Intermittent fasting is frequent in medical practice and this condition has been studied as a therapeutic intervention for some diseases. Increased life span and resistance to stress is observed in rodents submitted to intermittent fasting. However there is not much information on the evolution of infections in animals submitted to these diet manipulations. To study the evolution of fecal peritonitis in mice after 72 h fasting or after different time of intermittent fasting. After 72 h of fasting mice were submitted to cecal ligature and puncture or to an intraperitoneal injection of feces (1:6 or 1:9, weight/volume dilutions). Mice submitted to intermittent fasting, three days for two weeks or the day after the other day, during four months, received intraperitoneal injection of feces with the same dilutions. Mortality was evaluated up to 14 days, when the animals were killed to quantify the intraperitonel abscesses. The abscesses were classified with the values one, two or three according they were respectively up two, between two and five or higher than five millimeters in diameter. For each animal a score was obtained by the sum of values originated from the product of the number attributed to the abscesses versus the number of each abscess type. Control mice, paired by gender and age, were submitted to the same procedures. In mice submitted to 72 h fasting or intermittent fasting the signs of septic shock appeared earlier and were more severe, with higher mortality up to 24 h, although the global mortality evaluated by Kaplan-Meyer method was not significant after two weeks. Among the survivors the score of abscesses were significantly lower in mice submitted to fasting, mainly in groups treated with feces 1:9 dilution, in which occurred less mortality. Results demonstrate that acute or intermittent fasting increases the susceptibility to endotoxic shock and induces increased resistance to bacteria, demonstrated by reduction in number and volume of abscesses. / Jejum prolongado não é infrequente na prática médica e períodos intermitentes de jejum vêm sendo estudados como intervenção terapêutica para algumas doenças. Períodos intermitentes de jejum induzem aumento da longevidade e da resistência ao estresse em roedores. No entanto, pouco se conhece sobre o efeito dessas manipulações de dieta na evolução de infecções. Estudar a evolução de peritonite fecal em camundongos após jejum de 72 horas ou após períodos de jejuns intermitentes. Camundongos foram submetidos a jejum de 72 h e em seguida à ligadura e punção do ceco ou à injeção intra-peritoneal de fezes (diluídas a 1:6 ou a 1:9). Camundongos submetidos a jejum intermitente de três dias a cada duas semanas ou em dias alternados, durante quatro meses, foram submetidos a peritonite por injeção intra-peritoneal de fezes com as mesmas diluições. Foi avaliada a mortalidade até duas semanas, quando os animais foram sacrificados para contagem e mensuração dos abscessos intraperitoneais. Os abscessos recebiam os valores 1, 2 ou 3 conforme tivessem até 2, de 2 a 5 ou acima de 5 mm de diâmetro, respectivamente. Um escore para cada animal foi calculado pela soma dos valores obtidos da multiplicação do número de abscessos pelo valor atribuído ao seu tamanho. Animais controle, mantidos em dieta ad libitum , pareados por idade e sexo, foram submetidos aos mesmos procedimentos. Nos animais submetidos ao jejum agudo ou intermitente, as manifestações do choque séptico foram sempre mais precoces e mais graves, com maior mortalidade nas primeiras 48 h, embora nem sempre a diferença na sobrevivência (Kaplan-Meyer) tenha sido significativa. Nos sobreviventes, o escore dos abscessos era significativamente menor nos grupos submetidos a jejum, especialmente quando a peritonite fecal era induzida por injeção mais diluída de fezes (1:9), com menor mortalidade. Os resultados mostram que o jejum agudo ou o jejum intermitente aumentam a susceptibilidade ao choque endotóxico, mas aumenta resistência às bactérias, demonstrada pela menor extensão dos abscessos peritoneais formados.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Feline infectious peritonitis (FIP) is a highly contagious, progressive and invariably fatal viral disease of cats, and occasionally of wild felids, which results from antibody-mediated hypersensitivity reactions (types III and IV) in individuals incapable to produce a cell-mediated immune response. Although the prevalence of FIP is high worldwide, recent anatomopathological studies about this disease are scarce. Furthermore, the microscopic characteristics of the bone marrow of FIP-affected cats do not exist in the available literature. Based on this, the purpose of this dissertation is to describe possible bone marrow lesions seen in spontaneous cases of FIP. Therefore, the bone marrow collected systematically from the femoral diaphysis of 16 cats necropsied in the LPV-UFSM (Santa Maria, RS, Brazil), between January 2000 and June 2017, with a definitive diagnosis of FIP, were evaluated phenotypically (histopathology [hematoxylin and eosin] and histochemistry [Perls reaction]) and immunophenotypically (immunohistochemistry using anti-myeloid [MAC387] and anti-lymphoid [CD79αcy and CD3] markers). The results showed, regardless of the clinicopathological form of the disease (“dry” [noneffusive] or “wet” [effusive]), myeloid hyperplasia; erythroid hipoplasia; megakaryocytic dysplasia (dismegakaryocytopoiesis); and medullary plasmacytosis. In cases of “dry FIP”, but not in those of “wet PIF”, there was bone marrow and hepatic hemosiderosis. These lesions allowed establishing that cats with FIP develop myelodysplasia, a myeloproliferative lesion very similar to that reported in HIV-infected humans. It is suggested that, based on the findings described here, myelodysplasia is considered to be the main cause of hematological abnormalities observed in FIP, especially for non-regenerative anemia and thrombocytopenia, frequently developed by patients. / Peritonite infecciosa felina (PIF) é uma doença marcadamente contagiosa, progressiva e invariavelmente fatal de gatos, ocasionalmente de felideos selvagens, que decorre de uma reação de hipersensibilidade (tipos III e IV) em um indivíduo incapaz de montar uma resposta imune celular adequada. Apesar da prevalência da peritonite infecciosa felina (PIF) ser alta em praticamente o mundo todo, estudos anatomopatológicos recentes acerca dessa doença são escassos. Não obstante, as características microscópicas da medula óssea de gatos com PIF inexistem na literatura consultada. Com base nisso, o objetivo deste estudo é descrever possíveis alterações medulares ósseas vistas em casos espontâneos de PIF. Para isso, as medulas ósseas colhidas sistematicamente da região diafisária dos fêmures de 16 gatos necropsiados no LPV-UFSM (Santa Maria, RS, Brasil), entre janeiro de 2000 e junho de 2017, e que tiveram diagnóstico definitivo de PIF, foram avaliadas fenotípica (histopatologia [hematoxilina e eosina] e histoquímica [reação de Perls]) e imunofenotipicamente (imuno-histoquímica utilizando marcadores anti-mieloide (MAC387) e anti-linfoide (CD79 αcy e CD3). Os resultados permitem afirmar que, independentemente da apresentação clinicopatológica da doença (seca ou úmida), ocorre: 1) hiperplasia mieloide; 2) hipoplasia eritroide, 3) displasia megacariocítica (dismegacariocitopoiese) e 4) plasmocitose medular. Nos casos de PIF seca, mas não naqueles de PIF úmida, há hemossiderose medular óssea e hepática. Essas alterações permitem estabelecer que gatos com PIF desenvolvem mielodisplasia, uma lesão mieloproliferativa muito semelhante àquela relatada em humanos infectados pelo HIV. Sugere-se que a partir dos achados aqui descritos, mielodisplasia seja considerada a principal responsável pelas alterações hematológicas observadas na PIF, especialmente pela anemia e trombocitopenia arregenerativas tão frequentemente desenvolvidas pelos pacientes com essa doença.

Made available in DSpace on 2014-12-17T14:03:42Z (GMT). No. of bitstreams: 1 LucianaFC_DISSERT.pdf: 1219461 bytes, checksum: 86df41deecc523bb278b7a9bc3b86ec9 (MD5) Previous issue date: 2013-03-04 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis / Nos ?ltimos anos a heparina tem sido alvo de diversos estudos que visam ampliar seu uso como agente terap?utico, devido ? sua habilidade de modular a atividade de v?rias prote?nas que desempenham pap?is importantes na regula??o de processos fisiopatol?gicos. Em diversos experimentos e ensaios pr?-cl?nicos, a heparina tem demonstrado papel anti-inflamat?rio. Entretanto, seu uso cl?nico ? limitado, devido ? sua forte atividade anticoagulante e complica??es hemorr?gicas. Por essa raz?o, consider?vel esfor?o tem sido empregado na descoberta de an?logos da heparina (heparin?ide) com reduzidos efeitos colaterais, que retenham as propriedades anti-inflamat?rias da heparina. Nesse contexto, um heparin?ide (HL) obtido da cabe?a do camar?o Litopenaeus vannamei, de semelhan?a estrutural ? heparina, apresentou em estudos pr?vios atividade anti-inflamat?ria em modelo de peritonite aguda, com reduzido efeito anticoagulante in vitro e baixa atividade hemorr?gica. Assim, o presente trabalho teve como objetivo avaliar o efeito deste heparin?ide sobre a resposta inflamat?ria aguda em diferentes tempos (3 ou 6 horas ap?s a indu??o do est?mulo inflamat?rio), utilizando o modelo de peritonite aguda induzida em camundongos. Foi analisado tamb?m o efeito do HL sobre a atividade da elastase, uma enzima envolvida no recrutamento de leuc?citos. Al?m disso, para verificar se as diferentes doses do heparin?ide e da heparina alteram o equil?brio hemost?tico in vivo, foi avaliado o efeito desses compostos sobre o tempo de coagula??o do plasma nos animais submetidos ? inflama??o. Os resultados revelam que em 3 horas, todas as doses do heparin?ide foram capazes de interferir de forma eficiente no processo inflamat?rio agudo sem apresentar efeito anticoagulante e interfer?ncia no equil?brio hemost?tico, ao contr?rio da dose de extrapola??o da heparina que induziu forte hemorragia, al?m de apresentar alta atividade anticoagulante. Entretanto, no tempo de 6 horas ap?s a indu??o da inflama??o, apenas as doses de 0,1 e 1,0 μg/Kg da heparina e 1,0 μg/Kg do heparin?ide mantiveram o efeito antimigrat?rio, sem alterar o equil?brio hemost?tico. Esses resultados indicam que o efeito antimigrat?rio depende do tempo e da dose administrada. O HL e a heparina tamb?m foram capazes de inibir a atividade da enzima elastase. A descoberta desse composto bioativo no cefalot?rax do camar?o poder? despertar grande interesse biotecnol?gico, pois este composto poderia servir como um modelo estrutural interessante para o desenvolvimento de novos agentes terap?uticos espec?ficos para a peritonite

Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

Orientador: Pasqual Barretti / Resumo: A peritoniteé complicação grave e responsável pela maioria dos casos de falência da técnica de diálise peritoneal (DP). Os cocos Gram-positivos são o grupo etiológico principal, sendo os estafilococos coagulase-negativa (ECN) os germes mais comuns e o Staphylococcus aureus(S.aureus), associado a episódios mais graves e commenor frequência de resolução. O conhecimento dos fatores de risco e dospreditoresda sua evolução podem contribuir para a melhoria das estratégias de prevenção e de tratamento. Objetivo:Os objetivos do presente estudo foram avaliar os fatores de risco para o primeiro episódio de peritonite por estafilococos e os fatores associados à resolução e falência da técnica após resolução do episódio de peritonite, em uma grande coorte brasileira de pacientes em DP (BRAZPD). Métodos:De uma coorte de 5707 pacientes incidentes adultos, com mais de 90 dias de tratamento por DP, foram incluídos, entre dezembro de 2004 e novembro de 2011, aqueles que apresentaram um primeiro episódio de peritonite por S. aureus ou ECN. As covariáveis, potencialmente associadas aos desfechos, foram testadas em análise univariada e aquelas com p ≤ 0,10 incluídas no modelo multivariado. Resultados:Durante o seguimento,389pacientes apresentaram um primeiro episódio de peritonite estafilocócica. Destes, 234 foram causados por S. aureus e 155 por ECN. Os grupos que apresentaram peritonite por S. aureus ou por ECN foram semelhantes para a maior parte das características basais. Entre os pacientes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Peritonitis is a serious complication of peritoneal dialysis (PD) and the main cause of technique failure. Gram-positive cocci are the most frequent etiological group, coagulase-negative staphylococci (CNS) are the most common germs, and Staphylococcus aureus (S. aureus) is associated with more severe episodes and lower resolution rate. Objective: The objectives of this study were to evaluate the risk factors for the first episode of staphylococcal peritonitis, and the factors associated with resolution and technique failure after peritonitis episode resolution, in a large Brazilian cohort of PD patients (BRAZPD). Methods: From a cohort of 5707 adult incident patients with more than 90 days of PD treatment, between December 2004 and November 2011, those who had a first episode of S. aureus or CNS peritonitis were included. The covariates potentially associated with the outcomes were tested in univariate analysis and those with p ≤ 0.10 included in the multivariate model. Results: During follow-up, 389 patients had a first episode of staphylococcal peritonitis. Of these, 234 were caused by S. aureus and 155 by CNS. The groups of patients with S. aureus or CNS peritonitis were similar for most baseline characteristics. Among S. aureus peritonitis, there was resolution in 190 (81.2%); technique failure in 41 (21.6%), and episode-related death in 18 (7.7%). In the episodes by CNS, there were 127 resolutions (82.6%); 33 technique failures (25.8%), and 12 episode-related deaths (7.... (Complete abstract click electronic access below) / Doutor

Feline coronavirus (FCoV) is endemic in cat populations worldwide. Persistently, subclinically infected cats play a significant role in spreading the infection. Testing fecal samples of cats may facilitate efforts to decrease the viral burden within a population. Real-time RT-PCR is highly sensitive and specific for the detection of FCoV but must be performed in a fully equipped laboratory. A simple and accurate assay is needed to identify FCoV at the point-of-need. The aim of this study was to develop a rapid FCoV detection assay based on isothermal amplification technology, i.e., reverse transcription-recombinase polymerase amplification (RT-RPA). Primers were designed to target the highly conserved 3′ untranslated region of the 7b gene. Running on a constant temperature of 42 °C, reverse transcription as well as DNA amplification and detection was achieved in a maximum of 15 min. A probit analysis revealed a detection limit of 58.5 RNA copies/reaction. For cross-detection, nucleic acids from 19 viruses were tested. Both RT-RPA and real-time RT-PCR showed cross-detection with canine coronavirus and transmissible gastroenteritis virus, but not with other pathogens. To evaluate clinical performance, RNA was extracted from 39 fecal samples from cats. All samples were tested simultaneously with real-time RT-PCR resulting in a RT-RPA sensitivity and specificity of 90.9% and 100%, respectively. RT-RPA can be considered a promising simple method for rapid detection of FCoV.

Sepsis is the systemic inflammatory response to an infection. Severe sepsis with multi organ failure is one of the commonest causes of admission to intensive care units, and is associated with poor early and late outcomes. The pathophysiology of sepsis is complex, and poorly understood. This is reflected in the limited and contentious treatment options for sepsis. Genetic factors have been shown to be associated with the risk of and subsequent outcomes from infection. However, clear associations with bacterial sepsis are rare, and even when associations are present their functional effects are often unknown. Gene expression signatures in sepsis are investigated in this project using serial samples obtained from patients admitted to intensive care units with community-acquired pneumonia or faecal peritonitis. The evolving gene expression signatures that define the response to sepsis were identified with large changes seen in genes coding for ribosomal proteins RPS4Y1 and RPS26P54. The differences in the sepsis response between the two diagnostic classes were examined. The gene expression predictors of mortality in sepsis were determined and include genes from the class II MHC HLA-DRB4, HLA-DRB5 and the T cell differentiation protein MAL. The effects of important covariates on gene expression were investigated and their impact on survival related expression determined. The findings were confirmed in a validation cohort. A novel clustering of samples representing distinct inflammatory patterns in a clinically homogeneous population of sepsis patients was identified and related to differences in clinical behaviour. The biological relevance of the differentially expressed genes was ascertained by identifying enriched gene sets. The gene expression changes in sepsis were examined in the context of related clinically relevant immune phenomena: the sterile systemic inflammatory response in patients undergoing elective cardiac surgery and the phenomenon of endotoxin tolerance in PBMCs derived from healthy volunteers. The results highlight the complexities of clinical sepsis and identify hypotheses for future investigations.

INTRODUÇÃO: A realização de procedimentos invasivos e o comprometimento da função hepática têm sido apontados como importantes fatores predisponentes à peritonite bacteriana primária (PBE) em pacientes cirróticos. Apesar das bactérias gram-negativas ainda serem os agentes mais freqüentemente isolados, a incidência de infecção por bactérias gram positivas tem aumentado. OBJETIVOS: Analisar os fatores de risco para PBE em pacientes cirróticos e relacionar o perfil da flora infectante do líquido ascítico com o uso de antibióticos. MÉTODOS: Estudo retrospectivo de resultados de 1.114 paracenteses realizadas em 348 pacientes no período de 2005 a 2007 no Departamento de Gastroenterologia do Hospital das Clínicas da Universidade de São Paulo. Foram definidos dois grupos: com e sem PBE, segundo resultado da leucometria do líquido ascítico. Os seguintes fatores foram analisados: aspartato aminotransferase (AST); alanina aminotransferase (ALT); bilirrubinas totais; INR; creatinina; uso do propranolol e sua resposta hemodinâmica; antecedente de hemorragia digestiva alta; choque hipovolêmico; tratamento endoscópico de varizes de esôfago; sondagem vesical; cateteres intravenosos; gravidade da doença hepática (escores de Child-Pugh, MELD e MELD-Na); infecções associadas e o perfil da flora infectante, segundo o uso de antibióticos. RESULTADOS: 852 paracenteses em 303 pacientes foram incluídas. A etiologia mais freqüente da cirrose hepática foi hepatite crônica C (25,4%), seguida por álcool (24,1%). O diagnóstico de PBE foi estabelecido em 82 (9,6%) paracenteses, 27 (33%) da forma clássica e 55 (67%) com cultura negativa. No grupo com PBE, observamos níveis mais elevados de bilirrubinas totais e INR (p<0,0001 e p= 0,0016, respectivamente). Não houve diferença entre os grupos, quanto ao uso de betabloqueadores e risco de PBE (32,9% versus 37,3%, p=0,533) e a resposta hemodinâmica ao propranolol (68,2% versus 70%, p=1,00), assim como em relação às seguintes variáveis: hemorragia digestiva alta (6,1% versus 2,5%, p=0,074), escleroterapia endoscópica (2,4% versus 0,8%, p=0,178), sondagem vesical (4,9% versus 2,3%, p=0,138), cateterismo venoso (2,4% versus 1,7%, p= 0,649). O grupo com PBE apresentou maior percentual de pacientes Child C, 51% versus 37%, (p=0,022) e maior frequência de choque hipovolêmico 2,5% versus 0,3% (p=0,0484). Não houve diferença quanto às infecções associadas (p=1,00). No grupo com PBE, as bactérias gram-positivas foram isoladas em 55,6% e as gram-negativas em 44,4% (p=0,3848). Não houve relação entre a presença de infecção por gram positivos e o uso de quinolonas (p=1,00). O aumento de um ponto no escore MELD aumentou o risco de infecção em 1,059 vezes [IC 95% : 1,0266; 1,0930] ou 6%. Não houve diferença no risco de PBE quando analisamos faixas de valores do MELD. O aumento de um ponto no MELD-Na aumentou o risco de infecção em 1,0283 vezes [IC 95%: 1,0073; 1,0497] ou 2,8%. Entretanto, o aumento de um ponto de MELD-Na na faixa entre 6 e 15 aumentou a probabilidade de infecção em 1,3371vezes [IC 95%: 1,0230; 1,7476], entre 16 e 24 aumentou em 3,2371 vezes [IC 95%: 0,1958; 53,5291] e acima de 24 pontos em 14,2663 vezes [IC 95%: 1,2441; 163,5990]. CONCLUSÕES: Pacientes com PBE apresentaram níveis mais elevados das bilirrubinas e de INR, maior frequência de choque hipovolêmico e maior gravidade da cirrose hepática, avaliada pelos escores Child-Pugh, MELD e MELD-Na, sendo o declínio da função hepática, o principal fator de risco para desenvolvimento de PBE. O uso de betabloqueadores e a resposta hemodinâmica ao propranolol não foram associados à proteção contra PBE. O MELD-Na discriminou o risco de infecção em faixas de pontuação e de gravidade. Não houve diferença significante na frequência de infecção por bactérias gram positivas e gram negativas nos pacientes com PBE. Não observamos relação entre a frequência de infecção por gram positivos e uso de quinolonas / INTRODUCTION: Invasive procedures and the decline of the liver function have been considered predisposing factors for spontaneous bacterial peritonitis (SBP) in cirrhotic patients. In spite of the predominance of gram negative, the incidence of gram positive agents is increasing in literature. OBJETIVES: To analyze the risk factors for SBP in cirrhotic patients and to assess if there is increase in the frequency of infection by gram positive agents, according to the use of antibiotics. METHODS: In this retrospective study, the results of 1.114 paracentesis carried out in 348 patients from 2005 to 2007 in the Department of Gastroenterology of the University of São Paulo were enrolled. According to the result of ascitic fluid leucometry, two groups were formed: with and without SBP. The following factors were assessed: aspartate aminotransferase; alanine aminotransferase; bilirubin; INR; creatinine; use of propranolol and hemodynamic response; previous gastrointestinal hemorrhage; hypovolemic shock; endoscopic therapy of esophageal varices; vesical catheter, indwelling vascular catheter, severity of the underlying liver disease (scores Child-Pugh, MELD and MELD-Na); concurrent bacterial infections and the frequency of gram positive bacteria according to the use of antibiotics. RESULTS: 852 paracentesis performed in 303 patients were included. The most prevalent etiology of cirrhosis was hepatitis C virus infection (25.4%), followed by alcoholic (24.1%). The diagnosis of SBP was established in 82 (9.6%) paracentesis, 27 (33%) of them were classical SBP and 55 (67%) were negative-culture SBP. In the SBP group, we found higher levels of bilirubin and more enlarged INR (p<0.0001 e p= 0.0016, respectively). There was no difference between the groups regarding the risk of SBP and the use of betablockers (32.9% versus 37.3%, p=0.533) or hemodynamic response to propranolol therapy (68.2% versus 70%, p=1.00). The following parameters did not reach statistical significance: gastrointestinal bleeding (6.1% versus 2.5%, p=0.074), endoscopic sclerotherapy of varices (2.4% versus 0.8%, p=0.78), vesical catheters (4.9% versus 2.3%, p=0.138), vascular catheters (2.4% versus 1.7%, p= 0.649). The SBP group had a higher frequency of Child C status patients, 51% versus 37%, (p=0.022) and higher frequency of hypovolemic shock 2.5% versus 0.3% (p=0.0484). There was no difference in the frequency of SBP in patients with or without concurrent bacterial infections (p=1,00). In the SBP group, gram positive staining bacteria were found in 55.6% and gram negative in 44.4% (p=0.3848). We found no relationship between gram positive bacteria infection and the use of quinolones (p=1.00). Every single point increased in the MELD score increased the risk of SBP in 1.059 times [95% IC: 1.0266; 1.0930] or by 6%. There was no significant difference in the odds ratio for SBP according to the stratification of MELD values. Every single point increased in the MELD-Na increased the risk of infection in 1.0283 times [95% IC: 1.0073; 1.0497] or 2.8%. Nevertheless, every point increased in the MELDNa between 6 and 15 increased the probability of infection in 1.3371 times [95%] IC: 1.0230; 1.7476], between 16 and 24 in 3.2371 times [95% IC: 0.1958; 53.5291] and higher than 24 points in 14.2663 times [95% IC: 1.2441; 163.5990]. CONCLUSIONS: Patients with SBP had higher levels of bilirubin and INR, higher frequency of hypovolemic shock and more severe underlying liver cirrhosis, as assessed by the Child-Pugh score, MELD and MELD-Na, indicating that the decline of the liver function is the main risk factor for developing SBP in cirrhosis. The use of betablockers and the hemodynamic response to propranolol were not associated to protection against developing SBP. The odds ratios for developing SBP increased according to the stratification of MELD-Na values, but not according to MELD stratification. There was no significant difference in the frequency of gram positive and gram negative infections in patients with SBP. The use of quinolones was not associated with increased frequency of gram positive infections in this series .