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Sample records for acute streptococcal sepsis

  1. Group B Streptococcal b-Hemolysin Induces Mortality and Liver Injury in Experimental Sepsis

    E-print Network

    Nizet, Victor

    Group B Streptococcal b-Hemolysin Induces Mortality and Liver Injury in Experimental Sepsis Axel microabscesses surrounded by necrotic foci were found exclusively in the livers of HH mutant IN40­infected-hemolysin plays a crucial role in the pathophysiology of GBS sepsis by inducing liver failure and high mortality

  2. Failure of intrapartum antibiotics to prevent culture-proved neonatal group B streptococcal sepsis.

    PubMed

    Ascher, D P; Becker, J A; Yoder, B A; Weisse, M; Waecker, N J; Heroman, W M; Davis, C; Fajardo, J E; Fischer, G W

    1993-01-01

    Early-onset group B streptococci (GBS-EOS) sepsis may be prevented by intrapartum antibiotics administered for GBS maternal colonization, premature labor, or prolonged rupture of membranes. We sought to identify cases of neonatal GBS sepsis after apparent failure of intrapartum chemotherapy and to determine the factors associated with failure of intrapartum antibiotics in these cases. We identified 96 GBS blood culture-positive infants at five military medical centers from 1987 to 1990. Eighteen (18.7%) of these infants had mothers who had received intrapartum antibiotics; 16 of 18 cases were early-onset disease, 15 of which initially had symptoms at less than 1 hour of age. Two infants had late-onset disease develop at 3 weeks of age. At least one perinatal risk factor (prematurity, prolonged rupture of membranes > 12 hours, maternal fever) was present in each of the 16 cases. Indications for intrapartum antibiotics were suspected chorioamnionitis (13 cases), GBS colonization and prolonged rupture of membranes or prematurity (3), and GBS colonization alone (2). Maternal antibiotics included ampicillin (14 cases), cephadyl (1), vancomycin (1), clindamycin (1), and gentamicin alone (1). The median number of doses of ampicillin before delivery was 1 (range, 1 to 21), which was administered at a median of 4 hours (range, 1 to 84) before birth. The mean dose of ampicillin was 1.8 gm/dose (range, 1 to 2 gm/dose). Two of 16 (12.5%) infants with GBS-EOS died as a result of GBS sepsis. In our population of neonates with GBS-EOS, 18.4% (16 of 87) of the infants had positive blood cultures despite intrapartum antibiotics. Intrapartum antibiotics may fail to prevent GBS sepsis in a number of infants born to mothers colonized with GBS or to those with acute chorioamnionitis. PMID:8345385

  3. Acute nonrheumatic streptococcal myocarditis resembling ST-elevation acute myocardial infarction in a young patient

    PubMed Central

    Jurado, Margarita; Porres-Aguilar, Mateo; Olivas-Chacon, Cristina; Porres-Muñoz, Mateo; Mukherjee, Debabrata; Taveras, Juan

    2015-01-01

    Acute myocarditis can be induced by various concomitant disease processes including infections. Most of these cases are viral in origin; however, bacterial infections are also implicated to a lesser degree. Group A streptococcus is a frequent culprit in bacterial-induced myocarditis. Its diagnosis is suspected by the presence of signs and symptoms of rheumatic fever as established by the Jones criteria. The development and refinement of current diagnostic tools has improved our ability to identify specific pathogens. It has been found that group A streptococcus may be responsible for more cases of infection-induced acute myocarditis than previously thought, and often without the clinical features of rheumatic fever. We present the case of a 43-year-old man hospitalized with chest pain that was initially diagnosed as an acute ST-elevation myocardial infarction. Further evaluation confirmed that his chief complaint was due to acute nonrheumatic streptococcal myocarditis. PMID:25829649

  4. Improving Sepsis Management in the Acute Admissions Unit

    PubMed Central

    Adcroft, Laura

    2014-01-01

    Sepsis is a common condition with a major impact on healthcare resources and expenditure. We therefore wanted to investigate and improve how the acute admission unit (AAU) at the Great Western Hospital (GWH) is managing patients who present directly to the unit with sepsis. In order to obtain this information, an audit was undertaken against the College of Emergency Medicine standards used by the emergency department within GWH and across the UK. Data was retrospectively collected for 30 patients with a diagnosis of severe sepsis or septic shock. The notes were scrutinized with regard to the implementation of College of Emergency Medicine standards for the management of sepsis. This meant that performance in the AAU was compared against the emergency department at GWH and national figures. The data collected shows performance is below national standards with regard to documentation of high flow oxygen use (AAU: 24%, ED 100%; national median: 50%; CEM standard 95%), crystalloid fluid boluses (AAU: 52%; ED: 90%; national median: 83%; CEM standard 100%), lactate measurements (AAU: 66%, ED: 93%; national median: 80%; CEM standard 95%), and obtainment of blood cultures (AAU: 52%; ED 73%; national median: 77%; CEM standard: 95%). Only 3% of patients received all six parts of the sepsis bundle. Since auditing in 2012/2013 we have introduced a sepsis proforma based on a current proforma being used within Severn Deanery. This proforma uses the ‘Sepsis Six’ bundle appropriate to ward based care. We have raised awareness of sepsis implications and management through the creation of a ‘sepsis working group’ to educate both junior doctors and nurses. In turn, this has led to education through the use of posters, pocket reference cards, and teaching sessions. Re-audit shows significant improvement in administering all parts of the Sepsis Six bundle and an 8% improvement in patients receiving all six of the bundle.

  5. Improving management of severe sepsis and uptake of sepsis resuscitation bundle in an acute setting

    PubMed Central

    Kafle, Sumitra; Nath, Navdeep

    2014-01-01

    Severe sepsis still remains a major cause of morbidity and mortality, claiming between 36,000 to 64,000 lives annually in the UK, with a mortality rate of 35%.[1,2] The project aims to measure the management of severely septic patients in acute medical unit (AMU) in a district general hospital against best practice guidelines, before and after a set of interventions aiming to optimise patient management and outcomes. All new admissions who met the criteria for sepsis in AMU over a two week period were evaluated. Those who met the criteria for severe sepsis were further analysed. The criteria evaluated were time to first administration of oxygen, intravenous fluids, antibiotics, the taking of blood cultures, other relevant bloods tests (including lactate) and urine output monitoring. A re-audit was completed after the introduction of a set of interventions which included a “sepsis box.” A total of 32 patients (19 Males, 13 Females) were identified in the pre-intervention group. Twenty-two of these patients met the criteria for severe sepsis. Only 15 out of 32 (47%) had their lactate measured. Ten out of 22 (45%) received fluids within an hour. Twelve out of 22 (55%) had their blood culture sample taken after administration of antibiotics and only 12 out of 22 (55%) had antibiotics administrated within an hour of medical assessment. Post-intervention the results however improved dramatically. A total of 30 patients were identified in the post-intervention group (12 Males, 18 Females). Antibiotics administration within an hour went up by 22%. Lactate was performed in 26/30 (87%) patients presented with sepsis compared to 47% in the pre-intervention group. Similarly, identification of severe sepsis, and administration of intravenous fluids also showed improvement ultimately improving patient safety. Following the initial success, the trial was repeated over three months period, which showed sustainable improvement.

  6. Neonatal sepsis

    MedlinePLUS

    ... be caused by bacteria such as Escherichia coli ( E.coli ), Listeria , and some strains of streptococcus. The herpes ... sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics. 2011: 127:817-826.

  7. Contemporary context for early-onset group B streptococcal sepsis of the newborn.

    PubMed

    Cimolai, N; Roscoe, D L

    1995-01-01

    We examined early-onset newborn group B streptococcal (GBS) infection among the population of a large obstetric center in western Canada for the contemporary period 1987 to 1992. Attack rates for "definite" (bacteremic) and "presumptive" (urine group B antigen positive with clinical evidence) GBS infections were 0.85 and 0.90 per 1000. Ten GBS-associated stillbirths were recorded. Seven deaths occurred among bacteremic newborns (18.4%). Using definitions of Boyer and Gotoff, 87.2% of all mothers with infected newborns manifested at least one risk factor, and 69.8% of all febrile pregnancies with either definition of infected newborn and 61.9% of a subset of the same with bacteremic offspring had maternal temperature 38 degrees C or higher prior to delivery. For our population, recommendations for universal antepartum GBS screening and intrapartum prophylaxis must be discussed in the context of an existing low frequency of bacteremic disease and with the understanding that fever in pregnancy may be enough to warrant greater intervention that might further reduce the rate of infection. PMID:7710577

  8. Risk factors and outcome of atypical acute post-streptococcal glomerulonephritis in pediatrics.

    PubMed

    Takeno, Satoru; Wisanuyotin, Suwannee; Jiravuttipong, Apichat; Sirivichayakul, Chukiat; Limkittikul, Kriengsak

    2013-03-01

    We conducted this study to identify the clinical features and risk factors for atypical acute post-streptococcal glomerulonephritis (APSGN). Thirty-five cases of atypical APSGN treated at Srinagarind Hospital during 2002-2009 were compared with 27 typical cases. The clinical symptoms, anti-streptococcal antibody titers, and laboratory data at the first hospital visit were compared between the two groups. A marked elevation in anti-streptolysin O (ASO) titer was seen more commonly in the atypical APSGN group than in the typical APSGN group (p=0.025). Significantly more patients in the atypical APSGN group had a high urine specific gravity, hematuria and pyuria than patients in the typical APSGN group (p<0.01, p<0.031, and p<0.046, respectively). A high ASO titer, high urine specific gravity, severe hematuria and pyuria early in the illness were suggestive of a higher risk for an atypical presentation. PMID:23691638

  9. Sepsis

    MedlinePLUS

    Sepsis is an illness in which the body has a severe response to bacteria or other germs. ... The symptoms of sepsis are not caused by the germs themselves. Instead, chemicals the body releases cause the response. A bacterial infection anywhere ...

  10. Acute ventricular wall thickening: sepsis, thrombotic microangiopathy, or myocarditis?

    PubMed

    De Schryver, Nicolas; Hoton, Delphine; Castanares-Zapatero, Diego; Hantson, Philippe

    2015-01-01

    Background. Acute myocardial oedema has been documented in experimental models of ischemia-reperfusion injury or sepsis and is usually investigated by magnetic resonance imaging. Purpose. We describe a case of acute ventricular wall thickening documented by echocardiography in a patient developing sepsis and thrombotic microangiopathy. Case Description. A 40-year-old woman, with a history of mixed connective tissue disease, was admitted with laryngeal oedema and fever. She developed Streptococcus pneumoniae septicaemia and subsequent laboratory abnormalities were consistent with a thrombotic microangiopathy. Echocardiography revealed an impressive diffuse thickening of the whole myocardium (interventricular septum 18?mm; posterior wall 16?mm) with diffuse hypokinesia and markedly reduced left ventricular ejection fraction (31%). There was also a moderate pericardial effusion. Echocardiography was normal two months before. The patient died from acute heart failure. Macroscopic and microscopic examination of the heart suggested that the ventricular wall thickening was induced by oedematous changes, together with an excess of inflammatory cells. Conclusion. Acute ventricular wall thickening that corresponded to myocardial oedema as a first hypothesis was observed at echocardiography during the course of septicaemia complicated by thrombotic microangiopathy. PMID:25861483

  11. Acute Ventricular Wall Thickening: Sepsis, Thrombotic Microangiopathy, or Myocarditis?

    PubMed Central

    Hoton, Delphine; Castanares-Zapatero, Diego

    2015-01-01

    Background. Acute myocardial oedema has been documented in experimental models of ischemia-reperfusion injury or sepsis and is usually investigated by magnetic resonance imaging. Purpose. We describe a case of acute ventricular wall thickening documented by echocardiography in a patient developing sepsis and thrombotic microangiopathy. Case Description. A 40-year-old woman, with a history of mixed connective tissue disease, was admitted with laryngeal oedema and fever. She developed Streptococcus pneumoniae septicaemia and subsequent laboratory abnormalities were consistent with a thrombotic microangiopathy. Echocardiography revealed an impressive diffuse thickening of the whole myocardium (interventricular septum 18?mm; posterior wall 16?mm) with diffuse hypokinesia and markedly reduced left ventricular ejection fraction (31%). There was also a moderate pericardial effusion. Echocardiography was normal two months before. The patient died from acute heart failure. Macroscopic and microscopic examination of the heart suggested that the ventricular wall thickening was induced by oedematous changes, together with an excess of inflammatory cells. Conclusion. Acute ventricular wall thickening that corresponded to myocardial oedema as a first hypothesis was observed at echocardiography during the course of septicaemia complicated by thrombotic microangiopathy. PMID:25861483

  12. Sepsis

    MedlinePLUS

    ... slower than usual (late sepsis, usually associated with shock) breathing very quickly or difficulty breathing periods where ... tests (including white blood cell counts and blood cultures) are done to see whether bacteria are in ...

  13. Effects of honokiol on sepsis-induced acute kidney injury in an experimental model of sepsis in rats.

    PubMed

    Li, Nan; Xie, Hua; Li, Longkai; Wang, Jing; Fang, Ming; Yang, Ning; Lin, Hongli

    2014-08-01

    Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural product isolated from Magnolia officinalis (Houpo), has been shown to exhibit anti-inflammatory and antioxidant properties. Here, we investigated the effects of honokiol on sepsis-associated AKI in rats subjected to cecal ligation and puncture (CLP). We found that the administration of honokiol improved the survival of septic rats. Periodic acid-Schiff stain revealed that the morphological changes of kidney tissues in CLP rats were restored after honokiol treatment. Furthermore, honokiol reduced CLP-induced oxidative stress and inflammatory cytokine production. The levels of nitric oxide (NO) and inducible NO synthetase (iNOS) were attenuated by honokiol in septic rats. Finally, honokiol inhibited CLP-induced activation of NF-?B signaling in CLP rats. Our findings suggest that honokiol might be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI. PMID:24531855

  14. Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome.

    PubMed

    Toner, Philip; McAuley, Danny Francis; Shyamsundar, Murali

    2015-01-01

    Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS. PMID:26494395

  15. Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis.

    PubMed

    Lee, Icksoo; Hüttemann, Maik

    2014-09-01

    Mitochondrial dysfunction is increasingly recognized as an accomplice in most of the common human diseases including cancer, neurodegeneration, diabetes, ischemia/reperfusion injury as seen in myocardial infarction and stroke, and sepsis. Inflammatory conditions, both acute and chronic, have recently been shown to affect mitochondrial function. We here discuss the role of oxidative phosphorylation (OxPhos), focusing on acute inflammatory conditions, in particular sepsis and experimental sepsis models. We discuss mitochondrial alterations, specifically the suppression of oxidative metabolism and the role of mitochondrial reactive oxygen species in disease pathology. Several signaling pathways including metabolic, proliferative, and cytokine signaling affect mitochondrial function and appear to be important in inflammatory disease conditions. Cytochrome c oxidase (COX) and cytochrome c, the latter of which plays a central role in apoptosis in addition to mitochondrial respiration, serve as examples for the entire OxPhos system since they have been studied in more detail with respect to cell signaling. We propose a model in which inflammatory signaling leads to changes in the phosphorylation state of mitochondrial proteins, including Tyr304 phosphorylation of COX catalytic subunit I. This results in an inhibition of OxPhos, a reduction of the mitochondrial membrane potential, and consequently a lack of energy, which can cause organ failure and death as seen in septic patients. PMID:24905734

  16. Clinical evaluation of sivelestat for acute lung injury/acute respiratory distress syndrome following surgery for abdominal sepsis

    PubMed Central

    Tsuboko, Yoshiaki; Takeda, Shinhiro; Mii, Seiji; Nakazato, Keiko; Tanaka, Keiji; Uchida, Eiji; Sakamoto, Atsuhiro

    2012-01-01

    Background The efficacy of sivelestat in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has not been established. In part, this is due to the wide variety of factors involved in the etiology of ALI/ARDS. In this study, we examined the efficacy of sivelestat in patients with ALI/ARDS associated with abdominal sepsis. Methods The subjects were 49 patients with ALI/ARDS after surgery for abdominal sepsis. The efficacy of sivelestat was retrospectively assessed in two treatment groups, ie, a sivelestat group (n = 34) and a non-sivelestat group (n = 15). Results The sivelestat group showed significant improvements in oxygenation, thrombocytopenia, and multiple organ dysfunction score. The number of ventilator days (6.6 ± 6.1 versus 11.1 ± 8.4 days; P = 0.034) and length of stay in the intensive care unit (8.5 ± 6.2 versus 13.3 ± 9.5 days; P = 0.036) were significantly lower in the sivelestat group. The hospital mortality rate decreased by half in the sivelestat group, but was not significantly different between the two groups. Conclusion Administration of sivelestat to patients with ALI/ARDS following surgery for abdominal sepsis resulted in early improvements of oxygenation and multiple organ dysfunction score, early ventilator weaning, and early discharge from the intensive care unit. PMID:23091371

  17. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

    PubMed Central

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-01-01

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-? and IL-1?, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-? and IL-1? levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI. PMID:26334271

  18. Unusual fungal sepsis of Alternaria alternata in acute lymphoblastic leukaemia in an adult patient.

    PubMed

    Jain, S; Tarai, B; Tuli, P; Das, P

    2015-01-01

    We report a case of unusual fungal sepsis of Alternaria alternata in a patient of acute lymphoblastic leukaemia in 62-year-old male who presented with complaints of 'off and on' fever with decreased oral intake. On evaluation, haemogram showed low platelet count and 68% blast cells in peripheral blood. On flow cytometry of peripheral blood, the gated blasts (approximately 55%) highly express CD45, CD10, CD19, CD22 and condition was diagnosed as acute lymphoblastic leukaemia. He was started on standard induction treatment along with supportive therapies. During the course of treatment, two sets of paired blood cultures were sent 48 h apart. All of blood cultures were done on Bac-T alert 3D system. All of them yielded fungus. The fungus was then grown on Sabouraud's Dextrose agar media. It was identified as A. alternata. The patient condition worsened and later had cardiac arrest in ICU and could not be revived. PMID:26470977

  19. Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis

    PubMed Central

    Mulchandani, Nikhil; Yang, Weng-Lang; Khan, Mohammad Moshahid; Zhang, Fangming; Marambaud, Philippe; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2015-01-01

    Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV. The septic mice treated with AICAR exhibited elevated phosphorylation of AMPK? in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and interleukin-6 (IL-6), compared with the vehicle. Similarly, the expressions of TNF-?, IL-1?, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced. Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment. We further found that the beneficial effects of AICAR on septic mice were diminished in AMPK?2 deficient mice, showing that AMPK mediates these effects. In conclusion, our findings reveal a new functional role of activating AMPK in the CNS to attenuate inflammatory responses and acute lung injury in sepsis. PMID:26252187

  20. STAT3-dependent CXC chemokine formation and neutrophil migration in streptococcal M1 protein-induced acute lung inflammation.

    PubMed

    Zhang, Songen; Hwaiz, Rundk; Luo, Lingtao; Herwald, Heiko; Thorlacius, Henrik

    2015-06-01

    Streptococcus pyogenes cause infections ranging from mild pharyngitis to severe streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, it was hypothesized that STAT3 signaling might be involved in M1 protein-evoked lung inflammation. The STAT3 inhibitor, S3I-201, was administered to male C57Bl/6 mice before iv challenge with M1 protein. Bronchoalveolar fluid and lung tissue were harvested for quantification of STAT3 activity, neutrophil recruitment, edema, and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Levels of IL-6 and HMGB1 were determined in plasma. CXCL2-induced neutrophil chemotaxis was studied in vitro. Administration of S3I-201 markedly reduced M1 protein-provoked STAT3 activity, neutrophil recruitment, edema formation, and inflammatory changes in the lung. In addition, M1 protein significantly increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Treatment with S3I-201 had no effect on M1 protein-induced expression of Mac-1 on neutrophils. In contrast, inhibition of STAT3 activity greatly reduced M1 protein-induced formation of CXC chemokines in the lung. Interestingly, STAT3 inhibition markedly decreased plasma levels of IL-6 and HMGB1 in animals exposed to M1 protein. Moreover, we found that S3I-201 abolished CXCL2-induced neutrophil migration in vitro. In conclusion, these novel findings indicate that STAT3 signaling plays a key role in mediating CXC chemokine production and neutrophil infiltration in M1 protein-induced acute lung inflammation. PMID:25840996

  1. Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis

    PubMed Central

    Lange, Matthias; Szabo, Csaba; Traber, Daniel L.; Horvath, Eszter; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D.; Cox, Robert A.; Schmalstieg, Frank C.; Herndon, David N.; Enkhbaatar, Perenlei

    2015-01-01

    The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure following acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep and were euthanized at 4, 8, 12, 18, and 24 hours postinjury. Additional sheep received sham injury and were euthanized after 24 hours. Pulmonary function was assessed by determination of oxygenation index and pulmonary shunt fraction. In addition, lung tissue was harvested at the respective time points for the measurement of malondialdehyde, interleukin-6 (IL-6), poly(ADP ribose) (PAR), myeloperoxidase, and alveolar polymorphonuclear neutrophil score. The injury induced severe respiratory failure which was associated with an early increase in lipid peroxidation and IL-6 expression. The injury further led to an increase in PAR activity that reached its peak at 12 hours postinjury and declined afterward. In addition, progressive increases in markers of neutrophil accumulation in the lung were observed. The peak of neutrophil accumulation in the lung was associated with a severe depletion of circulating neutrophils. The results from our model may enhance the understanding of the pathophysiological alterations following ALI and sepsis and thus be useful in exploring therapeutic interventions directed at modifying the expression or activation of inflammatory mediators. PMID:22266977

  2. Prevention and treatment of sepsis-induced acute kidney injury: an update.

    PubMed

    Honore, Patrick M; Jacobs, Rita; Hendrickx, Inne; Bagshaw, Sean M; Joannes-Boyau, Olivier; Boer, Willem; De Waele, Elisabeth; Van Gorp, Viola; Spapen, Herbert D

    2015-12-01

    Sepsis-induced acute kidney injury (SAKI) remains an important challenge in critical care medicine. We reviewed current available evidence on prevention and treatment of SAKI with focus on some recent advances and developments. Prevention of SAKI starts with early and ample fluid resuscitation preferentially with crystalloid solutions. Balanced crystalloids have no proven superior benefit. Renal function can be evaluated by measuring lactate clearance rate, renal Doppler, or central venous oxygenation monitoring. Assuring sufficiently high central venous oxygenation most optimally prevents SAKI, especially in the post-operative setting, whereas lactate clearance better assesses mortality risk when SAKI is present. Although the adverse effects of an excessive "kidney afterload" are increasingly recognized, there is actually no consensus regarding an optimal central venous pressure. Noradrenaline is the vasopressor of choice for preventing SAKI. Intra-abdominal hypertension, a potent trigger of AKI in post-operative and trauma patients, should not be neglected in sepsis. Early renal replacement therapy (RRT) is recommended in fluid-overloaded patients' refractory to diuretics but compelling evidence about its usefulness is still lacking. Continuous RRT (CRRT) is advocated, though not sustained by convincing data, as the preferred modality in hemodynamically unstable SAKI. Diuretics should be avoided in the absence of hypervolemia. Antimicrobial dosing during CRRT needs to be thoroughly reconsidered to assure adequate infection control. PMID:26690796

  3. APACHE III Outcome Prediction in Patients Admitted to the Intensive Care Unit with Sepsis Associated Acute Lung Injury

    PubMed Central

    Chen, Lin

    2015-01-01

    Background and objective Acute Physiology and Chronic Health Evaluation (APACHE) III score has been widely used for prediction of clinical outcomes in mixed critically ill patients. However, it has not been validated in patients with sepsis-associated acute lung injury (ALI). The aim of the study was to explore the calibration and predictive value of APACHE III in patients with sepsis-associated ALI. Method The study was a secondary analysis of a prospective randomized controlled trial investigating the efficacy of rosuvastatin in sepsis-associated ALI (Statins for Acutely Injured Lungs from Sepsis, SAILS). The study population was sepsis-related ALI patients. The primary outcome of the current study was the same as in the original trial, 60-day in-hospital mortality, defined as death before hospital discharge, censored 60 days after enrollment. Discrimination of APACHE III was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with its 95% CI. Hosmer-Lemeshow goodness-of-fit statistic was used to assess the calibration of APACHE III. The Brier score was reported to represent the overall performance of APACHE III in predicting outcome. Main results A total of 745 patients were included in the study, including 540 survivors and 205 non-survivors. Non-survivors were significantly older than survivors (59.71±16.17 vs 52.00±15.92 years, p<0.001). The primary causes of ALI were also different between survivors and non-survivors (p = 0.017). Survivors were more likely to have the cause of sepsis than non-survivors (21.2% vs. 15.1%). APACHE III score was higher in non-survivors than in survivors (106.72±27.30 vs. 88.42±26.86; p<0.001). Discrimination of APACHE III to predict mortality in ALI patients was moderate with an AUC of 0.68 (95% confidence interval: 0.64–0.73). Conclusion this study for the first time validated the discrimination of APACHE III in sepsis associated ALI patients. The result shows that APACHE III score has moderate predictive value for in-hospital mortality among adults with sepsis-associated acute lung injury. PMID:26422633

  4. THE EPIDEMIOLOGY OF ACUTE RESPIRATORY DISTRESS SYNDROME IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH SEVERE SEPSIS

    PubMed Central

    Mikkelsen, Mark E.; Shah, Chirag V.; Meyer, Nuala J.; Gaieski, David F.; Lyon, Sarah; Miltiades, Andrea N.; Goyal, Munish; Fuchs, Barry D.; Bellamy, Scarlett L.; Christie, Jason D.

    2013-01-01

    Background Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis and sepsis-associated ARDS is associated with significant morbidity and mortality. To date, no study has directly examined the epidemiology of ARDS in severe sepsis from the earliest presentation to the health care system, the Emergency Department (ED). Methods Single-center retrospective, observational cohort study of 778 adults with severe sepsis presenting to the ED. The primary outcome was the development of ARDS requiring mechanical ventilation during the first 5 hospital days. ARDS was defined using the Berlin definition. We used multivariable logistic regression to identify risk factors associated independently with ARDS development. Results The incidence of ARDS was 6.2% (48 of 778 patients) in the entire cohort. ARDS development varied across the continuum of care: 0.9% of patients fulfilled criteria for ARDS in the ED, 1.4% admitted to the ward developed ARDS, and 8.9% admitted to the ICU developed ARDS. ARDS developed a median of 1 day after admission and was associated with a four-fold higher risk of in-hospital mortality (14% vs. 60%, p<0.001). Independent risk factors associated with increased risk of ARDS development included: intermediate (2–3.9 mmol/L) (p=0.04) and high (? 4) serum lactate levels (p=0.008), lung injury prediction score (LIPS) (p<0.001) and microbiologically-proven infection (p=0.01). Conclusions In patients presenting to the ED with severe sepsis, the rate of sepsis-associated ARDS development varied across the continuum of care. ARDS developed rapidly and was associated with significant mortality. Elevated serum lactate levels in the ED and a recently validated clinical prediction score were independently associated with the development of ARDS in severe sepsis. PMID:23903852

  5. Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study

    PubMed Central

    Venot, Marion; Weis, Lise; Clec’h, Christophe; Darmon, Michael; Allaouchiche, Bernard; Goldgran-Tolédano, Dany; Garrouste-Orgeas, Maité; Adrie, Christophe; Timsit, Jean-François; Azoulay, Elie

    2015-01-01

    Introduction Whether diabetes mellitus increases the risk of acute kidney injury (AKI) during sepsis is controversial. Materials and Methods We used a case-control design to compare the frequency of AKI, use of renal replacement therapy (RRT), and renal recovery in patients who had severe sepsis or septic shock with or without diabetes. The data were from the Outcomerea prospective multicenter database, in which 12 French ICUs enrolled patients admitted between January 1997 and June 2009. Results First, we compared 451 patients with severe sepsis or septic shock and diabetes to 3,277 controls with severe sepsis or septic shock and without diabetes. Then, we compared 318 cases (with diabetes) to 746 matched controls (without diabetes). Diabetic patients did not have a higher frequency of AKI (hazard ratio [HR], 1.18; P = 0.05]) or RRT (HR, 1.09; P = 0.6). However, at discharge, diabetic patients with severe sepsis or septic shock who experienced acute kidney injury during the ICU stay and were discharged alive more often required RRT (9.5% vs. 4.8%; P = 0.02), had higher serum creatinine values (134 vs. 103 µmoL/L; P<0.001) and had less often recovered a creatinine level less than 1.25 fold the basal creatinine (41.1% vs. 60.5%; P<0.001). Conclusions In patients with severe sepsis or septic shock, diabetes is not associated with occurrence of AKI or need for RRT but is an independent risk factor for persistent renal dysfunction in patients who experience AKI during their ICU stay. PMID:26020231

  6. The Immunomodulatory and Therapeutic Effects of Mesenchymal Stromal Cells for Acute Lung Injury and Sepsis.

    PubMed

    Ho, Mirabelle S H; Mei, Shirley H J; Stewart, Duncan J

    2015-11-01

    It is increasingly recognized that immunomodulation represents an important mechanism underlying the benefits of many stem cell therapies, rather than the classical paradigm of transdifferentiation and cell replacement. In the former paradigm, the beneficial effects of cell therapy result from paracrine mechanism(s) and/or cell-cell interaction as opposed to direct engraftment and repair of diseased tissue and/or dysfunctional organs. Depending on the cell type used, components of the secretome, including microRNA (miRNA) and extracellular vesicles, may be able to either activate or suppress the immune system even without direct immune cell contact. Mesenchymal stromal cells (MSCs), also referred to as mesenchymal stem cells, are found not only in the bone marrow, but also in a wide variety of organs and tissues. In addition to any direct stem cell activities, MSCs were the first stem cells recognized to modulate immune response, and therefore they will be the focus of this review. Specifically, MSCs appear to be able to effectively attenuate acute and protracted inflammation via interactions with components of both innate and adaptive immune systems. To date, this capacity has been exploited in a large number of preclinical studies and MSC immunomodulatory therapy has been attempted with various degrees of success in a relatively large number of clinical trials. Here, we will explore the various mechanism employed by MSCs to effect immunosuppression as well as review the current status of its use to treat excessive inflammation in the context of acute lung injury (ALI) and sepsis in both preclinical and clinical settings. PMID:25913273

  7. Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury

    PubMed Central

    Acosta-Herrera, Marialbert; Lorenzo-Diaz, Fabian; Pino-Yanes, Maria; Corrales, Almudena; Valladares, Francisco; Klassert, Tilman E.; Valladares, Basilio; Slevogt, Hortense; Ma, Shwu-Fan

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The ‘response to microorganisms’ was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the ‘neuron projection morphogenesis’ process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection morphogenesis', which have been never anticipated in ALI pathogenesis, promotes lung-protective effects of LVT with high levels of PEEP. PMID:26147972

  8. Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

    PubMed

    Li, Xiaolong; Zhang, Xianxiang; Yang, Enqin; Zhang, Nanyang; Cao, Shougen; Zhou, Yanbing

    2015-09-01

    The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis. PMID:26231659

  9. Prevention of group B streptococcal infection.

    PubMed

    Noya, F J; Baker, C J

    1992-03-01

    Group B streptococci continue to be major perinatal pathogens, both for mothers and their infants, and are associated with significant morbidity, mortality, and its attendant cost to society. Approaches to prevention are directed toward either eliminating exposure to the organism or enhancing host resistance, that is, chemoprophylaxis and immunoprophylaxis. Intrapartum chemoprophylaxis has been shown to effectively interrupt vertical transmission of group B streptococci from the genitally colonized mother to the infant and to decrease the incidence of both maternal and early-onset neonatal group B streptococcal disease. To avoid unnecessarily exposing large numbers of colonized women to antibiotics, only those with defined risk factors should be selected for intrapartum chemoprophylaxis. This regimen is ampicillin given intravenously, 2 g initially at onset of labor or rupture of membranes, followed by 1 g every 4 hours until delivery. Risk factors include premature onset of labor or rupture of membranes before 37 weeks' gestation, rupture of membranes of more than 12 hours, intrapartum fever, group B streptococcal bacteriuria, or having previously delivered an infant with group B streptococcal disease. Detection of anogenital colonization is accomplished either by culture late in the second or early in the third trimester or by intrapartum group B streptococcal antigen testing of vaginal swabs from those previously culture-negative or not cultured. Although this approach combines the advantages of several proposed strategies, it will still miss those cases of group B streptococcal disease developing in the absence of discernible risk factors. Intrapartum prophylaxis does not prevent late-onset group B streptococcal disease. Prenatal and postnatal chemoprophylaxis have not been shown to be effective. Symptomatic infants born to mothers given chemoprophylaxis should be evaluated for neonatal sepsis and treated accordingly. This approach is also suggested for asymptomatic premature infants, those whose mothers have not received adequate prophylaxis or have previously delivered infants with group B streptococcal disease, and for twin siblings of infants developing group B streptococcal disease. Successful implementation of this approach may be limited by the availability and sensitivity of the rapid antigen test used. Immunoprophylaxis, and active immunization in particular, is the most promising method of preventing perinatal group B streptococcal disease in mothers and their infants, including late-onset disease. Immunization of pregnant women with type III polysaccharide vaccine has resulted in adequate provision of functional antibody to the infants born to responders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1578122

  10. The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs.

    PubMed

    Hasegawa, N; Oka, Y; Nakayama, M; Berry, G J; Bursten, S; Rice, G; Raffin, T A

    1997-03-01

    The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury. PMID:9117028

  11. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis

    PubMed Central

    Xu, Chang; Chang, Anthony; Hack, Bradley K.; Eadon, Michael T.; Alper, Seth L.; Cunningham, Patrick N.

    2013-01-01

    Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration perm-selectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-? activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse. PMID:23903370

  12. Effect of Induced Mild Hypothermia on Acid-Base Balance During Experimental Acute Sepsis in Rats.

    PubMed

    Léon, Karelle; Pichavant-Rafini, Karine; Ollivier, Hélène; L'Her, Erwan

    2015-09-01

    The aim of this study was to determine the effect of induced mild hypothermia (34°C) on acid-base balance in septic rats. Twenty-eight male Sprague-Dawley rats median weight 306?g, range 251-333?g were used. After anesthesia and when the target temperature was reached (normothermia: 38°C or induced mild hypothermia: 34°C), sepsis was induced by cecal ligation and perforation. Measurements of cardiopulmonary parameters and blood samples were performed at T0h (occurring immediately after chirurgical procedures), T2h, T4h (at each temperature), and T6h (at 34°C only). Blood oxygen saturation, heart and respiratory rates, arterial blood pH, carbon dioxide partial pressure, sodium, potassium, chloride and calcium concentrations, hematocrit, blood lactate, tumor necrosis factor-? and interleukin-6 concentrations were measured on anesthetized rats. Other parameters such as bicarbonate concentration, hemoglobin concentration, base excess, and anion gap were estimated from measured parameters. Main results showed that an increase in both cytokines concentrations was observed in septic rats compared with sham rats. This increase was less marked at 34°C compared with 38°C. Moreover, sepsis induction led to a marked metabolic acidosis and hypothermia delayed this acidosis. Induced mild hypothermia delays the evolution of cytokines and metabolic acidosis during experimental sepsis. PMID:26083241

  13. Zinc Regulates the Acute Phase Response and Serum Amyloid A Production in Response to Sepsis through JAK-STAT3 Signaling

    PubMed Central

    Liu, Ming-Jie; Bao, Shengying; Napolitano, Jessica R.; Burris, Dara L.; Yu, Lianbo; Tridandapani, Susheela; Knoell, Daren L.

    2014-01-01

    Sepsis rapidly activates the host inflammatory response and acute phase response. Severe sepsis, complicated by multiple organ failure, is associated with overwhelming inflammation and high mortality. We previously observed that zinc (Zn) deficiency significantly increases mortality in a mouse model of polymicrobial sepsis due to over-activation of the inflammatory response. In order to identify potential mechanisms that account for Zn-responsive effects, we generated whole exome expression profiles from the lung tissue of septic mice that were maintained on Zn modified diets. Based on systems analysis, we observed that Zn deficiency enhances the acute phase response and particularly the JAK-STAT3 pathway, resulting in increased serum amyloid A production. In vitro studies of primary hepatocytes and HepG2 cells substantiated that Zn-deficiency augments serum amyloid A production through up-regulation of the JAK-STAT3 and NF-?B pathways. In contrast, Zn inhibited STAT3 activation through the up-regulation of SHP1 activity. Collectively, these findings demonstrate that Zn deficiency enhances the acute phase response through up-regulation of the JAK-STAT3 pathway, thereby perpetuating increased inflammation that may lead to increased morbidity and mortality in response to sepsis. PMID:24732911

  14. Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury

    PubMed Central

    Chen, Hong-Hwa; Chang, Chia-Lo; Lin, Kun-Chen; Sung, Pei-Hsun; Chai, Han-Tan; Zhen, Yen-Yi; Chen, Yi-Ching; Wu, Ying-Chung; Leu, Steve; Tsai, Tzu-Hsien; Chen, Chih-Hung; Chang, Hsueh-Wen; Yip, Hon-Kan

    2014-01-01

    This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-?, NF-?B, MMP-9, MIP-1, IL-1?), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-?) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury. PMID:25360211

  15. Role of high-mobility group box 1 in patients with acute obstructive suppurative cholangitis-induced sepsis

    PubMed Central

    Singh, Akanand; Feng, Yi; Mahato, Nisha; Li, Jinzheng; Wu, Chuanxin; Gong, Jianping

    2015-01-01

    Background High-mobility group box 1 (HMGB1) is a proinflammatory cytokine that plays an active role during the pathogenesis of inflammatory processes. The primary aim of this study was to detect whether HMGB1 is involved in the pathogenesis of acute obstructive suppurative cholangitis (AOSC). Methods We collected peripheral blood samples from 23 patients with AOSC and 23 healthy volunteers who served as normal controls. All participants were tested for HMGB1 mRNA level, HMGB1 protein, tumor necrosis factor alpha (TNF-alpha), and interleukin 10 (IL-10). HMGB1 mRNA levels were tested using real-time polymerase chain reaction. HMGB1 protein expression was measured using Western blot. TNF-alpha and IL-10 were tested using enzyme-linked immunosorbent assay. Results The expression of HMGB1 mRNA and HMGB1 protein was higher in the AOSC group than in the normal controls (P<0.01), and the levels gradually decreased to normal after treatment of the disease (P<0.01). The content of TNF-alpha and IL-10 in peripheral blood of patients with AOSC was significantly higher than that of normal controls (P<0.01) but decreased to normal levels after the necessary treatment (P<0.01). Conclusion The levels of HMGB1 mRNA and HMGB1 protein were elevated in patients with AOSC, which may play an important role in the inflammation of the bile duct and appears to be associated with the development of sepsis. This suggests the importance of monitoring HMGB1 levels in the management of AOSC-induced sepsis. PMID:25792849

  16. Epidemiology of severe sepsis

    PubMed Central

    Mayr, Florian B; Yende, Sachin; Angus, Derek C

    2014-01-01

    Severe sepsis is a leading cause of death in the United States and the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Respiratory tract infections, particularly pneumonia, are the most common site of infection, and associated with the highest mortality. The type of organism causing severe sepsis is an important determinant of outcome, and gram-positive organisms as a cause of sepsis have increased in frequency over time and are now more common than gram-negative infections. Recent studies suggest that acute infections worsen pre-existing chronic diseases or result in new chronic diseases, leading to poor long-term outcomes in acute illness survivors. People of older age, male gender, black race, and preexisting chronic health conditions are particularly prone to develop severe sepsis; hence prevention strategies should be targeted at these vulnerable populations in future studies. PMID:24335434

  17. Zebrafish and Streptococcal Infections.

    PubMed

    Saralahti, A; Rämet, M

    2015-09-01

    Streptococcal bacteria are a versatile group of gram-positive bacteria capable of infecting several host organisms, including humans and fish. Streptococcal species are common colonizers of the human respiratory and gastrointestinal tract, but they also cause some of the most common life-threatening, invasive infections in humans and aquaculture. With its unique characteristics and efficient tools for genetic and imaging applications, the zebrafish (Danio rerio) has emerged as a powerful vertebrate model for infectious diseases. Several zebrafish models introduced so far have shown that zebrafish are suitable models for both zoonotic and human-specific infections. Recently, several zebrafish models mimicking human streptococcal infections have also been developed. These models show great potential in providing novel information about the pathogenic mechanisms and host responses associated with human streptococcal infections. Here, we review the zebrafish infection models for the most relevant streptococcal species: the human-specific Streptococcus pneumoniae and Streptococcus pyogenes, and the zoonotic Streptococcus iniae and Streptococcus agalactiae. The recent success and the future potential of these models for the study of host-pathogen interactions in streptococcal infections are also discussed. PMID:26095827

  18. Case of Catheter Sepsis with Ralstonia gilardii in a Child with Acute Lymphoblastic Leukemia

    PubMed Central

    Wauters, Georges; Claeys, Geert; Verschraegen, Gerda; De Baere, Thierry; Vandecruys, Els; Van Simaey, Leen; De Ganck, Catharine; Vaneechoutte, Mario

    2001-01-01

    Acute lymphoblastic leukemia was diagnosed in a 7-year-old girl. Two months after insertion of a central venous catheter, she developed fever and complained of headache and abdominal pain. Physical examination revealed no focus of infection. A gram-negative nonfermenting bacillus was recurrently cultured from blood. Extensive biochemical testing and 16S ribosomal DNA sequencing led to the identification of Ralstonia gilardii. PMID:11724891

  19. Perinatal group B streptococcal infections.

    PubMed

    Gilbert, G L; Garland, S M

    1983-06-11

    Predisposing factors and clinical presentations associated with early-onset group B streptococcal (GBS) infections in 60 infants were reviewed. Over a three-year period, the incidence of these infections in The Royal Women's Hospital, Melbourne, was 2.0 per 1000 births. The clinical presentation ranged from fulminating sepsis to asymptomatic bacteraemia. In some cases, there was evidence of intrauterine fetal infection, despite intact membranes and a lack of clinical evidence of maternal infection. However, the over-all incidence of fever, before and after delivery, among the mothers of these babies was high. Early, or prophylactic, antibiotic therapy was generally associated with a favourable outcome. None of the infants who died from GBS infections had received antibiotic therapy before the onset of symptoms. The value of routine antenatal screening for vaginal carriage of group B streptococci, and the place of antibiotic prophylaxis, or immunoprophylaxis, are not yet established. However, prophylactic antibiotic therapy in mothers and babies considered to be at risk from GBS infection is recommended. PMID:6343814

  20. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.

    PubMed

    Sepehr, Reyhaneh; Audi, Said H; Maleki, Sepideh; Staniszewski, Kevin; Eis, Annie L; Konduri, Girija G; Ranji, Mahsa

    2013-07-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure. PMID:24672581

  1. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    PubMed Central

    SEPEHR, REYHANEH; AUDI, SAID H.; MALEKI, SEPIDEH; STANISZEWSKI, KEVIN; EIS, ANNIE L.; KONDURI, GIRIJA G.; RANJI, MAHSA

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure. PMID:24672581

  2. Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

    PubMed

    Choudhury, Soumen; Kandasamy, Kannan; Maruti, Bhojane Somnath; Addison, M Pule; Kasa, Jaya Kiran; Darzi, Sazad A; Singh, Thakur Uttam; Parida, Subhashree; Dash, Jeevan Ranjan; Singh, Vishakha; Mishra, Santosh Kumar

    2015-10-15

    Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1? and TNF?) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. PMID:26375251

  3. [Prophylaxis of streptococcic infection in military collectives].

    PubMed

    Belov, A B; Ogarkov, P I

    2010-02-01

    Peculiarities of clinical-epidemiological evidences of streptococcic infection in military collectives determine necessity of improvement of system of epidemiological survey for morbidity by actual streptococcuses and methodology of rational using of complex of sanitarium-prophylaxis (contraepidemic) measures. Microbiological monitoring and immunological screening along with traditional methods of epidemiological diagnostics permit to educe group of risk, epidemic stock of streptococcus and to organize optimal prophylactic measures. Among them the most effective are immunization by 23-valent pneumococcal vaccine in pestholes of acute pneumonia and bicillin-prophylaxis of angine, streptoderma, suppurativy-septic streptococcus and their complications. PMID:20536044

  4. Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-?B-mediated Inflammation.

    PubMed

    Liu, Zhiyong; Shi, Qiao; Liu, Jiao; Abdel-Razek, Osama; Xu, Yongan; Cooney, Robert N; Wang, Guirong

    2015-01-01

    Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24?h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p?

  5. Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-?B-mediated Inflammation

    PubMed Central

    Liu, Zhiyong; Shi, Qiao; Liu, Jiao; Abdel-Razek, Osama; Xu, Yongan; Cooney, Robert N; Wang, Guirong

    2015-01-01

    Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24?h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p?

  6. Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

    PubMed Central

    2013-01-01

    Introduction The pathophysiology of acute kidney injury (AKI) in sepsis is ill defined. We investigated parameters associated with low glomerular filtration, and their predictive value to discriminate transient from intrinsic septic AKI. Methods In 107 sepsis patients, AKI was defined by the Risk, Injury, Failure, Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was defined as RIFLE R, I, or F on the first day evolving to no AKI or not, respectively, over the following 5 days. Fractional excretion of sodium (FENa), urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1) was determined. Results Including versus not including the urinary-output criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and FENGAL were lower in no AKI versus transient AKI when AKI was defined based on creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in those with high versus low fractional sodium excretion, but this was only in patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in patients without AKI. The negative predictive value for either intrinsic AKI or not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92% and 94.5% respectively. Conclusions A low FENa and FEUrea is highly prevalent in the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending AKI than increase in serum creatinine. A combination of a high FENa and a low FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea is strongly predictive of transient AKI. PMID:24119730

  7. ASO titer or not? When to use streptococcal serology: a guide for clinicians.

    PubMed

    Parks, T; Smeesters, P R; Curtis, N; Steer, A C

    2015-05-01

    Clinicians frequently request serologic tests to provide evidence of prior infection by Streptococcus pyogenes, especially when suspecting a diagnosis of acute rheumatic fever or post-streptococcal glomerulonephritis. However, the interpretation of these tests is difficult and should take account of the clinical features, epidemiological setting, and pre-test probability, as well as the specific aspects of the assay. This review details the characteristics of streptococcal serologic assays and provides recommendations for their use and interpretation. PMID:25560708

  8. Pathogenesis of Group A Streptococcal Infections

    PubMed Central

    Cunningham, Madeleine W.

    2000-01-01

    Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. A resurgence of invasive streptococcal diseases and rheumatic fever has appeared in outbreaks over the past 10 years, with a predominant M1 serotype as well as others identified with the outbreaks. emm (M protein) gene sequencing has changed serotyping, and new virulence genes and new virulence regulatory networks have been defined. The emm gene superfamily has expanded to include antiphagocytic molecules and immunoglobulin-binding proteins with common structural features. At least nine superantigens have been characterized, all of which may contribute to toxic streptococcal syndrome. An emerging theme is the dichotomy between skin and throat strains in their epidemiology and genetic makeup. Eleven adhesins have been reported, and surface plasmin-binding proteins have been defined. The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. Vaccine strategies have focused on recombinant M protein and C5a peptidase vaccines, and mucosal vaccine delivery systems are under investigation. PMID:10885988

  9. Post-streptococcal glomerulonephritis (GN)

    MedlinePLUS

    ... body, such as the skin or throat. The strep bacterial infection causes the tiny blood vessels in ... rare complication of these infections. Risk factors include: Strep throat Streptococcal skin infections (such as impetigo )

  10. Sepsis Questions and Answers

    MedlinePLUS

    ... Improving Survival Medical Bibliography Data Reports Related Links Sepsis Questions and Answers Recommend on Facebook Tweet Share ... organ failure, and death. When can you get sepsis? Sepsis can occur to anyone, at any time, ...

  11. Neonatal sepsis: progress towards improved outcomes.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2014-01-01

    Neonates are predisposed to infections during the perinatal period due to multiple exposures and a relatively compromised immune system. The burden of disease attributed to neonatal infections varies by geographic region and maternal and neonatal risk factors. Worldwide, it is estimated that more than 1.4 million neonatal deaths annually are the consequence of invasive infections. Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal colonization, prolonged rupture of membranes, and maternal intra-amniotic infection. Intrapartum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections. Active surveillance has identified Gram-negative pathogens as an emerging etiology of early-onset invasive infections. Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents. Prophylactic fluconazole administration to very low birthweight (VLBW) neonates during the first 6 weeks of life reduces invasive candidiasis in neonatal intensive care units with high rates of fungal infection. Prevention of healthcare associated infections through antimicrobial stewardship, limited steroid use, early enteral feeding, limited use of invasive devices and standardization of catheter care practices, and meticulous hand hygiene are important and cost-effective strategies for reducing the burden of late-onset neonatal sepsis. PMID:24140138

  12. Neonatal streptococcal infections.

    PubMed Central

    Parker, M. T.

    1977-01-01

    Most serious neonatal streptococcal infections are caused by group-B streptococci. The pattern of serious group-B neonatal disease in Britain resembles that described in other countries; both "early-onset" and "late-onset" forms are seen, but reliable incidence rates have not yet been determined. Serological-type III strains predominate in neonatal meningitis in Britain, but not so markedly as in some parts of the U.S.A. A deficiency of group-II strains in meningitis is, however, apparent in both countries. Present information about the carriage of group-B streptococci suggests that antibiotic prophylaxis administered to mothers or infants is unlikely to reduce greatly the frequency of "early-onset" disease. The continuous presence of a suitable chemical disinfectant in the vagina during labour might be more effective. Insufficient is known about the epidemiology of "late-onset" neonatal disease for rational preventive measures to be designed. More information is required about the postnatal acquisition of group-B streptococci by neonates and its sources, and about passive transfer of type-specific antibody from the mother to her child. PMID:339212

  13. Staphylococcal and Streptococcal Superantigen Exotoxins

    PubMed Central

    Spaulding, Adam R.; Salgado-Pabón, Wilmara; Kohler, Petra L.; Horswill, Alexander R.; Leung, Donald Y. M.

    2013-01-01

    SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies. PMID:23824366

  14. Two cases of delayed diagnosis of postpartal streptococcal toxic shock syndrome.

    PubMed Central

    Schummer, Wolfram; Schummer, Claudia

    2002-01-01

    BACKGROUND: Puerperal sepsis due to group A beta-hemolytic streptococcal (GAS) toxic shock syndrome is associated with very high morbidity and mortality. Luckily it is now rare, but diagnosis is not always easy. This report demonstrates the problem of recognizing this disease, and summarizes the current knowledge on the pathomechanism and management of streptococcal toxic shock syndrome. CASE: Two cases of postpartum streptococcal toxic shock syndrome due to GAS are described. In both cases the correct diagnosis was delayed for several days. The first patient was sent home with the diagnosis of German measles; the second patient was transferred to our neurological intensive care unit with the diagnosis of meningitis. Both patients were admitted to the intensive care unit in profound shock, both developed multiple organ failure, and one patient died. CONCLUSIONS: GAS may produce virulence factors that cause host tissue pathology. Besides aggressive modern intensive care treatment, early diagnosis and correct choice of anti-streptococcal antibiotics are crucial. A possible adverse effect of non-steroidal anti-inflammatory agents requires confirmation in a multicenter study. PMID:12648316

  15. Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

    PubMed

    Delano, Matthew J; Ward, Peter A

    2016-01-01

    Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved. PMID:26727230

  16. Lancefield group C streptococcal endocarditis

    PubMed Central

    Finnegan, P.; Fitzgerald, M. X. M.; Cumming, G.; Geddes, A. M.

    1974-01-01

    Finnegan, P., Fitzgerald, M. X. M., Cumming, G., and Geddes, A. M. (1974).Thorax, 29, 245-247. Lancefield group C streptococcal endocarditis. Three cases of endocarditis due to Lancefield group C streptococcus are reported. These organisms are of low pathogenicity and they are infrequently responsible for infection in man. The cases reported emphasize, however, that they may cause serious and fatal illness. PMID:4831529

  17. CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

    PubMed Central

    Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

    2015-01-01

    Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

  18. Diagnosis of streptococcal pharyngotonsillitis in children and adolescents: clinical picture limitations?

    PubMed Central

    Barbosa, Aurelino Rocha; Oliveira, Cláudia Di Lorenzo; Fontes, Maria Jussara Fernandes; Lasmar, Laura Maria de Lima Bezário Facury; Camargos, Paulo Augusto Moreira

    2014-01-01

    OBJECTIVE: To assess the utility of clinical features for diagnosis of streptococcal pharyngotonsillitis in pediatrics. METHODS: A total of 335 children aged 1-18 years old and presenting clinical manifestations of acute pharyngotonsillitis (APT) were subjected to clinical interviews, physical examinations, and throat swab specimen collection to perform cultures and latex particle agglutination tests (LPATs) for group A streptococcus (GAS) detection. Signs and symptoms of patients were compared to their throat cultures and LPATs results. A clinical score was designed based on the multivariate logistic regression analysis and also was compared to throat cultures and LPATs results. Positive throat cultures and/or LPATs results were used as a reference standard to establish definitive streptococcal APT diagnosis. RESULTS: 78 children (23.4%) showed positivity for GAS in at least one of the two diagnostic tests. Coryza absence (odds ratio [OR]=1.80; p=0.040), conjunctivitis absence (OR=2.47; p=0.029), pharyngeal erythema (OR=3.99; p=0.006), pharyngeal exudate (OR=2.02; p=0.011), and tonsillar swelling (OR=2.60; p=0.007) were significantly associated with streptococcal pharyngotonsilitis. The highest clinical score, characterized by coryza absense, pharyngeal exudate, and pharyngeal erythema had a 45.6% sensitivity, a 74.5% especificity, and a likelihood ratio of 1.79 for streptococcal pharyngotonsilitis. CONCLUSIONS: Clinical presentation should not be used to confirm streptococcal pharyngotonsilitis, because its performance as a diagnostic test is low. Thus, it is necessary to enhance laboratory test availability, especially of LPATs that allow an acurate and fast diagnosis of streptococcal pharyngotonsilitis. PMID:25510990

  19. Streptococcal toxic shock syndrome complicating a peritonsillar abscess.

    PubMed

    Aalling, Mathilde; Klug, Tejs Ehlers

    2015-02-01

    A 68-year-old man was admitted to hospital in an acute confusional state with a 2-week history of fever, influenza-like illness and sore throat. He quickly developed coagulation disturbances, hypotension and renal function impairment. Despite broad-spectrum antibiotic therapy, he deteriorated. Group A streptococcus (GAS) was recovered from blood cultures, which gave the diagnosis streptococcal toxic shock syndrome (STSS). A computed tomography scan showed a right-sided peritonsillar abscess (PTA). Acute tonsillectomy was carried out and the patient recovered. STSS complicating PTA has not previously been described in the literature, but GAS is a common pathogen in PTA. Clinicians should be aware that STSS can develop secondary to tonsillar infections and that abscess development should be suspected in STSS patients who do not respond to antibiotic treatment. PMID:25342572

  20. Streptococcal infection, Tourette syndrome, and OCD

    PubMed Central

    Schrag, A; Gilbert, R; Giovannoni, G; Robertson, M M.; Metcalfe, C; Ben-Shlomo, Y

    2009-01-01

    Background: A causal relationship of common streptococcal infections and childhood neuropsychiatric disorders has been postulated. Objective: To test the hypothesis of an increased rate of streptococcal infections preceding the onset of neuropsychiatric disorders. Methods: Case-control study of a large primary care database comparing the rate of possible streptococcal infections in patients aged 2–25 years with obsessive-compulsive disorder (OCD), Tourette syndrome (TS), and tics with that in controls matched for age, gender, and practice (20 per case). We also examined the influence of sociodemographic factors. Results: There was no overall increased risk of prior possible streptococcal infection in patients with a diagnosis of OCD, TS, or tics. Subgroup analysis showed that patients with OCD had a slightly higher risk than controls of having had possible streptococcal infections without prescription of antibiotics in the 2 years prior to the onset of OCD (odds ratio 2.59, 95% confidence interval 1.18, 5.69; p = 0.02). Cases with TS or tics were not more likely to come from more affluent or urban areas, but more cases lived in areas with a greater proportion of white population (p value for trend = 0.05). Conclusions: The present study does not support a strong relationship between streptococcal infections and neuropsychiatric syndromes such as obsessive-compulsive disorder and Tourette syndrome. However, it is possible that a weak association (or a stronger association in a small susceptible subpopulation) was not detected due to nondifferential misclassification of exposure and limited statistical power. The data are consistent with previous reports of greater rates of diagnosis of Tourette syndrome or tics in white populations. GLOSSARY CI = confidence interval; GP = general practice; OCD = obsessive-compulsive disorder; OR = odds ratio; PANDAS = pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; SI = streptococcal infection; TS = Tourette syndrome. PMID:19794128

  1. Revising definitions of sepsis

    PubMed Central

    Drewry, Anne M.; Hotchkiss, Richard S.

    2015-01-01

    Standfirst The traditional definition of sepsis requires the presence of at least two systemic inflammatory response syndrome (SIRS) criteria in addition to a suspected or proven infection. A recent large retrospective study, however, suggests that the requirement for two SIRS criteria excludes one in eight patients with severe sepsis. PMID:25917556

  2. Bacterial Sepsis and Meningitis

    E-print Network

    Nizet, Victor

    Bacteriology Group B Streptococci Group A Streptococci Streptococcus Pneumoniae Other Streptococci Enterococcus#12;217 Bacterial Sepsis and Meningitis VICTOR NIZET and JEROME O. KLEIN 6 CHAPTER OUTLINE and Meningitis Characteristics of Infants who Develop Sepsis Nursery Outbreaks or Epidemics Pathogenesis Host

  3. Sepsis in the Neurologic Intensive Care Unit: Epidemiology and Outcome

    PubMed Central

    Sadaka, Farid; Cytron, Margaret A; Fowler, Kimberly; Javaux, Victoria M; O’Brien, Jacklyn

    2015-01-01

    Background Sepsis is a major contributor to mortality in patients admitted to a general intensive care unit (ICU). Early recognition and treatment of sepsis is key in improving outcomes. The epidemiology and outcome of sepsis in neurologic ICU (NeuroICU) has not been evaluated. Methods We retrospectively identified all patients admitted to our 16-bed NeuroICU between June 2009 and December 2013 using the acute physiologic and chronic health evaluation (APACHE) outcomes database. We excluded patients admitted with an infection, such as meningitis, encephalitis, brain or spinal abscess, or with any other infection. We compared NeuroICU patients who did to NeuroICU patients who did not develop sepsis after ICU admission. The diagnosis of sepsis was based on the SCCM/ACCP consensus conference definition. Results There were a total of 2,025 patients, out of which 29 patients (1.4%) developed sepsis. Patients who developed sepsis had a trend towards older age (67 ± 13 vs. 61 ± 11 years, P = 0.07), a trend towards more male gender (69.0% vs. 51.5%, P = 0.07), significantly higher APACHE III scores (58 ± 17 vs. 43 ± 21, P = 0.0001), and significantly higher acute physiologic scores (APS) (43 ± 16 vs. 32 ± 18, P = 0.001) than patients who did not develop sepsis. Patients who developed sepsis had higher ICU mortality (41.4% vs. 5.1%, odds ratio (OR) = 13.1; 95% confidence interval (CI), 6.1 - 28.2, P < 0.0001), and higher hospital mortality (44.8% vs. 8.2%, OR = 9.0; 95% CI, 4.3 - 19.0, P < 0.0001). Conclusions Sepsis developed in 1.4% of patients admitted to a NeuroICU. Predictors of sepsis development were comorbidities and worsening acute physiologic variables. Patients who developed sepsis had significantly higher mortality. Vigilance to development of sepsis in NeuroICU is paramount, especially in this era when early recognition and intervention of sepsis significantly improves outcomes. PMID:25368696

  4. Normal Ranges of Streptococcal Antibody Titers Are Similar Whether Streptococci Are Endemic to the Setting or Not ?

    PubMed Central

    Steer, Andrew C.; Vidmar, Suzanna; Ritika, Roselyn; Kado, Joseph; Batzloff, Michael; Jenney, Adam W. J.; Carlin, John B.; Carapetis, Jonathan R.

    2009-01-01

    Group A streptococcal (GAS) serology is used for the diagnosis of post-streptococcal diseases, such as acute rheumatic fever, and occasionally for the diagnosis of streptococcal pharyngitis. Experts recommend that the upper limits of normal for streptococcal serology be determined for individual populations because of differences in the epidemiology of GAS between populations. Therefore, we performed a study to determine the values of the upper limit of normal for anti-streptolysin O (ASO) and anti-DNase B (ADB) titers in Fiji. Participants with a history of GAS disease, including pharyngitis or impetigo, were excluded. A total of 424 serum samples from people of all ages (with a sample enriched for school-aged children) were tested for their ASO and ADB titers. Reference values, including titers that were 80% of the upper limit of normal, were obtained by regression analysis by use of a curve-fitting method instead of the traditional nonparametric approach. Normal values for both the ASO titer and the ADB titer rose sharply during early childhood and then declined gradually with age. The estimated titers that were 80% of the upper limit or normal at age 10 years were 276 IU/ml for ASO and 499 IU/ml for ADB. Data from our study are similar to those found in countries with temperate climates, suggesting that a uniform upper limit of normal for streptococcal serology may be able to be applied globally. PMID:19052157

  5. Immunoreactivity of anti-streptococcal monoclonal antibodies to human heart valves. Evidence for multiple cross-reactive epitopes.

    PubMed Central

    Gulizia, J. M.; Cunningham, M. W.; McManus, B. M.

    1991-01-01

    Association of group A streptococci with acute rheumatic fever and valvular heart disease is well established; however the basis of valve injury remains unclear. In this study, anti-streptococcal monoclonal antibodies (MAbs) cross-reactive with myocardium were reacted with sections from 22 rheumatic valves, nine normal, five endocarditic, one 'floppy,' and one Marfan valve. In immunohistochemical studies, MAb reactivity was observed with cardiac myocytes, smooth muscle cells, cell surface and cytoplasm of endothelial cells lining valves, and valvular interstitial cells. Endothelial basement membrane and elastin fibrils reacted with the MAbs, whereas collagen was unreactive. Similar reactivity was seen with sera from acute rheumatic fever patients. The anti-streptococcal MAbs reacted with intravalvular myosin and vimentin in Western blots, and purified elastin competitively inhibited the binding of the anti-streptococcal MAbs to whole group A streptococci. The data show that human heart valves have numerous sites of immunoreactivity with anti-streptococcal MAbs and acute rheumatic fever sera of potential importance in the pathogenesis of rheumatic valvular injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:1704188

  6. Neuronal Antibody Biomarkers for Sydenham’s Chorea Identify a New Group of Children with Chronic Recurrent Episodic Acute Exacerbations of Tic and Obsessive Compulsive Symptoms Following a Streptococcal Infection

    PubMed Central

    Singer, Harvey S.; Mascaro-Blanco, Adda; Alvarez, Kathy; Morris-Berry, Christina; Kawikova, Ivana; Ben-Pazi, Hilla; Thompson, Carol B.; Ali, Syed F.; Kaplan, Edward L.; Cunningham, Madeleine W.

    2015-01-01

    Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham’s chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A ?-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control’s 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group’s 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform movements and elevated antibodies against D2R; 2) the originally reported group with choreiform movements and elevated anti-D2R antibodies, similar to SC. Increased antibody mediated CaMKII activation was found in both groups and requires further study as a potential biomarker. PMID:25793715

  7. Pharmacological management of sepsis

    SciTech Connect

    Fletcher, J.R.

    1985-01-01

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinical trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.

  8. Sepsis Pathophysiology and Anesthetic Consideration

    PubMed Central

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

    Sepsis remains to be a significant health care issue associated with high mortality and healthcare cost, despite the extensive effort to better understand the pathophysiology of the sepsis. Recently updated clinical guideline for severe sepsis and septic shock, “Surviving Sepsis Campaign 2012”, emphasizes the importance of early goal-directed therapy, which can be implemented in intraoperative management of sepsis patients. Herein, we review the updates of current guideline and discuss its application to anesthesic management. Furthermore, we review the recent advance in knowledge of sepsis pathophysiology, focusing on immune modulation, which may lead to new clinical therapeutic approach to sepsis. PMID:25567335

  9. Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak

    PubMed Central

    Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolomé; Rossi, Marcello; Caylá, Joán A

    2014-01-01

    The aim was to describe an outbreak of group A ?-hemolytic streptococcal pharyngotonsillitis in health care professionals. This is a cross-sectional descriptive study of 17 clients who dined at the same table in a restaurant in Barcelona in July 2012. The frequency, timing and severity of symptoms were analyzed, as were demographic variables and others concerning the food ingested. The attack rate was 58.8%. Six of the 10 clients were positive for group A ?-hemolytic streptococcal. Six of the 13 individuals who handled the food involved in the dinner had symptoms. No association was identified with the food consumed. There is epidemiological evidence of foodborne group A ?-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

  10. Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak.

    PubMed

    Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolomé; Rossi, Marcello; Caylá, Joán A

    2014-04-01

    The aim was to describe an outbreak of group A ?-hemolytic streptococcal pharyngotonsillitis in health care professionals. This is a cross-sectional descriptive study of 17 clients who dined at the same table in a restaurant in Barcelona in July 2012. The frequency, timing and severity of symptoms were analyzed, as were demographic variables and others concerning the food ingested. The attack rate was 58.8%. Six of the 10 clients were positive for group A ?-hemolytic streptococcal. Six of the 13 individuals who handled the food involved in the dinner had symptoms. No association was identified with the food consumed. There is epidemiological evidence of foodborne group A ?-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

  11. Adult Zebrafish model of streptococcal infection

    PubMed Central

    Phelps, Hilary A.; Runft, Donna L.

    2009-01-01

    Streptococcal pathogens cause a wide array of clinical syndromes in humans, including invasive systemic infections resulting in high mortality rates. Many of these pathogens are human specific, and therefore difficult to analyze in vivo using typical animal models, as these models rarely replicate what is observed in human infections. This unit describes the use of the zebrafish (Danio rerio) as an animal model for streptococcal infection to analyze multiple disease states. This model closely mimics the necrotizing fasciitis/myositis pathology observed in humans from a Streptococcus pyogenes infection. The use of a zoonotic pathogen, Streptococcus iniae, which replicates systemic infections caused by many streptococcal pathogens, including dissemination to the brain, is also described. Included protocols describe both intraperitoneal and intramuscular infections, as well as methods for histological and quantitative measurements of infection. PMID:19412913

  12. Streptococcal pharyngitis: an uncommon cause of subdural empyema.

    PubMed

    Walden, Jeffrey Howard; Hess, Bryan; Rigby, Michael

    2015-01-01

    A 7-year-old girl with an unremarkable medical history presented to a local paediatric emergency department with a 7-day history of fever, sore throat and vomiting, and a 1-day history of rash. She was admitted to the hospital, with presumed Kawasaki disease. A few hours after admission, the patient had sudden onset of two witnessed tonic-clonic seizures and subsequent decreased mental status. She was transferred to the paediatric intensive care unit and started on broad-spectrum antibiotics. On hospital day 2, cerebral spinal fluid cultures and blood cultures grew Streptococcus pyogenes, and repeat physical examination was consistent with acute streptococcal pharyngitis. On hospital day 3, the patient developed left-sided hemiparesis and had another witnessed seizure. A CT scan was obtained and revealed a subdural abscess. She was transferred to a tertiary care centre and underwent craniotomy with evacuation of her subdural abscess. Surgical cultures eventually grew S. pyogenes. PMID:26385939

  13. The Pathogenesis of Sepsis

    PubMed Central

    Stearns-Kurosawa, Deborah J.; Osuchowski, Marcin F.; Valentine, Catherine; Kurosawa, Shinichiro; Remick, Daniel G.

    2013-01-01

    Sepsis is a serious clinical condition that represents a patient’s response to a severe infection and has a very high mortality rate. Normal immune and physiologic responses eradicate pathogens, and the pathophysiology of sepsis is due to the inappropriate regulation of these normal reactions. In an ideal scenario, the first pathogen contact with the inflammatory system should eliminate the microbe and quickly return the host to homeostasis. The septic response may accelerate due to continued activation of neutrophils and macrophages/monocytes. Upregulation of lymphocyte costimulatory molecules and rapid lymphocyte apoptosis, delayed apoptosis of neutrophils, and enhanced necrosis of cells/tissues also contribute to the pathogenesis of sepsis. The coagulation system is closely tied to the inflammatory response, with cross talk between the two systems driving the dysregulated response. Biomarkers may be used to help diagnose patients with sepsis, and they may also help to identify patients who would benefit from immunomodulatory therapies. PMID:20887193

  14. IL-35 is elevated in clinical and experimental sepsis and mediates inflammation.

    PubMed

    Cao, Ju; Xu, Fang; Lin, Shihui; Tao, Xintong; Xiang, Yu; Lai, Xiaofei; Zhang, Liping

    2015-12-01

    Sepsis carries considerable morbidity and mortality. IL-35 is a newly described cytokine, which plays a regulatory role in infection and immunity. In this study, we found that IL-35 concentration in serum samples from adult or child patients with sepsis was significantly higher compared with that from healthy controls. IL-35 gradually increased according to sepsis severity. Increased serum IL-35 was associated with LOD (Logistic Organ Dysfunction) or SAPS II (Simplified Acute Physiology Score) scores, and correlated with markers of inflammation. In murine abdominal sepsis, administration of anti-IL-35 p35 antibodies significantly diminished dissemination of the bacteria in septic animals, which was accompanied by enhanced local neutrophil recruitment and early increased release of inflammatory cytokines and chemokines. Therefore, sepsis is associated with enhanced release of IL-35. In abdominal sepsis, IL-35 likely facilitates bacterial dissemination. IL-35 plays a major role in the immunopathogenesis of sepsis. PMID:26342538

  15. Rhabdomyolysis after group C streptococcal infection

    PubMed Central

    Nordal, Hilde Haugedal; Kittang, Bård Reiakvam; Bindoff, Laurence A.

    2010-01-01

    We describe a young woman with a group C streptococcal throat infection complicated by rhabdomyolysis. Muscle biopsy from quadriceps was normal, and molecular studies showed no evidence of direct microbial invasion. This is only the second case in which the usually benign group C streptococcus has been linked with muscle destruction. PMID:24470895

  16. Translational research and biomarkers in neonatal sepsis.

    PubMed

    Delanghe, Joris R; Speeckaert, Marijn M

    2015-12-01

    As neonatal sepsis is a severe condition, there is a call for reliable biomarkers to differentiate between infected and noninfected newborns. Although blood culture has been considered as the gold standard, this analysis is still too slow and limited by false negative results. Use of CRP is hampered by a physiological 3-day increase, resulting in a low sensitivity to detect sepsis at an early stage. A moderate diagnostic accuracy of other acute phase proteins has been demonstrated (serum amyloid A, procalcitonin, lipopolysaccharide binding protein, mannose binding lectin and hepcidin). In neonatal sepsis, changed chemokine/cytokine levels are observed before those of acute phase reactants. High IL-6, IL-8, IL-10 and TNF-? concentrations are detected in infected infants. Soluble interleukin-2 receptor has been used to identify bacteremia, whereas low plasma RANTES concentrations are characteristic for septicemia. Several cell adhesion molecules contribute to the pathogenesis of sepsis. As an upregulated CD64 expression on granulocytes is found within 1-6h after bacterial invasion, serial CD64 measurements could guide antibiotic therapy. An increased CD11b/CD18 density can improve the diagnosis, and a positive correlation between CD11b and the severity of systemic inflammation has been reported. An early increase in sCD14-ST presepsin is also observed during sepsis, whereas high sTREM-1 values in early-onset neonatal sepsis (EOS) have been associated with mortality. Biomarkers resulting from proteomics are also promising. A 4-biomarker 'mass restricted' score has been validated as diagnostic for intra-amniotic infection and/or inflammation. S100A8 in amniotic fluid is a strong predictor of an increased incidence of EOS. Proteomic analysis of cord blood has revealed altered protein expression patterns. The ApoSAA score is useful for identifying sepsis and could guide prescription of antibiotics. (1)H-NMR and GC-MS metabolomics allow to diagnose septic shock, which is associated with increased concentrations of 2-hydroxybutyrate, 2-hydroxyisovalerate, 2-methylglutarate, creatinine, glucose and lactate. PMID:25661089

  17. Group B streptococcal septicemia of the newborn

    MedlinePLUS

    Group B strep; GBS; Neonatal sepsis ... already given birth to a baby with GBS sepsis Mother who has a fever of 100.4° ... Fluids given through a vein Medicines to reverse shock Medicines or procedures to correct blood clotting problems ...

  18. Severe peripartum sepsis.

    PubMed

    Sriskandan, S

    2011-12-01

    Despite global efforts to reduce maternal mortality, maternal deaths from bacterial sepsis have actually risen in the UK. The group A streptococcus, also known as Streptococcus pyogenes, is the leading cause of infection-related death in pregnancy and the puerperium. Many clinicians remain unaware of the risks posed to this particular group of otherwise fit, healthy patients despite the fact that S. pyogenes has been the leading infective cause of puerperal deaths since records began. S. pyogenes has a specific but unexplained predilection for the recently pregnant woman, and has an attributable mortality greater than many other invasive bacteria. Here, the epidemiology, aetiology, and management of severe peripartum sepsis are discussed, as are potential approaches to reduce risks. While fundamental changes in healthcare access can lead to dramatic reductions in maternal deaths in developing countries, an improvement in maternal sepsis deaths in the UK will require heightened awareness among both hospital and community-based clinical staff. PMID:22184573

  19. The failure of biologics in sepsis: where do we stand?

    PubMed

    Giamarellos-Bourboulis, Evangelos J

    2013-06-01

    The failure of the PROWESS-SHOCK study of recombinant human activated protein C (drotrecogin alfa) has generated much scepticism about the future of immunomodulatory interventions in sepsis. This review presents a summary of the few remaining promising strategies for immunointervention. These comprise intravenous clarithromycin, haemoperfusion through a polymyxin B-embedded fibre device (PMX-B), recombinant thrombomodulin (rTM) and intravenous immunoglobulin preparations enriched in IgM and IgA (IgMA). The great heterogeneity in the pathophysiology of sepsis mandates a highly individualised approach. This approach comprises: septic shock and multiple organ dysfunction syndrome arising in the field of ventilator-associated pneumonia as an indication for intravenous clarithromycin; abdominal severe sepsis/shock for PMX-B haemoperfusion; sepsis and acute coagulopathy for rTM; and early septic shock for IgMA. However, specific diagnostic tools should be developed to make this personalised approach more robust. PMID:23664229

  20. Post-infectious group A streptococcal autoimmune syndromes and the heart.

    PubMed

    Martin, William John; Steer, Andrew C; Smeesters, Pierre Robert; Keeble, Joanne; Inouye, Michael; Carapetis, Jonathan; Wicks, Ian P

    2015-08-01

    There is a pressing need to reduce the high global disease burden of rheumatic heart disease (RHD) and its harbinger, acute rheumatic fever (ARF). ARF is a classical example of an autoimmune syndrome and is of particular immunological interest because it follows a known antecedent infection with group A streptococcus (GAS). However, the poorly understood immunopathology of these post-infectious diseases means that, compared to much progress in other immune-mediated diseases, we still lack useful biomarkers, new therapies or an effective vaccine in ARF and RHD. Here, we summarise recent literature on the complex interaction between GAS and the human host that culminates in ARF and the subsequent development of RHD. We contrast ARF with other post-infectious streptococcal immune syndromes - post-streptococcal glomerulonephritis (PSGN) and the still controversial paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), in order to highlight the potential significance of variations in the host immune response to GAS. We discuss a model for the pathogenesis of ARF and RHD in terms of current immunological concepts and the potential for application of in depth "omics" technologies to these ancient scourges. PMID:25891492

  1. Sepsis: an update.

    PubMed

    Siqueira-Batista, Rodrigo; Gomes, Andréia Patrícia; Calixto-Lima, Larissa; Vitorino, Rodrigo Roger; Perez, Mario Castro Alvarez; Mendonça, Eduardo Gomes de; Oliveira, Maria Goreti de Almeida; Geller, Mauro

    2011-06-01

    This paper aims to provide an update on the main aspects of sepsis, a very relevant health care issue. A number of hypotheses have been proposed to explain its origin, involving interactions between microorganisms and the innate immune system, inflammation/immune mediation and the coagulation system. The clinical features of sepsis are variable and depend on the primary site of infection. The identification of early signs and symptoms is crucial for starting therapeutic measures fundamentally based on volume resuscitation, antibiotic therapy, use of steroids, anticoagulant therapy, biologic viability maintenance interventions and nutritional support. PMID:25299722

  2. The diagnosis of sepsis revisited - a challenge for young medical scientists in the 21st century

    PubMed Central

    2014-01-01

    In 1991, a well-meaning consensus group of thought leaders derived a simple definition for sepsis which required the breach of only a few static thresholds. More than 20 years later, this simple definition has calcified to become the gold standard for sepsis protocols and research. Yet sepsis clearly comprises a complex, dynamic, and relational distortion of human life. Given the profound scope of the loss of life worldwide, there is a need to disengage from the simple concepts of the past. There is an acute need to develop 21st century approaches which engage sepsis in its true form, as a complex, dynamic, and relational pattern of death. PMID:24383420

  3. Medical treatment of multiple streptococcal liver abscesses

    SciTech Connect

    Matlow, A.; Vellend, H.

    1983-04-01

    We describe four cases of multiple, cryptogenic, and streptococcal liver abscesses which were cured with antibiotic therapy. Two of the patients were referred for medical management as a last resort after open surgical drainage failed to eradicate the suppurative process. The other two patients were treated from the time of diagnosis with antimicrobial agents alone. Blood cultures or needle aspirates of the abscesses yielded a pure growth of streptococci in all instances. All isolates were susceptible to penicillin G. Cryptogenic streptococcal abscesses may represent a subset of multiple hepatic abscesses particularly amenable to successful medical therapy consisting of a minimum of 6 weeks parenteral antibiotic therapy followed by a period of oral antibiotics until clinical, biochemical, and radiological resolution of the abscesses has occurred.

  4. Management of invasive group A streptococcal infections.

    PubMed

    Waddington, Claire S; Snelling, Thomas L; Carapetis, Jonathan R

    2014-11-01

    Invasive group A streptococcal (GAS) disease in children includes deep soft tissue infection, bacteraemia, bacteraemic pneumonia, meningitis and osteomyelitis. The expression of toxins and super antigens by GAS can complicate infection by triggering an overwhelming systemic inflammatory response, referred to as streptococcal toxic shock syndrome (STSS). The onset and progression of GAS disease can be rapid, and the associated mortality high. Prompt antibiotics therapy and early surgical debridement of infected tissue are essential. Adjunctive therapy with intravenous immunoglobulin and hyperbaric therapy may improve outcomes in severe disease. Nosocomial outbreaks and secondary cases in close personal contacts are not uncommon; infection control measures and consideration of prophylactic antibiotics to those at high risk are important aspects of disease control. To reduce a substantial part of the global burden of GAS disease, an affordable GAS vaccine with efficacy against a broad number of strains is needed. PMID:25307276

  5. Revisiting caspases in sepsis

    PubMed Central

    Aziz, M; Jacob, A; Wang, P

    2014-01-01

    Sepsis is a life-threatening illness that occurs due to an abnormal host immune network which extends through the initial widespread and overwhelming inflammation, and culminates at the late stage of immunosupression. Recently, interest has been shifted toward therapies aimed at reversing the accompanying periods of immune suppression. Studies in experimental animals and critically ill patients have demonstrated that increased apoptosis of lymphoid organs and some parenchymal tissues contributes to this immune suppression, anergy and organ dysfunction. Immediate to the discoveries of the intracellular proteases, caspases for the induction of apoptosis and inflammation, and their striking roles in sepsis have been focused elaborately in a number of original and review articles. Here we revisited the different aspects of caspases in terms of apoptosis, pyroptosis, necroptosis and inflammation and focused their links in sepsis by reviewing several recent findings. In addition, we have documented striking perspectives which not only rewrite the pathophysiology, but also modernize our understanding for developing novel therapeutics against sepsis. PMID:25412304

  6. Sepsis Associated Encephalopathy

    PubMed Central

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

    Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis. PMID:26556425

  7. Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

    PubMed Central

    Acosta, Colleen D.; Kurinczuk, Jennifer J.; Lucas, D. Nuala; Tuffnell, Derek J.; Sellers, Susan; Knight, Marian

    2014-01-01

    Background In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. Methods and Findings A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR?=?1.82; 95% CI 1.82–2.51), were primiparous (aOR?=?1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR?=?1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR?=?12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR?=?2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR?=?3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR?=?8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range?=?1–7 d). Multiple pregnancy (aOR?=?5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR?=?4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%). Conclusions For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors' Summary PMID:25003759

  8. Streptococcal group B type antigen X in group L streptococci.

    PubMed Central

    Lämmler, C; Gürtürk, K; Blobel, H

    1987-01-01

    Extracts from 19 of 29 group L streptococcal cultures reacted distinctly with antiserum against group B streptococcal type antigen X in coagglutination and immunodiffusion tests. The X antigen corresponded to those obtained by streptococci of serological groups B and G. Images PMID:3116039

  9. New paradigms in sepsis: from prevention to protection of failing microcirculation.

    PubMed

    Hawiger, J; Veach, R A; Zienkiewicz, J

    2015-10-01

    Sepsis, also known as septicemia, is one of the 10 leading causes of death worldwide. The rising tide of sepsis due to bacterial, fungal and viral infections cannot be stemmed by current antimicrobial therapies and supportive measures. New paradigms for the mechanism and resolution of sepsis and consequences for sepsis survivors are emerging. Consistent with Benjamin Franklin's dictum 'an ounce of prevention is worth a pound of cure', sepsis can be prevented by vaccinations against pneumococci and meningococci. Recently, the NIH NHLBI Panel redefined sepsis as 'severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure'. Microvascular endothelial injury underlies sepsis-associated hypotension, edema, disseminated intravascular coagulation, acute respiratory distress syndrome and acute kidney injury. Microbial genome products trigger 'genome wars' in sepsis that reprogram the human genome and culminate in a 'genomic storm' in blood and vascular cells. Sepsis can be averted experimentally by endothelial cytoprotection through targeting nuclear signaling that mediates inflammation and deranged metabolism. Endothelial 'rheostats' (e.g. inhibitors of NF-?B, A20 protein, CRADD/RAIDD protein and microRNAs) regulate endothelial signaling. Physiologic 'extinguishers' (e.g. suppressor of cytokine signaling 3) can be replenished through intracellular protein therapy. Lipid mediators (e.g. resolvin D1) hasten sepsis resolution. As sepsis cases rose from 387 330 in 1996 to 1.1 million in 2011, and are estimated to reach 2 million by 2020 in the US, mortality due to sepsis approaches that of heart attacks and exceeds deaths from stroke. More preventive vaccines and therapeutic measures are urgently needed. PMID:26190521

  10. Sepsis-induced AKI revisited: pathophysiology, prevention and future therapies

    PubMed Central

    Zarbock, Alexander; Gomez, Hernando; Kellum, John A.

    2014-01-01

    Purpose of review Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis is the most common cause of AKI. Considerable evidence now suggests that the pathogenic mechanisms of sepsis-induced AKI are different from those seen in other etiologies of AKI. This review focuses on the recent advances in this area and discusses possible therapeutic interventions that might derive from these new insights into the pathogenesis of sepsis-induced AKI. Recent findings The traditional paradigm that sepsis-induced AKI arises from ischemia has been challenged by recent evidence that total renal blood flow (RBF) in is not universally impaired during sepsis, and AKI can develop in the presence of normal or even increased RBF. Animal and human studies suggest that adaptive responses of tubular epithelial cells to injurious signals are responsible for renal dysfunction. Simultaneously occurring renal inflammation and microcirculatory dysfunction further amplify these mechanisms. Summary An understanding of the pathologic mechanisms of sepsis-induced AKI emphasizes the important role of maladaptive responses to the septic insult. Preventive and therapeutic measures should be based on counteracting these maladaptive responses of tubular epithelial cells, inflammation, and microvascular dysfunction. PMID:25320909

  11. Sepsis-induced Cardiomyopathy

    PubMed Central

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  12. Glycocalyx in Sepsis Resuscitation.

    PubMed

    Chen, Leon

    2016-01-01

    Starling's forces are fundamental to our understanding of physiology. Based on his findings, hydrostatic pressure and oncotic pressure are crucial factors in the movement of intravascular and extravascular fluid. However, new literatures on endothelial glycocalyx, a layer of protective glycoprotein within the vasculature that was first discovered in the 1980s, are reshaping our standard models of Starling's forces. This article examines the nature of the endothelial glycocalyx and why understanding it may change the way we resuscitate patients with sepsis. PMID:26633157

  13. Maternal Sepsis and Septic Shock.

    PubMed

    Chebbo, Ahmad; Tan, Susanna; Kassis, Christelle; Tamura, Leslie; Carlson, Richard W

    2016-01-01

    The year 2015 marked the 200th anniversary of the birth of Ignaz Semmelweis, the Hungarian physician who identified unhygienic practices of physicians as a major cause of childbed fever or puerperal sepsis. Although such practices have largely disappeared as a factor in the development of chorioamnionitis and postpartum or puerperal endometritis, it is appropriate that this article on sepsis in pregnancy acknowledges his contributions to maternal health. This review describes the incidence and mortality of sepsis in pregnancy, methods to identify and define sepsis in this population, including scoring systems, causes, and sites of infection during pregnancy and parturition and management guidelines. PMID:26600449

  14. Development of a mortality prediction formula due to sepsis/severe sepsis in a medical intensive care unit

    PubMed Central

    Mohan, Anant; Shrestha, Prajowl; Guleria, Randeep; Pandey, Ravindra Mohan; Wig, Naveet

    2015-01-01

    Background: Although sepsis is one of the leading causes of mortality in hospitalized patients, information regarding early predictive factors for mortality and morbidity is limited. Materials and Methods: Patients fulfilling the Infectious Disease Society of America criteria of sepsis within the medical intensive care unit (ICU) were included over two years. Apart from baseline hematological, biochemical, and metabolic parameters, Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II and III (SAPS II and SAPS III), and Sequential Organ Function Assessment (SOFA) scores were calculated on day 1 of admission. Patients were followed till death or discharge from the ICU. Results: One hundred patients were enrolled over two years (54% males). The overall mortality was 53%, (69.5% in females, 38.8% in males (P < 0.01). Mortality was 65.7%, 55.7%, and 33.3% in patients with septic shock, severe sepsis, and sepsis, respectively. Patients who died were significantly older than the survivors (mean age, 57.37 ± 20.42 years and 44.29 ± 15.53 years respectively, P < 0.01). Nonsurvivors were significantly more anemic and had higher APACHE II, SAPS II, SAPS III, and SOFA scores. The presence of acute respiratory distress syndrome and renal dysfunction were associated with higher mortality (75% and 70.2%, respectively). There was no significant difference in the duration of mechanical ventilation or ICU stay between survivors and nonsurvivors. On multivariate analysis, significant predictors of mortality with odds ratio greater than 2 included the presence of anemia, SAPS II score greater than 35, SAPS III score greater than 47, and SOFA score greater than 6 at day 1 of admission. Conclusion: Several demographic and laboratory parameters as well as composite critical illness scoring systems are reliable early predictors of mortality in sepsis. A sepsis mortality prediction formula (AIIMS Sepsis Score) based on SAPS II, SAPS III, and SOFA scores and hemoglobin has greater predictive power than these scoring methods individually. Routine use of critical illness scoring systems and a composite mortality prediction formula may provide useful early prognostic information in sepsis/severe sepsis. PMID:26180378

  15. [Epidemiology and pathogenesis of streptococcal infection].

    PubMed

    Köhler, W

    1992-07-01

    The appearance of the "streptococcal toxic shock-like syndrome" led to a growing interest in infections caused by Streptococcus pyogenes (group-A-streptococci). Since 1987 some 800 cases with a lethality of 20% or more were observed. Contrary to toxic scarlet fever the site of primary infection are the lower respiratory tract or soft tissue infections. Erythrogenic toxins and low molecular weight mitogens, inducing cytokines (IL-2, IL-3, IL-6, TNF-alpha, IFN-gamma) seem to be involved in the pathogenesis of these severe infections. Morphologically and culturally the strains isolated from cases of toxic shock-like syndrome cannot be differentiated from isolates of epidemic scarlet fever or sporadic cases. At the same time, when in Scandinavia an epidemic by S.pyogenes type 1 with many cases of toxic shock was observed, the same type caused a scarlet fever epidemic without complications in eastern Germany. Erythrogenic toxin type A or its toxoid, respectively, can be used for successful immunizations of rabbits. Another--antibacterial-immunization can be done with the M-protein of S.pyogenes, which is limited by its type-specificity. Streptococcal vaccination is required especially for developing countries with a high incidence of rheumatic fever. Infections due to Streptococcus agalactiae (group-B streptococci) are often underestimated though they have a first position in septicemia and meningitis of newborns. Taxonomy and nomenclature of streptococci are often changing; a list of the presently known species is presented in table I. PMID:1500078

  16. Streptococcal Infections, Rheumatic Fever and School Health Services.

    ERIC Educational Resources Information Center

    Markowitz, Milton

    1979-01-01

    Because rheumatic fever is a potentially serious complication of a streptococcal sore throat which can lead to permanent heart disease, this article advocates the expansion of school health services in medically underserved areas. (JMF)

  17. Inhibition of Macrophage Migration by Nucleotide-Containing Streptococcal Preparations

    PubMed Central

    Bültmann, B.; Heymer, B.; Schachenmayr, W.; Haferkamp, O.; Schmidt, W. C.

    1973-01-01

    Certain extracts of streptococcal cell walls are known to inhibit macrophage migration in vitro. In this study, we attempted to identify the streptococcal components responsible for this phenomenon. Trypsinized cell walls and cytoplasm from groups A and B streptococci were extracted with hot formamide followed by acetone precipitation. Subsequent gel filtration in aqueous solutions yielded a fraction devoid of C-carbohydrate and containing mostly oligonucleotides, apparently derived from streptococcal cytoplasm. This fraction significantly inhibited the migration of peritoneal exudate cells from rats sensitized to groups A and B streptococci. It was noteworthy that no inhibition of migration was observed with cells from nonsensitized animals or control rats injected with BCG or complete Freund adjuvant. Similarly, no inhibition was obtained with formamide extracts of calf thymus RNA. Although the inhibition does not show specificity for streptococcal groups, it seems to have immunological specificity since prior sensitization with streptococci is required for migration inhibition. PMID:4542963

  18. Effective murolytic solubilization of streptococcal-group-specific antigen.

    PubMed Central

    Lämmler, C; Frede, C; Blobel, H

    1986-01-01

    Streptococcal-group-specific antigens were solubilized with a murolytic enzyme contained in the culture supernatant of Streptomyces globisporus. This facilitated the effective serogrouping of streptococci from humans and animals. PMID:3533993

  19. Surgical wound sepsis

    PubMed Central

    Cruse, P. J. E.

    1970-01-01

    With the help of a surgical nurse and using data-processing techniques, a prospective clinical study was conducted to determine the wound infection rate in two hospitals in Calgary. The overall sepsis rate was 5.2% and the clean wound rate 3.5%. The latter is the more meaningful figure as it allows for comparison between hospitals, specialties and individuals and is a good guide for hospital morbidity reviews. The groundwork for succeeding wound infection is laid in the operating theatre, and it is believed that wound infection would be reduced more by attention to Halsted's principles than by more rigid aseptic techniques. It is estimated that wound sepsis costs the Province of Alberta 1.5 million dollars per year for hospitalization alone. This amounts to roughly $1 per person per year. The annual cost of a prospective study such as the present one is approximately $7000. This is equivalent to the cost of hospitalizing 24 patients with infected wounds for one week (at $300 per week). One dividend of a prospective study is an associated reduction in infection rate. This reduction more than pays for the cost of the program. PMID:5414538

  20. Sepsis and ARDS: The Dark Side of Histones

    PubMed Central

    Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin

    2015-01-01

    Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases. PMID:26609197

  1. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

    PubMed Central

    Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis

    2007-01-01

    Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ? 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C );

  2. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. Methods In this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. Results The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). Conclusion and Significance We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children. PMID:26440279

  3. Sepsis Resuscitation: Consensus and Controversies.

    PubMed

    Montanaro, Nicholas

    2016-01-01

    Sepsis is a malignant intravascular inflammation representing the body's response to overwhelming and life-threatening infection. Sepsis can result in tissue damage, organ failure, and death. Critical care nurses are at the forefront for identifying sepsis and initiating the early goal-directed therapies that are known to improve survival. Among key factors in the successful resuscitation and stabilization of the septic patient are fluid management, establishment and maintenance of a secure airway, judicious use of pharmacological agents, and dynamic adjustments in therapy based on nuances detected in data from clinical monitoring. PMID:26633160

  4. Differential effects of the streptococcal fibronectin-binding protein, FBP54, on adhesion of group A streptococci to human buccal cells and HEp-2 tissue culture cells.

    PubMed Central

    Courtney, H S; Dale, J B; Hasty, D I

    1996-01-01

    We have previously demonstrated that fibronectin mediates streptococcal adhesion to host cells and that streptococci interact primarily with the N-terminal domain of fibronectin. FBP54 is a 54-kDa protein from group A streptococci that binds fibronectin. In this report, we show that the N-terminal domain of fibronectin reacts with FBP54 and preferentially blocks streptococcal adhesion to buccal epithelial cells. FBP54 blocked adhesion to human buccal epithelial cells by 80% in a dose-related fashion. In contrast, FBP54 had little effect on adhesion of group A streptococci to HEp-2 tissue culture cells. The fibronectin-binding domain of FBP54 has been localized to the first 89 N-terminal residues of the protein. Experiments using affinity-purified antibodies to this region indicated that the N terminus of FBP54 is exposed on the surface of streptococci in a manner that can interact with immobilized receptors. Analysis of sera from patients with post-streptococcal glomerulonephritis and acute rheumatic fever indicated that FBP54 is expressed in vivo and is immunogenic in the human host. These data indicate that FBP54 is a streptococcal adhesin that is expressed in the human host and that preferentially mediates adhesion to certain types of human cells. PMID:8698460

  5. Neonatal Sepsis and Inflammatory Mediators

    PubMed Central

    Reis Machado, Juliana; Soave, Danilo Figueiredo; da Silva, Marcos Vinícius; de Menezes, Liliana Borges; Etchebehere, Renata Margarida; Monteiro, Maria Luiza Gonçalves dos Reis; Antônia dos Reis, Marlene; Corrêa, Rosana Rosa Miranda; Celes, Mara Rúbia Nunes

    2014-01-01

    Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion. PMID:25614712

  6. Hyperuricemia: An Early Marker for Severity of Illness in Sepsis

    PubMed Central

    Akbar, Sana R.; Long, Dustin M.; Hussain, Kashif; Alhajhusain, Ahmad; Ahmed, Umair S.; Iqbal, Hafiz I.; Ali, Ailia W.; Leonard, Rachel; Dalton, Cheryl

    2015-01-01

    Background. Uric acid can acutely activate various inflammatory transcription factors. Since high levels of oxyradicals and lower antioxidant levels in septic patients are believed to result in multiorgan failure, uric acid levels could be used as a marker of oxidative stress and poor prognosis in patients with sepsis. Design. We conducted a prospective cohort study on Medical Intensive Care Unit (MICU) patients and hypothesized that elevated uric acid in patients with sepsis is predictive of greater morbidity. The primary end point was the correlation between hyperuricemia and the morbidity rate. Secondary end points were Acute Kidney Injury (AKI), mortality, Acute Respiratory Distress Syndrome (ARDS), and duration of stay. Results. We enrolled 144 patients. 54 (37.5%) had the primary end point of hyperuricemia. The overall morbidity rate was 85.2%. The probability of having hyperuricemia along with AKI was 68.5% and without AKI was 31.5%. Meanwhile the probability of having a uric acid value <7?mg/dL along with AKI was 18.9% and without AKI was 81.1% (p value < 0.0001). Conclusion. We report that elevated uric acid levels on arrival to the MICU in patients with sepsis are associated with poor prognosis. These patients are at an increased risk for AKI and ARDS. PMID:26294973

  7. Antimicrobial Peptides in Human Sepsis

    PubMed Central

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100?years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections. PMID:26347737

  8. Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain

    PubMed Central

    Granger, Jill I.; Ratti, Pietro-Luca; Datta, Subhash C.; Raymond, Richard M.; Opp, Mark R.

    2012-01-01

    Infection negatively impacts mental health, as evidenced by the lethargy, malaise, and cognitive deficits experienced during illness. These changes in central nervous system processes, collectively termed sickness behavior, have been shown in animal models to be mediated primarily by the actions of cytokines in brain. Most studies of sickness behavior to date have used bolus injection of bacterial lipopolysaccharide (LPS) or selective administration of the proinflammatory cytokines interleukin-1? (IL-1?) or IL-6 as the immune challenge. Such models, although useful for determining mechanisms responsible for acute changes in physiology and behavior, do not adequately represent the more complex effects on central nervous system (CNS) processes of a true infection with replicating pathogens. In the present study, we used the cecal ligation and puncture (CLP) model to quantify sepsis-induced alterations in several facets of physiology and behavior of mice. We determined the impact of sepsis on cage activity, body temperature, food and water consumption and body weights of mice. Because cytokines are critical mediators of changes in behavior and temperature regulation during immune challenge, we also quantified sepsis-induced alterations in cytokine mRNA and protein in brain during the acute period of sepsis onset. We now report that cage activity and temperature regulation in mice that survive are altered for up to 23 days after sepsis induction. Food and water consumption are transiently reduced, and body weight is lost during sepsis. Furthermore, sepsis decreases social interactions for 24 – 48 hours. Finally, mRNA and protein for IL-1?, IL-6, and tumor necrosis factor-? (TNF?) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6–72 hour post sepsis induction. Collectively, these data indicate that sepsis not only acutely alters physiology, behavior and cytokine profiles in brain, but that some brain functions are impaired for long periods in animals that survive. PMID:23146654

  9. Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis

    PubMed Central

    Ziegler, Tilman; Horstkotte, Jan; Schwab, Claudia; Pfetsch, Vanessa; Weinmann, Karolina; Dietzel, Steffen; Rohwedder, Ina; Hinkel, Rabea; Gross, Lisa; Lee, Seungmin; Hu, Junhao; Soehnlein, Oliver; Franz, Wolfgang M.; Sperandio, Markus; Pohl, Ulrich; Thomas, Markus; Weber, Christian; Augustin, Hellmut G.; Fässler, Reinhard; Deutsch, Urban; Kupatt, Christian

    2013-01-01

    Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target. PMID:23863629

  10. Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

    PubMed Central

    Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

    2014-01-01

    Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

  11. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePLUS

    ... exit disclaimer . Subscribe Surviving Sepsis Taming a Deadly Immune Response Many people have never heard of sepsis, ... and infants are most vulnerable. People with weakened immune systems, severe burns, physical trauma, or long-term ...

  12. [Acute postinfectious glomerulonephritis].

    PubMed

    Ramdani, Benyounès; Zamd, Mohamed; Hachim, Khadija; Soulami, Kenza; Ezzahidy, Madiha; Souiri, Malika; Fadili, Wafaa; Lahboub, Assia; Hanafi, Leila; Boujida, Meryem; Squalli, Saida; Benkirane, Amal; Benghanem, Mohamed Gharbi; Medkouri, Ghizlane

    2012-07-01

    Acute postinfectious glomerulonephritis are defined by an acute nonsuppurative inflammatory insult predominantly glomerular. Its current incidence is uncertain because of the frequency of subclinical forms. The most common infectious agent involved is beta hemolytic streptococcus group A. Acute postinfectious glomerulonephritis is uncommon in adults, and its incidence is progressively declining in developed countries. Humoral immunity plays a key role in the pathogenesis of kidney damage. Complement activation by the alternative pathway is the dominant mechanism, but a third way (lectin pathway) has been recently identified. The classic clinical presentation is sudden onset of acute nephritic syndrome after a free interval from a streptococcal infection. Treatment is essentially symptomatic and prevention is possible through improved hygiene and early treatment of infections. PMID:22483748

  13. Puerperal and intrapartum group A streptococcal infection.

    PubMed Central

    Anteby, E Y; Yagel, S; Hanoch, J; Shapiro, M; Moses, A E

    1999-01-01

    OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection. PMID:10598916

  14. Microreview Streptococcal toxins: role in pathogenesis and disease

    E-print Network

    Nizet, Victor

    Microreview Streptococcal toxins: role in pathogenesis and disease Timothy C. Barnett,1 Jason N an array of toxins that act against human cells or tissues, resulting in impaired immune responses and subversion of host physiological processes to benefit the invading microorganism. This toxin repertoire

  15. 2012LandesBioscience.Donotdistribute. Study of streptococcal hemoprotein receptor

    E-print Network

    Nizet, Victor

    acquisition and virulence of M1T1 group A streptococcus Samira Dahesh,1 Victor Nizet1,2,3 and Jason N. Cole1: hemoprotein, iron acquisition, iron starvation, laminin-binding, Shr, Streptococcus pyogenes, virulence, whole blood Abbreviations: GAS, group A streptococcus; Shr, streptococcal hemoprotein receptor; Sia

  16. Sepsis and Septic Shock: Lingering Questions.

    PubMed

    Dumont, Tiffany; Francis-Frank, Lyndave; Chong, Josebelo; Balaan, Marvin R

    2016-01-01

    Sepsis and septic shock are major health conditions in the United States, with a high incidence and mortality. The Surviving Sepsis Campaign, which was formed in 2002, formulates guidelines for the management of severe sepsis and septic shock and has actually demonstrated a reduction in mortality with institution of "sepsis bundles." Despite this, some elements of the guidelines have been questioned, and recent data suggest that strict compliance with bundles and protocols may not be necessary. Still, prompt recognition and treatment of sepsis and septic shock remain of utmost importance. PMID:26633153

  17. Scintigraphic evaluation in musculoskeletal sepsis

    SciTech Connect

    Merkel, K.D.; Fitzgerald, R.H. Jr.; Brown, M.L.

    1984-07-01

    In this article, the mechanism of technetium, gallium, and indium-labeled white blood cell localization in septic processes is detailed, and the method of interpretation of these three isotopes with relationship to musculoskeletal infection is outlined. Specific clinical application of technetium, gallium, and indium-labeled white blood cell imaging for musculoskeletal sepsis is reviewed.

  18. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

    PubMed Central

    2012-01-01

    Introduction Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration International Standard Randomized Control Trial Registry ISRCTN64637517. PMID:23232151

  19. Validity of C-reactive protein (CRP) for diagnosis of neonatal sepsis

    PubMed Central

    Hisamuddin, Effat; Hisam, Aliya; Wahid, Sughra; Raza, Ghulam

    2015-01-01

    Objective: To determine the validity of C-reactive protein levels for diagnosis of neonatal sepsis. Methods: A cross sectional (Validation) study was conducted at Neonatology unit in KRL general hospital (emergency/OPD) of 7 months duration from February 2012 to August 2012. By using purposive sampling technique, 147, sample size was calculated by using WHO sample size calculator taking sensitivity 75%, specificity 95%, expected prevalence 50%, desired precision 10% and confidence level 95%. Results: Mean age of the neonates was 5.72 days + 3.86. Male patients were 81(55.1%) while 66(44.9%) were female. Neonatal sepsis was observed in 43(29.25%) and were confirmed through blood culture while 104(70.75%) were not confirmed on blood culture as neonatal sepsis. The sensitivity and specificity of CRP in diagnosis of acute neonatal sepsis was 76.92% and 53.49% respectively while it had a positive predictive value of 80% and negative predictive value of 48.94%. Over all the diagnostic accuracy of CRP in diagnosis of neonatal sepsis was 70.07%. Conclusion: CRP estimation does have a role in the diagnosis of neonatal sepsis but the test is not specific enough to be relied upon as the only indicator. PMID:26150837

  20. Epigenetic coordination of acute systemic inflammation: potential therapeutic targets

    PubMed Central

    Vachharajani, Vidula; Liu, Tiefu; McCall, Charles E.

    2015-01-01

    Epigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator Sirtuin 1 (SIRT-1), a NAD+ sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper and hypo inflammatory responses of sepsis at the microvascular interface, which disseminates inflammatory injury to cause multiple organ failure. Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way treat sepsis by epigenetically restoring immunometabolic homeostasis. PMID:25088223

  1. Molecular basics of sepsis developement.

    PubMed

    Jedynak, Monika; Siemi?tkowski, Andrzej; Rygasiewicz, Karolina

    2012-01-01

    Bacterial infections and sepsis remain major causes of morbidity and mortality in intensive care units. The normal host response to infection is a complex process that serves to localise and control the invasion of microbes and to repair injured tissue. Local inflammatory processes are regulated through the production of cytokines by macrophages. In some cases, mediator release exceeds the boundaries of the local environment and results in the development of sepsis. It is well known that the innate immune system plays a crucial role in preventing microbial invasion. The human innate immune system consists of genetically programmed defence mechanisms that are directed against molecular components found only in microorganisms. Understanding the complexity of early response to infection with respect to innate immune response is required for the future development of drugs that will effectively control infectious diseases. PMID:23348491

  2. Streptococcus milleri and surgical sepsis.

    PubMed Central

    Tresadern, J. C.; Farrand, R. J.; Irving, M. H.

    1983-01-01

    For many years Viridans streptococci have been considered as commensal organisms in a wide variety of sites in the human body and only regarded as significant pathogens in subacute bacterial endocarditis. However, in recent years some reports have suggested that a particular species, Streptococcus milleri, can be a virulent pathogen, producing life-threatening sepsis particularly in surgical patients. We review here our experience of this organism in 23 general surgical patients over a 3 year period, and postulate that prophylactic use of antibiotic combinations such as gentamicin and metronidazole in patients undergoing colo-rectal surgery may be a factor promoting its emergence as a significant pathogen. Patients with established sepsis due to Streptococcus milleri should be considered for long-term antibiotic therapy as part of the treatment of their abscesses. PMID:6830135

  3. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-?), and tumor necrosis factor alpha (TNF-?), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  4. Clinical review: Corticotherapy in sepsis

    PubMed Central

    Prigent, Helene; Maxime, Virginie; Annane, Djillali

    2004-01-01

    The use of glucocorticoids (corticotherapy) in severe sepsis is one of the main controversial issues in critical care medicine. These agents were commonly used to treat sepsis until the end of the 1980s, when several randomized trials casted serious doubt on any benefit from high-dose glucocorticoids. Later, important progress in our understanding of the role played by the hypothalamic–pituitary–adrenal axis in the response to sepsis, and of the mechanisms of action of glucocorticoids led us to reconsider their use in septic shock. The present review summarizes the basics of the physiological response of the hypothalamic–pituitary–adrenal axis to stress, including regulation of glucocorticoid synthesis, the cellular mechanisms of action of glucocorticoids, and how they influence metabolism, cardiovascular homeostasis and the immune system. The concepts of adrenal insufficiency and peripheral glucocorticoid resistance are developed, and the main experimental and clinical data that support the use of low-dose glucocorticoids in septic shock are discussed. Finally, we propose a decision tree for diagnosis of adrenal insufficiency and institution of cortisol replacement therapy. PMID:15025773

  5. Enhanced expression of cell-specific surface antigens on endothelial microparticles in sepsis-induced disseminated intravascular coagulation.

    PubMed

    Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

    2015-05-01

    Sepsis-induced disseminated intravascular coagulation (DIC) is a major cause of death in patients admitted to intensive care units. Endothelial injury with microparticle production is reported in the pathogenesis of sepsis. Endothelial microparticles (EMPs) present several cell-specific surface antigens with different bioactivities, for example, tissue factor (TF), thrombomodulin (TM), and endothelial protein C receptor (EPCR). We investigated associations between these three different surface antigen-positive EMPs and sepsis-induced DIC. This cross-sectional study composed of 24 patients with sepsis and 23 healthy controls was conducted from November 2012 to September 2013. Blood samples were collected from patients within 24 h of diagnosis of severe sepsis and from healthy controls. Numbers of TF-positive EMPs (TF EMPs), TM-positive EMPs (TM EMPs), and EPCR-positive EMPs (EPCR EMPs) were measured by flow cytometry immediately thereafter. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were assessed in the severe sepsis patients at enrollment. We assessed DIC with the International Society of Thrombosis and Haemostasis (ISTH) overt DIC diagnostic criteria algorithm. Numbers of antigen-positive EMPs were increased significantly in both severe sepsis patients and controls and with the increase in ISTH DIC score. Numbers of TF EMPs and EPCR EMPs correlated significantly with Sequential Organ Failure Assessment score, and numbers of EPCR EMPs correlated significantly with Acute Physiology and Chronic Health Evaluation II score. Numbers of the three antigen-positive EMPs were increased significantly in severe sepsis patients versus those in healthy controls and with the increase of ISTH DIC score, suggesting that the specific bioactivity of each antigen-positive EMP may play a role in the progression of sepsis-induced DIC. PMID:25608138

  6. Early detection and markers of sepsis.

    PubMed

    Parsons, P E; Moss, M

    1996-06-01

    In vitro and animal models of sepsis have provided a template for studies of the pathogenesis of sepsis in patients at risk for and with the syndrome. Numerous potential markers have been identified in these models and then looked for in patients. No single marker or combination of markers convincingly identifies sepsis, predicts the development of sepsis, predicts the development of complications of sepsis, or predicts mortality. As discussed, the clinical studies have been complicated by many confounding variables, including the lack of adherence to rigorous definitions, differences in assay methods, differences in timing of the studies, and differences in outcome variables analyzed. In spite of the limitations, the studies have been critical in helping determine the pathogenesis of sepsis in humans. As new mediators and modulators of inflammation are identified, it will be important to study their role as markers, individually and in combination, in human disease. PMID:8792061

  7. Purification and properties of streptococcal nicotinamide adenine dinucleotide glycohydrolase.

    PubMed Central

    Grushoff, P S; Shany, S; Bernheimer, A W

    1975-01-01

    Highly purified streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) was obtained by utilizing disodium tetrathionate to protect the enzyme by blocking the sulfhydryl groups of streptococcal proteinase. This was followed by two-step ion-exchange chromatography. The pure enzyme, demonstrated as a single band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, had a specific activity of 11,200 NADase units per mg of protein and was devoid of hemolytic activity. NADase had a molecular weight of about 55,000 as determined by gel filtration, by summation of amino acid residues, and by sodium dodecyl sulfate/gel electrophoresis. The purified enzyme had optimal activity at pH 7.3 and at 40 C and a calculated Km of 5.1 times 10- minus 4 mM. It was inhibited by alpha-iodoacetamide. Images PMID:236282

  8. Antitumour effects of streptococcal lipoteichoic acids on Meth A fibrosarcoma.

    PubMed Central

    Usami, H.; Yamamoto, A.; Yamashita, W.; Sugawara, Y.; Hamada, S.; Yamamoto, T.; Kato, K.; Kokeguchi, S.; Ohokuni, H.; Kotani, S.

    1988-01-01

    The antitumour effects of lipoteichoic acids (LTA) extracted from Streptococcus pyogenes were studied in comparison with other streptococcal cellular components. LTA suppressed the tumour growth of both solid- and ascites-type Meth A fibrosarcoma as did the whole cells of S. pyogenes (OK-432). No other cellular components, such as cell wall peptidoglycan, group-specific C-carbohydrate or type-specific M protein, suppressed the growth of Meth A. LTA, but not the other cellular components, induced tumour necrosis factor (TNF) in Propionibacterium acnes-primed mice. LTA had no direct killing effects on Meth A cells. These results indicate that LTA may be an important antitumour component of OK-432 and that one of the antitumour mechanisms by this streptococcal preparation is the induction of TNF. PMID:3279996

  9. The Cold-Inducible RNA-Binding Protein (CIRP) Level in Peripheral Blood Predicts Sepsis Outcome

    PubMed Central

    Zhou, Yanyan; Dong, Haiyun; Zhong, Yanjun; Huang, Jia; Lv, Jianlei; Li, Jinxiu

    2015-01-01

    Objectives Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%). Design Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA. Results The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37–30.17) ng/mL and 1.68 (1.41–13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage. Conclusion An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis. PMID:26361390

  10. Clinical aspects of sepsis: an overview.

    PubMed

    Monti, Giacomo; Landoni, Giovanni; Taddeo, Daiana; Isella, Francesca; Zangrillo, Alberto

    2015-01-01

    Sepsis is one of the oldest and most elusive syndromes in medicine. With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was considered as a systemic infection by a pathogenic organism. Although the germ is probably the beginning of the syndrome and one of the major enemies to be identified and fought, sepsis is something wider and more elusive. In this chapter clinically relevant themes of sepsis will be approached to provide an insight of everyday clinical practice for healthcare workers often not directly involved in the patient's management. PMID:25319776

  11. Systems for Paediatric Sepsis: A Global Survey

    PubMed Central

    Kang, KT; Chandler, HK; Espinosa, V; Kissoon, N

    2014-01-01

    ABSTRACT Objectives: To evaluate the resources available for early diagnosis and treatment of paediatric sepsis at hospitals in developing and developed countries. Methods: This was a voluntary online survey involving 101 hospitals from 41 countries solicited through the World Federation of Pediatric Intensive and Critical Care Societies contact list and website. The survey was designed to assess the spectrum of sepsis epidemiology, patterns of applied therapies, availability of resources and barriers to optimal sepsis treatment. Results: Ninety per cent of respondents represented a tertiary or general hospital with paediatric intensive care facilities, including 63% from developed countries. Adequate triage services were absent in more than 20% of centres. Insufficiently trained personnel and lack of a sepsis protocol was reported in 40% of all sites. While there were specific guidelines for sepsis management in 78% of centres (n = 100), protocols for assessing sepsis patients were not applied in nearly 70% of centres. Lack of parental recognition of sepsis and failure of referring centres to diagnose sepsis were identified as major barriers by more than 50% of respondents. Conclusions: Even among centres with no significant resource constraints and advanced medical systems, significant deficits in sepsis care exist. Early recognition and management remains a key issue and may be addressed through improved triage, augmented support for referring centres and public awareness. Focussed research is necessary at the institutional level to identify and address specific barriers. PMID:25867557

  12. Substrate Specificity of Streptococcal Unsaturated Glucuronyl Hydrolases for Sulfated Glycosaminoglycan*

    PubMed Central

    Maruyama, Yukie; Nakamichi, Yusuke; Itoh, Takafumi; Mikami, Bunzo; Hashimoto, Wataru; Murata, Kousaku

    2009-01-01

    Unsaturated glucuronyl hydrolase (UGL) categorized into the glycoside hydrolase family 88 catalyzes the hydrolytic release of an unsaturated glucuronic acid from glycosaminoglycan disaccharides, which are produced from mammalian extracellular matrices through the ?-elimination reaction of polysaccharide lyases. Here, we show enzyme characteristics of pathogenic streptococcal UGLs and structural determinants for the enzyme substrate specificity. The putative genes for UGL and phosphotransferase system for amino sugar, a component of glycosaminoglycans, are assembled into a cluster in the genome of pyogenic and hemolytic streptococci such as Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes, which produce extracellular hyaluronate lyase as a virulent factor. The UGLs of these three streptococci were overexpressed in Escherichia coli cells, purified, and characterized. Streptococcal UGLs degraded unsaturated hyaluronate and chondroitin disaccharides most efficiently at approximately pH 5.5 and 37 °C. Distinct from Bacillus sp. GL1 UGL, streptococcal UGLs preferred sulfated substrates. DNA microarray and Western blotting indicated that the enzyme was constitutively expressed in S. agalactiae cells, although the expression level increased in the presence of glycosaminoglycan. The crystal structure of S. agalactiae UGL (SagUGL) was determined at 1.75 ? resolution by x-ray crystallography. SagUGL adopts ?6/?6-barrel structure as a basic scaffold similar to Bacillus UGL, but the arrangement of amino acid residues in the active site differs between the two. SagUGL Arg-236 was found to be one of the residues involved in its activity for the sulfated substrate through structural comparison and site-directed mutagenesis. This is the first report on the structure and function of streptococcal UGLs. PMID:19416976

  13. GENETIC BASIS OF MURINE ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL LUNG INFECTION

    EPA Science Inventory

    To evaluate the effect of genetic background and toll-like receptor 2 on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6

  14. The Group A Streptococcal Carrier State Reviewed: Still an Enigma.

    PubMed

    DeMuri, Gregory P; Wald, Ellen R

    2014-12-01

    Despite the common nature of group A streptococcal (GAS) infections, the carrier state of this organism is not well understood. In this article, we review the historical and recent research on the definition, epidemiology, and pathogenesis of the GAS carrier state. In addition, we outline trials of antimicrobial agents in the eradication of the carrier state and discuss indications for providing treatment to patients in the clinical setting. PMID:26625454

  15. Heterogeneity of group A streptococcal pyrogenic exotoxin type B.

    PubMed Central

    Barsumian, E L; Cunningham, C M; Schlievert, P M; Watson, D W

    1978-01-01

    Streptococcal pyrogenic exotoxin type B purified from culture filtrates of either the NY-5 or T-19 strain of group A streptococcus was found to be heterogeneous in charge. Three protein fractions with isoelectric points of 8.0, 8.4, and 9.0 were isolated by differential solubility in ethanol and acetate-buffered saline followed by isoelectric focusing and shown to be antigenically identical to streptococcal pyrogenic exotoxin type B. The molecular weights of all three fractions were approximately 17,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with aggregates forming in the presence of hyaluronic acid. Only the pI 8.4 fraction showed the characteristic activities of streptococcal pyrogenic exotoxin in rabbits: pyrogenicity and ability to enhance susceptibility to lethal endotoxin shock. The pI 8.0 and pI 9.0 fractions were not pyrogenic, but could be used to immunize against pyrogenicity. These two fractions failed either to enhance lethal endotoxin shock or to immunize against enhancement activity. When the isolated fractions were electrofocused again they appeared heterogeneous, suggesting an instability of the B toxin molecular forms. Images PMID:352946

  16. Neuropsychiatric Disorders Associated with Streptococcal Infection: A Case-Control Study among Privately Insured Children

    ERIC Educational Resources Information Center

    Leslie, Douglas L.; Kozma, Laura; Martin, Andres; Landeros, Angeli; Katsovich, Liliya; King, Robert A.; Leckman, James F.

    2008-01-01

    The link between streptococcal infections and the onset of a variety of neuropsychiatric disorders is studied using a national sample of privately insured children. Findings suggest that patients with new-onset of obsessive-compulsive disorder, Tourette syndrome or tic orders were more likely to have been diagnosed with streptococcal infections in…

  17. Invasive Group A Streptococcal Infection in High School Football Players, New York City, 2003

    PubMed Central

    Lee, Elsie; Bambino, Maribeth; Ackelsberg, Joel; Weiss, Don; Sathyakumar, Chiminyan; Kornblum, John; Barbot, Oxiris; Johnson, Dwight; Kaplan, Edward L.; Layton, Marcelle

    2005-01-01

    After being notified that 2 high school football teammates were hospitalized with confirmed or suspected invasive group A streptococcal infections, we conducted an investigation of possible spread among other team members. This investigation highlights a need for guidelines on management of streptococcal and other infectious disease outbreaks in team sport settings. PMID:15705342

  18. Dementia Increases Severe Sepsis and Mortality in Hospitalized Patients With Chronic Obstructive Pulmonary Disease

    PubMed Central

    Liao, Kuang-Ming; Lin, Tzu-Chieh; Li, Chung-Yi; Yang, Yea-Huei Kao

    2015-01-01

    Abstract Dementia increases the risk of morbidity and mortality in hospitalized patients. However, information on the potential effects of dementia on the risks of acute organ dysfunction, severe sepsis and in-hospital mortality, specifically among inpatients with chronic obstructive pulmonary disease (COPD), is limited. The observational analytic study was inpatient claims during the period from 2000 to 2010 for 1 million people who were randomly selected from all of the beneficiaries of the Taiwan National Health Insurance in 2000. In total, 1406 patients with COPD and dementia were admitted during the study period. Hospitalized patients with COPD and free from a history of dementia were randomly selected and served as control subjects (n?=?5334). The patient groups were matched according to age (±3 years), gender, and the year of admission, with a control/dementia ratio of 4. Only the first-time hospitalization data for each subject was analyzed. Logistic regression models were used to calculate the odds ratio (OR) of outcome measures (acute organ dysfunction, severe sepsis, and mortality), controlling for confounding factors (age, sex, comorbidity, infection site, hospital level, and length of stay). In COPD patients with dementia, the incidence rate of severe sepsis and hospital mortality was 17.1% and 4.8%, respectively, which were higher than the controls (10.6% and 2.3%). After controlling for potential confounding factors, dementia was found to significantly increase the odds of severe sepsis and hospital mortality with an adjusted OR (OR) of 1.38 (95% confidence interval [CI] 1.10–1.72) and 1.69 (95% CI 1.18–2.43), respectively. Dementia was also significantly associated with an increased OR of acute respiratory dysfunction (adjusted OR 1.39, 95% CI 1.09–1.77). In hospitalized COPD patients, the presence of dementia may increase the risks of acute respiratory dysfunction, severe sepsis, and hospital mortality, which warrants the attention of health care professionals. PMID:26061334

  19. Probing sepsis and sepsis-like conditions using untargeted SPIO nanoparticles.

    PubMed

    Wong, Richard; Shou, Jian; Wang, Yi

    2010-01-01

    Sepsis is the leading cause of death in critically ill patients in the United States. Current diagnosis of sepsis relies heavily on the patient's manifestation of septic symptoms, which occur at life-threatening late stage of sepsis. Because the underlying biological changes of sepsis occur hours to days before the clinical presentation of symptoms, early detection of the biological changes will provide crucial opportunities for early diagnosis and effective treatment of sepsis. As an candidate for early sepsis detection, we propose using a novel quantitative susceptibility mapping (QSM) MRI that quantifiably measure the activity of the immune system during sepsis progression. It has been observed that Kupffer cells, comprising 80% of the liver's macrophages, play a pivotal role in the early response to system infection, a condition characteristic of sepsis. Further, it has been observed that phagocytosis by Kupffer cells is a major mechanism by which nanoparticle-based contrast agents, such as Feridex, are cleared from the body. By quantifying the amount of superparamagnetic iron-oxide nanoparticles uptaken by these macrophages and correlating this result to immune system response and the progression of sepsis, we can utilize commonly used contrast agents as markers in monitoring and diagnosing sepsis condition. This study offers an in vitro proof of concept; RAW264.7 murine monocytes were treated with lipopolysaccharide to induce a sepsis-like cell condition, incubated with the FDA-approved contrast agent Feridex IV, and imaged using QSM MRI for the quantification of iron. PMID:21095733

  20. Improving the Odds of Surviving Sepsis

    MedlinePLUS

    ... Improving the Odds of Surviving Sepsis Inside Life Science View All Articles | Inside Life Science Home Page Improving the Odds of Surviving Sepsis ... Threatening Bacterial Infection Remains Mysterious This Inside Life Science article also appears on LiveScience . Learn about related ...

  1. [Advances in the study of the relationship between autophagy and sepsis-induced lung injury].

    PubMed

    Wang, Xingtong; Li, Hengyu; Xia, Zhaofan

    2014-08-01

    Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI. PMID:25508029

  2. [Advances in the study of the relationship between autophagy and sepsis-induced lung injury].

    PubMed

    Wang, Xingtong; Li, Hengyu; Xia, Zhaofan

    2014-08-01

    Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI. PMID:25429812

  3. Hemostasis and endothelial damage during sepsis.

    PubMed

    Johansen, Maria Egede

    2015-08-01

    The sepsis syndrome represents a disease continuum, including severe sepsis and septic shock associated with high mortality. One of the main problems in severe sepsis and septic shock, resulting in organ failure and death, are disturbances in the hemostasis due to sepsis-related coagulopathy. Sepsis-related coagulopathy affects not only traditional coagulation factors, but also the platelets and endothelium. Functional testing of the hemostatic system has found application in critical illness. Thrombelastography (TEG) provides an overview of the hemostatic system allowing for an evaluation of interactions between coagulation factors and platelets. Additionally, the role of the endothelium during sepsis can be explored through testing of biomarkers of endothelial damage. The three studies comprising this PhD thesis all investigate important aspects of the disturbed hemostasis during sepsis, including endothelial damage. Together, the specific findings from the three studies improve the existing understanding of sepsis-related coagulopathy, and the possible influences of some of the treatments offered these patients. The first study investigates the occurrence of antimicrobial-induced thrombocytopenia among critically ill patients. In sepsis, thrombocytopenia is a predictor of poor outcome, and reports, of mainly casuistic nature, have previously hypothesized that specific antimicrobial agents could induce in sepsis-related thrombocytopenia. This hypothesis was tested using a randomized designed set-up, encompassing 1147 critically ill patients, and no significant difference in risk of thrombocytopenia was observed among patients receiving large amounts of antimicrobials vs. patients receiving standard-of-care. As a consequence, the risk of antimicrobial-induced thrombocytopenia in the general population of critically ill patients seemingly does not represent a substantial problem and thrombocytopenia during critical illness is most likely due to other factors such as infection severity. In the second study of the thesis, the role of endothelial damage during sepsis was explored. Levels of biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin (sTM), respectively) were determined in a cohort of 1103 critically ill patients. The results showed that only high levels of sTM were associated with a markedly increased risk of 90-day mortality, as well as multi-organ failure. The finding suggests that profound damage to the endothelium is centrally involved in the pathogenesis of death in sepsis. Thus, the endothelium may be a target for new interventions against sepsis. In the third study, we investigated, using a randomized controlled trial, how mild induced hypothermia (cooling to 32-34°C for 24 hours, MIH) influenced sepsis-related coagulopathy using TEG; functional coagulopathy improved in patients exposed to the intervention compared with the control group. This improvement of coagulopathy parameters during MIH persisted after rewarming. These results not only add to the understanding of the effect of hypothermia on the hemostatic system, but indicate that MIH reduces sepsis-related coagulopathy assessed by TEG. Overall, this thesis emphasizes that the role of the hemostatic system during sepsis is not only complex, but centrally involved in disease severity and prognosis. The endothelium seems to play a central role in the morbidity and mortality of sepsis, which cannot be explained simply by the presences of organ failure. Thus, restoring the broken endothelium and reducing coagulopathy appears to be essential in order to significantly improve sepsis out-comes. MIH could be a promising intervention in sepsis, in part due to the improvement of the coagulopathy. Despite the increased focus on the hemostatic system during sepsis, it seems that continued research on restoring disrupted hemostasis - including endothelial damage - is needed. PMID:26239597

  4. In Vitro Model of Sepsis-Induced Renal Epithelial Reactive Nitrogen Species Generation

    PubMed Central

    Pathak, Elina; Mayeux, Philip R.

    2010-01-01

    Sepsis-induced acute kidney injury (AKI) is a complex disease characterized by generation of inducible nitric oxide synthase (iNOS)–derived reactive nitrogen species (RNS) by the renal tubular epithelium. While most in vitro models of sepsis use combinations of lipopolysaccharide and cytokines to simulate exposure to inflammatory mediators thought to play a role in sepsis, the relevance of these models is limited. To address the need for a model that more closely mimics the tubular microenvironment during sepsis, we developed an in vitro model where mIMCD-3 (murine tubular epithelial) cells are treated with media containing 5% serum collected from mice at 4 h after cecal ligation and puncture (CLP) or sham surgery (no sepsis). After exposure to CLP serum, induction of iNOS messenger RNA occurred and NO generation was significantly increased compared to sham. This increase was accompanied by increased RNS as measured by oxidation of 5-(and-6)-carboxy-2,7?-dichlorodihydrofluorescein diacetate (carboxy-H2DCF-DA) and 2-(3,6-diamino-9H-xanthen-9-yl)-benzoic acid, methyl ester (dihydrorhodamine 123) and moderate cytotoxicity in cells treated with CLP serum, similar to what is observed in mice subjected to CLP. Since iNOS has been shown to play an important role in sepsis-induced AKI, the iNOS inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL) was tested in this in vitro model. L-NIL completely blocked NO generation, RNS generation, and cytotoxicity, similar to its effects in vivo. Therefore, this new in vitro model exhibits many of the characteristics observed in vivo, suggesting that it is a relevant model for studying the mechanism of sepsis-induced renal epithelial RNS generation and injury. PMID:20176626

  5. Dynamic Changes in Amino Acid Concentration Profiles in Patients with Sepsis

    PubMed Central

    Xie, Aimei; Liu, Dan; Rao, Weiqiao; Lan, Liping; Li, Xuan; Li, Fang; Xiao, Kun; Wang, Huijuan; Yan, Peng; Li, Xin; Xie, Lixin

    2015-01-01

    Objectives The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies. Methods Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured. Results The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively. Conclusions Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic. Trial Registration ClinicalTrial.gov identifier NCT01818830. PMID:25849571

  6. Sepsis

    MedlinePLUS

    ... receive oxygen and intravenous fluids. Other types of treatment, such as respirators or kidney dialysis, may be necessary. Sometimes, surgery is needed to clear up an infection. NIH: National Institute of General Medical Sciences

  7. Sepsis

    MedlinePLUS

    ... This page last reviewed on October 01, 2015 Social Media Links Bookmark & Share Free Subscriptions Twitter Facebook YouTube RSS Feeds Page Footer NIGMS Home Site Map Contact Us Your Privacy Accessibility Disclaimers FOIA U.S. Department of Health and ...

  8. [Micromethod for the identification of streptococcal, enterococcal and staphylococcal species].

    PubMed

    Gassama, A; Boye, C S; Ndao, S K; Kairé, O; Coly, I; Macondo, E A; Sow, A I; Diaw, L; Diop-Diop, M; Mboup, S

    1999-01-01

    The aim of this study was to set accurate and reliable methods in the identification of streptococcal, enterococcal and staphylococcal species. Micro CSB Strep and Staph system consists each of a strip with cupules containing dehydrated substrates for biochemical identification of bacterial species. Baye's theorem was used to validate tests. Reactions from micromethods were clear and easily read. Identification of 229 strains of streptococci and enterococci was correct for most species with 98.7% species with 99.3% sensitivity. 41 strains of staphylococci were also correctly identified with 85.2% of specificity and 97.68% of sensitivity. PMID:10797992

  9. Management of neonatal sepsis in term newborns

    PubMed Central

    Du Pont-Thibodeau, Geneviève; Joyal, Jean-Sébastien

    2014-01-01

    Neonatal sepsis is a common and deadly disease. It is broadly defined as a systemic inflammatory response, occurring in the first four weeks of life, as a result of a suspected or proven infection. Yet, more reliable and consistently applied diagnostic criteria would help improve our knowledge of the disease epidemiology. Several therapeutic attempts to control systemic inflammation in sepsis were unsuccessful. Immediate empirical administration of broad-spectrum anti-microbials, aggressive fluid resuscitation, and vaso-active or inotropic support (or both) are the mainstays of the therapeutic management of neonatal sepsis. PMID:25165566

  10. Sepsis, venous return, and teleology.

    PubMed

    McNeilly, R G

    2014-11-01

    An understanding of heart-circulation interaction is crucial to our ability to guide our patients through an episode of septic shock. Our knowledge has advanced greatly in the last one hundred years. There are, however, certain empirical phenomena that may lead us to question the wisdom of our prevailing treatment algorithm. Three extreme but iatrogenically possible haemodynamic states exist. Firstly, inappropriately low venous return; secondly, overzealous arteriolar constriction; and finally, misguided inotropy and chronotropy. Following an unsuccessful fluid challenge, it would be logical to first set the venous tone, then set the cardiac rate and contractility, and finally set the peripheral vascular resistance. It is hypothesized that a combination of dihydroergotamine, milrinone and esmolol should be superior to a combination of noradrenaline and dobutamine for surviving sepsis. PMID:25245463

  11. A prospective treatment for sepsis

    PubMed Central

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

    The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs) from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC), which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient’s body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs’ reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1) urgent neutralization of notorious BATs from blood of septic patients; 2) applicability in parallel with conventional treatments; 3) potential to minimize side effects of the malady; 4) applicability for a vast range of BATs; 5) potential to eliminate contact of BATs with internal tissues and organs; 6) tolerability by patients sensitive to antiserum injections; 7) capability for universal application; 8) affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10) being a single-use, disposable, and stand-alone device. Before using it for clinical trials in human beings, it should pass animal evaluations accurately; however, research works should optimize its implementation in human beings. For optimization, it needs appropriate investments, collaboration of scientists in many fields of research, and development through several interdisciplinary sciences such as medical engineering, nanotechnology, immunology, biochemistry, emergency medicine, internal, and infectious diseases. PMID:26005330

  12. A prospective treatment for sepsis.

    PubMed

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

    The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs) from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC), which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient's body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs' reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1) urgent neutralization of notorious BATs from blood of septic patients; 2) applicability in parallel with conventional treatments; 3) potential to minimize side effects of the malady; 4) applicability for a vast range of BATs; 5) potential to eliminate contact of BATs with internal tissues and organs; 6) tolerability by patients sensitive to antiserum injections; 7) capability for universal application; 8) affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10) being a single-use, disposable, and stand-alone device. Before using it for clinical trials in human beings, it should pass animal evaluations accurately; however, research works should optimize its implementation in human beings. For optimization, it needs appropriate investments, collaboration of scientists in many fields of research, and development through several interdisciplinary sciences such as medical engineering, nanotechnology, immunology, biochemistry, emergency medicine, internal, and infectious diseases. PMID:26005330

  13. Procalcitonin as a Predictor of Sepsis and Outcome in Severe Trauma Patients: A Prospective Study

    PubMed Central

    Rajkumari, Nonika; Mathur, Purva; Sharma, Satyapriya; Gupta, Babita; Bhoi, Sanjeev; Misra, Mahesh C

    2013-01-01

    Introduction: Despite the advances in medical sciences, the morbidity and mortality due to sepsis in severe trauma patients remains high; hence the need for early and accurate diagnosis. Very few prospective studies are available in a country like India, which tried to analyze the prediction of sepsis using serum procalcitonin (PCT) in such a large scale among trauma patients. This study explores the role of the biomarker PCT in early diagnosis of sepsis and prediction of outcomes in severe trauma cases. Materials and Methods: We studied the patient population prospectively in two different groups. One with acute trauma but no clinical evidence of sepsis and the second group with clinical evidence of sepsis and are followed. Bronchoalveolar lavage, tracheal aspirates, pus, urine, body fluids from sterile body sites, etc., were collected including blood for culture and serum for PCT assays. Such assays were done on samples collected on days 1 and 4 and then compared. Additionally, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were also tested. Antimicrobial sensitivity tests were carried out for all the isolates from the clinical samples and correlated with the clinically suspected cases of sepsis. Outcomes of the patients were noted. Results: Patients with high initial PCT levels (>2 ng/ml) in severe trauma cases had poor outcomes and risk of developing complications. Its correlation with severe outcomes was better marked as compared with CRP and ESR levels. The difference in PCT levels between days 1 and 4 in group two patients was statistically significant (P = 0.006) but were not statistically significant for CRP (P = 0.646) and ESR (P = 0.935). The study also shows that PCT levels fall in response to appropriate antimicrobial treatment. Conclusion: PCT is a useful biomarker for early and accurate prediction of sepsis in severe trauma patients. If used in adjunct to clinical findings, it proves to be a good biomarker for early diagnosis, treatment and for monitoring response to therapy in confirmed cases of sepsis. It will prove to be a good supportive indicator of sepsis in early stages for the trauma patients in a low resource country like India. PMID:24701102

  14. Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

    PubMed Central

    2014-01-01

    Introduction Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis. Methods Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (?65 years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured. Results The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P?sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P?sepsis (P?sepsis. PMID:24962182

  15. Induced expression and functional effects of aquaporin-1 in human leukocytes in sepsis

    PubMed Central

    2013-01-01

    Introduction Gene expression profiling was performed via DNA microarrays in leukocytes from critically ill trauma patients nonseptic upon admission to the ICU, who subsequently developed either sepsis (n = 2) or severe sepsis and acute respiratory distress syndrome (n = 3). By comparing our results with published expression profiling studies in animal models of sepsis and lung injury, we found aquaporin-1 to be differentially expressed across all studies. Our aim was to determine how the water channel aquaporin-1 is involved in regulating the immune response in critically ill patients during infection acquired in the ICU. Methods Following the results of the initial genetic screening study, we prospectively followed aquaporin-1 leukocyte expression patterns in patients with ICU-acquired sepsis who subsequently developed septic shock (n = 16) versus critically ill patients who were discharged without developing sepsis (n = 13). We additionally determined aquaporin-1 expression upon lipopolysaccharide (LPS) exposure and explored functional effects of aquaporin-1 induction in polymorphonuclear granulocytes (PMNs). Results Leukocyte aquaporin-1 expression was induced at the onset of sepsis (median 1.71-fold increase; interquartile range: 0.99 to 2.42, P = 0.012 from baseline) and was further increased upon septic shock (median 3.00-fold increase; interquartile range: 1.20 to 5.40, P = 0.023 from sepsis, Wilcoxon signed-rank test); no difference was observed between baseline and discharge in patients who did not develop sepsis. Stimulation of PMNs by LPS led to increased expression of aquaporin-1 in vitro, which could be abrogated by the NF-?B inhibitor EF-24. PMN hypotonic challenge resulted in a transient increase of the relative cell volume, which returned to baseline after 600 seconds, while incubation in the presence of LPS resulted in persistently increased cell volume. The latter could be abolished by blocking aquaporin-1 with mercury and restored by incubation in ?-mercaptoethanol, which abrogated the action of mercury inhibition. Conclusions Aquaporin-1 is induced in leukocytes of patients with ICU-acquired sepsis and exhibits higher expression in septic shock. This phenomenon may be due to LPS-triggered NF-?B activation that can also lead to alterations in plasma membrane permeability. PMID:24028651

  16. Cefprozil versus penicillin V in treatment of streptococcal tonsillopharyngitis.

    PubMed Central

    Milatovic, D; Adam, D; Hamilton, H; Materman, E

    1993-01-01

    In a randomized multicenter study, the efficacy and safety of cefprozil were compared with those of penicillin in the treatment of group A streptococcal tonsillopharyngitis in children. Of the 409 patients enrolled, 323 were evaluable for their clinical and bacteriological responses; of these 323 children, 172 received cefprozil and 151 received penicillin V. The clinical responses in patients treated with cefprozil were significantly better than those in patients who received penicillin (95.3 versus 88.1%; P = 0.023). Eradication of the original serotype of group A streptococci was achieved in 91.3% of patients treated with cefprozil and 87.4% of patients treated with penicillin, the difference not being statistically significant (P = 0.125). However, there were significantly more symptomatic patients among the bacteriological failures in the penicillin group (68.4%) than in the cefprozil group (26.7%). beta-Lactamase-producing Staphylococcus aureus was more frequently isolated from the throat flora during penicillin therapy than during cefprozil treatment. No difference in the incidence of adverse events probably related or of unknown relationship to the study drugs was observed in the two treatment groups (5.2% of those treated with cefprozil and 6.0% of those treated with penicillin). Cefprozil can be considered a safe and reliable drug for the treatment of streptococcal pharyngitis in children. PMID:8215273

  17. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

    Synopsis Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation and early initiation of therapy are required to prevent adverse outcomes. The following chapter reviews recent trends in epidemiology, and provides an update on risk factors, diagnostic methods and management of neonatal sepsis. PMID:23481106

  18. Sepsis: From Pathophysiology to Individualized Patient Care

    PubMed Central

    László, Ildikó; Trásy, Domonkos; Molnár, Zsolt; Fazakas, János

    2015-01-01

    Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review. PMID:26258150

  19. Hospital variations in severe sepsis mortality.

    PubMed

    Wang, Henry E; Donnelly, John P; Shapiro, Nathan I; Hohmann, Samuel F; Levitan, Emily B

    2015-01-01

    This study sought to characterize variations in severe sepsis mortality between hospitals in the United States. Hospital discharge data (2012) were used from the University HealthSystem Consortium (UHC), a cooperative of US not-for-profit academic medical centers and affiliated hospitals. Discharge diagnosis codes were used to define severe sepsis as the presence of a serious infection with at least 1 organ dysfunction on hospital presentation. Expected mortality was determined from UHC risk adjustment mortality models. Among the 188 hospitals in the analysis, there were 256 509 patients with severe sepsis on admission. The median number of severe sepsis cases per hospital was 1202 (interquartile range [IQR] = 718-1940). Severe sepsis observed mortality (median = 8.6%; IQR = 6.8%-10.3%; range = 0.9%-18.2%) and observed-to-expected (O:E) mortality ratios (median = 0.91; IQR = 0.77-1.05; range = 0.16-1.95) varied across the hospitals. Variations in institutional severe sepsis observed mortality rates and O:E mortality ratios were observed in this national consortium of major medical centers. PMID:24814940

  20. CECAL LIGATION AND PUNCTURE INDUCED MURINE SEPSIS DOES NOT CAUSE LUNG INJURY

    PubMed Central

    Iskander, Kendra N.; Craciun, Florin L.; Stepien, David M.; Duffy, Elizabeth R.; Kim, Jiyoun; Moitra, Rituparna; Vaickus, Louis J.; Osuchowski, Marcin F.; Remick, Daniel G.

    2012-01-01

    Objective The cause of death in murine models of sepsis remains unclear. The primary purpose of this study was to determine if significant lung injury develops in mice predicted to die following cecal ligation and puncture induced sepsis compared to those predicted to live. Design Prospective, laboratory controlled experiments. Setting University research laboratory. Subjects Adult, female, outbred ICR mice. Interventions Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Two groups of mice were sacrificed at 24 and 48 hours post-CLP and samples were collected. These mice were further stratified into groups predicted to die (Die-P) and predicted to live (Live-P) based on plasma interleukin 6 (IL-6) levels obtained 24 hours post-CLP. Multiple measures of lung inflammation and lung injury were quantified in these two groups. Results from a group of mice receiving intratracheal normal saline without surgical intervention were also included as a negative control. As a positive control, bacterial pneumonia was induced with Pseudomonas aeruginosa to cause definitive lung injury. Separate mice were followed for survival until day 28 post-CLP. These mice were used to verify the IL-6 cut-offs for survival prediction. Measurements and Main Results Following sepsis, both the Die-P and Live-P mice had significantly suppressed measures of respiratory physiology but maintained normal levels of arterial oxygen saturation. Bronchoalveolar lavage (BAL) levels of pro and anti-inflammatory cytokines were not elevated in the Die-P mice compared to the Live-P. Additionally, there was no increase in the recruitment of neutrophils to the lung, pulmonary vascular permeability, or histological evidence of damage. In contrast, all of these pulmonary injury and inflammatory parameters were increased in mice with Pseudomonas pneumonia. Conclusions These data demonstrate that mice predicted to die during sepsis have no significant lung injury. In murine intra-abdominal sepsis, pulmonary injury cannot be considered the etiology of death in the acute phase. PMID:23222255

  1. Role of Mitochondrial Oxidants in an In Vitro Model of Sepsis-Induced Renal Injury

    PubMed Central

    Pathak, Elina; MacMillan-Crow, Lee Ann

    2012-01-01

    Oxidative stress has been implicated to play a major role in multiorgan dysfunction during sepsis. To study the mechanism of oxidant generation in acute kidney injury (AKI) during sepsis, we developed an in vitro model of sepsis using primary cultures of mouse cortical tubular epithelial cells exposed to serum (2.5–10%) collected from mice at 4 h after induction of sepsis by cecal ligation and puncture (CLP) or Sham (no sepsis). CLP serum produced a concentration-dependent increase in nitric oxide (NO) (nitrate + nitrite) release at 6 h and cytotoxicity (lactate dehydrogenase release) at 18 h compared with Sham serum treatment. Before cytotoxicity there was a decrease in mitochondrial membrane potential, which was followed by increased superoxide and peroxynitrite levels compared with Sham serum. The role of oxidants was evaluated by using the superoxide dismutase mimetic and peroxynitrite scavenger manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin tetratosylate hydroxide (MnTmPyP). MnTmPyP (10–100 ?M) produced a concentration-dependent preservation of ATP and protection against cytotoxicity. MnTmPyP blocked mitochondrial superoxide and peroxynitrite generation produced by CLP serum but had no effect on NO levels. Although MnTmPyP did not block the initial CLP serum-induced fall in mitochondrial membrane potential, it allowed mitochondrial membrane potential to recover. Data from this in vitro model suggest a time-dependent generation of mitochondrial oxidants, mitochondrial dysfunction, and renal tubular epithelial cell injury and support the therapeutic potential of manganese porphyrin compounds in preventing sepsis-induced AKI. PMID:22011433

  2. We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS)

    E-print Network

    Nizet, Victor

    We conducted genetic and functional analyses of isolates from a patient with group B streptococcal with antioxidant properties (6,15), and these 2 factors act in concert to im- pair macrophage-based immune

  3. Replacement of the mitral valve in an infant with group B streptococcal endocarditis.

    PubMed

    Walker, T A; Aru, G M; Ebeid, M R

    2001-01-01

    Endocarditis due to group B streptococcus is very rare in infants, and may be associated with significant morbidity and mortality. Review of the literature reveals only a single reported case of an infant with this type of streptococcal endocarditis involving the mitral valve. This infant had underlying congenital heart disease, and died shortly after catheterization. We now report group B streptococcal endocarditis occurring in an infant with a structurally normal heart who was treated successfully by replacement of the mitral valve. PMID:11233405

  4. Etiology of pediatric fever in western Kenya: a case-control study of falciparum malaria, respiratory viruses, and streptococcal pharyngitis.

    PubMed

    O'Meara, Wendy P; Mott, Joshua A; Laktabai, Jeremiah; Wamburu, Kabura; Fields, Barry; Armstrong, Janice; Taylor, Steve M; MacIntyre, Charles; Sen, Reeshi; Menya, Diana; Pan, William; Nicholson, Bradly P; Woods, Christopher W; Holland, Thomas L

    2015-05-01

    In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1-3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed. PMID:25758648

  5. Factors which affect mortality in neonatal sepsis

    PubMed Central

    Turhan, Esma Ebru; Gürsoy, Tu?ba; Oval?, Fahri

    2015-01-01

    Aim: Neonatal sepsis is an important cause of mortality and morbidity in newborns. The causative agents may be different in different units and may change in time. It was aimed to examine the microbiological agents leading to sepsis, clinical features and antibiotic resistances in babies with sepsis hospitalized in our unit in a two-year period. Material and Methods: The clinical features, microbiological and laboratory results, antibiotic resistance patterns and mortality rates of the newborns with sepsis followed up in our unit between 2010 and 2011 were examined in the patient record system. Results: 351 babies diagnosed with sepsis among 3219 patients hospitalized in the neonatal intensive care unit were included in the study. The mean gestational age was found to be 30.1±4.1 weeks, the mean birth weight was found to be 1417.4±759.1 g and the mean hospitalization time was found to be 43.6±34.4 days. Blood cultures were found to be positive in 167 (47.6%) patients, urine cultures were found to be positive in 6 (7.1%) patients and cerebrospinal fluid cultures were found to be positive in 34 (9.6%) cases. Candida grew in 5 patients (2 patients with early-onset sepsis and 3 patients with late-onset sepsis). The most common cause of sepsis was found to be staphylococci (coagulase negative staphylococcus was found in 65 patients (51%) and Staphylococcus aureus was found in 38 patients (39%). 49.6% (n=63) of the gram positive bacteriae and 60% (n=21) of the gram negative bacteriae were resistant to antibiotics. Six (7.1%) of the patients who were infected with these bacteriae were lost. In total 24 babies were lost because of sepsis. The bacteriae which caused to mortality with the highest rate included E. coli, coagulase negative staphylocicci, S. aureus and Klebsiella. Low birth weight, mechanical ventilation and parenteral nutrition were found to be significant risk factors in terms of mortality. Conclusions: Staphylococci were found to be the most common agents in neonatal sepsis. Low birth weight, mechanical ventilation and parenteral nutrition are significant risk factors in terms of mortality. PMID:26568693

  6. Monocyte Tumor Necrosis Factor-?–Converting Enzyme Catalytic Activity and Substrate Shedding in Sepsis and Noninfectious Systemic Inflammation*

    PubMed Central

    O’Callaghan, David J. P.; O’Dea, Kieran P.; Scott, Alasdair J.; Takata, Masao

    2015-01-01

    Objectives: To determine the effect of severe sepsis on monocyte tumor necrosis factor-?–converting enzyme baseline and inducible activity profiles. Design: Observational clinical study. Setting: Mixed surgical/medical teaching hospital ICU. Patients: Sixteen patients with severe sepsis, 15 healthy volunteers, and eight critically ill patients with noninfectious systemic inflammatory response syndrome. Interventions: None. Measurements and Main Results: Monocyte expression of human leukocyte antigen-D-related peptide, sol-tumor necrosis factor production, tumor necrosis factor-?–converting enzyme expression and catalytic activity, tumor necrosis factor receptor 1 and 2 expression, and shedding at 48-hour intervals from day 0 to day 4, as well as p38-mitogen activated protein kinase expression. Compared with healthy volunteers, both sepsis and systemic inflammatory response syndrome patients’ monocytes expressed reduced levels of human leukocyte antigen-D-related peptide and released less sol-tumor necrosis factor on in vitro lipopolysaccharide stimulation, consistent with the term monocyte deactivation. However, patients with sepsis had substantially elevated levels of basal tumor necrosis factor-?–converting enzyme activity that were refractory to lipopolysaccharide stimulation and this was accompanied by similar changes in p38-mitogen activated protein kinase signaling. In patients with systemic inflammatory response syndrome, monocyte basal tumor necrosis factor-?–converting enzyme, and its induction by lipopolysaccharide, appeared similar to healthy controls. Changes in basal tumor necrosis factor-?–converting enzyme activity at day 0 for sepsis patients correlated with Acute Physiology and Chronic Health Evaluation II score and the attenuated tumor necrosis factor-?–converting enzyme response to lipopolysaccharide was associated with increased mortality. Similar changes in monocyte tumor necrosis factor-?–converting enzyme activity could be induced in healthy volunteer monocytes using an in vitro two-hit inflammation model. Patients with sepsis also displayed reduced shedding of monocyte tumor necrosis factor receptors upon stimulation with lipopolysaccharide. Conclusions: Monocyte tumor necrosis factor-?–converting enzyme catalytic activity appeared altered by sepsis and may result in reduced shedding of tumor necrosis factor receptors. Changes seemed specific to sepsis and correlated with illness severity. A better understanding of how tumor necrosis factor-?–converting enzyme function is altered during sepsis will enhance our understanding of sepsis pathophysiology, which will help in the assessment of patient inflammatory status and ultimately may provide new strategies to treat sepsis. PMID:25867908

  7. Experimental Models of C. albicans-Streptococcal Co-infection.

    PubMed

    Sobue, Takanori; Diaz, Patricia; Xu, Hongbin; Bertolini, Martinna; Dongari-Bagtzoglou, Anna

    2016-01-01

    Interactions of C. albicans with co-colonizing bacteria at mucosal sites can be synergistic or antagonistic in disease development, depending on the bacterial species and mucosal site. Mitis group streptococci and C. albicans colonize the oral mucosa of the majority of healthy individuals. These streptococci have been termed "accessory pathogens," defined by their ability to initiate multispecies biofilm assembly and promote the virulence of the mixed bacterial biofilm community in which they participate. To demonstrate whether interactions with Mitis group streptococci limit or promote the potential of C. albicans to become an opportunistic pathogen, in vitro and in vivo co-infection models are needed. Here, we describe two C. albicans-streptococcal co-infection models: an organotypic oral mucosal tissue model that incorporates salivary flow and a mouse model of oral co-infection that requires reduced levels of immunosuppression compared to single fungal infection. PMID:26519070

  8. [Rational dosing intervals in streptococcal infections of the pharynx].

    PubMed

    Rauchegger, H; Picker, H; Guggenbichler, J P; Allerberger, F

    1989-03-31

    Optimum therapy of streptococcal pharyngitis is still a matter of great debate. Kill kinetics of streptococci group A were investigated under the influence of fluctuating concentrations of penicillin V, ampicillin, cefalexin and erythromycin. Antibiotic concentrations in our in vitro model were adjusted to concentrations found in vivo in tonsillar tissue, penicillin V showed superior antimicrobial activity to ampicillin, cefalexin and erythromycin. Only the eight hourly administration of concentrations determined after the in vivo administration of either 100,000 IU/kg BW penicillin or 100 mg/kg BW of ampicillin or cefalexin effectively eradicated streptococci in the kinetic model. beta-lactamase forming bacteroides did not interfere with the elimination of streptococci by non beta-lactamase stable antibiotics. These data suggest that penicillin V constitutes the optimum choice of antibiotic. Efficient eradication can be achieved by the administration of a total daily dosage of 100,000 IU/kg BW at 8 hourly intervals. PMID:2652891

  9. Inflammasome/IL-1? Responses to Streptococcal Pathogens

    PubMed Central

    LaRock, Christopher N.; Nizet, Victor

    2015-01-01

    Inflammation mediated by the inflammasome and the cytokine IL-1? are some of the earliest and most important alarms to infection. These pathways are responsive to the virulence factors that pathogens use to subvert immune processes, and thus are typically activated only by microbes with potential to cause severe disease. Among the most serious human infections are those caused by the pathogenic streptococci, in part because these species numerous strategies for immune evasion. Since the virulence factor armament of each pathogen is unique, the role of IL-1? and the pathways leading to its activation varies for each infection. This review summarizes the role of IL-1? during infections caused by streptococcal pathogens, with emphasis on emergent mechanisms and concepts countering paradigms determined for other organisms. PMID:26500655

  10. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

    PubMed

    LaRock, Christopher N; Nizet, Victor

    2015-11-01

    Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. PMID:25701232

  11. [Characteristics of group A streptococcal meningitis in children].

    PubMed

    Levy, C; Bidet, Ph; Bonacorsi, S; Béchet, S; Cohen, R

    2014-11-01

    Group A streptococcal (GAS) meningitis in children are rare. The aim of this study was to analyze the clinical, biological and outcome data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV). From 2001 through 2012, 4,564 children suffering from proven bacterial meningitis were recorded in the data base. Among them, 0.7 % were GAS infections. The median age was 5.6 years. A history of community acquired infection before the onset of GAS meningitis was frequent. Apart from the identification of the bacterial species, GAS meningitis were clinically and biologically indistinguishable from meningitis caused by other pathogens notably S. pneumoniae. Case fatality rate was 8 %. PMID:25456677

  12. Acute abdomen due to group A streptococcus bacteremia caused by an isolate with a mutation in the csrS gene.

    PubMed

    Kaneko, Masahiko; Maruta, Masaki; Shikata, Hisaharu; Hanayama, Masakazu; Ikebe, Tadayoshi

    2015-11-01

    Streptococcus pyogenes (group A streptococcus) is an aerobic gram-positive coccus that causes infections ranging from non-invasive pharyngitis to severely invasive necrotizing fasciitis. Mutations in csrS/csrR and rgg, negative regulator genes of group A streptococcus, are crucial factors in the pathogenesis of streptococcal toxic shock syndrome, which is a severe, invasive infection characterized by sudden onset of shock and multiorgan failure, resulting in a high mortality rate. Here we present a case of group A streptococcal bacteremia in a 28-year-old Japanese woman with no relevant previous medical history. The patient developed progressive abdominal symptoms that may have been due to spontaneous bacterial peritonitis, followed by a state of shock, which did not fulfill the proposed criteria for streptococcal toxic shock. The isolate was found to harbor a mutation in the negative regulator csrS gene, whereas the csrR and rgg genes were intact. It was noteworthy that this strain carrying a csrS mutation had caused group A streptococcal bacteremia characterized by acute abdomen as the presenting symptom in a young individual who had been previously healthy. This case indicates that group A streptococcus with csrS mutations has potential virulence factors that are associated with the onset of group A streptococcal bacteremia that does not meet the diagnostic criteria for streptococcal toxic shock syndrome. PMID:26231317

  13. Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics.

    PubMed

    Kuhn, Pierre; Dheu, Céline; Bolender, Chantal; Chognot, Didier; Keller, Laurence; Demil, Houria; Donato, Lionel; Langer, Bruno; Messer, Jean; Astruc, Dominique

    2010-09-01

    In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance. PMID:20670228

  14. Neonatal sepsis in Dubai, United Arab Emirates.

    PubMed

    Koutouby, A; Habibullah, J

    1995-06-01

    The case records of all neonates admitted to the neonatal unit of Al Wasl Hospital (Dubai) in a period of 60 months (May 1987-April 1992) were analysed. One-hundred-and-six neonates had confirmed sepsis. The most common causative organisms were Group B Streptococci (23 per cent), E. coli (17 per cent), Staph. epidermidis (17 per cent), and Klebsiella pneumoniae (16 per cent). Group B Streptococcus presented as the most common organism in very early (< or = 24 hours) and early onset (2-6 days) of sepsis (34 per cent, 21/61), Klebsiella pneumoniae (24 per cent), Staphylococcal epidermidis (18 per cent) and Candida (13 per cent) were most common organisms causing late onset of sepsis (7-30 days). Pseudomonas aeruginosa and Klebsiella pneumoniae had highest mortality (71 per cent, 5/7; and 59 per cent, 10/17, respectively). Lowest mortality (4 per cent, 1/25) was observed in Group B Streptococcus sepsis. Prematurity, low birth weight, and nosocomial sepsis were high risk factors associated with fatal outcome. PMID:7636939

  15. Improving Outcomes in Patients With Sepsis.

    PubMed

    Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

    2016-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. PMID:25216849

  16. A Multiplex Assay for Detection of Staphylococcal and Streptococcal Exotoxins

    PubMed Central

    Sharma, Preeti; Wang, Ningyan; Chervin, Adam S.; Quinn, Cheryl L.; Stone, Jennifer D.; Kranz, David M.

    2015-01-01

    Staphylococcal and streptococcal exotoxins, also known as superantigens, mediate a range of diseases including toxic shock syndrome, and they exacerbate skin, pulmonary and systemic infections caused by these organisms. When present in food sources they can cause enteric effects commonly known as food poisoning. A rapid, sensitive assay for the toxins would enable testing of clinical samples and improve surveillance of food sources. Here we developed a bead-based, two-color flow cytometry assay using single protein domains of the beta chain of T cell receptors engineered for high-affinity for staphylococcal (SEA, SEB and TSST-1) and streptococcal (SpeA and SpeC) toxins. Site-directed biotinylated forms of these high-affinity agents were used together with commercial, polyclonal, anti-toxin reagents to enable specific and sensitive detection with SD50 values of 400 pg/ml (SEA), 3 pg/ml (SEB), 25 pg/ml (TSST-1), 6 ng/ml (SpeA), and 100 pg/ml (SpeC). These sensitivities were in the range of 4- to 80-fold higher than achieved with standard ELISAs using the same reagents. A multiplex format of the assay showed reduced sensitivity due to higher noise associated with the use of multiple polyclonal agents, but the sensitivities were still well within the range necessary for detection in food sources or for rapid detection of toxins in culture supernatants. For example, the assay specifically detected toxins in supernatants derived from cultures of Staphylococcus aureus. Thus, these reagents can be used for simultaneous detection of the toxins in food sources or culture supernatants of potential pathogenic strains of Staphylococcus aureus and Streptococcus pyogenes. PMID:26305471

  17. A Multiplex Assay for Detection of Staphylococcal and Streptococcal Exotoxins.

    PubMed

    Sharma, Preeti; Wang, Ningyan; Chervin, Adam S; Quinn, Cheryl L; Stone, Jennifer D; Kranz, David M

    2015-01-01

    Staphylococcal and streptococcal exotoxins, also known as superantigens, mediate a range of diseases including toxic shock syndrome, and they exacerbate skin, pulmonary and systemic infections caused by these organisms. When present in food sources they can cause enteric effects commonly known as food poisoning. A rapid, sensitive assay for the toxins would enable testing of clinical samples and improve surveillance of food sources. Here we developed a bead-based, two-color flow cytometry assay using single protein domains of the beta chain of T cell receptors engineered for high-affinity for staphylococcal (SEA, SEB and TSST-1) and streptococcal (SpeA and SpeC) toxins. Site-directed biotinylated forms of these high-affinity agents were used together with commercial, polyclonal, anti-toxin reagents to enable specific and sensitive detection with SD50 values of 400 pg/ml (SEA), 3 pg/ml (SEB), 25 pg/ml (TSST-1), 6 ng/ml (SpeA), and 100 pg/ml (SpeC). These sensitivities were in the range of 4- to 80-fold higher than achieved with standard ELISAs using the same reagents. A multiplex format of the assay showed reduced sensitivity due to higher noise associated with the use of multiple polyclonal agents, but the sensitivities were still well within the range necessary for detection in food sources or for rapid detection of toxins in culture supernatants. For example, the assay specifically detected toxins in supernatants derived from cultures of Staphylococcus aureus. Thus, these reagents can be used for simultaneous detection of the toxins in food sources or culture supernatants of potential pathogenic strains of Staphylococcus aureus and Streptococcus pyogenes. PMID:26305471

  18. Anticoagulant modulation of inflammation in severe sepsis

    PubMed Central

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-01-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. PMID:25938026

  19. Clinical review: The liver in sepsis

    PubMed Central

    2012-01-01

    During sepsis, the liver plays a key role. It is implicated in the host response, participating in the clearance of the infectious agents/products. Sepsis also induces liver damage through hemodynamic alterations or through direct or indirect assault on the hepatocytes or through both. Accordingly, liver dysfunction induced by sepsis is recognized as one of the components that contribute to the severity of the disease. Nevertheless, the incidence of liver dysfunction remains imprecise, probably because current diagnostic tools are lacking, notably those that can detect the early liver insult. In this review, we discuss the epidemiology, diagnostic tools, and impact on outcome as well as the pathophysiological aspects, including the cellular events and clinical picture leading to liver dysfunction. Finally, therapeutic considerations with regard to the weakness of the pertinent specific approach are examined. PMID:23134597

  20. Current concept of abdominal sepsis: WSES position paper

    PubMed Central

    2014-01-01

    Although sepsis is a systemic process, the pathophysiological cascade of events may vary from region to region. Abdominal sepsis represents the host’s systemic inflammatory response to bacterial peritonitis. It is associated with significant morbidity and mortality rates, and is the second most common cause of sepsis-related mortality in the intensive care unit. The review focuses on sepsis in the specific setting of severe peritonitis. PMID:24674057

  1. Invasive group B streptococcal infection in infants in Shenzhen, China

    PubMed Central

    Zhang, Jiaosheng; Zhao, Ruizhen; Dong, Yimei; Zheng, Yuejie

    2015-01-01

    Objective: In this study, we aim to investigate the distribution and antibiotic susceptibility of Group B Streptococcus (GBS) in infants younger than 90 days in Shenzhen, China. Methods: A retrospective study was conducted to evaluate GBS infection over an 4-year period. Starting from January 2010, we evaluated the laboratory data, clinical manifestations, treatment and outcomes of patients admitted to our hospital with invasive GBS infection. Furthermore, we analyzed distribution of isolates from infants < 90 days with GBS or non-GBS invasive infection. Results: The registered cases of invasive GBS infection (n = 40, male: 23, female: 17) were classified as sepsis (n = 24), meningitis (n = 2), or both (n = 14). Patients with sepsis recovered completely. Among patients with meningitis, 1 (6.3%) died from ventricular hemorrhage, and 4 (25%) showed sequelae during the follow up of 3 months. Among the 377 isolates (45 from the 40 infants with invasive GBS infection, 332 from infants with non-GBS invasive infections), the detection rate of GBS was 11.9% (45/377), accounted for 11.2% of sepsis and 18.4% of meningitis cases. All 45 isolates were susceptible to penicillin, vancomycin, linezolid, tigecycline, and quinolones. Resistance to erythromycin, clindamycin, and tetracycline was found in 19 (42%), 29 (64%), and 42 (93%) isolates, respectively. Conclusion: GBS is an important pathogen in infants < 90 days in Shenzhen, China, which results in high mortality and neurological sequelae. GBS strains show strong resistance to clindamycin and erythromycin. PMID:25932259

  2. Hepatosplanchnic circulation in cirrhosis and sepsis

    PubMed Central

    Prin, Meghan; Bakker, Jan; Wagener, Gebhard

    2015-01-01

    Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage. Sepsis and cirrhosis result in similar circulatory changes and resultant multi-organ dysfunction. This review provides an overview of the hepatosplanchnic circulation in the healthy state and in cirrhosis, examines the signaling pathways that may play a role in the physiology of cirrhosis, discusses the physiology common to cirrhosis and sepsis, and reviews important issues in management. PMID:25759525

  3. Fluid Resuscitation in Sepsis: Reexamining the Paradigm

    PubMed Central

    Tirupakuzhi Vijayaraghavan, Bharath Kumar; Cove, Matthew Edward

    2014-01-01

    Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis. PMID:25180196

  4. Usefulness of procalcitonin serum level for the discrimination of severe sepsis from sepsis: a multicenter prospective study.

    PubMed

    Endo, Shigeatsu; Aikawa, Naoki; Fujishima, Seitaro; Sekine, Isao; Kogawa, Kazuhiro; Yamamoto, Yasuhiro; Kushimoto, Shigeki; Yukioka, Hidekazu; Kato, Noboru; Totsuka, Kyoichi; Kikuchi, Ken; Ikeda, Toshiaki; Ikeda, Kazumi; Yamada, Hiroyuki; Harada, Kazuaki; Satomura, Shinji

    2008-06-01

    Procalcitonin serum level has been recommended as a new marker of bacterial infectious diseases. The aim of this prospective, multicenter study was to determine the clinical usefulness of procalcitonin in differentiating patients with sepsis from those with severe sepsis. Eighty-two patients were enrolled: 20 without systemic inflammatory response syndrome (SIRS), 9 with SIRS, 34 with sepsis, and 19 with severe sepsis. The patients with severe sepsis had significantly higher procalcitonin levels (median, 36.1 ng/ml) than those with sepsis (median, 0.6 ng/ml). With a procalcitonin cutoff value of 2.0 ng/ml, sensitivity for the detection of severe sepsis and specificity for the detection of sepsis were 94.7% and 78.1%, respectively. A good correlation was found between the serum procalcitonin level and the Sepsis-Related Organ Failure Assessment (SOFA) score (r = 0.680), although no correlation was found between the C-reactive protein (CRP) level and the SOFA score. In conclusion, the procalcitonin serum level may be useful not only for aiding the diagnosis of sepsis but also for discriminating between sepsis and severe sepsis. PMID:18574663

  5. Epidermal wound healing in severe sepsis and septic shock in humans

    PubMed Central

    Koskela, Marjo; Gäddnäs, Fiia; Ala-Kokko, Tero I; Laurila, Jouko J; Saarnio, Juha; Oikarinen, Aarne; Koivukangas, Vesa

    2009-01-01

    Introduction The effect of sepsis on epidermal wound healing has not been previously studied. It was hypothesised that epidermal wound healing is disturbed in severe sepsis. Methods Blister wounds were induced in 35 patients with severe sepsis and in 15 healthy controls. The healing of the wounds was followed up by measuring transepidermal water loss and blood flow in the wound, reflecting the restoration of the epidermal barrier function and inflammation, respectively. The first set of suction blisters (early wound) was made within 48 hours of the first sepsis-induced organ failure and the second set (late wound) four days after the first wound. In addition, measurements were made on the intact skin. Results The average age of the whole study population was 62 years (standard deviation [SD] 12). The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission was 25 (SD 8). The two most common causes of infections were peritonitis and pneumonia. Sixty-six percent of the patients developed multiple organ failure. The decrease in water evaporation from the wound during the first four days was lower in septic patients than in the control subjects (56 g/m2 per hour versus 124 g/m2 per hour, P = 0.004). On the fourth day, septic patients had significantly higher blood flow in the wound compared with the control subjects (septic patients 110 units versus control subjects 47 units, P = 0.001). No difference in transepidermal water loss from the intact skin was found between septic patients and controls. Septic patients had higher blood flow in the intact skin on the fourth and on the eighth day of study compared with the controls. Conclusions The restoration of the epidermal barrier function is delayed and wound blood flow is increased in patients with severe sepsis. PMID:19552820

  6. Revised sequence of the Porphyromonas gingivalis prtT cysteine protease/hemagglutinin gene: homology with streptococcal pyrogenic exotoxin B/streptococcal proteinase.

    PubMed Central

    Madden, T E; Clark, V L; Kuramitsu, H K

    1995-01-01

    The prtT gene from Porphyromonas gingivalis ATCC 53977 was previously isolated from an Escherichia coli clone possessing trypsinlike protease activity upstream of a region encoding hemagglutinin activity (J. Otogoto and H. Kuramitsu, Infect. Immun. 61;117-123, 1993). Subsequent molecular analysis of this gene has revealed that the PrtT protein is larger than originally reported, encompassing the hemagglutination region. Results of primer extension experiments indicate that the translation start site was originally misidentified. An alternate open reading frame of nearly 2.7 kb, which encodes a protein in the size range of 96 to 99 kDa, was identified. In vitro transcription-translation experiments confirm this size, and Northern (RNA) blot experiments indicate that the protease is translated from a 3.3-kb mRNA. Searching the EMBL protein database revealed that the amino acid sequence of the revised PrtT is similar to sequences of two related proteins from Streptococcus pyogenes. PrtT is 31% identical and 73% similar over 401 amino acids to streptococcal pyrogenic exotoxin B. In addition, it is 36% identical and 74% similar over 244 amino acids with streptococcal proteinase, which is closely related to streptococcal pyrogenic exotoxin B. The similarity is particularly high at the putative active site of streptococcal proteinase, which is similar to the active sites of the family of cysteine proteases. Thus, we conclude that PrtT is a 96- to 99-kDa cysteine protease and hemagglutinin with significant similarity to streptococcal enzymes. PMID:7806362

  7. Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

    PubMed Central

    Weiss, Scott L.; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C.; Salloo, Asma; Singhi, Sunit C.; Erickson, Simon; Roy, Jason A.; Bush, Jenny L.; Nadkarni, Vinay M.; Thomas, Neal J.

    2015-01-01

    Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted. PMID:25734408

  8. Factors associated with severe sepsis: prospective study of 94 neutropenic febrile episodes.

    PubMed

    Jeddi, Ramzi; Achour, Mériem; Amor, Ramzi Ben; Aissaoui, Lamia; Bouterâa, Walid; Kacem, Karima; Lakhal, Raihane Ben; Abid, Héla Ben; BelHadjAli, Zaher; Turki, Amel; Meddeb, Balkis

    2010-02-01

    Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0.5 x 10(9)/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3-58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28.7%), six clinically documented (6.3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and -). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0.8 mmol/l; p=0.05, OR=3.9, 95% CI: 1.3-45.7), hypoproteinemia (<62 g/l; p=0.006, OR=4.1, 95% CI: 1.4-11.4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0.019, OR=2.7, 95% CI: 1.02-7.39). However, heart rate/systolic blood pressure ratio <1.1 (p<0.001, OR=0.1, 95% CI: 0.03-0.31) and Creactive protein <80 mg (p=0.001, OR=0.14, 95% CI: 0.04-0.54) were not predictive. PMID:20132659

  9. Neonatal group A streptococcal meningitis: a case report and review of the literature

    PubMed Central

    Lardhi, Amer A

    2008-01-01

    Introduction Group A streptococcus is a rare cause of neonatal meningitis. A review of MEDLINE database since1966 revealed only 15 documented cases of group A streptococcal meningitis in neonates. Case report A previously healthy 28 days old male neonate presented with a history of irritability, fever, and focal seizures. Cerebrospinal fluid analysis and culture confirmed the diagnosis of group A streptococcal meningitis. The clinical course was complicated by the development of brain abscess. The patient made full recovery following a surgical drainage of the abscess and a 6-week total course of antibiotics. Conclusion Although it is an uncommon organism, clinician should always consider group A streptococcal infection and its potential complications in the differential diagnosis and management of neonatal meningitis. PMID:18710558

  10. Plasma soluble Tim-3 emerges as an inhibitor in sepsis: sepsis contrary to membrane Tim-3 on monocytes.

    PubMed

    Ren, F; Li, J; Jiang, X; Xiao, K; Zhang, D; Zhao, Z; Ai, J; Hou, C; Jia, Y; Han, G; Xie, L

    2015-11-01

    Immune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim-3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim-3 (sTim-3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim-3 and human leukocyte antigen-DR (HLA-DR) on the circulating monocytes were detected using flow cytometry. Plasma sTim-3 was detected by enzyme-linked immunosorbent assay. Inflammatory factors and two kinds of A disintegrin and metalloprotease (ADAM) - ADAM10 and ADAM17 were assessed. The Tim-3 and HLA-DR on the monocytes decreased with increasing sepsis severity. The sTim-3 was reduced in the sepsis and severe sepsis patients but was elevated in the septic shock patients who exhibited significant immunosuppression as predicted by HLA-DR. sTim-3 levels were negatively correlated with IL-12 and TNF-?. ADAM10 and ADAM17, sheddases of Tim-3, exhibited trends toward elevations in the septic shock group. In conclusion, sTim-3 was involved in the development of sepsis. The homeostasis-promoting role of the Tim-3 on the monocytes was disrupted, while the inhibitory role of sTim-3 emerged during sepsis-induced immunosuppression. PMID:26373631

  11. A novel streptococcal integrative conjugative element involved in iron acquisition

    PubMed Central

    Heather, Zoe; Holden, Matthew T G; Steward, Karen F; Parkhill, Julian; Song, Lijiang; Challis, Gregory L; Robinson, Carl; Davis-Poynter, Nicholas; Waller, Andrew S

    2008-01-01

    In this study, we determined the function of a novel non-ribosomal peptide synthetase (NRPS) system carried by a streptococcal integrative conjugative element (ICE), ICESe2. The NRPS shares similarity with the yersiniabactin system found in the high-pathogenicity island of Yersinia sp. and is the first of its kind to be identified in streptococci. We named the NRPS product ‘equibactin’ and genes of this locus eqbA–N. ICESe2, although absolutely conserved in Streptococcus equi, the causative agent of equine strangles, was absent from all strains of the closely related opportunistic pathogen Streptococcus zooepidemicus. Binding of EqbA, a DtxR-like regulator, to the eqbB promoter was increased in the presence of cations. Deletion of eqbA resulted in a small-colony phenotype. Further deletion of the irp2 homologue eqbE, or the genes eqbH, eqbI and eqbJ encoding a putative ABC transporter, or addition of the iron chelator nitrilotriacetate, reversed this phenotype, implicating iron toxicity. Quantification of 55Fe accumulation and sensitivity to streptonigrin suggested that equibactin is secreted by S. equi and that the eqbH, eqbI and eqbJ genes are required for its associated iron import. In agreement with a structure-based model of equibactin synthesis, supplementation of chemically defined media with salicylate was required for equibactin production. PMID:18990191

  12. Clinical Characteristics of Community-Acquired Viridans Streptococcal Pneumonia

    PubMed Central

    Choi, Sun Ha; Choi, Keum-Ju; Lim, Jae-Kwang; Seo, Hyewon; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

    2015-01-01

    Background Viridans streptococci (VS) are a large group of streptococcal bacteria that are causative agents of community-acquired respiratory tract infection. However, data regarding their clinical characteristics are limited. The purpose of the present study was to investigate the clinical and radiologic features of community-acquired pneumonia (CAP) with or without parapneumonic effusion caused by VS. Methods Of 455 consecutive CAP patients with or without parapneumonic effusion, VS were isolated from the blood or pleural fluid in 27 (VS group, 5.9%) patients. Streptococcus pneumoniae was identified as a single etiologic agent in 70 (control group) patients. We compared various clinical parameters between the VS group and the control group. Results In univariate analysis, the VS group was characterized by more frequent complicated parapneumonic effusion or empyema and bed-ridden status, lower incidences of productive cough, elevated procalcitonin (>0.5 ng/mL), lower age-adjusted Charlson comorbidity index score, and more frequent ground glass opacity (GGO) or consolidation on computed tomography (CT) scans. Multivariate analysis demonstrated that complicated parapneumonic effusion or empyema, productive cough, bed-ridden status, and GGO or consolidation on CT scans were independent predictors of community-acquired respiratory tract infection caused by VS. Conclusion CAP caused by VS commonly presents as complicated parapneumonic effusion or empyema. It is characterized by less frequent productive cough, more frequent bed-ridden status, and less common CT pulmonary parenchymal lesions. However, its treatment outcome and clinical course are similar to those of pneumococcal pneumonia. PMID:26175772

  13. Methods and compositions for diagnosing and preventing a group B streptococcal infection

    DOEpatents

    Brady, Linda Jeannine (Gainesville, FL); Seifert, Kyle N. (Harrisonburg, VA); Adderson, Elisabeth E. (Memphis, TN); Bohnsack, John F. (Salt Lake City, UT)

    2009-09-15

    The present invention provides a group B streptococcal (GBS) surface antigen, designated epsilon antigen, that is co-expressed with the delta antigen on a subset of serotype III GBS. Epsilon is expressed on more pathogenic Restriction Digest Pattern (RDP) III-3 GBS, but not on RDP types 1, 2, or 4. Accordingly, the present invention provides compositions and methods for detecting a group B streptococcus serotype III, RDP III-3 strain. Vaccines and methods of identifying agents which inhibit adhesion of a group B streptococcal cell to a host cell are also provided.

  14. Improving the management of sepsis in a district general hospital by implementing the ‘Sepsis Six’ recommendations

    PubMed Central

    Kumar, Prashant; Jordan, Mark; Caesar, Jenny; Miller, Sarah

    2015-01-01

    Sepsis is a common condition with a major global impact on healthcare resources and expenditure. The Surviving Sepsis Campaign has been vigorous in promoting internationally recognised pathways to improve the management of septic patients and decrease mortality. However, translating recommendations into practice is a challenging and complex task that requires a multi-faceted approach with sustained engagement from local stakeholders. Whilst working at a district general hospital in New Zealand, we were concerned by the seemingly inconsistent management of septic patients, often leading to long delays in the initiation of life-saving measures such as antibiotic, fluid, and oxygen administration. In our hospital there were no clear systems, protocols or guidelines in place for identifying and managing septic patients. We therefore launched the Sepsis Six resuscitation bundle of care in our hospital in an attempt to raise awareness amongst staff and improve the management of septic patients. We introduced a number of simple low-cost interventions that included educational sessions for junior doctors and nursing staff, as well as posters and modifications to phlebotomy trolleys that acted as visual reminders to implement the Sepsis Six bundle. Overall, we found there to a be a steady improvement in the delivery of the Sepsis Six bundle in septic patients with 63% of patients receiving appropriate care within one hour, compared to 29% prior to our interventions. However this did not translate to an improvement in patient mortality. This project forms part of an on going process to instigate a fundamental culture change among local healthcare professionals regarding the management of sepsis. Whilst we have demonstrated improved implementation of the Sepsis Six bundle, the key challenge remains to ensure that momentum of this project continues and forms a platform for sustainable clinical improvement in the long term.

  15. Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats.

    PubMed Central

    Allen, J B; Malone, D G; Wahl, S M; Calandra, G B; Wilder, R L

    1985-01-01

    Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments to susceptible rats induces acute and chronic polyarthritis, as well as noncaseating hepatic granulomas. To gain insight into the role of the thymus in the pathogenesis of this experimental model, pathologic responses and cell wall tissue distribution were compared in congenitally athymic rats (rnu/rnu) and their euthymic littermates (NIH/rnu). Within 24 h, both rat strains developed acute arthritis, characterized by polymorphonuclear leukocytic exudate in the synovium and joint spaces. This acute process was maximal at day 3 and gradually subsided. Beginning 2-3 wk after injection, the euthymic, but not the athymic, rats developed the typical exacerbation of arthritis, characterized by synovial cell hyperplasia with villus formation and T helper/inducer lymphocyte-rich mononuclear cell infiltration. This process eventually resulted in marginal erosions and destruction of periarticular bone and cartilage. Parallel development of acute and chronic hepatic lesions was observed. Bacterial cell wall antigen distribution and persistence were similar in the athymic and euthymic rats. Cell wall antigens were demonstrated in the cytoplasm of cells within subchondral bone marrow, synovium, liver, and spleen, coincident with the development of the acute lesions, and persisted in these sites, although in decreasing amounts, for the duration of the experiment. Our findings provide evidence that the acute and chronic phases of the experimental model are mechanistically distinct. The thymus and functional thymus derived-lymphocytes appear not to be required for the development of the acute exudative disease but are essential for the development of chronic proliferative and erosive disease. Induction of disease is dependent upon cell wall dissemination to and persistence in the affected tissues. Images PMID:3876354

  16. Synergistic hemolysis phenomenon shown by an alpha-toxin-producing Clostridium perfingens and streptococcal CAMP factor in presumptive streptococcal grouping.

    PubMed Central

    Gubash, S M

    1978-01-01

    A new phenomenon of synergistic hemolysis by Clostridium perfringens alpha-toxin and the streptococcal CAMP factor on human and guinea pig erythrocytes is described. A possible mode of action of the CAMP factors is suggested. On human blood agar all of the tested isolates of group B streptococci gave an arrowhead-shaped zone of hemolysis; 74% of group A gave a crescent-shaped lytic zone, whereas all isolates of groups C and G and the remaining 26% of group A streptococci gave a bullet-shaped lytic zone. By comparison, in the CAMP test incubated aerobically and anaerobically, 70 and 91%, respectively, of streptococci other than group B gave positive, arrowhead-shaped lytic zones. If all intermediate positive reactions in the CAMP tests were read as negative after aerobic incubation, only 89% of group B streptococci would be properly identified. The synergistic hemolysis phenomenon, using an alpha-toxin-producing C. perfringens and human blood agar, provided a reliable test for presumptive identification of group B streptococci, with promising potential to differentiate in the same test group A streptococci from other groups. Images PMID:215600

  17. Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

    PubMed Central

    Zhao, Yunzhao; Han, Gang; Li, Weiqin; Huang, Qian; Tong, Zhihui; Li, Jieshou

    2012-01-01

    Background The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. Objective This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. Methods Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. Results Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. Conclusions Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care. Trial Registration ClinicalTrials.gov NCT01568853 PMID:23091606

  18. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study

    PubMed Central

    Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-01-01

    Objective To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Design Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients’ designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Setting Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Participants Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. Main outcome measure ‘Suspected infection’ was the established gold standard to assess clinical decision support clinimetric performance. Results A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying ‘suspected infection’ as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. Conclusion A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis. PMID:26688744

  19. Tolerance to endotoxin-induced expression of the interleukin-1 beta gene in blood neutrophils of humans with the sepsis syndrome.

    PubMed Central

    McCall, C E; Grosso-Wilmoth, L M; LaRue, K; Guzman, R N; Cousart, S L

    1993-01-01

    The induction of genes of host cells stimulated by microbial products such as endotoxin and the tolerance of cells to endotoxin excitation play critical roles in the pathogenesis of microbial-induced acute disseminated inflammation with multiorgan failure (the sepsis syndrome). One gene that is induced in phagocytic cells by endotoxin and that appears to play an essential role in the pathogenesis of the sepsis syndrome is IL-1 beta. We report here that blood neutrophils (PMN) of patients with the sepsis syndrome (sepsis PMN) are consistently tolerant to endotoxin-induced expression of the IL-1 beta gene, as determined by decreased synthesis of the IL-1 beta protein and reductions in IL-1 beta mRNA. This down-regulation of the IL-1 beta gene in sepsis PMN occurs concomitant with an upregulation in the constitutive expression of the type 2 IL-1 receptor (IL-1R2). These phenotypic changes do not persist in PMN of patients recovering from the sepsis syndrome. Tolerance has stimulus and response specificity since sepsis PMN tolerant to endotoxin can respond normally to Staphylococcus aureus stimulation of IL-1 beta production and they normally secrete elastase. Uninfected patients with severe trauma or shock from causes are not tolerant to endotoxin and tolerance is not limited to patients infected with Gram-negative bacteria. The mechanism responsible for tolerance involves pretranslational events and is not due to loss of the CD14 surface protein, a receptor required for endotoxin induction of IL-1 beta in PMN. The physiological significance of the tolerance to endotoxin and increased expression of IL-1R2 on sepsis PMN is unknown, but may represent an attempt by the host to protect itself from the deleterious effects of disseminated inflammation. Images PMID:7680670

  20. Sepsis and the innate-like response.

    PubMed

    Douglas, James J; Tsang, Jennifer L Y; Walley, Keith R

    2014-02-01

    Innate-like lymphocytes are a recently described subset of the immune response with known antibacterial properties. This human trial in critically ill patients provides the first evidence of the drop in MAIT cells during bacterial sepsis, which compounds the already known immune defects. The persistent depletion and potential for nosocomial infections is an interesting finding and one likely to provide fertile grounds for future studies. PMID:24322274

  1. Pneumococcal sepsis-induced purpura fulminans in an asplenic adult patient without disseminated intravascular coagulation.

    PubMed

    Saraceni, Christine; Schwed-Lustgarten, Daniel

    2013-12-01

    Acute perturbations in the hemostatic balance of anticoagulation and procoagulation antecede the manifestation of purpura fulminans, a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin. Hallmarks include small vessel thrombosis, tissue necrosis and disseminated intravascular thrombosis. The course may be rapidly fulminant resulting in multiorgan failure with thrombotic occlusion of the vasculature, leading to distal extremity ischemia and necrosis. Depletion of protein C (PC) has been emphasized in the pathogenesis. Early intravenous antibiotic administration and hemodynamic support are cornerstones in management. Herein, we report a case of pneumococcal sepsis-induced purpura fulminans limited to the skin in an asplenic adult patient without the development disseminated intravascular coagulation. PMID:24185261

  2. Mechanical Ventilation for ARDS Patients – For a Better Understanding of the 2012 Surviving Sepsis Campaign Guidelines

    PubMed Central

    Takeuchi, Muneyuki; Tachibana, Kazuya

    2015-01-01

    The mortality rate among patients suffering acute respiratory distress syndrome (ARDS) remains high despite implementation at clinical centers of the lung protective ventilatory strategies recommended by the International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. This suggests that such strategies are still sub-optimal for some ARDS patients. For these patients, tailored use of ventilator settings should be considered, including: further reduction of tidal volumes, administration of neuromuscular blocking agents if the patient’s spontaneous breathing is incompatible with mechanical ventilation, and adjusting positive end-expiratory pressure (PEEP) settings based on transpulmonary pressure levels. PMID:25567337

  3. Management of perianal sepsis in immunosuppressed patients.

    PubMed

    Muñoz-Villasmil, J; Sands, L; Hellinger, M

    2001-05-01

    Despite improvements in the supportive care of immunosuppressed patients controversy still surrounds the surgical management and outcome of anorectal sepsis in these patients. We reviewed 83 immunocompromised patients with diagnosis of perianal sepsis from 1995 to 1997. Sixty-six patients (80%) were followed for a mean of 15 months. Mean age was 44 years and 76 per cent were males. Twenty-eight per cent were HIV+, 34 per cent had inflammatory bowel disease on steroids, 20 per cent had malignancies, and 18 per cent had diabetes. Twenty-eight per cent had anal fistula, 2 per cent had perianal abscess, and 40 per cent had both. Primary sites of fistula were: transsphincteric (38%), intersphincteric (33%), superficial (20%), and suprasphincteric (3%), and multiple tracks (6%). Horseshoeing was present in 14 per cent of cases. The most commonly practiced surgical procedures were primary fistulotomy (n = 23) and fistulotomy plus drainage (n = 28). Seven patients underwent fistulotomy and ostomy and eight patients were treated with fistulectomy plus drainage. Most wounds (91%) healed within 8 weeks. Incontinence (6%) and recurrence (7%) were the most commonly observed complications. These results are similar to those seen in the general population. Perianal sepsis can be safely managed in immunocompromised patients, with high rates of healing and low complication rates. An aggressive sphincter-preserving approach in the management of these patients may be undertaken. PMID:11379655

  4. Protective effects of guanosine against sepsis-induced damage in rat brain and cognitive impairment.

    PubMed

    Petronilho, Fabricia; Périco, Susane Raquel; Vuolo, Francieli; Mina, Francielle; Constantino, Larissa; Comim, Clarissa M; Quevedo, João; Souza, Diogo Onofre; Dal-Pizzol, Felipe

    2012-08-01

    The development of cognitive impairment in sepsis is associated with neurotoxic effects caused by oxidative stress. We have assessed the effects of acute and extended administration of guanosine (GUA) on brain oxidative stress parameters and cognitive impairment in rats submitted to sepsis by cecal ligation and perforation (CLP). To achieve this goal, male Wistar rats underwent either sham operation or CLP with GUA. Rats subjected to CLP were treated with intraperitoneal injection of GUA (8 mg/kg after CLP) or vehicle. Twelve and 24 h after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day, another group of rats was submitted to the behavioral tasks. GUA administration reduced TBARS and carbonyl levels in some brain regions between 12 and 24 h after CLP, and ameliorated cognitive impairment evaluated 10 days after CLP. Our data provide the first experimental demonstration that GUA was able to reduce the consequences of CLP-induced sepsis in rats, by decreasing oxidative stress parameters in the brain and recovering the memory impairment. PMID:22497789

  5. Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

    PubMed Central

    Kojic, Dubravka; Siegler, Benedikt H; Uhle, Florian; Lichtenstern, Christoph; Nawroth, Peter P; Weigand, Markus A; Hofer, Stefan; Brenner, Thorsten

    2015-01-01

    Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects - i.e., sepsis induced immunosuppression - but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. PMID:25992320

  6. Obesity and One-Year Outcomes in Older Americans with Severe Sepsis

    PubMed Central

    Prescott, Hallie C.; Chang, Virginia W.; O’Brien, James M.; Langa, Kenneth M.; Iwashyna, Theodore

    2014-01-01

    Objectives While critical care physicians view obesity as an independent poor prognostic marker, growing evidence suggests that obesity is, instead, associated with improved mortality following ICU admission. However, this prior empirical work may be biased by preferential admission of obese patients to ICUs, and little is known about other patient-centered outcomes following critical illness. We sought to determine whether one-year mortality, health care utilization, and functional outcomes following a severe sepsis hospitalization differ by BMI. Design Observational cohort study. Patients We analyzed 1,404 severe sepsis hospitalizations (1999–2005) among Medicare beneficiaries enrolled in the nationally representative Health & Retirement Study, of which 597 (42.5%) were normal weight, 473 (33.7%) were overweight, and 334 (23.8%) were obese or severely obese, as assessed at their survey prior to acute illness. Underweight patients were excluded a priori. Interventions None. Measurements and Main Results Using Medicare claims, we identified severe sepsis hospitalizations and measured inpatient health care facility use and calculated total and itemized Medicare spending in the year following hospital discharge. Using the National Death Index, we determined mortality. We ascertained pre- and post-morbid functional status from survey data. Patients with greater BMIs experienced higher 1-year mortality compared to non-obese patients, and there was a dose response relationship such that obese (OR=0.59, 95%CI 0.39, 0.88) and severely obese patients (OR=0.46, 95%CI 0.26, 0.80) had the lowest mortality. Total days in a health care facility and Medicare expenditures were greater for obese patients (p<0.01 for both comparisons), but average daily utilization (p=0.44) and Medicare spending were similar (p=0.65) among normal, overweight and obese survivors. Total function limitations following severe sepsis did not differ by BMI category (p=0.64). Conclusions Obesity is associated with improved mortality among severe sepsis patients. Due to longer survival, obese sepsis survivors use more health care and result in higher Medicare spending in the year following hospitalization. Median daily health care utilization was similar across BMI categories. PMID:24717466

  7. Improved Diagnostic Accuracy of Group A Streptococcal Pharyngitis With Use of Real-Time Biosurveillance

    E-print Network

    Nizet, Victor

    prediction rules do not incorporate real-time incidence data to adjust estimates of disease risk decision rule for diagnosing group A streptococcal (GAS) pharyngitis in patients aged 15 years or older. For example, when the RLPP was greater than 0.30, managing patients with Centor scores of 1 as if the scores

  8. Cloning, sequence analysis, and expression in Escherichia coli of a streptococcal plasmin receptor.

    PubMed Central

    Lottenberg, R; Broder, C C; Boyle, M D; Kain, S J; Schroeder, B L; Curtiss, R

    1992-01-01

    Plasmin(ogen) receptors are expressed by many gram-positive and gram-negative bacteria. We previously isolated a plasmin receptor from a pathogenic group A streptococcal strain (C. C. Broder, R. Lottenberg, G. O. von Mering, K. H. Johnston, and M. D. P. Boyle, J. Biol. Chem. 266:4922-4928, 1991). The gene encoding this plasmin receptor, plr, was isolated from a lambda gt11 library of chromosomal DNA from group A streptococcal strain 64/14 by screening plaques with antibodies raised against the purified streptococcal plasmin receptor protein. The gene was subcloned by using a low-copy-number plasmid and stably expressed in Escherichia coli, resulting in the production of an immunoreactive and functional receptor protein. The DNA sequence of the gene contained an open reading frame encoding 335 amino acids with a predicted molecular weight of 35,787. Upstream of the open reading frame, putative promoter and ribosomal binding site sequences were identified. The experimentally derived amino acid sequences of the N terminus and three cyanogen bromide fragments of the purified streptococcal plasmin receptor protein corresponded to the predicted sequence encoded by plr. The deduced amino acid sequence for the plasmin receptor protein revealed significant similarity (39 to 54% identical amino acid residues) to glyceraldehyde 3-phosphate dehydrogenases. Images PMID:1322883

  9. Paedatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection in an Indian Adolescent--A Case Report

    ERIC Educational Resources Information Center

    Sharma, Sachin; Vaish, Supriya; Chopra, Saurabh; Singh, Vindyaprakash; Sharma, Priyanka

    2012-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infection (PANDAS) is a unique constellation of signs and symptoms that exist in a subset of children with rapid onset or exacerbation of obsessive-compulsive disorder (OCD) and/or tic disorders due to an initial autoimmune reaction to a Group A Beta Hemolytic…

  10. Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis.

    PubMed

    Hikone, Mayu; Kobayashi, Ken-Ichiro; Washino, Takuya; Ota, Masayuki; Sakamoto, Naoya; Iwabuchi, Sentaro; Ohnishi, Kenji

    2015-12-01

    Streptococcal toxic shock syndrome (TSS) is a systemic illness usually caused in the setting of infection by group A Streptococcus (GAS). The primary infections are often invasive infections of the respiratory tract or necrotizing infections of the skin and soft tissue, but some infections occur without relevant focus. GAS vaginitis is a rare condition among adult women and is accordingly thought to be uncommon as a cause of streptococcal TSS. Here we report the cases of two postmenopausal women with streptococcal TSS secondary to GAS vaginitis, one aged 55 and one aged 60. Both came to our emergency department with complaints or symptoms of abdominal pain, fever, hypotension, and multi-organ failure. In both cases, the relevant factor associated with streptococcal infection was a recent episode of GAS vaginitis. Both underwent fluid management and 14 days of antibiotic treatment and fully recovered without complications. Vaginitis was likely to be the primary infectious trigger of TSS in these two cases. Intrauterine device insertion, endometrial biopsy, and post-partum state have all been previously reported in TSS patients, and the female genital tract has been described as a portal of entry. GAS vaginitis warrants appropriate treatment as it may progress to severe systemic infection as described. PMID:26386777

  11. Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein.

    PubMed

    Persson, Sandra T; Wilk, Laura; Mörgelin, Matthias; Herwald, Heiko

    2015-12-01

    The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a pathogen-associated molecular pattern to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal protein kinase and the subsequent induction and mobilization of the transcription factors NF-?B and AP-1. We also determined the imprint of the inflammatory mediators released, such as interleukin-8 (IL-8), growth-related oncogene alpha, migration inhibitory factor, extracellular matrix metalloproteinase inducer, IL-1?, IL-1 receptor a, and ST2, in response to streptococcal M1 protein. The expression of IL-8 is dependent on Toll-like receptor 2 activity and subsequent activation of the mitogen-activated protein kinases ERK and p38. Notably, this signaling seems to be distinct for IL-8 release, and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate in a proinflammatory manner in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein. PMID:26416902

  12. Participatory Medicine: A Home Score for Streptococcal Pharyngitis Enabled by Real-Time Biosurveillance

    E-print Network

    Nizet, Victor

    Participatory Medicine: A Home Score for Streptococcal Pharyngitis Enabled by Real) pharyngitis. Objective: To help patients decide when to visit a clinician for the evaluation of sore throat patients aged 15 years or older with pharyngitis who visited a clinic from September 2006 to December 2008

  13. Identification of group C streptococcal antigen extracts with lectin-bound polystyrene particles.

    PubMed Central

    Slifkin, M; Gil, G M

    1984-01-01

    Crude extracts of Dolichos biflorus can be coupled to polystyrene particles to yield an agglutination reagent for the detection of group C streptococcal antigen extracts. The reagent is relatively inexpensive and simple to prepare and can be employed for the definitive identification of this beta-hemolytic streptococcus. PMID:6690470

  14. Public Awareness of Sepsis Is Low in Sweden.

    PubMed

    Mellhammar, Lisa; Christensson, Bertil; Linder, Adam

    2015-12-01

    Background. ?Sepsis is a serious and common condition with high mortality and morbidity. The public awareness, knowledge, and perception of sepsis in Sweden are unknown. Methods. ?A survey was performed using an online interview distributed to adults, aged 18-74, between March 6 and 9, 2015. Results. ?A total of 1001 people responded to the survey. Twenty-one percent of participants had heard of sepsis, whereas more than 86% had heard of each of the other conditions listed; for example, stroke (95%), chronic obstructive pulmonary disease (COPD) (95%), and leukemia (92%). Of those who had heard of sepsis, 93% responded that it is an infection or blood poisoning in an open question. The respondents who had heard of each disease estimated its mortality. For sepsis, the mortality was estimated at an average of 30%, which was at the same level as estimated mortalities for prostate and breast cancer but lower than for stroke, COPD, and leukemia. Conclusions. ?The awareness and knowledge of sepsis is low. The mortality for sepsis is not as overestimated as for many other diseases. The lack of awareness of sepsis might be a target to improve the outcome for sepsis patients by reducing the prehospital delay and hence enable early interventions. An increased general awareness might also raise interest for funding for research in this area and for its priority in healthcare support. PMID:26634220

  15. Public Awareness of Sepsis Is Low in Sweden

    PubMed Central

    Mellhammar, Lisa; Christensson, Bertil; Linder, Adam

    2015-01-01

    Background.?Sepsis is a serious and common condition with high mortality and morbidity. The public awareness, knowledge, and perception of sepsis in Sweden are unknown. Methods.?A survey was performed using an online interview distributed to adults, aged 18–74, between March 6 and 9, 2015. Results.?A total of 1001 people responded to the survey. Twenty-one percent of participants had heard of sepsis, whereas more than 86% had heard of each of the other conditions listed; for example, stroke (95%), chronic obstructive pulmonary disease (COPD) (95%), and leukemia (92%). Of those who had heard of sepsis, 93% responded that it is an infection or blood poisoning in an open question. The respondents who had heard of each disease estimated its mortality. For sepsis, the mortality was estimated at an average of 30%, which was at the same level as estimated mortalities for prostate and breast cancer but lower than for stroke, COPD, and leukemia. Conclusions.?The awareness and knowledge of sepsis is low. The mortality for sepsis is not as overestimated as for many other diseases. The lack of awareness of sepsis might be a target to improve the outcome for sepsis patients by reducing the prehospital delay and hence enable early interventions. An increased general awareness might also raise interest for funding for research in this area and for its priority in healthcare support. PMID:26634220

  16. TRPV1 and SP: key elements for sepsis outcome?

    PubMed Central

    Bodkin, Jennifer Victoria; Fernandes, Elizabeth Soares

    2013-01-01

    Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depends on the severity of systemic inflammation, which can be directly influenced by several factors, including the immune response of the patient. Currently, there is a lack of effective drugs to treat sepsis, and thus there is a need to develop new drugs to improve sepsis outcome. Several mediators involved in the formation of sepsis have now been identified, but the mechanisms underlying the pathology remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) receptor and the neuropeptide substance P (SP) have recently been demonstrated as important targets for sepsis and are located on sensory neurones and non-neuronal cells. Herein, we highlight and review the importance of sensory neurones for the modulation of sepsis, with specific focus on recent findings relating to TRPV1 and SP, with their distinct abilities to alter the transition from local to systemic inflammation and also modify the overall sepsis outcome. We also emphasize the protective role of TRPV1 in this context. LINKED ARTICLES This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 PMID:23145480

  17. Role of Extracellular and Intracellular MicroRNAs in Sepsis

    PubMed Central

    Essandoh, Kobina; Fan, Guo-Chang

    2014-01-01

    Sepsis is the major cause of death in the intensive care unit (ICU). Numerous biomarkers have been studied to identify the cause and severity of sepsis but these factors cannot differentiate between infectious and non-infectious inflammatory response. MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate the expression of genes by repressing translation or degrading mRNA. Importantly, miRNAs can be released outside cells and easily detectable in bodily fluids such as blood, sweat, urine and breast milk. Numerous studies have explored the idea of utilizing extracellular miRNAs as biomarkers for sepsis by profiling the dysregulation of miRNAs in blood samples of sepsis patients. So far, miR-223, miR-146a and miR-150 have been identified to have promising prognostic and diagnostic value to sepsis. In addition, various intracellular miRNAs have been implicated to play critical roles in regulating the TLR-NF-?B pathway, which is a well-known inflammatory signaling pathway involved in the process of sepsis. Here, we summarize the recent progress on the role of extracellular and intracellular miRNAs in sepsis. Specifically, we discuss the possible role of circulating miRNA biomarkers for the diagnosis of sepsis and how intracellular miRNAs regulate the inflammatory responses in sepsis. PMID:25086335

  18. Experimental treatments for mitochondrial dysfunction in sepsis: A narrative review

    PubMed Central

    Zheng, Guilang; Lyu, Juanjuan; Huang, Jingda; Xiang, Dan; Xie, Meiyan; Zeng, Qiyi

    2015-01-01

    Sepsis is a systemic inflammatory response to infection. Sepsis, which can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome, is an important cause of mortality. Pathogenesis is extremely complex. In recent years, cell hypoxia caused by mitochondrial dysfunction has become a hot research field. Sepsis damages the structure and function of mitochondria, conversely, mitochondrial dysfunction aggravated sepsis. The treatment of sepsis lacks effective specific drugs. The aim of this paper is to undertake a narrative review of the current experimental treatment for mitochondrial dysfunction in sepsis. The search was conducted in PubMed databases and Web of Science databases from 1950 to January 2014. A total of 1,090 references were retrieved by the search, of which 121 researches met all the inclusion criteria were included. Articles on the relationship between sepsis and mitochondria, and drugs used for mitochondrial dysfunction in sepsis were reviewed retrospectively. The drugs were divided into four categories: (1) Drug related to mitochondrial matrix and respiratory chain, (2) drugs of mitochondrial antioxidant and free radical scavengers, (3) drugs related to mitochondrial membrane stability, (4) hormone therapy for septic mitochondria. In animal experiments, many drugs show good results. However, clinical research lacks. In future studies, the urgent need is to develop promising drugs in clinical trials. PMID:25983774

  19. Rhabdomyolysis in Community Acquired Bacterial Sepsis – A Retrospective Cohort Study

    PubMed Central

    Kumar, Anita A.; Bhaskar, Emmanuel; Palamaner Subash Shantha, Ghanshyam; Swaminathan, Porchelvan; Abraham, Georgi

    2009-01-01

    Background and Objectives Rhabdomyolysis is often associated with sepsis and gram positive bacterial pathogens are reported to be the most frequent cause of sepsis induced rhabdomyolysis. We report the pattern of infecting bacterial pathogens and associated causal factors in a South-Indian cohort. Design, Setting, Participants & Measurements Retrospective cohort study of adult patients with community acquired bacterial sepsis complicated by rhabdomyolysis from March 2003 - August 2008. Rhabdomyolysis was defined as serum creatine kinase >2000 IU/L. The study population was divided into group-I (sepsis with gram positive pathogens), group–II (sepsis with gram negative pathogens) and group-III (culture negative sepsis). Results 103 patients (group I -15, group II- 34 and group III- 54) formed the study cohort. Mean age was 55 years and two-third had diabetes. Mean creatine kinase was 7114 IU/L and mean serum creatinine on admission was 2.4 mg/dl. Causative pathogen of sepsis was identified in 47.5%. Gram negative pathogens were more frequently (33%) associated with rhabdomyolysis than gram positive pathogens (14.5%). Lung was the commonest foci of sepsis (38.8%). 78.6% of the study population had one or more additional causal factor for rhabdomyolysis like statin intake, chronic alcoholism, hypokalemia, hypernatremia and hypophosphatemia. Mortality was 59%. Conclusions Gram negative bacterial pathogens were more frequently associated with rhabdomyolysis than gram positive pathogens. Rhabdomyolysis in patients with sepsis is multifactorial and is associated with high mortality. PMID:19787056

  20. Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse.

    PubMed

    Anderson, Seán T; Commins, Seán; Moynagh, Paul N; Coogan, Andrew N

    2015-01-01

    Post-septic encephalopathy is a poorly understood condition in survivors of sepsis that is characterised by cognitive and affective impairments. In this study we have sought to better understand this condition by undertaking a comprehensive behavioural and cognitive assessment of mice who had previously survived sepsis. Mice were treated with lipopolysaccharide (LPS; 5mg/kg) and one month after this assessed on a battery of tests. Post-septic animals were found to display significantly more immobility in the tail suspension test and show a significantly decreased sucrose preference. Acute fluoxetine treatment reversed the increase in immobility in the tail suspension test in post-septic animals. Post-septic animals also showed less overall exploratory behaviour in the novel object recognition task and also showed increased anxiety-like behaviour in the elevated plus maze. Post-septic mice did not show signs of cognitive impairment, as assessed in the Morris watermaze, the 8-arm radial maze or on preference for the novel object in the novel object recognition task. Immunohistochemical analysis revealed significant upregulation of the microglial marker CD-11b, F4/80 and IBA-1 in the hippocampus of post-septic animals, as well as significant downregulation of the plasticity-related immediate early gene products ARC and EGR1. We also observed a decrease in neural stem cell proliferation in the dentate gyrus of post-septic animals as judged by BrdU incorporation. Co-treatment with the NF-?B pathway inhibitor PDTC attenuated the long-lasting effects of LPS on most of the affected parameters, but not on neural stem cell proliferation. These results show that LPS-induced sepsis in the mouse is followed by long-lasting increases in depressive- and anxiety-like behaviours, as well as by changes in neuroinflammatory- and neural plasticity-associated factors, and that attenuation of the severity of sepsis by PDTC attenuates many of these effects. PMID:25063709

  1. Different regulation of Toll-like receptor 4 expression on blood CD14+ monocytes by simvastatin in patients with sepsis and severe sepsis

    PubMed Central

    Shao, Huanzhang; Wang, Cunzhen; Zhu, Wenliang; Huang, Xiaopei; Guo, Zhisong; Zhang, Huifeng; Qin, Bingyu

    2015-01-01

    We have demonstrated that regulation of Toll-like receptor 4 (TLR4) surface expression levels on blood CD14+ monocytes by simvastatin treatment in patient with sepsis is different from that in patients with severe sepsis. In patients with sepsis simvastatin treatment statistically significantly decreased TLR4 surface expression level on blood CD14+ monocytes, while in patients with severe sepsis simvastatin treatment had no significant influence on TLR4 surface expression level on blood CD14+ monocytes. The changes of plasma interleukin-6 (IL-6) induced by simvastatin in patients with sepsis and severe sepsis were similar with that of TLR4. Our results indicated simvastatin treatment differently influenced inflammation process in patients with sepsis and severe sepsis, which might partially explain the discrepancy, presented by previous trials, about the therapeutic effects of simvastatin treatment in patients with sepsis and severe sepsis. PMID:26550333

  2. MFHAS1 Is Associated with Sepsis and Stimulates TLR2/NF-?B Signaling Pathway Following Negative Regulation

    PubMed Central

    Zhong, Jing; Shi, Qi-Qing; Zhu, Min-Min; Shen, Jian; Wang, Hui-Hui; Ma, Duan; Miao, Chang-Hong

    2015-01-01

    Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) has a potential immunoregulatory role dependent on Toll-like receptors (TLRs). TLR2, associated with deleterious systemic inflammation, cardiac dysfunction, and acute kidney injury, acts synergistically in sepsis. The role of MFHAS1 in targeting TLR2 involved in sepsis has not been examined thus far. This study aimed to examine the relationship of MFHAS1 and sepsis, and the effect of MFHAS1 on the TLR2 signaling pathway. Blood samples were collected from eight sepsis patients after surgery and eight patients undergoing selective surgery to determine blood MFHAS1 levels. HEK 293 cells, RAW 264.7 macrophages and THP-1 monocytes were used to confirm the effect of MFHAS1 on TLR2 signaling pathway. Our study showed that blood MFHAS1 was significantly elevated in septic patients, and MFHAS1 was more increased in mononuclear cells from septic patients. Pam3CSK4 (TLR2 ligand) was found to induce MFHAS1 production in RAW 264.7 murine macrophages and THP-1 human monocytes in a time-dependent manner. MFHAS1 has dual effects on TLR2 signaling pathway and inflammation, i.e., inhibitory effect at 6 hours, and then stimulatory effect after 24 hours through the activation of TLR2/NF-?B signaling pathway, and MFHAS1 induced the phosphorylation of JNK and p38 after TLR2 stimulation. PMID:26599367

  3. Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial

    PubMed Central

    2011-01-01

    Background By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. Methods/Design The 6S trial will randomise 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. Discussion The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed. Trial Registration ClinicalTrials.gov: NCT00962156 PMID:21269526

  4. Severe sepsis and septic shock in the elderly: An overview

    PubMed Central

    Nasa, Prashant; Juneja, Deven; Singh, Omender

    2012-01-01

    The incidence of severe sepsis and septic shock is increasing in the older population leading to increased admissions to the intensive care units (ICUs). The elderly are predisposed to sepsis due to co-existing co-morbidities, repeated and prolonged hospitalizations, reduced immunity, functional limitations and above all due to the effects of aging itself. A lower threshold and a higher index of suspicion is required to diagnose sepsis in this patient population because the initial clinical picture may be ambiguous, and aging increases the risk of a sudden deterioration in sepsis to severe sepsis and septic shock. Management is largely based on standard international guidelines with a few modifications. Age itself is an independent risk factor for death in patients with severe sepsis, however, many patients respond well to timely and appropriate interventions. The treatment should not be limited or deferred in elderly patients with severe sepsis only on the grounds of physician prejudice, but patient and family preferences should also be taken into account as the outcomes are not dismal. Future investigations in the management of sepsis should not only target good functional recovery but also ensure social independence and quality of life after ICU discharge. PMID:24701398

  5. A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma.

    PubMed

    Cuenca, Alex G; Delano, Matthew J; Kelly-Scumpia, Kindra M; Moreno, Claudia; Scumpia, Philip O; Laface, Drake M; Heyworth, Paul G; Efron, Philip A; Moldawer, Lyle L

    2011-01-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells whose numbers dramatically increase in chronic and acute inflammatory diseases, including cancer, autoimmune disease, trauma, burns and sepsis. Studied originally in cancer, these cells are potently immunosuppressive, particularly in their ability to suppress antigen-specific CD8(+) and CD4(+) T-cell activation through multiple mechanisms, including depletion of extracellular arginine, nitrosylation of regulatory proteins, and secretion of interleukin 10, prostaglandins and other immunosuppressive mediators. However, additional properties of these cells, including increased reactive oxygen species and inflammatory cytokine production, as well as their universal expansion in nearly all inflammatory conditions, suggest that MDSCs may be more of a normal component of the inflammatory response ("emergency myelopoiesis") than simply a pathological response to a growing tumor. Recent evocative data even suggest that the expansion of MDSCs in acute inflammatory processes, such as burns and sepsis, plays a beneficial role in the host by increasing immune surveillance and innate immune responses. Although clinical efforts are currently underway to suppress MDSC numbers and function in cancer to improve antineoplastic responses, such approaches may not be desirable or beneficial in other clinical conditions in which immune surveillance and antimicrobial activities are required. PMID:21085745

  6. Targeting HMGB1 in the treatment of sepsis

    PubMed Central

    Wang, Haichao; Ward, Mary F.; Sama, Andrew E.

    2013-01-01

    Introduction Sepsis refers to the host’s deleterious and non-resolving systemic inflammatory response to microbial infections, and represents the leading cause of death in the intensive care unit. The pathogenesis of sepsis is complex, but partly mediated by a newly identified alarmin molecule, the high mobility group box 1 (HMGB1). Areas covered Here we review the evidence that support extracellular HMGB1 as a late mediator of experimental sepsis with a wider therapeutic window, and discuss the therapeutic potential of HMGB1-neutralizing antibodies and small molecule inhibitors (herbal components) in experimental sepsis. Expert opinion It will be important to evaluate the efficacy of HMGB1-targeting strategies for the clinical management of human sepsis in the future. PMID:24392842

  7. Functional relevance of IL-10 promoter polymorphisms for sepsis development

    PubMed Central

    2010-01-01

    The induced production of proinflammatory and anti-inflammatory cytokines is considered important for the development of sepsis and its sequelae. Polymorphisms in the IL-10 gene promoter could influence its expression and sepsis susceptibility. Results obtained by Dr Ling and colleagues demonstrated that the -1082A allele was significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose-dependent fashion. They also showed that this polymorphism was significantly associated with sepsis development after major trauma. These and other research data clearly demonstrated that the -1082 A/G polymorphism in the IL-10 gene promoter has an important impact on susceptibility of sepsis and sepsis outcome. PMID:20236506

  8. Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model

    PubMed Central

    2011-01-01

    Background Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model. Methods Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology. Results Arterial pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 105) CFU/ml for NaCl treated pigs (p = 0.4159). Conclusions Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model. PMID:21875435

  9. Hypomagnesemia in Critically Ill Sepsis Patients

    PubMed Central

    Velissaris, Dimitrios; Karamouzos, Vassilios; Pierrakos, Charalampos; Aretha, Diamanto; Karanikolas, Menelaos

    2015-01-01

    Magnesium (Mg), also known as “the forgotten electrolyte”, is the fourth most abundant cation overall and the second most abundant intracellular cation in the body. Mg deficiency has been implicated in the pathophysiology of many diseases. This article is a review of the literature regarding Mg abnormalities with emphasis on the implications of hypomagnesemia in critical illness and on treatment options for hypomagnesemia in critically ill patients with sepsis. Hypomagnesemia is common in critically ill patients, and there is strong, consistent clinical evidence, largely from observational studies, showing that hypomagnesemia is significantly associated with increased need for mechanical ventilation, prolonged ICU stay and increased mortality. Although the mechanism linking hypomagnesemia with poor clinical outcomes is not known, experimental data suggest mechanisms contributing to such outcomes. However, at the present time, there is no clear evidence that magnesium supplementation improves outcomes in critically ill patients with hypomagnesemia. Large, well-designed clinical trials are needed to evaluate the role of magnesium therapy for improving outcomes in critically ill patients with sepsis. PMID:26566403

  10. Hypomagnesemia in Critically Ill Sepsis Patients.

    PubMed

    Velissaris, Dimitrios; Karamouzos, Vassilios; Pierrakos, Charalampos; Aretha, Diamanto; Karanikolas, Menelaos

    2015-12-01

    Magnesium (Mg), also known as "the forgotten electrolyte", is the fourth most abundant cation overall and the second most abundant intracellular cation in the body. Mg deficiency has been implicated in the pathophysiology of many diseases. This article is a review of the literature regarding Mg abnormalities with emphasis on the implications of hypomagnesemia in critical illness and on treatment options for hypomagnesemia in critically ill patients with sepsis. Hypomagnesemia is common in critically ill patients, and there is strong, consistent clinical evidence, largely from observational studies, showing that hypomagnesemia is significantly associated with increased need for mechanical ventilation, prolonged ICU stay and increased mortality. Although the mechanism linking hypomagnesemia with poor clinical outcomes is not known, experimental data suggest mechanisms contributing to such outcomes. However, at the present time, there is no clear evidence that magnesium supplementation improves outcomes in critically ill patients with hypomagnesemia. Large, well-designed clinical trials are needed to evaluate the role of magnesium therapy for improving outcomes in critically ill patients with sepsis. PMID:26566403

  11. Alterations in zinc binding capacity, free zinc levels and total serum zinc in a porcine model of sepsis.

    PubMed

    Hoeger, Janine; Simon, Tim-Philipp; Doemming, Sabine; Thiele, Christoph; Marx, Gernot; Schuerholz, Tobias; Haase, Hajo

    2015-08-01

    Zinc is crucial for immune function. In addition, the redistribution of zinc and other nutrients due to infection is an integral part of the host immune response to limit availability to pathogens. However, the major zinc binding protein albumin is down regulated during the acute phase response, implicating a decrease in zinc binding capacity. A prospective animal study with eight female German landrace pigs was conducted to investigate alterations in zinc binding capacity, total serum zinc and free zinc levels in the initial phase of sepsis. Sepsis was induced by instillation of autologous feces via midline laparotomy. Total serum zinc declined significantly after 1 h (10.89 ± 0.42 µM vs. 7.67 ± 0.41 µM, p < 0.001), total serum copper and iron reached a significant reduction at 4 h. Urinary excretion of zinc declined in line with total serum zinc. In comparison to total serum zinc, free zinc levels declined to a lesser, though significant, extent. Zinc binding capacity of serum decreased over time, whereby free zinc levels after addition of zinc correlated negatively with total serum protein and albumin levels. In addition IL-6 and TNF-? concentrations were measured and increased significantly 2 h after induction of sepsis. Hence, total serum zinc was the first marker of inflammation in our experiment, and might therefore be a promising biomarker for the early diagnosis of sepsis. Furthermore the observation of a substantially different serum free zinc homeostasis during sepsis provides valuable information for a potential therapeutic zinc supplementation, which has to take buffering capacity by serum proteins into account. PMID:25940830

  12. Application of the C3-Binding Motif of Streptococcal Pyrogenic Exotoxin B to Protect Mice from Invasive Group A Streptococcal Infection

    PubMed Central

    Kuo, Chih-Feng; Tsao, Nina; Cheng, Miao-Hui; Yang, Hsiu-Chen; Wang, Yu-Chieh; Chen, Ying-Pin; Lin, Kai-Jen

    2015-01-01

    Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345–398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection. PMID:25629609

  13. Erythrocyte antinuclear antibodies in sera of chickens hyperimmunized with group A streptococcal vaccine.

    PubMed Central

    Luster, M I; Leslie, G A

    1976-01-01

    Chickens hyperimmunized with group A streptococcal vaccine often synthesize high levels of antibody to group A streptococcal carbohydrate (SACHO). Indirect immunofluorescent analysis revealed that sera of these chickens also contain antinuclear antibodies capable of reacting with chicken erythrocyte nuclei (EANA) at titers up to 2,560. Removal of the anti-SACHO antibodies from hyperimmune serum did not significantly reduce EANA titers, indicating that anti-SACHO antibodies are not responsible for the EANA reactions. The time course for antibody development as well as the immunoglobulin class distribution of EANA and anti-SACHO antibodies were very similar. Localization of EANA activity to Fab fragments indicated that the immunfluorescent reaction represents an antigen-antibody reaction. Findings point out an important consequence of using chicken immunoglobulin Y in immunofluorescent assays. The purified Fc fragment of immunoglobulin Y is cytophilic for the substrate when tested at high concentrations, which suggests that some cytophilic immunoglobulins are involved in the reaction. PMID:773827

  14. Impact of chemically-modified tetracycline 3 on intertwined physiological, biochemical, and inflammatory networks in porcine sepsis/ARDS.

    PubMed

    Sadowsky, David; Nieman, Gary; Barclay, Derek; Mi, Qi; Zamora, Ruben; Constantine, Gregory; Golub, Lorne; Lee, Hsi-Ming; Roy, Shreyas; Gatto, Louis A; Vodovotz, Yoram

    2015-01-01

    Sepsis can lead to multiple organ dysfunction, including the Acute Respiratory Distress Syndrome (ARDS), due to intertwined, dynamic changes in inflammation and organ physiology. We have demonstrated the efficacy of Chemically-Modified Tetracycline 3 (CMT-3) at reducing inflammation and ameliorating pathophysiology in the setting of a clinically realistic porcine model of ARDS. Here, we sought to gain insights into the derangements that characterize sepsis/ARDS and the possible impact of CMT-3 thereon, by combined experimental and computational studies. Two groups of anesthetized, ventilated pigs were subjected to experimental sepsis via placement of a peritoneal fecal clot and intestinal ischemia/reperfusion by clamping the superior mesenteric artery for 30 min. The treatment group (n = 3) received CMT-3 at 1 hour after injury (T1), while the control group (n = 3) received a placebo. Multiple inflammatory mediators, along with clinically relevant physiologic and blood chemistry variables, were measured serially until death of the animal or T48. Principal Component Analysis (PCA) and Dynamic Bayesian Network (DBN) inference were used to relate these variables. PCA revealed a separation of cardiac and pulmonary physiologic variables by principal component, and a decreased rank of oxygen index and arterial PO2/FiO2 ratio in the treatment group compared to control. DBN suggested a conserved network structure in both control and CMT-3 animals: a response driven by positive feedback between interleukin-6 and lung dysfunction. Resulting networks further suggested that in control animals, acute kidney injury, acidosis, and respiratory failure play an increased role in the response to insult compared to CMT-3 animals. These combined in vivo and in silico studies in a high fidelity, clinically applicable animal model suggest a dynamic interplay between inflammatory, physiologic, and blood chemistry variables in the setting of sepsis and ARDS that may be dramatically altered by pleiotropic interruption of inflammation by CMT-3. PMID:26064799

  15. Impact of chemically-modified tetracycline 3 on intertwined physiological, biochemical, and inflammatory networks in porcine sepsis/ARDS

    PubMed Central

    Sadowsky, David; Nieman, Gary; Barclay, Derek; Mi, Qi; Zamora, Ruben; Constantine, Gregory; Golub, Lorne; Lee, Hsi-Ming; Roy, Shreyas; Gatto, Louis A; Vodovotz, Yoram

    2015-01-01

    Sepsis can lead to multiple organ dysfunction, including the Acute Respiratory Distress Syndrome (ARDS), due to intertwined, dynamic changes in inflammation and organ physiology. We have demonstrated the efficacy of Chemically-Modified Tetracycline 3 (CMT-3) at reducing inflammation and ameliorating pathophysiology in the setting of a clinically realistic porcine model of ARDS. Here, we sought to gain insights into the derangements that characterize sepsis/ARDS and the possible impact of CMT-3 thereon, by combined experimental and computational studies. Two groups of anesthetized, ventilated pigs were subjected to experimental sepsis via placement of a peritoneal fecal clot and intestinal ischemia/reperfusion by clamping the superior mesenteric artery for 30 min. The treatment group (n = 3) received CMT-3 at 1 hour after injury (T1), while the control group (n = 3) received a placebo. Multiple inflammatory mediators, along with clinically relevant physiologic and blood chemistry variables, were measured serially until death of the animal or T48. Principal Component Analysis (PCA) and Dynamic Bayesian Network (DBN) inference were used to relate these variables. PCA revealed a separation of cardiac and pulmonary physiologic variables by principal component, and a decreased rank of oxygen index and arterial PO2/FiO2 ratio in the treatment group compared to control. DBN suggested a conserved network structure in both control and CMT-3 animals: a response driven by positive feedback between interleukin-6 and lung dysfunction. Resulting networks further suggested that in control animals, acute kidney injury, acidosis, and respiratory failure play an increased role in the response to insult compared to CMT-3 animals. These combined in vivo and in silico studies in a high fidelity, clinically applicable animal model suggest a dynamic interplay between inflammatory, physiologic, and blood chemistry variables in the setting of sepsis and ARDS that may be dramatically altered by pleiotropic interruption of inflammation by CMT-3. PMID:26064799

  16. Distribution and isolation frequency of eight streptococcal species in saliva from predentate and dentate children and adults.

    PubMed

    Tappuni, A R; Challacombe, S J

    1993-01-01

    The isolation frequency and distribution of eight recently defined streptococcal species have been investigated in the saliva of adults and that of both predentate and dentate children. The effects of frequency of sugar intake and tooth presence on the distribution of streptococcal species were also analyzed. Saliva samples were collected from 121 subjects divided into three study groups: (a) 56 predentate children (predentate group), (b) 37 dentate children (dentate group), and (c) 28 adults (adult group). Up to 17 biochemical and enzymatic tests were used to categorize streptococcal isolates into S. mitis, S. oralis, S. salivarius, S. anginosus, S. sanguis, S. vestibularis, S. mutans, and S. gordonii. The mean total and streptococcal salivary colony-forming units (CFU) were lowest in the predentate group and highest in the adult group. Streptococci were found in all the study subjects, and there was no obvious relationship between the total or streptococcal CFU and the number of teeth or the frequency of sugar intake. There was a wide variation in the isolation frequency of streptococcal species in the three study groups. S. mitis, S. oralis, and S. salivarius were the most frequent species isolated, and together they comprised 83% of the total streptococcal isolates. In contrast to studies using older classifications, S. sanguis was a minor species in the saliva though found more often in adults than in children (p < 0.04). S. anginosus was a minor species found in about 10% of adults and children. S. gordonii was detected rarely and only in dentate subjects. S. mutans was detected only in dentate subjects, significantly greater in adults (57.1%) than in children (5.4%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8418104

  17. Incorporating Interprofessional Evidenced-Based Sepsis Simulation Education for Certified Nursing Assistants (CNAs) and Licensed Care Providers Within Long-term Care Settings for Process and Quality Improvement.

    PubMed

    Mihaljevic, Susan E; Howard, Valerie M

    2016-01-01

    Improving resident safety and quality of care by maximizing interdisciplinary communication among long-term care providers is essential in meeting the goals of the United States' Federal Health care reform. The new Triple Aim goals focus on improved patient outcomes, increasing patient satisfaction, and decreased health care costs, thus providing consumers with quality, efficient patient-focused care. Within the United States, sepsis is the 10th leading cause of death with a 28.6% mortality rate in the elderly, increasing to 40% to 60% in septic shock. As a result of the Affordable Care Act, the Centers for Medicare & Medicaid services supported the Interventions to Reduce Acute Care Transfers 3.0 program to improve health care quality and prevent avoidable rehospitalization by improving assessment, documentation, and communication among health care providers. The Interventions to Reduce Acute Care Transfers 3.0 tools were incorporated in interprofessional sepsis simulations throughout 19 long-term care facilities to encourage the early recognition of sepsis symptoms and prompt communication of sepsis symptoms among interdisciplinary teams. As a result of this simulation training, many long-term care organizations have adopted the STOP and WATCH and SBAR tools as a venue to communicate resident condition changes. PMID:26633155

  18. Activated Complement Factors as Disease Markers for Sepsis

    PubMed Central

    Charchaflieh, Jean; Rushbrook, Julie; Worah, Samrat; Zhang, Ming

    2015-01-01

    Sepsis is a leading cause of death in the United States and worldwide. Early recognition and effective management are essential for improved outcome. However, early recognition is impeded by lack of clinically utilized biomarkers. Complement factors play important roles in the mechanisms leading to sepsis and can potentially serve as early markers of sepsis and of sepsis severity and outcome. This review provides a synopsis of recent animal and clinical studies of the role of complement factors in sepsis development, together with their potential as disease markers. In addition, new results from our laboratory are presented regarding the involvement of the complement factor, mannose-binding lectin, in septic shock patients. Future clinical studies are needed to obtain the complete profiles of complement factors/their activated products during the course of sepsis development. We anticipate that the results of these studies will lead to a multipanel set of sepsis biomarkers which, along with currently used laboratory tests, will facilitate earlier diagnosis, timely treatment, and improved outcome. PMID:26420913

  19. Proteomic and epigenomic markers of sepsis-induced delirium (SID)

    PubMed Central

    Sfera, Adonis; Price, Amy I.; Gradini, Roberto; Cummings, Michael; Osorio, Carolina

    2015-01-01

    In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143–152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis? PMID:26579527

  20. Mortality in Sepsis and its relationship with Gender

    PubMed Central

    Nasir, Nosheen; Jamil, Bushra; Siddiqui, Shahla; Talat, Najeeha; Khan, Fauzia A.; Hussain, Rabia

    2015-01-01

    Background and Objective: Sepsis remains a leading cause of death across the world, carrying a mortality rate of 20–50%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients. Methods: This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNF?) levels and patients were followed up for clinical outcome. Results: There were 54% males and 46% females, with no significant difference of age or comorbids between genders. Respiratory tract infection was the commonest source of sepsis, and was more common in females (60%) compared to males (39%) (p=0.034). Males had a higher mortality (p=0.048, RR 1.73) and plasma IL-6 level(p=0.040) compared to females. Mean IL-6 plasma level was significantly (p<0.01) higher in patients who died vs. who recovered. Conclusion: Our study shows that males with sepsis have a 70% greater mortality rate, and mortality is associated with a higher IL-6 plasma level. PMID:26649014

  1. Severity of polymicrobial sepsis modulates mitochondrial function in rat liver.

    PubMed

    Herminghaus, A; Barthel, F; Heinen, A; Beck, C; Vollmer, C; Bauer, I; Weidinger, A; Kozlov, A V; Picker, O

    2015-09-01

    Mitochondrial dysfunction is assumed to be an important contributor to multi organ dysfunction syndrome. Here, the effects of varying degrees of sepsis on hepatic mitochondrial function were investigated. Moderate or more severe sepsis was induced in rats using a colon ascendens stent peritonitis (CASP)-model (16 G and 14 G stent respectively). Respiratory control ratio (RCR) was significantly higher in the 16 G-group and unchanged in the 14 G-group compared with healthy controls. The ADP/O ratio was similar in all groups. Our results indicate that different severities of sepsis differently influence the mitochondrial function, which could be a sign of adaptive reaction. PMID:26277734

  2. Pediatric Severe Sepsis in US Children’s Hospitals

    PubMed Central

    Balamuth, Fran; Weiss, Scott L.; Neuman, Mark I.; Scott, Halden; Brady, Patrick W.; Paul, Raina; Farris, Reid W.D.; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S.; Alpern, Elizabeth R.

    2014-01-01

    Objective To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Design Observational cohort study from 2004–2012. Setting Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Patients Children ?18 years of age. Measurements and Main Results We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition-Clinical Modification (ICD9-CM) based coding strategies: 1) combinations of ICD9-CM codes for infection plus organ dysfunction (combination code cohort); 2) ICD9-CM codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and intensive care unit (ICU) length of stay (LOS), and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified, 176,124 hospitalizations (3.1% of all hospitalizations), while the sepsis code cohort identified 25,236 hospitalizations (0.45%), a 7-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p<0.001 for trend in each cohort). LOS (hospital and ICU) and costs decreased in both cohorts over the study period (p<0.001). Overall hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2%, (95% CI: 20.7–21.8 vs. 8.2%,(95% CI: 8.0–8.3). Over the 9 year study period, there was an absolute reduction in mortality of 10.9% (p<0.001) in the sepsis code cohort and 3.8% (p<0.001) in the combination code cohort. Conclusions Prevalence of pediatric severe sepsis increased in the studied US children’s hospitals over the past 9 years, though resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to 7-fold depending on the strategy used for case ascertainment. PMID:25162514

  3. In-111 WBC imaging in musculoskeletal sepsis

    SciTech Connect

    Thompson, L.; Ouzounian, T.J.; Webber, M.M.; Amstutz, H.C.

    1984-01-01

    This study evaluated the accuracy and utility of the In-111 labeled WBC imaging in a series of patients who were suspected of having musculoskeletal sepsis. The labeling of the WBCs was patterned after a method previously described, in which the WBCs are labeled with In-111 oxine in plasma. The WBCs from 100 ml of blood are separated and incubated with In-111 oxine complex, and then 500 ..mu..Ci. of the labeled cells were reinjected into the patient. Images of the areas in question were obtained at 24 hrs. In some instances, 48 hour images were also obtained. Images were interpreted using consistent criteria. Forty imaging procedures were done on 39 patients. These included 39 total joint protheses, and 17 other images to evaluate possible osteomyelitis, septic arthritis or deep abscesses. Of these studies, 15 were positive, and 42 negative. The findings were then correlated with operative culture and pathology in 21, aspiration cultures and gram stains in 14, and with clinical findings in the remaining 21. This correlation showed 41 true negatives, 12 true positives, 1 false negative, and 2 false positives. The sensitivity was 92.9% and the specificity was 95.2%l. The false negative occurred in a patient on chronic suppressive antibiotic therapy for an infected total hip replacement. The false positive images occurred in a patient with active rheumatoid arthritis and in a patient imaged one month post operative placement of the prosthesis. These images were very useful in several septic patients who had many possible sites of infection. The authors conclude that In-III imaging is an accurate and useful non-invasive method of evaluating musculoskeletal sepsis.

  4. The gene for type A streptococcal exotoxin (erythrogenic toxin) is located in bacteriophage T12.

    PubMed Central

    Weeks, C R; Ferretti, J J

    1984-01-01

    The infection of Streptococcus pyogenes T25(3) with the temperate bacteriophage T12 results in the conversion of the nontoxigenic strain to type A streptococcal exotoxin (erythrogenic toxin) production. Although previous research has established that integration of the bacteriophage genome into the host chromosome is not essential for exotoxin production, the location of the gene on the bacteriophage or bacterial chromosome had not been determined. In the present investigation, recombinant DNA techniques were used to determine whether the gene specifying type A streptococcal exotoxin (speA) production is located on the bacteriophage chromosome. Bacteriophage T12 was obtained from S. pyogenes T25(3)(T12) by induction with mitomycin C, and after isolation of bacteriophage DNA by phenol-chloroform extraction, the DNA was digested with restriction enzymes and ligated with Escherichia coli plasmid pHP34 or the Streptococcus-E. coli shuttle vector pSA3. Transformation of E. coli HB101 with the recombinant molecules allowed selection of E. coli clones containing bacteriophage T12 genes. Immunological assays with specific antibody revealed the presence of type A streptococcal exotoxin in sonicates of E. coli transformants. Subcloning experiments localized the speA gene to a 1.7-kilobase segment of the bacteriophage T12 genome flanked by SalI and HindIII sites. Introduction of the pSA3 vector containing the speA gene into Streptococcus sanguis (Challis) resulted in transformants that secreted the type A exotoxin. Immunological analysis showed that the type A streptococcal exotoxin produced by E. coli and S. sanguis transformants was identical to the type A exotoxin produced by S. pyogenes T25(3)(T12). Southern blot hybridizations with the cloned fragment confirmed its presence in the bacteriophage T12 genome and its absence in the T25(3) nonlysogen. Therefore, the gene for type A streptococcal exotoxin is located in the bacteriophage genome, and conversion of S. pyogenes T25(3) to toxigenicity occurs in a manner similar to the conversion of Corynebacterium diphtheriae to toxigenicity by bacteriophage beta. Images PMID:6389348

  5. [Sepsis caused by methicillin-resistant Staphylococcus aureus: the shadow of a persistent threat].

    PubMed

    Sifuentes-Osornio, José; Pérez-Patrigeon, Santiago

    2006-01-01

    Clinical case. This 27 year-old male was referred admitted with severe acute pancreatitis (SAP) after heavy consumption of alcohol and sepsis (bacteremia and multilobar pneumonia) due to methicillin-resistant Staphylococcus aureus (MRSA); he required mechanical ventilation and haemodyalisis, and developed fungemia by fluconazol-resistant Candida albicans. He was treated with caspofungin for 20 days and vancomycin for six weeks, and he was discharged after 51 days of hospitalization. This case shows the painful evolution of a patient admitted to the intensive care unit (ICU) with MRSA sepsis. According to the National Nosocomial Infections Study (USA), S. aureus is the cause of up to 35% of hospital-acquired pneumonia and bacteremia. Using molecular tools (e.g. pulse gel electrophoresis), different families of MRSA have been well described. Use of i.v. catheters, long-term hospitalization, surgery and previous use of antimicrobials are considered major risk factors for MRSA. In Mexico, Alpuche-Aranda, et al (1986) reported a prevalence of 5% in a pediatric hospital. However, a recent report from the National Resistance Network showed a MRSA prevalence of 36% in 2004. In this institution, we observed a rate of MRSA of 100% in the ICU during 2005. This case shows an episode of SAP after heavy alcohol consumption, complicated with severe infections such as candidemia and MRSA sepsis; fortunately he had a favorable outcome after a multidisciplinary and aggressive approach. This case fulfilled all the risk factors for an MRSA infection, in a setting with a very high rate of methicillin-resistance, which compels the medical community to implement adequate and efficacious epidemiological control measures. PMID:17432292

  6. Neutrophils, nitric oxide, and microvascular permeability in severe sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    STUDY OBJECTIVES: Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients wi...

  7. HDL in sepsis – risk factor and therapeutic approach

    PubMed Central

    Morin, Emily E.; Guo, Ling; Schwendeman, Anna; Li, Xiang-An

    2015-01-01

    High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40–70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis. PMID:26557091

  8. Why we need a new definition of sepsis

    PubMed Central

    Lanspa, Michael J.

    2015-01-01

    On April 23, 2015, Kaukonen and colleagues published an article in the New England Journal of Medicine entitled “Systemic inflammatory response syndrome criteria in defining severe sepsis”, which investigated the sensitivity and validity of using SIRS criteria to define intensive care unit (ICU) patients with severe sepsis. This study used admission data of over 100,000 patients in order to investigate patients with severe sepsis who either met or didn’t meet SIRS criteria. The investigators found that in-hospital mortality increased linearly with the number of SIRS criteria met; raising concern that SIRS criterion is not sensitive enough. This study of SIRS criteria raises important questions about the recognition and diagnosis of severe sepsis.

  9. Platelet granule secretion mechanisms: Are they modified in sepsis?

    PubMed

    Xu, Xiaohan; Sun, Bingwei

    2015-11-01

    Sepsis is a progressive systemic inflammatory response syndrome associated with multi-organ dysfunction caused by overwhelming infection. In sepsis, platelet factor 4, ?-thromboglobulin, and other inflammatory mediators are secreted from platelet granules to participate in the inflammatory response and increase sepsis-related impairments. Recently, an increasing number of studies showed a critical role of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes in the platelet granule secretion. However, whether SNARE complex-regulated platelet granule secretion is involved in the pathophysiology of sepsis is unclear. Thus, in this review, we discussed the recent advances of SNARE complexes and their regulators in platelets as well as the mechanism of SNARE complexes on mediating platelet granule secretion. PMID:26403438

  10. Biomarkers for Sepsis: What Is and What Might Be?

    PubMed Central

    Biron, Bethany M.; Ayala, Alfred; Lomas-Neira, Joanne L.

    2015-01-01

    Every year numerous individuals develop the morbid condition of sepsis. Therefore, novel biomarkers that might better inform clinicians treating such patients are sorely needed. Difficulty in identifying such markers is in part due to the complex heterogeneity of sepsis, resulting from the broad and vague definition of this state/condition based on numerous possible clinical signs and symptoms as well as an incomplete understanding of the underlying pathobiology of this complex condition. This review considers some of the attempts that have been made so far, looking at both the pro- and anti-inflammatory response to sepsis, as well as genomic analysis, as sources of potential biomarkers. Irrespective, for functional biomarker(s) of sepsis to successfully translate from the laboratory to a clinical setting, the biomarker must be target specific and sensitive as well as easy to implement/interpret, and be cost effective, such that they can be utilized routinely in patient diagnosis and treatment. PMID:26417200

  11. A generic pathogen capture technology for sepsis diagnosis

    E-print Network

    Cooper, Ryan Mcomber

    2013-01-01

    Sepsis is a systemic inflammatory response that results the presence and persistence of microorganisms or their toxins in the bloodstream and it is diagnosed by detecting the presence of pathogens in blood. Despite ...

  12. Anti-inflammatory effect of Momordica charantia in sepsis mice.

    PubMed

    Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

    2014-01-01

    Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPAR? and PPAR?. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-? tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-?B, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. PMID:25153878

  13. Molecular diagnosis of sepsis: New aspects and recent developments

    PubMed Central

    Lehman, L.; Hunfeld, K.-P.; Kost, G.

    2014-01-01

    By shortening the time to pathogen identification and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefits for the management of patients with sepsis. While a number of reviews on the diagnosis of sepsis have recently been published we here present up-to-date new developments including multiplex PCR, mass spectrometry and array techniques. We focus on those techniques that are commercially available and for which clinical studies have been performed and published. PMID:24678402

  14. Sepsis and Septic Shock in the Equine Neonate.

    PubMed

    Fielding, Christopher Langdon; Magdesian, Kiragos Gary

    2015-12-01

    Sepsis and septic shock represent a major cause of morbidity and mortality in equine neonates and in all species. Early recognition of the condition is important, but definitive examination and laboratory variables to predict equine neonatal sepsis are lacking. Early and aggressive treatment should include broad-spectrum antimicrobial coverage, source control, and hemodynamic support. Field practitioners and intensive care clinicians work together in the management of this condition because the recognition and initial treatment should begin as early as possible. PMID:26612744

  15. Nonthyroidal illnesses syndrome in full-term newborns with sepsis.

    PubMed

    Silva, Maria Helena Baptista Nunes da; Araujo, Maria Cristina Korbage de; Diniz, Edna Maria de Albuquerque; Ceccon, Maria Esther Jurfest Rivero; Carvalho, Werther Brunow de

    2015-12-01

    Objective To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. Materials and methods We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. Results 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. Conclusions This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock. Arch Endocrinol Metab. 2015;59(6):528-34. PMID:26677087

  16. Improving time to antibiotics and implementing the “Sepsis 6”

    PubMed Central

    McGregor, Calum

    2014-01-01

    It has been shown that completion of the “Sepsis 6” within 1 hour reduces mortality (1). This project aims to assess compliance with this standard and evaluate the effectiveness of a sepsis improvement plan in a district general hospital in the UK. A baseline audit was performed, examining case notes of “septic patients” retrospectively (those on intravenous antibiotics). Compliance with each element of the sepsis six plus time to first antibiotic (TTFA) was assessed. A sepsis improvement plan was introduced consisting of staff education, reinforcing vigilance, regular multidisciplinary meetings and incorporating a standardised approach through the use of a sepsis proforma. Following the introduction of this, and after some refinement, the average time to antibiotic fell from 6 hours to 1.4 hours. In conclusion, an educational drive along with a systematic change in processes has seen reduced TTFA along with enhanced compliance with most elements of the sepsis 6. Through continued assessment and further improving upon systematic processes with continued education we would anticipate consistent improvement in the management of septic patients.

  17. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

    PubMed Central

    Lee, Sang Hoon; Park, Moo Suk; Park, Byung Hoon; Jung, Won Jai; Lee, In Seon; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Chung, Kyung Soo

    2015-01-01

    Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients. PMID:26351639

  18. Predictive values for procalcitonin in the diagnosis of neonatal sepsis

    PubMed Central

    Mohsen, Abdel Hakeem Abdel; Kamel, Bothina Ahmed

    2015-01-01

    Background: Early diagnosis of neonatal sepsis followed by appropriate treatment decreases mortality and morbidity in infants. The aim of this study is to assess the role of procalcitonin (PCT) as a marker in the early diagnosis of neonatal sepsis. Methods: We present a cross sectional study where 35 neonates with early onset sepsis (admitted to the Neonatal Intensive Care Units at El-Minia Children University Hospital from August 2012 to August 2013) were included in the study. Another 35 healthy neonates with no clinical or biological data of infection were included as a control group. Subjects were subjected to a thorough history taking and routine laboratory investigations. Serum PCT and C-reactive protein (CRP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Mean levels of PCT and CRP in neonates with sepsis were significantly higher than in the control group (p=0.0001). There was a moderate, but significant, positive correlation between PCT and C-reactive protein (p=0.001, r=0.55) and an insignificant correlation between procalcitonin and total leukocytic count among the neonates with sepsis (p=0.2, r=0.2). In addition, procalcitonin had high sensitivity, specificity, a high positive predictive value, and a high negative predictive value (80%, 85.7%, 84.8%, and 81.1% respectively). Procalcitonin showed higher sensitivity when compared to CRP. Conclusion: Procalcitonin is a sensitive, independent, and useful biomarker in comparison to CRP in early diagnosis of neonatal sepsis. PMID:26396733

  19. Role of Circulating Lymphocytes in Patients with Sepsis

    PubMed Central

    de Pablo, Raul; Monserrat, Jorge; Prieto, Alfredo; Alvarez-Mon, Melchor

    2014-01-01

    Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed. PMID:25302303

  20. Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis

    PubMed Central

    Tsai, Tsen-Ni; Ho, Jia-Jing; Liu, Maw-Shung; Lee, Tzu-Ying; Lu, Mei-Chin; Liu, Chia-Jen; Huang, Li-Ju; Lue, Sheng-I; Yang, Rei-Chen

    2015-01-01

    This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway. PMID:26221596

  1. Enzyme-linked immunosorbent assay for detection of type A streptococcal exotoxin: kinetics and regulation during growth of Streptococcus pyogenes.

    PubMed Central

    Houston, C W; Ferretti, J J

    1981-01-01

    We describe the detection and quantitation of type A streptococcal exotoxin (erythrogenic toxin, streptococcal pyrogenic exotoxin) by an enzyme-linked immunosorbent assay. This sensitive and specific technique detected microgram amounts of type A exotoxin and was useful for studying the kinetics and regulation of type A exotoxin production during the growth of Streptococcus pyogenes NY5. Maximum production of type A exotoxin was observed during the mid-log phase of growth, similar to the production of other streptococcal extracellular products. When S. pyogenes NY5 was grown at 42 degrees C, decreases in both growth and type A exotoxin production were observed. The results obtained when we studied the influence of nutrient additives and metal ions on the production of type A exotoxin led to the conclusion that none of these factors significantly affected type A exotoxin synthesis and that regulation was constitutive. Images PMID:7026447

  2. Clinical Performance of a New Soluble CD14-Subtype Immunochromatographic Test for Whole Blood Compared with Chemiluminescent Enzyme Immunoassay: Use of Quantitative Soluble CD14-Subtype Immunochromatographic Tests for the Diagnosis of Sepsis

    PubMed Central

    Sato, Masayuki; Takahashi, Gaku; Shibata, Shigehiro; Onodera, Makoto; Suzuki, Yasushi; Inoue, Yoshihiro; Endo, Shigeatsu

    2015-01-01

    We previously reported that a soluble CD14-subtype (sCD14-ST) immunochromatographic test (ICT) for plasma is more convenient than chemiluminescent enzyme immunoassay (CLEIA), but plasma separation makes bedside measurements difficult. We developed a new sCD14-ST ICT for whole blood and investigated whether quantitative determinations of sCD14-ST by ICT were useful for diagnosing sepsis and severe sepsis/septic shock. We studied 20 patients who fulfilled two or more systemic inflammatory response syndrome (SIRS) criteria and 32 patients who had been diagnosed with sepsis or severe sepsis/septic shock. Whole blood was collected on day 0 (on admission) and day 7, and the sCD14-ST concentration was quantitatively measured by CLEIA and ICT for whole blood. The patients’ Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), and Mortality in Emergency Department Sepsis (MEDS) scores were also calculated. The cut-off values obtained by the quantitative measurements made by ICT were 464.5 pg/mL for sepsis and 762.7 pg/mL for severe sepsis/septic shock (P < 0.0001). A Bland–Altman plot showed that no fixed bias or proportional bias was detected between CLEIA and quantitative ICT for whole blood. sCD14-ST concentrations were significantly correlated with APACHE II, SOFA, and MEDS scores (P < 0.0001). These results suggest that the new sCD14-ST ICT for whole blood may be a useful tool for the convenient, rapid bedside diagnosis and treatment of sepsis. PMID:26623644

  3. Early sepsis does not increase the risk of late sepsis in very low birth weight neonates

    PubMed Central

    Wynn, James L.; Hansen, Nellie I.; Das, Abhik; Cotten, C. Michael; Goldberg, Ronald N.; Sánchez, Pablo J.; Bell, Edward F.; Van Meurs, Krisa P.; Carlo, Waldemar A.; Laptook, Abbot R.; Higgins, Rosemary D.; Benjamin, Daniel K.; Stoll, Barbara J.

    2012-01-01

    Objective To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). Study design Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the NICHD Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ?72 hr of birth (EOS) or >72 hr (LOS) and antimicrobial therapy for ?5 days or death <5 d while receiving therapy. Regression models were used to assess risk of death or LOS by 120d and LOS by 120d among survivors to discharge or 120d, adjusting for gestational age and other covariates. Results Of 34,396 infants studied 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120d did not differ overall for infants with EOS compared with those without EOS [RR:0.99 (0.89-1.09)] but was reduced in infants born at <25wk gestation [RR:0.87 (0.76-0.99), p=0.048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR:0.88 (0.75-1.02)], but LOS risk was shorter in infants with BW 401-750 g who had EOS [RR:0.80 (0.64-0.99), p=0.047]. Conclusions Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function. PMID:23295144

  4. Late-onset neonatal sepsis: recent developments

    PubMed Central

    Dong, Ying; Speer, Christian P

    2015-01-01

    The incidence of neonatal late-onset sepsis (LOS) is inversely related to the degree of maturity and varies geographically from 0.61% to 14.2% among hospitalised newborns. Epidemiological data on very low birth weight infants shows that the predominant pathogens of neonatal LOS are coagulase-negative staphylococci, followed by Gram-negative bacilli and fungi. Due to the difficulties in a prompt diagnosis of LOS and LOS-associated high risk of mortality and long-term neurodevelopmental sequelae, empirical antibiotic treatment is initiated on suspicion of LOS. However, empirical therapy is often inappropriately used with unnecessary broad-spectrum antibiotics and a prolonged duration of treatment. The increasing number of multidrug-resistant Gram-negative micro-organisms in neonatal intensive care units (NICU) worldwide is a serious concern, which requires thorough and efficient surveillance strategies and appropriate treatment regimens. Immunological strategies for preventing neonatal LOS are not supported by current evidence, and approaches, such as a strict hygiene protocol and the minimisation of invasive procedures in NICUs represent the cornerstone to reduce the burden of neonatal LOS. PMID:25425653

  5. ACUTE LEUKEMIAS ACUTE MYELOGENOUS

    E-print Network

    Trisomy 8(+8), t(9;22), t(6;9) 90% myeloblasts AML-M2 Acute Myeloblastic Leukemia with Maturation Black B, & Choloacetate Esterase t(8;21) #12;9/16/2013 4 AML-M3 Acute Promyelocytic Leukemia between chromosomes 8 and 21 AML with a translocation or inversion in chromosome 16 AML with changes

  6. Systematic review of use of ?-blockers in sepsis

    PubMed Central

    Chacko, Cyril Jacob; Gopal, Shameer

    2015-01-01

    Background and Aims: We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of ?-blockers on the outcome of a patient with severe sepsis and septic shock. Material and Methods: Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Results: Most studies found a benefit from ?-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic ?-blocker usage in sepsis was also associated with improved mortality. The administration of ?-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. Conclusion: There is insufficient evidence to justify the routine use of ?-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of ?-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of ?-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of ?-blockers in sepsis in current clinical practice. PMID:26702201

  7. Early and Late Onset Sepsis in Late Preterm Infants

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Cotten, C. Michael; Clark, Reese H.; Benjamin, Daniel K.; Smith, P. Brian

    2009-01-01

    Background Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants. Methods This is an observational cohort study of infants < 121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007. Results During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (OR 4.39, 95% CI 1.71–11.23, P=0.002; and OR 3.37, 95% CI 2.35–4.84, P<0.001, respectively). Conclusion Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit. PMID:19953725

  8. Impact of sepsis on CD4 T cell immunity

    PubMed Central

    Cabrera-Perez, Javier; Condotta, Stephanie A.; Badovinac, Vladimir P.; Griffith, Thomas S.

    2014-01-01

    Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state. PMID:24791959

  9. Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

    PubMed Central

    Panigada, Mauro; Zacchetti, Lucia; L’Acqua, Camilla; Cressoni, Massimo; Anzoletti, Massimo Boscolo; Bader, Rossella; Protti, Alessandro; Consonni, Dario; D’Angelo, Armando; Gattinoni, Luciano

    2015-01-01

    Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. Methods This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6–13) vs 5 (4–7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93–0.98, p = 0.003). Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality. PMID:26308340

  10. Etiology of Cellulitis and Clinical Prediction of Streptococcal Disease: A Prospective Study

    PubMed Central

    Bruun, Trond; Oppegaard, Oddvar; Kittang, Bård R.; Mylvaganam, Haima; Langeland, Nina; Skrede, Steinar

    2016-01-01

    Background.?The importance of bacteria other than group A streptococci (GAS) in different clinical presentations of cellulitis is unclear, commonly leading to treatment with broad-spectrum antibiotics. The aim of this study was to describe the etiological and clinical spectrum of cellulitis and identify clinical features predicting streptococcal etiology. Methods.?We prospectively enrolled 216 patients hospitalized with cellulitis. Clinical details were registered. Bacterial culture was performed from blood, cutaneous or subcutaneous tissue, and/or swabs from skin lesions. Paired serum samples were analyzed for anti-streptolysin O and anti-deoxyribonuclease B antibodies. Results.?Serology or blood or tissue culture confirmed ?-hemolytic streptococcal (BHS) etiology in 72% (146 of 203) of cases. An additional 13% (27 of 203) of cases had probable BHS infection, indicated by penicillin response or BHS cultured from skin swabs. ?-hemolytic streptococcal etiology was predominant in all clinical subgroups, including patients without sharply demarcated erythema. ?-hemolytic group C or G streptococci (GCS/GGS) were more commonly isolated than GAS (36 vs 22 cases). This predominance was found in the lower extremity infections. Group C or G streptococci in swabs were associated with seropositivity just as often as GAS. Staphylococcus aureus was cultured from swabs as a single pathogen in 24 cases, 14 (64%) of which had confirmed BHS etiology. Individual BHS-associated clinical characteristics increased the likelihood of confirmed BHS disease only slightly; positive likelihood ratios did not exceed 2.1. Conclusions.??-hemolytic streptococci were the dominating cause of cellulitis in all clinical subgroups and among cases with S aureus in cutaneous swabs. Group C or G streptococci were more frequently detected than GAS. No single clinical feature substantially increased the probability of confirmed BHS etiology.

  11. Invasive group A streptococcal infections in adults, France (2006-2010).

    PubMed

    Plainvert, C; Doloy, A; Loubinoux, J; Lepoutre, A; Collobert, G; Touak, G; Trieu-Cuot, P; Bouvet, A; Poyart, C

    2012-07-01

    Severe invasive group A streptococcal diseases have re-emerged during the past 10-20 years. In order to provide a better insight into the current epidemiological situation in France, we analysed the questionnaires regarding all invasive strains received at the National Reference Center for Streptococci (CNR-Strep) between 2006 and 2010 from patients aged ? 18 and characterized them by emm typing, spe gene detection and antibiotic resistance. Among the 1542 invasive GAS strains studied, 78% (n=1206) were from blood cultures, and a streptococcal toxic shock syndrome (STSS) was described in 22% (n=340) of cases, mainly associated with necrotizing fasciitis (NF) and pleuro-pulmonary infections (p<0.001). The in-hospital fatality rate was 15%. A total of 83 different emm types were recovered but the three predominant emm types, representing almost 60% of the isolates, were emm1 (24%), emm28 (17%) and emm89 (15%). The preponderance of each emm type varied according to the year, with a significant constant increase of emm28 strains, whereas emm1 strains, representing approximately 32% of GAS invasive isolates in 2007 and 2008, dropped to <15% in 2010 (p<0.001). The distribution of phage-associated superantigen genes (speA, speC and ssa) was linked to certain emm types. Between 2006 and 2010, the percentage that was macrolide-resistant decreased from 11% to 5%, confirming the trend observed in 2007. Fortunately, emm1 strains associated with the most life-threatening clinical manifestations remain susceptible to all anti-streptococcal antibiotics. PMID:21883669

  12. Improving the care of sepsis: Between system redesign and professional responsibility: A roundtable discussion in the world sepsis day, September 25, 2013, Riyadh, Saudi Arabia

    PubMed Central

    Arabi, Yaseen; Alamry, Ahmed; Levy, Mitchell M.; Taher, Saadi; Marini, Abdellatif M.

    2014-01-01

    This paper summarizes the roundtable discussion in September 25, 2013, Riyadh, Saudi Arabia as part of the World Sepsis Day held in King Abdulaziz Medical City, Riyadh. The objectives of the roundtable discussion were to (1) review the chasm between the current management of sepsis and best practice, (2) discuss system redesign and role of the microsystem in sepsis management, (3) emphasize the multidisciplinary nature of the care of sepsis and that improvement of the care of sepsis is the responsibility of all, (4) discuss the bundle concept in sepsis management, and (5) reflect on the individual responsibility of the health care team toward sepsis with a focus on accountability and the moral agent. PMID:24987470

  13. Platelet activation is a key event in the pathogenesis of streptococcal infections.

    PubMed

    Jia, Ming; Xiong, Yuling; Lu, Hua; Li, Ruqing; Wang, Tiantian; Ye, Yanyao; Song, Min; Li, Bing; Jiang, Tianlun; Zhao, Shuming

    2015-01-01

    Diverse Streptococcus species including Streptococcus Pneumoniae, Sanguis, Gordonii, Mitis and Mutans cause life-threatening conditions including pneumonia, bacteremia and meningitis. These diseases bear a high morbidity and mortality and for this reason, understanding the key events in the pathogenesis of these infections have a great significance in their prevention and/or treatment. Here, we describe as how the activation of the platelets and their affinity to bind to bacterial proteins act as early key events in the pathogenesis of Streptococcal infections. PMID:25961531

  14. Ability to bind salivary alpha-amylase discriminates certain viridans group streptococcal species.

    PubMed

    Kilian, M; Nyvad, B

    1990-11-01

    A collection of 144 viridans group streptococcal strains recently characterized as part of a taxonomic study was examined for the ability to bind salivary alpha-amylase. This property was found in most strains of Streptococcus gordonii and Streptococcus mitis and in occasional strains of Streptococcus anginosus and Streptococcus salivarius. In contrast, all strains of Streptococcus sanguis, Streptococcus oralis, Streptococcus vestibularis, and Streptococcus mutans lacked alpha-amylase-binding capacity. A rapid and easy assay described in this paper may be an important supplementary test for identification of oral streptococci. PMID:2254435

  15. Prognostic Value of Venoarterial Carbon Dioxide Gradient in Patients with Severe Sepsis and Septic Shock

    PubMed Central

    Troskot, Rosana; Šimurina, Tatjana; Žižak, Mirza; Majstorovi?, Karolina; Marinac, Ivana; Šuti?, Ines Mrakov?i?

    2010-01-01

    Aim To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco2) and its prognostic value for survival of patients with severe sepsis and septic shock. Methods The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO2 and the partial pressure of mixed venous CO2, which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios. Results There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco2 values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P?=?0.015) but not in ventilated ones (P?=?0.270). Conclusion V-a Pco2 was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more likely to be admitted with a less favorable clinical status, and other variables seem to have a more important role in their outcome. PMID:21162162

  16. Blood Culture Proven Early Onset Sepsis and Late Onset Sepsis in Very-Low-Birth-Weight Infants in Korea

    PubMed Central

    Lee, Soon Min; Chang, Meayoung

    2015-01-01

    Neonatal sepsis remains one of the most important causes of death and co-morbidity in very-low-birth-weight (VLBW) infants. The aim of this study was to determine the current incidences of early-onset sepsis (EOS) and late-onset sepsis (LOS), the distribution of pathogens, and the impact of infection on co-morbidities in VLBW infants. We analyzed the data including sepsis episode from 2,386 VLBW infants enrolled in Korean Neonatal Network from January 2013 to June 2014. We defined EOS as a positive blood culture occurring between birth and 7 days of life and LOS after 7 days of life. Sepsis was found in 21.1% of VLBW infants. The risk of sepsis was inversely related to birth weight and gestational age. EOS was found in only 3.6% of VLBW infants, however the mortality rate was as high as 34.1%. EOS was associated with the increased odds for bronchopulmonary dysplasia and intraventricular hemorrhage. The vast majority of EOS was caused by Gram-positive organisms, particularly coagulase-negative staphylococci (30.6%). LOS developed in 19.4% of VLBW infants with a 16.1% mortality rate. Pathogens in LOS were dominated by coagulase-negative staphylococci (38.3%). Twenty-five percent and fifty percent of first LOS episode occurred after 12 days and 20 days from birth, respectively. Younger and smaller VLBW infants showed the earlier occurrence day for the 25% of first LOS episode. This study provides a recent nationwide epidemiology of sepsis in VLBW infants in Korea. Based on this study, successful strategies to reduce infections would improve survival and reduce morbidity. PMID:26566360

  17. Proteome changes in mesenteric lymph induced by sepsis.

    PubMed

    Zhang, Ping; Li, Yan; Zhang, Lian-Dong; Wang, Liang-Hua; Wang, Xi; He, Chao; Lin, Zhao-Fen

    2014-12-01

    The present study aimed to examine the changes in mesenteric lymph during the development of sepsis and to identify the distinct proteins involved, as targets for further study. The sepsis animal model was constructed by cecal ligation and puncture (CLP). The mesenteric lymph was collected from 28 adult male Sprague?Dawley rats, which were randomly divided into the following four groups (n=7 per group): CLP?6 h, CLP?24 h, sham?6 h and sham?24 h groups. Capillary high performance liquid chromatography?tandem mass spectrometry was performed to analyze the proteome in mesenteric lymph. A comprehensive bioinformatic analysis was then conducted to investigate the distinct proteins. Compared with the sham group, 158 distinct proteins were identified in the lymph samples from the CLP group. Five of these proteins associated with the same lipid metabolism pathway were selected, apolipoprotein E (ApoE), annexin A1 (Anxa1), neutrophil gelatinase?associated lipocalin (NGAL), S100a8 and S100a9. The expression of ApoE, Anxa1, NGAL, S100a8 and S100a9 were all elevated in the progression of sepsis. The five proteins were reported to be closely associated with disease development and may be a potential target for the diagnosis and treatment of sepsis. In conclusion, identifying proteome changes in mesenteric lymph provides a novel perspective to understand the pathological mechanisms underlying sepsis. PMID:25242054

  18. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    PubMed Central

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  19. Use of miRNAs as Biomarkers in Sepsis

    PubMed Central

    Dumache, Raluca; Rogobete, Alexandru Florin; Bedreag, Ovidiu Horea; Sarandan, Mirela; Cradigati, Alina Carmen; Papurica, Marius; Dumbuleu, Corina Maria; Nartita, Radu; Sandesc, Dorel

    2015-01-01

    Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19–23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis. PMID:26221578

  20. Sepsis: Links between Pathogen Sensing and Organ Damage

    PubMed Central

    Crouser, Elliott; Exline, Matthew; Knoell, Daren; Wewers, Mark D.

    2012-01-01

    The host’s inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial inflammatory response in early sepsis and to bolster this response in late sepsis. The persistence of MODS after the initial inflammatory surge can also be a determining factor to host survival. MODS is due to the cellular damage and death induced by sepsis. The mechanism of this cell death depends in part upon mitochondrial dysfunction. Damaged mitochondria have increased membrane permeability prompting their autophagic removal if few mitochondria are involved but apoptotic cell death may occur if the mitochondrial losses are more extensive. In addition. severe loss of mitochondria results in low cell energy stores, necrotic cell death, and increased inflammation driven by the release of cell components such as HMGB1. Therapies, which aim at improving cellular energy reserves such as the promotion of mitochondrial biogenesis by insulin, may have a role in future sepsis therapies. Finally, both the inflammatory responses and the susceptibility to organ failure may be modulated by nutritional status and micronutrients, such as zinc, Therapies aimed at micronutrient repletion may further augment approaches targeting PRR function and mitochondrial viability. PMID:18691095

  1. Targeting myeloid differentiation 2 for treatment of sepsis.

    PubMed

    Duan, Guangjie; Zhu, Jiang; Xu, Jianhua; Liu, Yousheng

    2014-01-01

    Sepsis continues to be a leading cause of intensive care unit (ICU) death. Gram-negative bacteria are among the most important pathogens of sepsis and their LPS content is regarded to be an important stimulator that elicits the systemic inflammatory reaction. MD-2 is a small secreted glycoprotein that can bind to both the hydrophobic portion of LPS and to the extracellular domain of TLR4. The interaction between MD-2 and LPS bridges the two TLR4 molecules and induces the dimerization of LPS-MD-2-TLR4, which forms the structural basis for biological functions of TLR4/MD-2 complex. Due to its essential role in mediating the interaction between LPS and TLR4, MD-2 has been extensively explored as a therapeutic target for treatment of inflammatory disorders such as sepsis. Eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site. Although eritoran showed positive results in phase I and phase II clinical trials of severe sepsis, a phase III clinical study for severe sepsis has failed. More effective therapeutic strategies are in need to treat this devastating clinical disorder. PMID:24896325

  2. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    PubMed

    Gheorghi??, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; C?runtu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death. PMID:25763364

  3. Translocation of gut flora and its role in sepsis.

    PubMed

    Vaishnavi, C

    2013-01-01

    Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. Sometimes instead of bacteria, inflammatory compounds are responsible for clinical symptoms as in systemic inflammatory response syndrome (SIRS). The difference between sepsis and SIRS is that pathogenic bacteria are isolated from patients with sepsis but not with those of SIRS. Bacterial translocation occurs more frequently in patients with intestinal obstruction and in immunocompromised patients and is the cause of subsequent sepsis. Factors that can trigger bacterial translocation from the gut are host immune deficiencies and immunosuppression, disturbances in normal ecological balance of gut, mucosal barrier permeability, obstructive jaundice, stress, etc. Bacterial translocation occurs through the transcellular and the paracellular pathways and can be measured both directly by culture of mesenteric lymph nodes and indirectly by using labeled bacteria, peripheral blood culture, detection of microbial DNA or endotoxin and urinary excretion of non-metabolisable sugars. Bacterial translocation may be a normal phenomenon occurring on frequent basis in healthy individuals without any deleterious consequences. But when the immune system is challenged extensively, it breaks down and results in septic complications at different sites away from the main focus. The factors released from the gut and carried in the mesenteric lymphatics but not in the portal blood are enough to cause multi-organ failure. Thus, bacterial translocation may be a promoter of sepsis but not the initiator. This paper reviews literature on the translocation of gut flora and its role in causing sepsis. PMID:24064638

  4. Clinical and Microbiological Characteristics of Invasive Group A Streptococcal Infections Before and After Implementation of a Universal Varicella Vaccine Program.

    PubMed

    Frère, Julie; Bidet, Philippe; Tapiéro, Bruce; Rallu, Fabien; Minodier, Philippe; Bonacorsi, Stephane; Bingen, Edouard; Ovetchkine, Philippe

    2016-01-01

    Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly. PMID:26409062

  5. A child with rapidly progressive necrotizing group a streptococcal Tenon's capsule infection one day after strabismus surgery.

    PubMed

    Yau, Gary L; Warder, Daniel; Farmer, James P; Urton, Todd; Strube, Yi Ning J

    2015-10-01

    Periorbital infections after strabismus surgery are rare. We describe the first reported case of necrotizing group A streptococcal infection of the conjunctiva and Tenon's capsule complicating uneventful strabismus surgery in a 23-month-old boy, successfully managed with conservative intraoperative debridement and with targeted local and systemic antibiotics. PMID:26486034

  6. Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

    ERIC Educational Resources Information Center

    Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S., IV; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

    2011-01-01

    Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders…

  7. GENES, IN ADDITION TO TOLL-LIKE RECEPTOR 2, PLAY A ROLE IN ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL PNEUMONIA

    EPA Science Inventory

    Streptococcus infection in human populations continues to be a major cause of morbidity and mortality. To evaluate the effect of genetic background and toll-like receptor 2 (TLR2) on antibacterial defense to streptococcal infection, eight genetically diverse strains of mic...

  8. [A case of Fasciola hepatica mimicking sepsis without eosinophilia].

    PubMed

    Oner Vatan, Asl?; Mete, Bilgül; Yemi?en, Mücahit; Kaya, Abdurrahman; Kantarc?, Fatih; Salto?lu, Ne?e

    2014-06-01

    Fasciolosis is a rare cause of hepatobiliary system infections and caused by the trematode Fasciola hepatica. It primarily infects sheeps or goats, and humans are accidental hosts. On laboratory findings, marked eosinophilia is present in most of the cases. Here, we report a case of fasciolosis without eosinophilia who was presented as sepsis and responded to therapy in second dose of triclabendazole. Sepsis like clinical presentation has been reported in few cases. Forty-eight year old female patient presented with high fever, abdominal pain, hypotension and tachycardia. The patient was considered as sepsis secondary to liver abscess, which was demonstrated on the initial abdominal ultrasonography (USG) findings. Therefore, empirical antibiotic therapy was started. Due to failure of the treatment, the image was found to be compatible with fasciolosis on control magnetic resonance imaging (MRI) and USG. On detailed anamnesis, history of eating watercress was learned and the diagnosis of fasciolosis was confirmed by serological tests. PMID:25016123

  9. Identification of group B streptococcal antigen with lectin-bound polystyrene particles.

    PubMed Central

    Slifkin, M; Cumbie, R

    1987-01-01

    The lectin of the tomato, Lycopersicon esculentum, or of the potato, Solanum tuberosum, can be passively coupled to amide-modified polystyrene spheres to be used as a detection reagent for the specific identification of group B streptococcal cultures grown in selective or nonselective Todd-Hewitt broth for 5 and 4 h, respectively. Agglutination occurred when the lectin reagents were allowed to react with either the cell suspension, clarified broth, or antigen extracts from group B streptococci grown in Todd-Hewitt broth. No agglutination occurred when these lectins were allowed to react with strains of serogroup A, C, D, F, or G streptococci. False-negative agglutination responses may occur with certain serotype of group B streptococci grown on Columbia sheep blood agar. A 20-min staining time permitted the specific labeling of fixed smears of group B streptococci with fluorescein-conjugated Lycopersicon lectin. The lectin from the solanaceous plant Datura stramonium did not agglutinate group B streptococci or other clinically significant streptococcal serogroups. PMID:3301888

  10. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis

    PubMed Central

    Jain, S. K.; Gill, M. S.; Pawar, H. S.; Suresh, Sarasija

    2014-01-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin. PMID:25425755

  11. Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS): Experience at a Tertiary Referral Center

    PubMed Central

    Helm, Caitlin E.; Blackwood, R. Alexander

    2015-01-01

    Background Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an autoimmune disorder presenting with obsessive compulsive disorder and/or tics. Like Sydenham’s chorea, its presumed pathogenesis consists of autoantibodies cross-reacting with neurons in response to a group A beta-hemolytic streptococcal infection (GASI). There are currently no diagnostic laboratory findings and management ranges from antibiotic prophylaxis to intravenous immunoglobulin to plasmapheresis. The diagnosis remains controversial, resulting in inconsistent referrals and significant patient anxiety. Methods A retrospective study was performed on all patients referred to the Pediatric Infectious Disease Division with a pre-referral diagnosis of PANDAS. Patients were analyzed by demographics, medical history, co-morbidities, symptoms, prior treatment, laboratory tests, management strategies, and treatment outcomes. Results From 2003 to 2013, there were 21 patients with a pre-referral diagnosis of PANDAS. Only five met the diagnostic criteria. No patient at referral had an objective scale to monitor symptoms. Eight referrals had a major psychiatric disorder, and none fulfilled diagnostic criteria (p<0.01). Discussion The majority of the patients referred with a pre-diagnosis of PANDAS do not fulfill diagnostic criteria nor do they have objective criteria for symptom monitoring. Major psychiatric disorders do not seem to be associated with PANDAS, and better physician education may prevent misdiagnoses. Multidisciplinary management is recommended. PMID:26196024

  12. ?? T cells mitigate the organ injury and mortality of sepsis

    PubMed Central

    Tschöp, Johannes; Martignoni, André; Goetzman, Holly S.; Choi, Lisa G.; Wang, Quan; Noel, John G.; Ogle, Cora K.; Pritts, Timothy A.; Johannigman, Jay A.; Lentsch, Alex B.; Caldwell, Charles C.

    2009-01-01

    Sepsis is a difficult condition to treat and is associated with a high mortality rate. Sepsis is known to cause a marked depletion of lymphocytes, although the function of different lymphocyte subsets in the response to sepsis is unclear. ?? T cells are found largely in epithelial-rich tissues, and previous studies of ?? T cells in models of sepsis have yielded divergent results. In the present study, we examined the function of ?? T cells during sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in ?? T cells had decreased survival times and increased tissue damage after CLP compared with wild-type mice. Furthermore, bacterial load was increased in ?? T cell-deficient mice, yet antibiotic treatment did not change mortality. Additionally, we found that recruitment of neutrophils and myeloid suppressor cells to the site of infection was diminished in ?? T cell-deficient mice. Finally, we found that circulating levels of IFN-? were increased, and systemic levels of IL-10 were decreased in ?? T cell-deficient mice after CLP compared with wild-type mice. ?? T cell-deficient mice also had increased intestinal permeability after CLP compared with wild-type mice. Neutralization of IFN-? abrogated the increase in intestinal permeability in ?? T cell-deficient mice. The intestines taken from ?? T cell-deficient mice had decreased myeloperoxidase yet had increased tissue damage as compared with wild-type mice. Collectively, our data suggest that ?? T cells modulate the response to sepsis and may be a potential therapeutic target. PMID:18063696

  13. Optical detection of sepsis markers using liquid crystal based biosensors

    NASA Astrophysics Data System (ADS)

    McCamley, Maureen K.; Artenstein, Andrew W.; Opal, Steven M.; Crawford, Gregory P.

    2007-02-01

    A liquid crystal based biosensor for the detection and diagnosis of sepsis is currently in development. Sepsis, a major clinical syndrome with a significant public health burden in the US due to a large elderly population, is the systemic response of the body to a localized infection and is defined as the combination of pathologic infection and physiological changes. Bacterial infections are responsible for 90% of cases of sepsis in the US. Currently there is no bedside diagnostic available to positively identify sepsis. The basic detection scheme employed in a liquid crystal biosensor contains attributes that would find value in a clinical setting, especially for the early detection of sepsis. Utilizing the unique properties of liquid crystals, such as birefringence, a bedside diagnostic is in development which will optically report the presence of biomolecules. In a septic patient, an endotoxin known as lipopolysaccharide (LPS) is released from the outer membrane of Gram-negative bacteria and can be found in the blood stream. It is hypothesized that this long chained molecule will cause local disruptions to the open surface of a sensor containing aligned liquid crystal. The bulk liquid crystal ampli.es these local changes at the surface due to the presence of the sepsis marker, providing an optical readout through polarizing microscopy images. Liquid crystal sensors consisting of both square and circular grids, 100-200 ?m in size, have been fabricated and filled with a common liquid crystal material, 5CB. Homeotropic alignment was confirmed using polarizing microscopy. The grids were then contacted with either saline only (control), or saline with varying concentrations of LPS. Changes in the con.guration of the nematic director of the liquid crystal were observed through the range of concentrations tested (5mg/mL - 1pg/mL) which have been confirmed by a consulting physician as clinically relevant levels.

  14. Cystitis - acute

    MedlinePLUS

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  15. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    PubMed

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction:Chun-Hua Yang and Tian-Biao ZhouAssociation of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progressionJournal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi:10.1177/1470320314568521This article has been retracted at the request of the Editors and the Publisher.After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System (JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. ONLINE FIRST ARTICLES THESE ARTICLES WILL NOT BE PUBLISHED IN AN ISSUE: Wenzhuang Tang, Tian-Biao Zhou, and Zongpei JiangAssociation of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathyJournal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi:10.1177/1470320314563426Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang ZhouRole of renin-angiotensin-aldosterone system inhibitors in radiation nephropathyJournal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi:10.1177/1470320314563424Weiqiang Zhong, Zongpei Jiang, and Tian-Biao ZhouAssociation between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian populationJournal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi:10.1177/1470320314566019Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan LiRelationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian populationJournal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi:10.1177/1470320314563425Chun-Hua Yang and Tian-Biao ZhouRelationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathyJournal of Renin-Angiotensin-Aldosterone System 1470320314566221, first published on February 1, 2015 doi:10.1177/1470320314566221Chun-Hua Yang and Tian-Biao ZhouAssociation of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progressionJournal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi:10.1177/1470320314568521 ARTICLES PUBLISHED IN AN ISSUE: Guohui Liu, Tian-Biao Zhou, Zongpei Jiang, and Dongwen ZhengAssociation of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian populationJournal of Renin-Angiotensin-Aldosterone System March 2015 16: 165-171, first published on November 14, 2014 doi:10.1177/1470320314557849Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang, and Tian-Biao ZhouAssociation of aldosterone synthase (CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathyJournal of Renin-Angiotensin-Aldosterone System September 2015 16: 660-665, first published on August 20, 2014 doi:10.1177/1470320314524011. PMID:25650383

  16. Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood

    E-print Network

    Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood Molly Abstract Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood. PLoS Pathog 7(10): e1002307

  17. Transcriptomic analysis of peritoneal cells in a mouse model of sepsis: confirmatory and novel results in early and late sepsis

    PubMed Central

    2012-01-01

    Background The events leading to sepsis start with an invasive infection of a primary organ of the body followed by an overwhelming systemic response. Intra-abdominal infections are the second most common cause of sepsis. Peritoneal fluid is the primary site of infection in these cases. A microarray-based approach was used to study the temporal changes in cells from the peritoneal cavity of septic mice and to identify potential biomarkers and therapeutic targets for this subset of sepsis patients. Results We conducted microarray analysis of the peritoneal cells of mice infected with a non-pathogenic strain of Escherichia coli. Differentially expressed genes were identified at two early (1 h, 2 h) and one late time point (18 h). A multiplexed bead array analysis was used to confirm protein expression for several cytokines which showed differential expression at different time points based on the microarray data. Gene Ontology based hypothesis testing identified a positive bias of differentially expressed genes associated with cellular development and cell death at 2 h and 18 h respectively. Most differentially expressed genes common to all 3 time points had an immune response related function, consistent with the observation that a few bacteria are still present at 18 h. Conclusions Transcriptional regulators like PLAGL2, EBF1, TCF7, KLF10 and SBNO2, previously not described in sepsis, are differentially expressed at early and late time points. Expression pattern for key biomarkers in this study is similar to that reported in human sepsis, indicating the suitability of this model for future studies of sepsis, and the observed differences in gene expression suggest species differences or differences in the response of blood leukocytes and peritoneal leukocytes. PMID:23009705

  18. Serum miR-574-5p: a prognostic predictor of sepsis patients.

    PubMed

    Wang, Huijuan; Meng, Kun; Chen, Wei jun; Feng, Dan; Jia, Yanhong; Xie, Lixin

    2012-03-01

    Serum micro-RNAs (miRNAs) can be used for the diagnosis and prognosis of various diseases. Using genome-wide scans, we sought to identify serum miRNAs that could be used as prognostic predictors for sepsis patients. We used microarray screens to identify differentially expressed serum miRNAs by comparing samples from 12 surviving and 12 nonsurviving sepsis patients. These differentially expressed serum miRNAs were validated by quantitative reverse transcriptase-polymerase chain reaction assays for 118 sepsis patients. The validated miRNAs along with sepsis patients' clinical indictors were analyzed in a multivariate logistic regression model. Microarray analysis showed that miR-297 and miR-574-5p were differentially expressed in sepsis survivors and nonsurvivors. Upon validation with 118 sepsis patients' samples, these two miRNA expressions were significantly different, with P < 0.001. miR-297 was more closely associated with survival from sepsis, whereas miR-574-5p was associated with death from sepsis. Multivariable logistic regression analysis showed that a combination of sepsis stage, Sepsis-Related Organ Failure Assessment scores, and miR-574-5p was correlated with the death of sepsis patients. The predictive capability of these three combined variables was analyzed by a receiver operating characteristic curve; the area under the curve was 0.932 (95% confidence interval, 0.887-0.977). When the cutoff point was set at 0.288, these three combined variables provided 78.13% sensitivity and 91.84% specificity. Our results showed that serum miR-574-5p was correlated with the death of sepsis patients. The combined predictive capability of sepsis stage, Sepsis-Related Organ Failure Assessment scores, and serum miR-574-5p for the death of sepsis patients was better than any single indicator. PMID:22344312

  19. The FASEB Journal Research Communication A group B streptococcal pilus protein promotes

    E-print Network

    Nizet, Victor

    -positive bacterium Group B Streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in newborns) (3), and Streptococcus pneumoniae (4). Pili, also known as fimbriae, are non- flagellar polymeric-Sinai Medical Center, Los Angeles, California, USA ABSTRACT Group B Streptococcus (GBS) is a major cause

  20. Group B Streptococcal b-Hemolysin/Cytolysin Directly Impairs Cardiomyocyte Viability and Function

    E-print Network

    Nizet, Victor

    of pneumonia, sepsis and meningitis in human newborns [1,2]. Despite recent advances in universal screening, United States of America Abstract Background: Group B Streptococcus (GBS) is a leading cause of neonatal@ucsd.edu Introduction The Gram-positive pathogen Group B Streptococcus (GBS, Streptococcus agalactiae) is a major cause

  1. A single streptococcal gene can confer innate immune resistance and virulence to a

    E-print Network

    Nizet, Victor

    . Keywords: Group B Streptococcus; Lactococcus; Virulence; Macrophage; Neutrophil; Phagocytosis factors that contribute to the pathogenesis of group B Streptococcus (GBS, Streptococcus agalactiae), the leading cause of pneumonia, sepsis, 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j

  2. Late-Onset Group B Streptococcal Infection in Identical Twins: Insight to Disease Pathogenesis

    E-print Network

    Nizet, Victor

    INTRODUCTION Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, sepsis, and meningitis% of cases by bacterial penetration of the blood­brain barrier to produce meningitis.2 Mortality in late-onset GBS infections is lower than for early-onset disease; however, 20% to 40% of infants with meningitis

  3. Substrate utilization in sepsis and multiple organ failure.

    PubMed

    Tappy, Luc; Chioléro, René

    2007-09-01

    Sepsis and multiple organ failure are characterized by an excessive release of inflammatory mediators and a marked stimulation of stress hormones. These in turn have profound effects on energy and substrate metabolism: energy expenditure is generally increased, and increased lipolysis and fat oxidation are observed. Net protein breakdown occurs and leads to accelerated wasting. Most of these effects can be produced in healthy humans by administration of bacterial endotoxin or by tumor necrosis factor-alpha. Hyperlactatemia is a hallmark of sepsis and critical illness, and its severity is related to mortality. An increased lactate production, possibly secondary to activation of Na-K adenosine 5'-triphosphatase and to muscle mitochondrial dysfunction, is involved. Lactate production by immune cells and wound tissue may also play a role. Long-chain, n-3 polyunsaturated fatty acids have anti-inflammatory effects that may be beneficial in sepsis. They also decrease the stimulation of stress hormones induced by bacterial endotoxin, possibly through an effect exerted at the level of the central nervous sytem. Their use in patients with sepsis does not lead to adverse metabolic effects. PMID:17713404

  4. Therapeutic interventions in sepsis: current and anticipated pharmacological agents

    PubMed Central

    Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

    2014-01-01

    Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

  5. Extracellular histones are major mediators of death in sepsis.

    PubMed

    Xu, Jun; Zhang, Xiaomei; Pelayo, Rosana; Monestier, Marc; Ammollo, Concetta T; Semeraro, Fabrizio; Taylor, Fletcher B; Esmon, Naomi L; Lupu, Florea; Esmon, Charles T

    2009-11-01

    Hyperinflammatory responses can lead to a variety of diseases, including sepsis. We now report that extracellular histones released in response to inflammatory challenge contribute to endothelial dysfunction, organ failure and death during sepsis. They can be targeted pharmacologically by antibody to histone or by activated protein C (APC). Antibody to histone reduced the mortality of mice in lipopolysaccharide (LPS), tumor necrosis factor (TNF) or cecal ligation and puncture models of sepsis. Extracellular histones are cytotoxic toward endothelium in vitro and are lethal in mice. In vivo, histone administration resulted in neutrophil margination, vacuolated endothelium, intra-alveolar hemorrhage and macro- and microvascular thrombosis. We detected histone in the circulation of baboons challenged with Escherichia coli, and the increase in histone levels was accompanied by the onset of renal dysfunction. APC cleaves histones and reduces their cytotoxicity. Co-infusion of APC with E. coli in baboons or histones in mice prevented lethality. Blockade of protein C activation exacerbated sublethal LPS challenge into lethality, which was reversed by treatment with antibody to histone. We conclude that extracellular histones are potential molecular targets for therapeutics for sepsis and other inflammatory diseases. PMID:19855397

  6. A rare nonfatal presentation of disseminated Chromobacterium violaceum sepsis.

    PubMed

    Saboo, Ashwin Rajendra; Vijaykumar, Ramaa; Save, Sushma Uttam; Bavdekar, Sandeep Bhalchandra

    2015-10-01

    We present a case of disseminated Chromobacterium violaceum sepsis with multiple liver and splenic abscesses presenting with skin lesions and cardiogenic shock, and later diagnosed to have chronic granulomatous disease. The patient was treated with prolonged antimicrobial therapy, after which she recovered and remained asymptomatic on follow-up. PMID:23380618

  7. A critique of fluid bolus resuscitation in severe sepsis

    PubMed Central

    2012-01-01

    Resuscitation of septic patients by means of one or more fluid boluses is recommended by guidelines from multiple relevant organizations and as a component of surviving sepsis campaigns. The technique is considered a key and life-saving intervention during the initial treatment of severe sepsis in children and adults. Such recommendations, however, are only based on expert opinion and lack adequate experimental or controlled human evidence. Despite these limitations, fluid bolus therapy (20 to 40 ml/kg) is widely practiced and is currently considered a cornerstone of the management of sepsis. In this pointof-view critique, we will argue that such therapy has weak physiological support, has limited experimental support, and is at odds with emerging observational data in several subgroups of critically ill patients or those having major abdominal surgery. Finally, we will argue that this paradigm is now challenged by the findings of a large randomized controlled trial in septic children. In the present article, we contend that the concept of large fluid bolus resuscitation in sepsis needs to be investigated further. PMID:22277834

  8. [Metabolic therapy and pulmonary disfunction in patients with obstetric sepsis].

    PubMed

    Iakovlev, A Iu; Za?tsev, P M; Zubeev, P S; Mokrov, K B; Balandina, A V; Gushchina, N N; Kucherenko, V E

    2011-01-01

    The role of reamberin, a succinate-containing infusion preparation in correlation of pulmonary metabolic and respiratory disturbances in patients with obstetric puerperal sepsis was estimated. The prospective randomized study enrolled 43 patients with puerperal obstetric sepsis complicated by polyorganic deficiency (SOFA 8-10). Nineteen patients of the 1st group and 24 patients of the 2nd group were additionally treated with reamberin in a dose of 800 ml/day for 8 days. The venous and arterial difference by glucose, lactate, pyruvate, diene conjugates, malondialdehyde and ceruloplasmin was investigated. The blood gases were determined with the Ciba Corning 45 apparatus. Lower metabolic activity of the lungs with prevalence of the glucose anaerobic metabolism and lower activity of the intrapulmonary antioxidant protection were observed in the patients with obstetric sepsis. The use of reamberin in the complex therapy of obstetric sepsis promoted maintenance of the initial balance and anaeroibic and aerobic pulmonary metabolism, thus providing shorter terms of the decompensation and recovery of the lungs respiratory function. PMID:21913408

  9. Crosstalk between the coagulation and complement systems in sepsis

    PubMed Central

    Lupu, Florea; Keshari, Ravi S.; Lambris, John D.; Coggeshall, K. Mark

    2014-01-01

    Sepsis is a potent activator of the hemostatic and complement systems. While local activation of these proteolytic cascades contributes to the host defense, their uncontrolled systemic activation has major tissue damaging effects that lead to multiple organ failure and death. We have extensively studied the activation of complement and coagulation cascades in experimental sepsis using baboons challenged with live bacteria, such as Gram-negative Escherichia coli or Gram-positive Staphylococcus aureus and Bacillus anthracis, or with the bacterial product peptidoglycan. We observed that these challenges rapidly induce disseminated intravascular coagulation and robust complement activation. We applied a potent C3 convertase inhibitor, compstatin, which prevented sepsis-induced complement activation, reduced thrombocytopenia, decreased the coagulopathic responses, and preserving the endothelial anticoagulant properties. Overall, our work demonstrates that live bacteria and bacterial products activate the complement and coagulation cascades, and that blocking formation of complement activation products, especially during the organ failure stage of severe sepsis could be a potentially important therapeutic strategy. PMID:24759136

  10. Marked alterations of neutrophil functions during sepsis-induced immunosuppression.

    PubMed

    Demaret, Julie; Venet, Fabienne; Friggeri, Arnaud; Cazalis, Marie-Angélique; Plassais, Jonathan; Jallades, Laurent; Malcus, Christophe; Poitevin-Later, Françoise; Textoris, Julien; Lepape, Alain; Monneret, Guillaume

    2015-12-01

    Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3-4 and d 6-8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10(dim)CD16(dim)). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations. PMID:26224052

  11. Pro- and Synbiotics to Prevent Sepsis in Major Surgery and Severe Emergencies

    PubMed Central

    Bengmark, Stig

    2012-01-01

    Septic morbidity associated with advanced surgical and medical treatments is unacceptably high, and so is the incidence of complications occurring in connection with acute emergencies such as severe trauma and severe acute pancreatitis. Only considering the US, it will annually affect approximately (app) 300 million (mill) of a population of almost one million inhabitants and cause the death of more than 200,000 patients, making sepsis the tenth most common cause of death in the US. Two major factors affect this, the lifestyle-associated increased weakness of the immune defense systems, but more than this the artificial environment associated with modern treatments such as mechanical ventilation, use of tubes, drains, intravascular lines, artificial nutrition and extensive use of synthetic chemical drugs, methods all known to reduce or eliminate the human microbiota and impair immune functions and increase systemic inflammation. Attempts to recondition the gut by the supply of microorganisms have sometimes shown remarkably good results, but too often failed. Many factors contribute to the lack of success: unsuitable choice of probiotic species, too low dose, but most importantly, this bio-ecological treatment has never been given the opportunity to be tried as an alternative treatment. Instead it has most often been applied as complementary to all the other treatments mentioned above, including antibiotic treatment. The supplemented lactic acid bacteria have most often been killed already before they have reached their targeted organs. PMID:22413064

  12. Detection of circulating lipopolysaccharide-bound monocytes in children with gram-negative sepsis.

    PubMed

    Takeshita, S; Nakatani, K; Tsujimoto, H; Kawamura, Y; Sekine, I

    2000-11-01

    The possibility that gram-negative sepsis can be diagnosed by detection of lipopolysaccharide (LPS) bound on the surface of monocytes in the circulation of patients with gram-negative sepsis was investigated. Peripheral monocytes were analyzed by flow cytometer and an anti-LPS monoclonal antibody in 3 groups: children with gram-negative sepsis, children with gram-positive sepsis, and healthy children. LPS-bound monocytes were found in all patients with gram-negative sepsis but not in children with gram-positive sepsis or in healthy children. Therefore, the flow cytometry method developed for this study may be a novel method for diagnosing gram-negative sepsis. PMID:11015235

  13. Decreased Risk of Ventilator-Associated Pneumonia in Sepsis Due to Intra-Abdominal Infection

    PubMed Central

    Philippart, François; Bouroche, Gaëlle; Timsit, Jean-François; Garrouste-Orgeas, Maité; Azoulay, Elie; Darmon, Michael; Adrie, Christophe; Allaouchiche, Bernard; Ara-Somohano, Claire; Ruckly, Stéphane; Dumenil, Anne-Sylvie; Souweine, Bertrand; Goldgran-Toledano, Dany; Bouadma, Lila; Misset, Benoît

    2015-01-01

    Rationale Experimental studies suggest that intra-abdominal infection (IAI) induces biological alterations that may affect the risk of lung infection. Objectives To investigate the potential effect of IAI at ICU admission on the subsequent occurrence of ventilator-associated pneumonia (VAP). Methods We used data entered into the French prospective multicenter Outcomerea database in 1997–2011. Consecutive patients who had severe sepsis and/or septic shock at ICU admission and required mechanical ventilation for more than 3 days were included. Patients with acute pancreatitis were not included. Measurements and Main Results Of 2623 database patients meeting the inclusion criteria, 290 (11.1%) had IAI and 2333 (88.9%) had other infections. The IAI group had fewer patients with VAP (56 [19.3%] vs. 806 [34.5%], P<0.01) and longer time to VAP (5.0 vs.10.5 days; P<0.01). After adjustment on independent risk factors for VAP and previous antimicrobial use, IAI was associated with a decreased risk of VAP (hazard ratio, 0.62; 95% confidence interval, 0.46–0.83; P<0.0017). The pathogens responsible for VAP were not different between the groups with and without IAI (Pseudomonas aeruginosa, 345 [42.8%] and 24 [42.8%]; Enterobacteriaceae, 264 [32.8%] and 19 [34.0%]; and Staphylococcus aureus, 215 [26.7%] and 17 [30.4%], respectively). Crude ICU mortality was not different between the groups with and without IAI (81 [27.9%] and 747 [32.0%], P = 0.16). Conclusions In our observational study of mechanically ventilated ICU patients with severe sepsis and/or septic shock, VAP occurred less often and later in the group with IAIs compared to the group with infections at other sites. PMID:26339904

  14. Apolipoprotein E-mediated immune regulation in sepsis.

    PubMed

    Kattan, Omar M; Kasravi, F Behzad; Elford, Erica L; Schell, Michael T; Harris, Hobart W

    2008-07-15

    Lipids and lipoproteins have emerged as key constituents of the immune response to microbial infection. We, therefore, sought to understand the complex interaction between lipoprotein metabolism and sepsis. Apolipoprotein E (apoE), a component of plasma lipoproteins, has been suggested to bind and traffic Ags for NKT cell activation. However, apoE's role in sepsis has not been demonstrated. In this study, we examined the effect of exogenous apoE in a rat model of septic peritonitis, induced by cecal ligation and puncture. We demonstrate that 48 h after serial injections of apoE, septic mortality increased in a dose-dependent manner. While sepsis resulted in increased splenic and decreased hepatic and circulating NKT cell populations, serial injections of apoE for 24 h after cecal ligation and puncture increased the frequency, cell number, and BrdU uptake in splenic and hepatic NKT cell populations, while concomitantly depleting these populations in the circulation. These changes were correlated with elevated alanine amino transferase levels, an indicator of liver injury. Interestingly, while sepsis increased hepatic T cell apoptosis and necrosis, apoE reversed these changes. apoE also promoted increases in predominantly Th1 cytokine levels in sera and a decrease in IL-4, the main NKT cell-derived Th2 cytokine. Consequently, apoE treatment is associated with increased sepsis-induced mortality, and increased NKT cell frequency and proliferation in the liver and spleen, with concomitant decreases in these NKT cell parameters in the peripheral circulation. apoE treatment also promoted a Th1 cytokine response, increased the degree of liver injury, and decreased apoptosis in hepatic lymphocytes. PMID:18606694

  15. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview

    PubMed Central

    Rhee, Hanna; Cameron, Daniel J

    2012-01-01

    Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed. PMID:22393303

  16. Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

    SciTech Connect

    Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

    2007-01-01

    The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

  17. Microbial Analysis of Bite Marks by Sequence Comparison of Streptococcal DNA

    PubMed Central

    Kennedy, Darnell M.; Stanton, Jo-Ann L.; García, José A.; Mason, Chris; Rand, Christy J.; Kieser, Jules A.; Tompkins, Geoffrey R.

    2012-01-01

    Bite mark injuries often feature in violent crimes. Conventional morphometric methods for the forensic analysis of bite marks involve elements of subjective interpretation that threaten the credibility of this field. Human DNA recovered from bite marks has the highest evidentiary value, however recovery can be compromised by salivary components. This study assessed the feasibility of matching bacterial DNA sequences amplified from experimental bite marks to those obtained from the teeth responsible, with the aim of evaluating the capability of three genomic regions of streptococcal DNA to discriminate between participant samples. Bite mark and teeth swabs were collected from 16 participants. Bacterial DNA was extracted to provide the template for PCR primers specific for streptococcal 16S ribosomal RNA (16S rRNA) gene, 16S–23S intergenic spacer (ITS) and RNA polymerase beta subunit (rpoB). High throughput sequencing (GS FLX 454), followed by stringent quality filtering, generated reads from bite marks for comparison to those generated from teeth samples. For all three regions, the greatest overlaps of identical reads were between bite mark samples and the corresponding teeth samples. The average proportions of reads identical between bite mark and corresponding teeth samples were 0.31, 0.41 and 0.31, and for non-corresponding samples were 0.11, 0.20 and 0.016, for 16S rRNA, ITS and rpoB, respectively. The probabilities of correctly distinguishing matching and non-matching teeth samples were 0.92 for ITS, 0.99 for 16S rRNA and 1.0 for rpoB. These findings strongly support the tenet that bacterial DNA amplified from bite marks and teeth can provide corroborating information in the identification of assailants. PMID:23284761

  18. Acute Pancreatitis and Pregnancy

    MedlinePLUS

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  19. Heparin Reduced Mortality and Sepsis in Severely Burned Children

    PubMed Central

    Zayas, G.J.; Bonilla, A.M.; Saliba, M.J

    2007-01-01

    Summary Objectives. In El Salvador, before 1999, morbidity and mortality in severely burned children were high. In 1998, all children with burns of 40% or larger size died and sepsis was found. With heparin use in 1999, some similarly burned children survived, and sepsis, pain, procedures, and scars were noted to be less. This retrospective study presents the details. Methods. A study was conducted at the National Children's Hospital in El Salvador of all children with burns over 20% size treated in 1998, when no heparin was used, and in 1999, when heparin was added to burns treatment, using an ethics committee approved protocol in use in twelve other countries. Sodium aqueous heparin solution USP from an intestinal source was infused intravenously and applied topically onto burn surfaces and within blisters for the first 1-3 days post-burn. Then heparin, in diminishing doses, was continued only topically until healing. The treatments in 1998 and 1999 were otherwise the same, except that fewer procedures were needed in 1999. Results. There were no significant differences in gender, age, weight, burn aetiology, or burn size between the burned children in 1998 and those in 1999. Burn pain was relieved and pain medicine was not needed in children treated with heparin in 1999. In 1998, one child survived who had a 35% size burn, and the eight children died who had burns of 40% and over. The survival rate was one out of nine (11%). The average burn size was 51.7%. With heparin use in 1999, six of the ten children survived burns of 50.7% average size. The increase in survival with heparin from 11% to 60% and, therefore, the decrease in mortality from 89% to 40% were significant (p < 0.04). Clinical symptoms and positive blood cultures documented bacterial sepsis in the nine children in 1998. In 1999, the blood cultures for sepsis were positive in the four children who died and negative in the six who survived. The nine versus four differences in the incidence of sepsis between 1998 and 1999 was significant (p < 0.008). The survivors had notably smooth skin. Conclusions. The use of heparin in this study relieved burn pain, significantly reduced mortality and sepsis with fewer procedures, and discernibly improved cosmetic results. PMID:21991064

  20. Selective downregulation of neutrophils by a phosphatidic acid generation inhibitor in a porcine sepsis model.

    PubMed

    Oka, Y; Hasegawa, N; Nakayama, M; Murphy, G A; Sussman, H H; Raffin, T A

    1999-02-01

    Effects of lisofylline (1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine), a functional inhibitor of phosphatidic acid (PA) generation derived from de novo synthesis, on neutrophil function were examined in a porcine sepsis model. Hanford minipigs (18-25 kg) were randomly separated into six groups of six animals each: (1) saline control group; (2) sepsis control group, infused with Pseudomonas aeruginosa (1 x 10(6) colony-forming units/kg/min) for 2 h; (3) lisofylline control group, given a 25 mg/kg bolus of lisofylline 30 min prior to time zero, followed by a continuous infusion of 10 mg/kg/h throughout the study; (4) lisofylline pretreatment sepsis group, given lisofylline 30 min prior to sepsis, (5) lisofylline 1-h post-treatment sepsis group, and (6) lisofylline 2-h post-treatment sepsis group. All animals were studied for 6 h. Neutrophils were isolated at -0.5, 2, and 6 h. In the pretreatment and 1-h post-treatment groups, sepsis-induced neutrophil attachment to fibronectin was significantly attenuated. Sepsis-enhanced phagocytic activity was significantly reduced in the lisofylline pretreatment sepsis group, but not in the post-treatment groups. No treatment affected phorbol 12-myristate 13-acetate-induced chemiluminescence and basal filamentous actin content, which increased in sepsis, and cap formation, which declined in sepsis. Sepsis caused neutropenia, pretreatment produced neutrophilia, and 1-h post-treatment caused the neutropenia to recover to control levels. Interestingly, toward the end of the 6-h period, the neutrophil count was higher in the lisofylline control group than in the saline control groups. Thus, the inhibition of PA generation from de novo synthesis during sepsis not only can selectively downregulate some neutrophil functions but can also reverse neutropenia. PMID:9927533

  1. [Group A streptococcal meningitis: Streptococcus pneumoniae is not the only one to seep into the CSF fluid leak!].

    PubMed

    Zappella, N; Barrelet, A; Pangon, B; Laurent, V; Bruneel, F

    2013-11-01

    We reported a case of group A streptococcal meningitis in a patient with a CSF fluid leak. This case underlined several relevant points: (i) an unfrequent cause of bacterial meningitis; (ii) the main diagnosis to evoke when the direct examination of CSF shows Gram+ cocci with a negative pneumococcal antigen; (iii) that bacteria other than Streptococcus pneumoniae are possible in front of a meningitis associated with a CSF fluif leak. PMID:24161291

  2. Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.

    PubMed Central

    Song, X Y; Gu, M; Jin, W W; Klinman, D M; Wahl, S M

    1998-01-01

    Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. PMID:9637694

  3. A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method

    PubMed Central

    Yang, Hang; Linden, Sara B.; Wang, Jing; Yu, Junping; Nelson, Daniel C.; Wei, Hongping

    2015-01-01

    The increasing emergence of multi-drug resistant streptococci poses a serious threat to public health worldwide. Bacteriophage lysins are promising alternatives to antibiotics; however, their narrow lytic spectrum restricted to closely related species is a central shortcoming to their translational development. Here, we describe an efficient method for rapid screening of engineered chimeric lysins and report a unique “chimeolysin”, ClyR, with robust activity and an extended-spectrum streptococcal host range against most streptococcal species, including S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis, as well as representative enterococcal and staphylococcal species (including MRSA and VISA). ClyR is the first lysin that demonstrates activity against the dominant dental caries-causing pathogen as well as the first lysin that kills all four of the bovine mastitis-causing pathogens. This study demonstrates the success of the screening method resulting in a powerful lysin with potential for treating most streptococcal associated infections. PMID:26607832

  4. A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method.

    PubMed

    Yang, Hang; Linden, Sara B; Wang, Jing; Yu, Junping; Nelson, Daniel C; Wei, Hongping

    2015-01-01

    The increasing emergence of multi-drug resistant streptococci poses a serious threat to public health worldwide. Bacteriophage lysins are promising alternatives to antibiotics; however, their narrow lytic spectrum restricted to closely related species is a central shortcoming to their translational development. Here, we describe an efficient method for rapid screening of engineered chimeric lysins and report a unique "chimeolysin", ClyR, with robust activity and an extended-spectrum streptococcal host range against most streptococcal species, including S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis, as well as representative enterococcal and staphylococcal species (including MRSA and VISA). ClyR is the first lysin that demonstrates activity against the dominant dental caries-causing pathogen as well as the first lysin that kills all four of the bovine mastitis-causing pathogens. This study demonstrates the success of the screening method resulting in a powerful lysin with potential for treating most streptococcal associated infections. PMID:26607832

  5. Complication of Invasive Molar Pregnancy with Clostridium perfringens Sepsis.

    PubMed

    Singh, Sanmeet; Angra, Kunal; Davis, Bonnie; Shokrani, Babak

    2014-01-01

    Clostridium perfringens (CP) is an anaerobic, Gram-positive bacillus associated with malignant diseases and near-term pregnancies. The necrotic tissue that results from these disease processes fuels the proliferation of CP, leading to gas gangrene and subsequently sepsis. Herein, we report a case of a 41-year-old female patient with a history of invasive molar pregnancy that was further complicated with a CP infection. Although past research has shown a link between Clostridium infection and choriocarcinoma (Chern-Horng and Hsieh, 1999), no previous cases of CP infection have been associated with invasive molar pregnancy. We also report complete resolution of the CP sepsis and its associated symptoms following the hysterectomy. PMID:24716030

  6. Dynamics of central venous catheter-related sepsis in rats.

    PubMed Central

    Paston, M J; Meguid, R A; Muscaritoli, M; Forbes, B; Yang, Z J; Meguid, M M

    1993-01-01

    To determine when catheter-related sepsis clears after removal of an infected central venous catheter (CVC) and when a new sterile CVC can be inserted without risk of recolonization, a catheter infected with 10(5) CFU of Staphylococcus epidermidis per ml was inserted into 40 Fischer 344 rats. Five control rats had sterile catheters. Insertion of an infected CVC was followed by a significant rise in leukocytes after 4 days and the presence of S. epidermidis in lungs, livers, spleens, kidneys, and the catheter tip, as examined by bacteriological assay. After the infected catheter was removed, the rat recovered from the induced catheter-related sepsis within 12 h. When a new sterile CVC was inserted into the femoral vein, the leukocyte count remained normal, and all catheter tips and tissue cultures were sterile 4 days later. PMID:8315012

  7. Kluyvera ascorbata sepsis in an extremely low birth weight infant.

    PubMed

    Sharma, D; Dasi, T; Murki, S; Oleti, T P

    2015-01-01

    Kluyvera ascorbata belongs to Enterobacteriaceae family and is a gram negative micro-organism. This bacteria is usually considered a commensal, however it can cause significant infections rarely. This organism is usually resistant to most commonly used antibiotics used as first line in neonatal units. Antimicrobial agents active against Kluyvera strains include third-generation cephalosporins, fluoroquinolones, and aminoglycosides. We report a case of an extremely low birth weight male infant who presented on day 4 of life with clinical features of sepsis, multi-organ dysfunction, shock and pulmonary haemorrhage. Neonatal sepsis was associated with marked elevation of C-reactive protein and a falling platelet count. Infant expired on day 5 of life in spite of aggressive supportive care and treatment with meropenem. with growth of Kluyvera ascorbataon blood culture. PMID:26068354

  8. Interrelationship between procalcitonin and organ failure in sepsis.

    PubMed

    Anand, Dimple; Das, Sabari; Ray, Sumit; Bhargava, Seema; Srivastava, Lalit Mohan

    2014-01-01

    Sepsis suffers from lack of specific clinical symptoms which contribute to one of the major causes of mortality. In the present study, our aim was to evaluate the role of a recent biomarker Procalcitonin (PCT) in predicting organ dysfunction. 71 patients admitted with sepsis were included in the study. PCT levels were measured at 0, 24, 72 h and 7th day and sequential organ failure assessment score (SOFA) scores were calculated. PCT levels significantly decreased (p < 0.001) in 89.3 % of surviving patients, whereas, in 60 % non surviving patients the PCT level increased significantly (p < 0.001). A significant positive correlation between PCT and SOFA score was observed in survivors at each hour. These observations indicate that PCT concentration is significantly associated with severity of multi organ dysfunction and also helps in determining the prognosis of septic patients. PMID:24478557

  9. Association between sepsis and Rocky Mountain spotted fever.

    PubMed

    Bacci, Marcelo Rodrigues; Namura, José Jorge

    2012-01-01

    Rocky Mountain spotted fever (RMSF) is a disease caused by the Gram-negative coccobacillus Rickettsia ricketsii which has been on the rise since the last decade in the USA. The symptoms are common to the many viral diseases, and the classic triad of fever, rash and headache is not always present when RMSF is diagnosed. It may progress to severe cases such as renal failure, disseminated intravascular coagulation and septicaemia. This report aims to present a fulminant case of RMSF associated with sepsis. It describes a female patient's case that quickly progressed to sepsis and death. The patient showed non-specific symptoms for 5 days before being admitted to a hospital. The fact that she lived in an area highly infested with Amblyomma aureolatum ticks was unknown to the medical staff until the moment she died. PMID:23220832

  10. Increased release of sMD-2 during human endotoxemia and sepsis: a role for endothelial cells.

    PubMed

    Wolfs, Tim G A M; Dunn-Siegrist, Irène; van't Veer, Cornelis; Hodin, Caroline M I M; Germeraad, Wilfred T V; van Zoelen, Marieke A D; van Suylen, Robert-Jan; Peutz-Kootstra, Carine J; Elson, Greg; Pugin, Jérôme; Buurman, Wim A

    2008-06-01

    MD-2 is the crucial cofactor of TLR4 in the detection of LPS. Here, we show that soluble MD-2 (sMD-2) circulates in plasma of healthy individuals as a polymeric protein. The total amount of sMD-2 in septic plasma was strongly elevated and contained both sMD-2 polymers and monomers, the latter representing the putative biologically active form of MD-2. Moreover, during experimental human endotoxemia, the monomeric and total sMD-2 content in plasma increased with the kinetics of an acute phase protein. The increase in sMD-2 monomers was paralleled by enhanced TLR4 costimulatory activity. The presence of functional sMD-2 during endotoxemia and sepsis was confirmed by immunodepletion. Immunohistochemistry revealed that MD-2 expression in septic patients was strongly enhanced on endothelium and multiple inflammatory cells in lung and liver. In vitro studies showed that sMD-2 release appears to be restricted to endothelial cells and dendritic cells. Release of sMD-2 by endothelial cells was strongly enhanced by LPS and TNF-alpha stimulation. Taken together, this study demonstrates the increase of both circulating polymeric and functional monomeric sMD-2 during endotoxemia and sepsis, and evidence is provided that the endothelium is involved in this process. PMID:18384879

  11. Effect of bacterial sepsis on gluconeogenic capacity in the rat

    SciTech Connect

    Holman, J.M. Jr.; Saba, T.M.

    1988-08-01

    Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of (/sup 14/C)alanine to (/sup 14/C)glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting.

  12. Randomized Controlled Trial of Calcitriol in Severe Sepsis

    PubMed Central

    Raed, Anas; Donnino, Michael W.; Ginde, Adit A.; Waikar, Sushrut S.

    2014-01-01

    Rationale: Vitamin D and its metabolites have potent immunomodulatory effects in vitro, including up-regulation of cathelicidin, a critical antimicrobial protein. Objectives: We investigated whether administration of 1,25-dihydroxyvitamin D (calcitriol) to critically ill patients with sepsis would have beneficial effects on markers of innate immunity, inflammation, and kidney injury. Methods: We performed a double-blind, randomized, placebo-controlled, physiologic study among 67 critically ill patients with severe sepsis or septic shock. Patients were randomized to receive a single dose of calcitriol (2 ?g intravenously) versus placebo. The primary outcome was plasma cathelicidin protein levels assessed 24 hours after study drug administration. Secondary outcomes included leukocyte cathelicidin mRNA expression, plasma cytokine levels (IL-10, IL-6, tumor necrosis factor-?, IL-1?, and IL-2), and urinary kidney injury markers. Measurements and Main Results: Patients randomized to calcitriol (n = 36) versus placebo (n = 31) had similar plasma cathelicidin protein levels at 24 hours (P = 0.16). Calcitriol-treated patients had higher cathelicidin (P = 0.04) and IL-10 (P = 0.03) mRNA expression than placebo-treated patients 24 hours after study drug administration. Plasma cytokine levels (IL-10, IL-6, tumor necrosis factor-?, IL-1?, and IL-2) and urinary kidney injury markers were similar in calcitriol- versus placebo-treated patients (P > 0.05 for all comparisons). Calcitriol had no effect on clinical outcomes nor were any adverse effects observed. Conclusions: Calcitriol administration did not increase plasma cathelicidin protein levels in critically ill patients with sepsis and had mixed effects on other immunomodulatory markers. Additional phase II trials investigating the dose and timing of calcitriol as a therapeutic agent in specific sepsis phenotypes may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 01689441). PMID:25029202

  13. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  14. Vascular endothelial cell Toll-like receptor pathways in sepsis.

    PubMed

    Khakpour, Samira; Wilhelmsen, Kevin; Hellman, Judith

    2015-11-01

    The endothelium forms a vast network that dynamically regulates vascular barrier function, coagulation pathways and vasomotor tone. Microvascular endothelial cells are uniquely situated to play key roles during infection and injury, owing to their widespread distribution throughout the body and their constant interaction with circulating blood. While not viewed as classical immune cells, endothelial cells express innate immune receptors, including the Toll-like receptors (TLRs), which activate intracellular inflammatory pathways mediated through NF-?B and the MAP kinases. TLR agonists, including LPS and bacterial lipopeptides, directly upregulate microvascular endothelial cell expression of inflammatory mediators. Intriguingly, TLR activation also modulates microvascular endothelial cell permeability and the expression of coagulation pathway intermediaries. Microvascular thrombi have been hypothesized to trap microorganisms thereby limiting the spread of infection. However, dysregulated activation of endothelial inflammatory pathways is also believed to lead to coagulopathy and increased vascular permeability, which together promote sepsis-induced organ failure. This article reviews vascular endothelial cell innate immune pathways mediated through the TLRs as they pertain to sepsis, highlighting links between TLRs and coagulation and permeability pathways, and their role in healthy and pathologic responses to infection and sepsis. PMID:26403174

  15. Early onset Haemophilus influenzae sepsis in the newborn infant.

    PubMed

    Kinney, J S; Johnson, K; Papasian, C; Hall, R T; Kurth, C G; Jackson, M A

    1993-09-01

    Neonatal sepsis caused by Haemophilus influenzae is characterized by an early onset syndrome associated with pneumonia, shock and neutropenia. Over a 30-month period 13 infants referred to this hospital had early onset H. influenzae sepsis. Obstetric complications included preterm labor (92%), prolonged rupture of membranes > 12 hours (63%), maternal fever (64%), chorioamnionitis (43%), vaginal discharge (44%) and premature rupture of membranes (15%). All 13 infants were symptomatic at delivery and 7 required immediate intubation. Pneumonia and respiratory distress were the prominent clinical findings. H. influenzae was isolated from infant blood, maternal blood, placenta and genital tract. Isolates were predominantly non-type b, beta-lactamase-negative. A study to determine the prevalence of H. influenzae colonization of the genital tract among women attending clinic at the hospital with the most cases showed a rate of 0.3%. Perinatal risk factors and clinical findings in the infants are similar to disease caused by other organisms associated with early onset sepsis. PMID:8414801

  16. Nanomechanics of the Endothelial Glycocalyx in Experimental Sepsis

    PubMed Central

    Wiesinger, Anne; Peters, Wladimir; Chappell, Daniel; Kentrup, Dominik; Reuter, Stefan; Pavenstädt, Hermann; Oberleithner, Hans; Kümpers, Philipp

    2013-01-01

    The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P<0.0001) and stiffness (0.34 ± 0.03 vs. 0.21 ± 0.01 pN/mn, P<0.0001) in septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-? alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis. PMID:24278345

  17. Critical points for sepsis management at the patient bedside.

    PubMed

    Tulli, G

    2003-01-01

    Following an interpretative philosophy, dyna-mic and faithful to the complexity theory, a clinical pathway is outlined close to the reality, at the patient bedside, that is comprehensive of the diagnostic process in its temporal dynamism, of the therapeutic process in its specificity (antibiotic therapy, surgical souce control), in the use of organs supportive therapy (haemodynamic, respiratory, renal, etc.) and in the use of adjunctive and immunomodulatory therapies (APC, AT, etc.). The importance of the contextual activation of microbiological, immunological and coagulative monitorings is underlined. Through a critical review of the more recent literature, a strict relationship, in sepsis and septic shock, between inflammation and coagulation is described, that allowed the activated protein C (drotrecogin alpha activated) success, in terms of reduction of the absolute and relative mortality. This therapeutic success is contextualized into two other important therapeutic successes, recently obtained in severe sepsis and septic shock, based on the medical evidence, one using low doses of corticosteroids and the other using the early (6 h) goal directed haemodynamic therapy to restore a balance between oxygen delivery and oxygen demand. Once systemic inflammation is complicated by organ failure, there are few options. Treatment with activated protein C lowers the risk of death but is associated with an increased risk of bleeding and is likely to be expensive. The strategies described by the groups of Rivers and Annane offer the opportunity for good therapeutic results, by preventing the progression or even the development of sepsis and its complications: septic shock and multiple organ dysfunction. PMID:12677162

  18. Streptococcal screen

    MedlinePLUS

    Rapid strep test ... to identify group A streptococcus, the cause of strep throat. It takes about 7 minutes to get ... order this test if you have signs of strep throat, which include: Fever Sore throat Tender and ...

  19. Streptococcal Infections

    MedlinePLUS

    ... disease) Group B strep can cause blood infections, pneumonia and meningitis in newborns. A screening test during pregnancy can tell if you have it. If you do, I.V. antibiotics during labor can save your baby's ... and pneumonia in adults. Antibiotics are used to treat strep ...

  20. Branched DNA-based Alu quantitative assay for cell-free plasma DNA levels in patients with sepsis or systemic inflammatory response syndrome.

    PubMed

    Hou, Yan-Qiang; Liang, Dong-Yu; Lou, Xiao-Li; Zhang, Mei; Zhang, Zhen-Huan; Zhang, Lu-Rong

    2016-02-01

    Cell-free circulating DNA (cf-DNA) can be detected by various of laboratory techniques. We described a branched DNA-based Alu assay for measuring cf-DNA in septic patients. Compared to healthy controls and systemic inflammatory response syndrome (SIRS) patients, serum cf-DNA levels were significantly higher in septic patients (1426.54 ± 863.79 vs 692.02 ± 703.06 and 69.66 ± 24.66 ng/mL). The areas under the receiver operating characteristic curve of cf-DNA for normal vs sepsis and SIRS vs sepsis were 0.955 (0.884-1.025), and 0.856 (0.749-0.929), respectively. There was a positive correlation between cf-DNA and interleukin 6 or procalcitonin or Acute Physiology and Chronic Health Evaluation II. The cf-DNA concentration was higher in intensive care unit nonsurviving patients compared to surviving patients (2183.33 ± 615.26 vs 972.46 ± 648.36 ng/mL; P < .05). Branched DNA-based Alu assays are feasible and useful to quantify serum cf-DNA levels. Increased cf-DNA levels in septic patients might complement C-reactive protein and procalcitonin in a multiple marker format. Cell-free circulating DNA might be a new marker in discrimination of sepsis and SIRS. PMID:26589770

  1. Acute Inflammation

    MedlinePLUS

    The official consumer website of: Visit ACFAS.org | About ACFAS | Información en Español Advanced Search Home » Foot & Ankle Conditions » Acute Inflammation Text Size Print Bookmark Acute Inflammation What Is Acute Inflammation? Inflammation is the body’s normal protective response to an injury, irritation, ...

  2. Immunomodulation in Sepsis: The Role of Endotoxin Removal by Polymyxin B-Immobilized Cartridge

    PubMed Central

    Ferrer, Ricard; Artigas, Antonio

    2013-01-01

    Severe sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Endotoxin is a component of gram-negative bacteria and plays an important role in the pathogenesis of septic shock when it is recognized by immune cells. Removal of endotoxin could be an effective adjunctive approach to the management of sepsis. Devices to adsorb endotoxin or inflammatory cytokines have been designed as a strategy to treat severe sepsis, especially sepsis caused by gram-negative bacteria. Polymyxin B-immobilized cartridge has been successfully used to treat patients with sepsis of abdominal origin. Although this cartridge was conceived to adsorb endotoxin, several other immunological mechanisms have been elucidated, and this device has also yielded promising results in patients with nonseptic respiratory failure. In this paper, we summarize the immune modulation actions of Polymyxin B-immobilized cartridge to explore its potential usefulness beyond endotoxin elimination. PMID:24249974

  3. Unificando los criterios de sepsis neonatal tardía: propuesta de un algoritmo de vigilancia diagnóstica

    PubMed Central

    Zea-Vera, Alonso; Turin, Christie G.; Ochoa, Theresa J.

    2015-01-01

    Las infecciones constituyen una de las principales causas de muerte en el periodo neonatal. El diagnóstico de sepsis neonatal representa un gran desafío ya que los recién nacidos presentan signos clínicos muy inespecíficos y los exámenes auxiliares tienen una baja sensibilidad. Con el objetivo de mejorar el diagnóstico correcto de esta patología proponemos un algoritmo de vigilancia diagnóstica para sepsis neonatal tardía en el Perú y países de la región. El algoritmo permite clasificar a los episodios como sepsis confirmada, probable o posible, y sobretodo busca identificar aquellos episodios que no corresponden a sepsis, evitando calificar otras patologías como “sepsis”. Un mejor diagnóstico permitiría tener tasas más reales de sepsis neonatal, mejorar el uso de antibióticos y evitar sus efectos negativos en el recién nacido, así como una visión más exacta de su impacto en la salud pública. PMID:25123879

  4. Bath Salts: A Newly Recognized Cause of Acute Kidney Injury

    PubMed Central

    McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil

    2012-01-01

    Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity. PMID:24555135

  5. PRESENCE OF PRE-EXISTING ANTIBODIES MEDIATE SURVIVAL IN SEPSIS

    PubMed Central

    Moitra, Rituparna; Beal, Dominic R.; Belikoff, Bryan G.; Remick, Daniel G.

    2011-01-01

    Sepsis is one of the leading causes of death in hospitals worldwide. Even with optimal therapy, severe sepsis results in 50% mortality, indicating variability in the response of individuals towards treatment. We hypothesize that the presence of pre-existing antibodies present in the blood before the onset of sepsis induced by cecal ligation and puncture (CLP) in mice, accounts for the differences in their survival. A Plasma Enhanced Killing (PEK) assay was performed to calculate the PEK capacity of plasma i.e. the ability of plasma to augment PMN killing of bacteria. PEK was calculated as PEK= (1/log (N)) × 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing. A range of PEK in plasma collected from mice prior to CLP was observed, documenting individual differences in bacterial killing capacity. Mortality was predicted based on plasma IL-6 levels at 24 hr post CLP. Mice predicted to die (Die-P) had a lower PEK (<14) and higher peritoneal bacterial counts 24 hr post sepsis compared to those predicted to live (Live-P) with a PEK>16. Mice with PEK<14 were 3.1 times more likely to die compared to the PEK>16 group. To understand the mechanism of defense conferred by the pre-existing antibodies, binding of IgM or IgG to enteric bacteria was documented by flow cytometry. To determine the relative contribution of IgM or IgG, the immunoglobulins were specifically immuno-depleted from the naïve plasma samples and the PEK of the depleted plasma measured. Compared to naïve plasma, depletion of IgM had no effect on the PEK. However, depletion of IgG increased PEK suggesting that an inhibitory IgG binds to antigenic sites on bacteria preventing optimal opsonization of the bacteria. These data demonstrate that prior to CLP; circulating inhibitory IgG antibodies exist that prevent bacterial killing by PMNs in a CLP model of sepsis. PMID:21921828

  6. Inadequate Exercise as a Risk Factor for Sepsis Mortality

    PubMed Central

    Williams, Paul T.

    2013-01-01

    Objective Test whether inadequate exercise is related to sepsis mortality. Research Design and Methods Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Results Sepsis was the underlying cause in 54 deaths (sepsisunderlying) and a contributing cause in 184 deaths (sepsiscontributing), or 238 total sepsis-related deaths (sepsistotal). Inadequate exercise was associated with 2.24-fold increased risk for sepsisunderlying (95%CI: 1.21 to 4.07-fold, P?=?0.01), 2.11-fold increased risk for sepsiscontributing (95%CI: 1.51- to 2.92-fold, P<10?4), and 2.13-fold increased risk for sepsistotal (95%CI: 1.59- to 2.84-fold, P<10?6) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsistotal risk was greater in diabetics (P?=?10?5), cancer survivors (P?=?0.0001), and heart attack survivors (P?=?0.003) and increased with waist circumference (P?=?0.0004). The sepsistotal risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsistotal risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P?=?0.0001) when adjusted, which was significantly greater (P?=?0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P?=?0.0006). Conclusion Inadequate exercise is a risk factor for sepsis mortality, particular in diabetics. PMID:24324580

  7. Association between pre–biopsy white blood cell count and prostate biopsy – related sepsis

    PubMed Central

    Bulut, Suleyman; Aktas, Binhan Kagan; Gokkaya, Cevdet Serkan; Akdemir, Alp Ozgur; Erkmen, Akif Ersoy; Memis, Ali

    2015-01-01

    Introduction Despite all preventive measures and improved biopsy techniques, serious, life–threatening complications of prostate biopsy, including sepsis, still exist. In the present study, in order to identify the risk factors that may be associated with sepsis development after prostate–biopsy, we aimed to analyze retrospectively the data of our patients who underwent transrectal ultrasound–guided prostate biopsy. Material and methods We retrospectively reviewed the data of 889 patients who underwent prostate biopsy at our clinic. We compared pre–biopsy parameters (age, prostate volume, white blood cell (WBC) count, fasting blood glucose, free and total prostate specific antigen levels) between patients who developed sepsis and those who were sepsis–free following prostate biopsy. Results 28 patients (3.1%) developed sepsis. Among the risk factors evaluated, only pre–biopsy WBC count was found to be a significant risk factor for biopsy–related sepsis. A 5.1 fold increase was detected in the risk for sepsis development, when the cut–off value of WBC was accepted as 11.165/?L, OR: 5.1 (95% CI: 2.3–11.5). The post–biopsy sepsis development rate in patients with pre–biopsy WBC count greater and less than 11.165/?L was 13.7% (n = 10) and 3% (n = 18) respectively. Conclusions Patients with a pre–biopsy WBC count greater than 11.165/?L should be informed of the increased risk of developing post–biopsy sepsis. PMID:25914844

  8. Sepsis-induced Cardiac Mitochondrial Damage and Potential Therapeutic Interventions in the Elderly

    PubMed Central

    Zang, Qun S.; Wolf, Steven E.; Minei, Joseph P.

    2014-01-01

    The incidence of sepsis and its attendant mortality risk are significantly increased with aging. Thus, severe sepsis in the elderly is likely to become an emerging concern in critical care units. Cardiac dysfunction is an important component of multi-organ failure after sepsis. In our laboratory, utilizing a pneumonia-related sepsis animal model, our research has been focused on the mechanisms underlying sepsis-induced cardiac failure. In this review, based on findings from others and ours, we discussed age-dependent decay in mitochondria and the role of mitochondrial reactive oxygen species (mtROS) in sepsis-induced cardiac inflammation and autophagy. Our recent discovery of a potential signal transduction pathway that triggers myocardial mitochondrial damage is also discussed. Because of the significance of mitochondria damage in the aging process and in sepsis pathogenesis, we hypothesize that specific enhancing mitochondrial antioxidant defense by mitochondria-targeted antioxidants (MTAs) may provide important therapeutic potential in treating elder sepsis patients. In this review, we summarized the categories of currently published MTA molecules and the results of preclinical evaluation of MTAs in sepsis and aging models. PMID:24729939

  9. Elevated Expression of IL-23/IL-17 Pathway-Related Mediators Correlates with Exacerbation of Pulmonary Inflammation During Polymicrobial Sepsis1

    PubMed Central

    Cauvi, David M.; Williams, Michael R.; Bermudez, Jose A.; Armijo, Gabrielle; De Maio, Antonio

    2014-01-01

    Sepsis is a leading cause of death in the United States, claiming more than 215,000 lives every year. A primary condition observed in septic patients is the incidence of acute respiratory distress syndrome (ARDS), which is characterized by the infiltration of neutrophils into the lung. Prior studies have shown differences in pulmonary neutrophil accumulation in C57BL/6J (B6) and A/J mice after endotoxic and septic shock. However, the mechanism by which neutrophils accumulate in the lung after polymicrobial sepsis induced by cecal ligation and puncture (CLP) still remains to be fully elucidated. We show in this study that lung inflammation, characterized by neutrophil infiltration and expression of inflammatory cytokines, was aggravated in B6 as compared to A/J mice and correlated with high expression of p19, the IL-23-specific subunit. Furthermore, LPS stimulation of B6- and A/J-derived macrophages, one of the main producers of IL-23 and IL-12, revealed that B6 mice favored the production of IL-23 whereas A/J-derived macrophages expressed higher levels of IL-12. In addition, expression of IL-17, known to be upregulated by IL-23, was also more elevated in the lung of B6 mice when compared to A/J mice. In contrast, pulmonary expression of IFN-? was much more pronounced in A/J than in B6 mice, which was most likely a result of a higher production of IL-12. The expression of the IL-17-dependent neutrophil recruitment factors CXCL2 and G-CSF was also higher in B6 mice. Altogether, these results suggest that increased activation of the IL-23/IL-17 pathway has detrimental effects on sepsis-induced lung inflammation, whereas activation of the IL-12/IFN-? pathway may lead, in contrast, to less pronounced inflammatory events. These two pathways may become possible therapeutic targets for the treatment of sepsis-induced ARDS. PMID:24978886

  10. [Uterine gas gangrene through clostridium perfringens sepsis after uterus rupture postpartum].

    PubMed

    Montavon, C; Krause, E; Holzgreve, W; Hösli, I

    2005-10-01

    Anaerobic infections with Clostridium perfringens (CP) occur rarely but are associated with considerable maternal mortality. We report the case of a patient who developed uterine gas gangrene postpartum and discuss the management of this infection. A 28-year-old patient, GII, PII with history of Caesarean in 2002, delivered a healthy girl per vacuum extraction. Postpartally she presented with an acute abdomen and a laparotomy was performed. The uterotomy suture was intact but a parametrane tear had to be resutured. 36 hours later the patient's condition worsened quickly. Cellulitis was diagnosed and after receiving the results of the wound swabs (CP positive) from the uterus and haematoma, tazobactam and clindamycin were administered. Her condition continued to deteriorate and gaseous gangrene was seen with unilateral extension to the abdomen reaching as far as the axilla cranially and to the thigh caudally. Due to the extensive infection it was necessary to perform a hysterectomy, necrosis removal and splitting of the fascia followed by several debridements and leaving the wound open in order to avoid anaerobic conditions. The patient was discharged after 21 days. She developed a post-traumatic syndrome with severe depression. Clostridium perfringens is ubiquitous and is found vaginally in ca. 1 - 10 % of healthy women and usually does not cause a serious infection. Under the right conditions it can cause an endometritis leading to sepsis. Early recognition and interdisciplinary treatment are of extreme importance. In this case the surgical treatment through hysterectomy combined with targeted antibiotic therapy, ultimately saved the patient's life. PMID:16317627

  11. Non-Classical monocytes display inflammatory features: Validation in Sepsis and Systemic Lupus Erythematous

    PubMed Central

    Mukherjee, Ratnadeep; Kanti Barman, Pijus; Kumar Thatoi, Pravat; Tripathy, Rina; Kumar Das, Bidyut; Ravindran, Balachandran

    2015-01-01

    Given the importance of monocytes in pathogenesis of infectious and other inflammatory disorders, delineating functional and phenotypic characterization of monocyte subsets has emerged as a critical requirement. Although human monocytes have been subdivided into three different populations based on surface expression of CD14 and CD16, published reports suffer from contradictions with respect to subset phenotypes and function. This has been attributed to discrepancies in reliable gating strategies for flow cytometric characterization and purification protocols contributing to significant changes in receptor expression. By using a combination of multicolour flow cytometry and a high-dimensional automated clustering algorithm to confirm robustness of gating strategy and analysis of ex-vivo activation of whole blood with LPS we demonstrate the following: a. ‘Classical’ monocytes are phagocytic with no inflammatory attributes, b. ‘Non-classical’ subtype display ‘inflammatory’ characteristics on activation and display properties for antigen presentation and c. ‘Intermediate’ subtype that constitutes a very small percentage in circulation (under physiological conditions) appear to be transitional monocytes that display both phagocytic and inflammatory function. Analysis of blood from patients with Sepsis, a pathogen driven acute inflammatory disease and Systemic Lupus Erythmatosus (SLE), a chronic inflammatory disorder validated the broad conclusions drawn in the study. PMID:26358827

  12. Always expect the unexpected: lung abscess due to pseudomonas aeruginosa mimicking pulmonary aspergilloma in acute B-cell leukemia.

    PubMed

    Dieks, J-K; von Bueren, A O; Schaefer, I-M; Menke, J; Lex, C; Krause, U; Zenker, D; Kühnle, I; Kramm, C M

    2013-11-01

    We report on a case of Pseudomonas aeruginosa sepsis and consecutive lung abscess in a 13-year-old patient with acute B-cell leukemia. At first, radiographic findings strongly suggested presence of pulmonary aspergilloma and only microbiological testing of the surgically enucleated mass revealed the correct underlying pathogen and confirmed final diagnosis. PMID:24166086

  13. Immune-modulating therapy in acute pancreatitis: Fact or fiction

    PubMed Central

    Akinosoglou, Karolina; Gogos, Charalambos

    2014-01-01

    Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future. PMID:25386069

  14. Lactate and lactate clearance in acute cardiac care patients

    PubMed Central

    Lazzeri, Chiara; Picariello, Claudio; Dini, Carlotta Sorini; Gensini, Gian Franco; Valente, Serafina

    2012-01-01

    Hyperlactataemia is commonly used as a diagnostic and prognostic tool in intensive care settings. Recent studies documented that serial lactate measurements over time (or lactate clearance), may be clinically more reliable than lactate absolute value for risk stratification in different pathological conditions. While the negative prognostic role of hyperlactataemia in several critical ill diseases (such as sepsis and trauma) is well established, data in patients with acute cardiac conditions (i.e. acute coronary syndromes) are scarce and controversial. The present paper provides an overview of the current available evidence on the clinical role of lactic acid levels and lactate clearance in acute cardiac settings (acute coronary syndromes, cardiogenic shock, cardiac surgery), focusing on its prognostic role. PMID:24062898

  15. Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells.

    PubMed

    Dileepan, Thamotharampillai; Smith, Erica D; Knowland, Daniel; Hsu, Martin; Platt, Maryann; Bittner-Eddy, Peter; Cohen, Brenda; Southern, Peter; Latimer, Elizabeth; Harley, Earl; Agalliu, Dritan; Cleary, P Patrick

    2016-01-01

    Group A streptococcal (GAS) infection induces the production of Abs that cross-react with host neuronal proteins, and these anti-GAS mimetic Abs are associated with autoimmune diseases of the CNS. However, the mechanisms that allow these Abs to cross the blood-brain barrier (BBB) and induce neuropathology remain unresolved. We have previously shown that GAS infection in mouse models induces a robust Th17 response in nasal-associated lymphoid tissue (NALT). Here, we identified GAS-specific Th17 cells in tonsils of humans naturally exposed to GAS, prompting us to explore whether GAS-specific CD4+ T cells home to mouse brains following i.n. infection. Intranasal challenge of repeatedly GAS-inoculated mice promoted migration of GAS-specific Th17 cells from NALT into the brain, BBB breakdown, serum IgG deposition, microglial activation, and loss of excitatory synaptic proteins under conditions in which no viable bacteria were detected in CNS tissue. CD4+ T cells were predominantly located in the olfactory bulb (OB) and in other brain regions that receive direct input from the OB. Together, these findings provide insight into the immunopathology of neuropsychiatric complications that are associated with GAS infections and suggest that crosstalk between the CNS and cellular immunity may be a general mechanism by which infectious agents exacerbate symptoms associated with other CNS autoimmune disorders. PMID:26657857

  16. The cost of hospital care for management of invasive group A streptococcal infections in England.

    PubMed

    Hughes, G J; VAN Hoek, A J; Sriskandan, S; Lamagni, T L

    2015-06-01

    The objective of this study was to estimate the direct financial costs of hospital care for management of invasive group A streptococcal (GAS) infections using hospital records for cases diagnosed in England. We linked laboratory-confirmed cases (n = 3696) identified through national surveillance to hospital episode statistics and reimbursement codes. From these codes we estimated the direct hospital costs of admissions. Almost all notified invasive GAS cases (92% of 3696) were successfully matched to a primary hospital admission. Of these, secondary admissions (within 30 days of primary admission) were further identified for 593 (17%). After exclusion of nosocomial cases (12%), the median costs of primary and secondary hospital admissions were estimated by subgroup analysis as £1984-£2212 per case, totalling £4·43-£6·34 million per year in England. With adjustment for unmatched cases this equated to £4·84-£6·93 million per year. Adults aged 16-64 years accounted for 48% of costs but only 40% of cases, largely due to an increased number of surgical procedures. The direct costs of hospital admissions for invasive GAS infection are substantial. These estimated costs will contribute to a full assessment of the total economic burden of invasive GAS infection as a means to assess potential savings through prevention measures. PMID:25262779

  17. Epidemiology of Group B Streptococcal Disease in the United States: Shifting Paradigms

    PubMed Central

    Schuchat, Anne

    1998-01-01

    Since its emergence 25 years ago, group B streptococcus has become recognized as a cause of serious illness in newborns, pregnant women, and adults with chronic medical conditions. Heavy colonization of the genital tract with group B streptococcus also increases the risk that a woman will deliver a preterm low-birthweight infant. Early-onset infections (occurring at <7 days of age) are associated with much lower fatality than when they were first described, and their incidence is finally decreasing as the use of preventive antibiotics during childbirth increases among women at risk. New serotypes of group B streptococcus have emerged as important pathogens in adults and newborns. Clinical and laboratory practices—in obstetrics, pediatrics, and clinical microbiology—have an impact on disease and/or its prevention, and protocols established at the institutional level appear to be critical tools for the reduction of perinatal disease due to group B streptococcus. Since intrapartum antibiotics will prevent at best only a portion of the full burden of group B streptococcal disease, critical developments in vaccine evaluation, including study of polysaccharide-protein conjugate vaccines, offer the potential for enhanced prevention in the relatively near future. PMID:9665980

  18. Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase

    PubMed Central

    Law, Ruby H. P.; Casey, Lachlan W.; Valkov, Eugene; Bertozzi, Carlo; Stamp, Anna; Jovcevski, Blagojce; Aquilina, J. Andrew; Whisstock, James C.; Walker, Mark J.; Kobe, Bostjan

    2015-01-01

    Group A Streptococcus (GAS) is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen). Streptococcal surface enolase (SEN) is an octameric ?-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen) on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen) binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SENK312A and SENK362A is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen) to its binding sites, leading to more efficient plasmin(ogen) binding and activation. PMID:25807546

  19. Effects of meteorologic factors and schooling on the seasonality of group A streptococcal pharyngitis

    NASA Astrophysics Data System (ADS)

    Hervás, Daniel; Hervás-Masip, Juan; Ferrés, Laia; Ramírez, Antonio; Pérez, José L.; Hervás, Juan A.

    2015-10-01

    The objective of this study was to determine the seasonal pattern of group A streptococcal pharyngitis in children attended at a hospital emergency department in the Mediterranean island of Mallorca (Spain), and its association with meteorologic factors and schooling. We conducted a retrospective review of the medical records of children aged 1-15 years with a diagnosis of Streptococcus pyogenes pharyngitis between January 2006 and December 2011. The number of S. pyogenes pharyngitis was correlated to temperature, humidity, rainfall, atmospheric pressure, wind speed, solar radiation, and schooling, using regression and time series techniques. A total of 906 patients (median, 4 years old) with S. pyogenes pharyngitis, confirmed by throat culture, were attended during the study period. A seasonal pattern was observed with a peak activity in June and a minimum in September. Mean temperature, solar radiation, and school holidays were the best predicting variables (R 2 = 0.68; p < 0.001). S. pyogenes activity increased with the decrease of mean temperature (z = -2.4; p < 0.05), the increase of solar radiation (z = 4.2; p < 0.001), and/or the decrease in school holidays (z = -2.4; p < 0.05). In conclusion, S. pyogenes pharyngitis had a clear seasonality predominating in springtime, and an association with mean temperature, solar radiation, and schooling was observed. The resulting model predicted 68 % of S. pyogenes pharyngitis.

  20. Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013.

    PubMed

    Rudolph, Karen; Bruce, Michael G; Bruden, Dana; Zulz, Tammy; Reasonover, Alisa; Hurlburt, Debby; Hennessy, Thomas

    2016-01-01

    The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n = 8), 5.8% (n = 20), and 1.2% (n = 4) of the isolates, respectively. A total of 51 emm types were identified, of which emm1 (11.1%) was the most prevalent, followed by emm82 (8.8%), emm49 (7.8%), emm12 and emm3 (6.6% each), emm89 (6.2%), emm108 (5.5%), emm28 (4.7%), emm92 (4%), and emm41 (3.8%). The five most common emm types accounted for 41% of isolates. The emm types in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development. PMID:26560536

  1. Properties and type antigen patterns of group B streptococcal isolates from pigs and nutrias.

    PubMed Central

    Wibawan, I W; Lämmler, C; Smola, J

    1993-01-01

    All 59 group B streptococcal cultures isolated from pigs and nutrias reacted with group B-specific antiserum and gave a positive CAMP reaction in the zone of staphylococcal beta-lysin. Most of the cultures were pigmented; all cultures hydrolyzed Na hippurate and utilized salicin, maltose, and saccharose but not esculin, mannitol, or inulin. Fifty-three percent of the group B streptococci from pigs and none of those from nutrias were lactose positive. Serotyping revealed that most of the group B streptococci from pigs were of serotype III and most of those from nutrias were of type Ia/c. Protein c was present as c beta antigen. All group B streptococci were susceptible to penicillin and bacitracin (10 U), and most of the porcine cultures were resistant to tetracycline. According to these results, group B streptococci from pigs and nutrias differ from bovine and human group B streptococci and seem to play no role in cross-infections between animals or between animals and humans. PMID:8458981

  2. DIFFERENTIAL REGULATION OF PROTEIN SYNTHESIS IN SKELETAL MUSCLE AND LIVER OF NEONATAL PIGS IN EXPERIMENTALLY-INDUCED SEPSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sepsis decreases muscle protein synthesis and increases liver protein synthesis in adults. To examine the differential responses of protein synthesis in the two tissues during sepsis, translational control mechanisms were examined in neonatal pigs treated with lipopolysaccharide (LPS). Protein syn...

  3. An Expanding Role for Apolipoprotein E in Sepsis and Inflammation

    PubMed Central

    Chuang, Kelley; Elford, Erica L.; Tseng, Jill; Leung, Briana; Harris, Hobart W.

    2010-01-01

    Background Apolipoprotein E (apoE), a component of plasma lipoproteins, plays an important, but poorly defined role in sepsis. We have shown that injecting apoE increases septic mortality in a rat model of gram-negative bacterial sepsis, with concomitant hepatic natural killer T (NKT) cell proliferation and activation. The presumed mechanism for this apoE-mediated mortality is that apoE can bind and traffic antigens, presumed to include lipopolysaccharide (LPS), and promote activation of dendritic cells (DC) with subsequent NKT activation and cytokine release. Thus, we sought to prove that LPS was the antigen responsible for the increased NKT activation enhanced by the presence of apoE. Methods We isolated murine marrow-derived DCs, pulsed them with lipid antigen [LPS, and positve controls alpha-galactosylceramide (?-GalCer) and isogloboside 3 (iGb3)] with or without apoE, and then co-cultured the DCs with hybridoma NKTs. NKT activation was measured by interleukin-2 (IL-2) supernatant levels using ELISA. Results LPS at different concentrations was a weak stimulus for NKT activation regardless of apoE presence. When apoE was present, iGb3, an endogenous ligand analog, elicited more than a two-fold increase in IL-2 response when compared to iGb3 alone (p<0.05). Conclusions These results indicate an endogenous ligand, not LPS, may be responsible for NKT activation. A molecular remnant similar to iGb3 could act as a damage-associated molecular pattern and play a prominent role in animal models of sepsis. PMID:20409531

  4. Early onset sepsis in very low birth weight newborn infants.

    PubMed

    Pisani, Valentina; Bizzarri, Bianca; Cardi, Veronica; Pedicino, Roberto; Natale, Fabio; Stolfi, Ilaria; Castronovo, Antonella; De Curtis, Mario

    2012-10-01

    Early onset sepsis (EOS) is a severe problem affecting very low birth weight (VLBW) infants and is associated with a threefold increased risk of mortality. Although advances in perinatal care have led to improved survival of VLBW infants over recent decades, survival without major neonatal morbidity has not increased. The authors reviewed the current literature on EOS, focusing on the peculiarities concerning risk factors, etiology, diagnosis, treatment and outcome in very low birth weight infants, and on the recent advances in the management of this condition. PMID:23016613

  5. Computing network-based features from physiological time series: application to sepsis detection.

    PubMed

    Santaniello, Sabato; Granite, Stephen J; Sarma, Sridevi V; Winslow, Raimond L

    2014-01-01

    Sepsis is a systemic deleterious host response to infection. It is a major healthcare problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identify sepsis by using static scores derived from bed-side measurements individually, i.e., without systematically accounting for potential interactions between these signals and their dynamics. In this study, we apply network-based data analysis to take into account interactions between bed-side physiological time series (PTS) data collected in ICU patients, and we investigate features to distinguish between sepsis and non-sepsis conditions. We treated each PTS source as a node on a graph and we retrieved the graph connectivity matrix over time by tracking the correlation between each pair of sources' signals over consecutive time windows. Then, for each connectivity matrix, we computed the eigenvalue decomposition. We found that, even though raw PTS measurements may have indistinguishable distributions in non-sepsis and early sepsis states, the median /I of the eigenvalues computed from the same data is statistically different (p <; 0.001) in the two states and the evolution of /I may reflect the disease progression. Although preliminary, these findings suggest that network-based features computed from continuous PTS data may be useful for early sepsis detection. PMID:25570825

  6. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been desc...

  7. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defense and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

  8. Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  9. Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  10. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactoferrin, a normal component of human colostrum, milk, tears, and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NE...

  11. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolotis in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC...

  12. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

  13. Financial Implications of Sepsis Prevention, Early Identification, and Treatment: A Population Health Perspective.

    PubMed

    Angelelli, Joseph

    2016-01-01

    Each day an estimated 2000 to 3000 new cases of sepsis are identified and treated in US hospitals. Despite the enormity of the problem, less than one-half of all US adults have heard of sepsis. This article reviews the financial costs of sepsis in the United States, examining the evidence for its economic impact across both hospitals and nursing homes. A brief description of payment models and government programs to promote more coordinated care between hospitals and nursing homes is provided to highlight areas where advances in sepsis care may be incentivized and sustained in new systems emerging in response to the Affordable Care Act. Finally, the costs of sepsis care to the Medicare program in a specific health care market (Pittsburgh) are estimated to highlight the challenges and opportunities for interorganizational collaborative strategies in value-based models of care delivery. PMID:26633159

  14. Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

    SciTech Connect

    Ouzounian, T.J.; Thompson, L.; Grogan, T.J.; Webber, M.M.; Amstutz, H.C.

    1987-08-01

    The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement.

  15. Chemical composition and immunological specificity of cell wall polysaccharide group antigens of streptococcal groups P and U.

    PubMed Central

    Wessman, G E

    1975-01-01

    The group antigens of streptococcal groups P and U were extracted with formamide and purified on diethylaminoethyl-Sephadex A-25 and Sephadex G-200. The antigens were shown to be polysaccharides located in the cell walls of the organisms. In a precipitin test, the P and U group antigens did not cross-react with homologous sera of each other, nor with specific antiserum of the group antigen of group E streptococci. The polysaccharide comprising the group P antigen contained rhamnose, glucose, galactose, glucosamine, and galactosamine; the group U antigen was similar in composition but lacked galactosamine and contained more galactose. Images PMID:49302

  16. The International Sepsis Forum's controversies in sepsis: corticosteroids should not be routinely used to treat septic shock

    PubMed Central

    Bernard, Gordon

    2002-01-01

    Corticosteroid treatment of severe sepsis has been one of the most controversial clinical issues in critical care. In fact, few agents can claim to have been evaluated in scores of studies spanning 3–4 decades. Yet, convincing proof that corticosteroids are useful pharmacologic agents in the treatment of this major clinical problem remains elusive. Recently, interest has resurfaced but this time the focus is on a steroid replacement approach for what has now been termed "relative adrenal insufficiency" rather than relying on the pharmacologic effects of steroids. This route holds promise, but proof remains lacking. PMID:12398771

  17. Septris: A Novel, Mobile, Online, Simulation Game That Improves Sepsis Recognition and Management

    PubMed Central

    Daines, William; Tsui, Jamie; Strehlow, Matthew; Maggio, Paul; Shieh, Lisa

    2015-01-01

    Problem Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated. Approach Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming. The authors sought to assess the game’s dissemination and its impact on learners’ sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests. Outcomes By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P < .001). Retrospective self-reporting on their ability to identify and manage sepsis also improved (P < .001). Over 85% of learners reported that they would or would maybe recommend Septris. Next Steps Future evaluation of Septris should assess its effectiveness among different providers, resource settings, and cultures; generate information about how different learners make clinical decisions; and evaluate the correlation of game scores with sepsis knowledge. PMID:25517703

  18. Sepsis in intensive care unit patients with traumatic brain injury: factors associated with higher mortality

    PubMed Central

    Cardozo, Luis Carlos Maia; da Silva, Redson Ruy

    2014-01-01

    Objective Patients with traumatic brain injury are particularly susceptible to sepsis, which may exacerbate the systemic inflammatory response and lead to organ dysfunction. The influence of clinical variables on the mortality of intensive care unit patients with traumatic brain injury and sepsis was investigated. Methods The present investigation was a retrospective study involving 175 patients with traumatic brain injury who were treated in a period of 1 year at a reference hospital for trauma and who had sepsis, severe sepsis, or septic shock. Demographic and clinical data were obtained, and the SOFA score was calculated at the time sepsis was found and after 72 hours. Results There was a predominance of young men with severe traumatic brain injury, multiple head injuries, sepsis with a pulmonary focus, prolonged hospital stay, and high mortality (37.7%). Circulatory and respiratory failure had a high incidence, but renal and coagulation failure were less frequent, and liver failure was not observed. After logistic regression, the presence of septic shock and respiratory failure 72 hours after the sepsis diagnosis was associated with higher mortality, with an odds ratio of 7.56 (95%CI=2.04-27.31, p=0.0024) and 6.62 (95%CI=1.93-22.78, p=0.0027), respectively. In addition, there was a higher mortality among patients who had no organ failure on D1 but who developed the condition after 72 hours of sepsis and in those patients who already had organ failure at the time sepsis was diagnosed and remained in this condition after 72 hours. Conclusion Septic shock and progressive organ (particularly respiratory) dysfunction increases the mortality of patients with traumatic brain injury and sepsis. PMID:25028949

  19. Gut-Origin sepsis; evolution of a concept

    PubMed Central

    Deitch, Edwin A.

    2012-01-01

    The concept of bacterial translocation and gut-origin sepsis as a cause of systemic infectious complications and the multiple organ dysfunction syndrome (MODS) in surgical and ICU patients has emerged over the last several decades, although the exact clinical relevance of these phenomenon continue to be debated. Thus, the goal of this review will be to trace the evolution of gut-origin sepsis and gut-induced MODS and put these disorders and observations into clinical perspective. Additionally, the mechanisms leading to gut-derived complications will be explored as well as therapeutic options to limit or prevent these complications. From this work, several major conclusions emerge. First, that bacterial translocation occurs clinically and is responsible for increased infectious complications in patients undergoing major abdominal surgery. However, the phenomenon of bacterial translocation is not sufficient to explain the development of MODS in ICU patients. Instead, the development of MODS in these high risk patients is likely due to gut injury and the systemic spread of non-microbial, tissue injurious factors that reach the systemic circulation via the intestinal lymphatics. These observations have resulted in the gut lymph hypothesis of MODS. PMID:22534256

  20. Protein C and acute inflammation: a clinical and biological perspective.

    PubMed

    Christiaans, Sarah C; Wagener, Brant M; Esmon, Charles T; Pittet, Jean Francois

    2013-10-01

    The protein C system plays an active role in modulating severe systemic inflammatory processes such as sepsis, trauma, and acute respiratory distress syndrome (ARDS) via its anticoagulant and anti-inflammatory properties. Plasma levels of activated protein C (aPC) are lower than normal in acute inflammation in humans, except early after severe trauma when high plasma levels of aPC may play a mechanistic role in the development of posttraumatic coagulopathy. Thus, following positive results of preclinical studies, a clinical trial (PROWESS) with high continuous doses of recombinant human aPC given for 4 days demonstrated a survival benefit in patients with severe sepsis. This result was not confirmed by subsequent clinical trials, including the recently published PROWESS-SHOCK trial in patients with septic shock and a phase II trial with patients with nonseptic ARDS. A possible explanation for the major difference in outcome between PROWESS and PROWESS-SHOCK trials is that lung-protective ventilation was used for the patients included in the recent PROWESS-SHOCK, but not in the original PROWESS trial. Since up to 75% of sepsis originates from the lung, aPC treatment may not have added enough to the beneficial effect of lung-protective ventilation to show lower mortality. Thus whether aPC will continue to be used to modulate the acute inflammatory response in humans remains uncertain. Because recombinant human aPC has been withdrawn from the market, a better understanding of the complex interactions between coagulation and inflammation is needed before considering the development of new drugs that modulate both coagulation and acute inflammation in humans. PMID:23911436

  1. Differential Localization of the Streptococcal Accessory Sec Components and Implications for Substrate Export

    PubMed Central

    Yen, Yihfen T.; Cameron, Todd A.; Bensing, Barbara A.; Seepersaud, Ravin; Zambryski, Patricia C.

    2013-01-01

    The accessory Sec system of Streptococcus gordonii is comprised of SecY2, SecA2, and five proteins (Asp1 through -5) that are required for the export of a serine-rich glycoprotein, GspB. We have previously shown that a number of the Asps interact with GspB, SecA2, or each other. To further define the roles of these Asps in export, we examined their subcellular localization in S. gordonii and in Escherichia coli expressing the streptococcal accessory Sec system. In particular, we assessed how the locations of these accessory Sec proteins were altered by the presence of other components. Using fluorescence microscopy, we found in E. coli that SecA2 localized within multiple foci at the cell membrane, regardless of whether other accessory Sec proteins were expressed. Asp2 alone localized to the cell poles but formed a similar punctate pattern at the membrane when SecA2 was present. Asp1 and Asp3 localized diffusely in the cytosol when expressed alone or with SecA2. However, these proteins redistributed to the membrane in a punctate arrangement when all of the accessory Sec components were present. Cell fractionation studies with S. gordonii further corroborated these microscopy results. Collectively, these findings indicate that Asp1 to -3 are not integral membrane proteins that form structural parts of the translocation channel. Instead, SecA2 serves as a docking site for Asp2, which in turn attracts a complex of Asp1 and Asp3 to the membrane. These protein interactions may be important for the trafficking of GspB to the cell membrane and its subsequent translocation. PMID:23204472

  2. Functional Analysis of the Quorum-Sensing Streptococcal Invasion Locus (sil)

    PubMed Central

    Belotserkovsky, Ilia; Baruch, Moshe; Peer, Asaf; Dov, Eran; Ravins, Miriam; Mishalian, Inbal; Persky, Merav; Smith, Yoav; Hanski, Emanuel

    2009-01-01

    Group A streptococcus (GAS) causes a wide variety of human diseases, and at the same time, GAS can also circulate without producing symptoms, similar to its close commensal relative, group G streptococcus (GGS). We previously identified, by transposon-tagged mutagenesis, the streptococcal invasion locus (sil). sil is a quorum-sensing regulated locus which is activated by the autoinducer peptide SilCR through the two-component system SilA-SilB. Here we characterize the DNA promoter region necessary for SilA-mediated activation. This site is composed of two direct repeats of 10 bp, separated by a spacer of 11 bp. Fusion of this site to gfp allowed us to systematically introduce single-base substitutions in the repeats region and to assess the relative contribution of various positions to promoter strength. We then developed an algorithm giving different weights to these positions, and performed a chromosome-wide bioinformatics search which was validated by transcriptome analysis. We identified 13 genes, mostly bacteriocin related, that are directly under the control of SilA. Having developed the ability to quantify SilCR signaling via GFP accumulation prompted us to search for GAS and GGS strains that sense and produce SilCR. While the majority of GAS strains lost sil, all GGS strains examined still possess the locus and ?63% are able to respond to exogenously added SilCR. By triggering the autoinduction circle using a minute concentration of synthetic SilCR, we identified GAS and GGS strains that are capable of sensing and naturally producing SilCR, and showed that SilCR can be sensed across these streptococci species. These findings suggest that sil may be involved in colonization and establishment of commensal host-bacterial relationships. PMID:19893632

  3. Molecular characterization of the cfb gene encoding group B streptococcal CAMP-factor.

    PubMed

    Podbielski, A; Blankenstein, O; Lütticken, R

    1994-11-01

    An internal fragment of the cfb gene from group B streptococcal (GBS) strain R268 was amplified by polymerase chain reaction (PCR) using degenerate primers with sequences derived from the CAMP-factor amino acid (aa) sequence of GBS strain NCTC8181 [Rühlmann et al. (1988) FEBS Lett 235:262-266]. After cloning and sequencing this fragment, the remainder of cfb and the adjacent 5' and 3' sequences were amplified by inverted PCR of genomic DNA and directly sequenced from the PCR product. Within the 1560 bp sequenced, a complete cfb gene deviating in two deduced aa residues from the published sequence was identified. In addition, the cfbR268 sequence contained a 29-aa leader peptide. Using primers directed to the 5' and 3' ends of cfb for PCR, a cfb gene of uniform size could be detected in 19 clinical GBS isolates including three phenotypically CAMP-negative strains. Utilizing Northern blot analysis and primer extension assays, the cfbR268 promoter was located and the length of the cfb transcript was assessed at about 1100 bp. In a parallel experiment, no cfb transcript could be detected from the CAMP-negative GBS strain 74-360. The complete cfbR268 gene and different portions of its 5' and 3' ends were cloned into the plasmid pJLA602 and expressed in E. coli DH5 alpha. The recombinant peptides could be detected by Western immunoblots with polyclonal antiserum. Only the full-sized recombinant CAMP-factor was found to exert co-hemolytic activity in a sheep-blood agar assay. This co-hemolytic activity could be inhibited by anti-CAMP antiserum. PMID:7715536

  4. Metal-Mediated Modulation of Streptococcal Cysteine Protease Activity and Its Biological Implications

    PubMed Central

    Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Landero Figueroa, Julio A.; Caruso, Joseph A.

    2014-01-01

    Streptococcal cysteine protease (SpeB), the major secreted protease produced by group A streptococcus (GAS), cleaves both host and bacterial proteins and contributes importantly to the pathogenesis of invasive GAS infections. Modulation of SpeB expression and/or its activity during invasive GAS infections has been shown to affect bacterial virulence and infection severity. Expression of SpeB is regulated by the GAS CovR-CovS two-component regulatory system, and we demonstrated that bacteria with mutations in the CovR-CovS two-component regulatory system are selected for during localized GAS infections and that these bacteria lack SpeB expression and exhibit a hypervirulent phenotype. Additionally, in a separate study, we showed that expression of SpeB can also be modulated by human transferrin- and/or lactoferrin-mediated iron chelation. Accordingly, the goal of this study was to investigate the possible roles of iron and other metals in modulating SpeB expression and/or activity in a manner that would potentiate bacterial virulence. Here, we report that the divalent metals zinc and copper inhibit SpeB activity at the posttranslational level. Utilizing online metal-binding site prediction servers, we identified two putative metal-binding sites in SpeB, one of which involves the catalytic-dyad residues 47Cys and 195His. Based on our findings, we propose that zinc and/or copper availability in the bacterial microenvironment can modulate the proteolytic activity of SpeB in a manner that preserves the integrity of several other virulence factors essential for bacterial survival and dissemination within the host and thereby may exacerbate the severity of invasive GAS infections. PMID:24799625

  5. Characterization of Five Zoonotic Streptococcus suis Strains from Germany, Including One Isolate from a Recent Fatal Case of Streptococcal Toxic Shock-Like Syndrome in a Hunter.

    PubMed

    Eisenberg, Tobias; Hudemann, Christoph; Hossain, Hamid M; Hewer, Angela; Tello, Khodr; Bandorski, Dirk; Rohde, Manfred; Valentin-Weigand, Peter; Baums, Christoph Georg

    2015-12-01

    A Streptococcus suis isolate from a German hunter with streptococcal toxic shock-like syndrome (STSLS) and four additional zoonotic isolates were genotyped as mrp(+) epf* (variant 1890) sly(+) cps2(+). All five zoonotic German strains were characterized by high multiplication in human blood samples ex vivo, but induction of only low levels of proinflammatory cytokines compared to a Chinese STSLS strain. PMID:26424844

  6. Role for Streptococcal Collagen-Like Protein 1 in M1T1 Group A Streptococcus Resistance to Neutrophil Extracellular Traps

    E-print Network

    Nizet, Victor

    Role for Streptococcal Collagen-Like Protein 1 in M1T1 Group A Streptococcus Resistance of the most highly expressed proteins in the invasive M1T1 serotype group A Streptococcus (GAS), a globally A Streptococcus (GAS) (Streptococcus pyogenes) is among the top 10 human pathogens worldwide and is responsible

  7. Detection of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta during experimental endotoxemia and human sepsis.

    PubMed

    O'Grady, N P; Tropea, M; Preas, H L; Reda, D; Vandivier, R W; Banks, S M; Suffredini, A F

    1999-01-01

    Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta regulate leukocyte activation and trafficking. To assess the role of MIP-1alpha and MIP-1beta in human inflammation, healthy subjects were studied during experimental endotoxemia with prior administration of ibuprofen, a cyclooxygenase inhibitor, or dimeric p75 tumor necrosis factor (TNF)-alpha receptor, a TNF antagonist; septic patients were also studied. Following endotoxin, blood levels of both MIP-1 molecules rose acutely and fell to baseline by 6 h (P=. 001). While MIP-1 mediates fever in animals independent of cyclooxygenase blockade, in subjects given endotoxin and ibuprofen, MIP-1 levels increased and fever was suppressed. MIP-1 levels were not diminished by inhibiting circulating TNF-alpha in humans. In septic patients, elevated levels of MIP-1alpha and MIP-1beta were detected within 24 h of sepsis and fell in parallel with TNF-alpha and interleukin-6 (P<.01). MIP-1alpha and MIP-1beta increase during acute inflammation but are not associated with fever in endotoxemic humans during cyclooxygenase blockade. PMID:9841832

  8. Novel Pharmacologic Approaches to the Management of Sepsis: Targeting the Host Inflammatory Response

    PubMed Central

    Wheeler, Derek S.; Zingarelli, Basilia; Wheeler, William J.; Wong, Hector R.

    2009-01-01

    Sepsis is currently the 10th leading cause of death overall and accounts for significant healthcare expenditures in the developed world. There are now more deaths attributable to sepsis than coronary artery disease, stroke, or cancer, and it is widely believed that the incidence of sepsis and sepsis-related mortality will continue to rise. Based on these sobering statistics, there is great interest in identifying novel treatments for managing critically ill children and adults with sepsis. Unfortunately, to date, there have been very few successful therapeutic agents employed in the clinical setting. Despite these disappointing results, new therapeutic agents continue to be identified, and there is reason for optimism and hope for the future. Herein, we will briefly review several novel therapeutic adjuncts for the management of critically ill patients with sepsis. We will largely focus on those therapies that directly target the host inflammatory response, specifically those that result in activation of the transcription factor, nuclear factor (NF)-?B. We will also reference some of the patents recently filed that pertain to the host innate immune response and sepsis. PMID:19519586

  9. Platelet and mean platelet volume kinetics in adult patients with sepsis.

    PubMed

    Aydemir, Hande; Piskin, Nihal; Akduman, Deniz; Kokturk, Furuzan; Aktas, Elif

    2015-01-01

    The aims of this study were to evaluate the kinetics of platelet counts and mean platelet volume (MPV) in adults with sepsis and to determine whether the responses are infection-specific. This retrospective cohort study included patients admitted to a tertiary-care teaching hospital with microbiologically proven nosocomial sepsis between January 2006 and January 2011. Platelet counts and MPV measurements were examined daily for 5 days after the onset of sepsis. During the study period, 151 of the 214 sepsis episodes were associated with thrombocytopenia. Gram-positive microorganisms were the most frequently isolated. The decrease in platelet counts was statistically significant for the first 3 days of sepsis in Gram-positive septic patients, for 4 days in Gram-negative septic patients and for all 5 days in fungal septic patients (p?sepsis in Gram-positive septic patients and for all 5 days in the other groups (p?sepsis has a stronger association with thrombocytopenia and increased MPV. PMID:22731700

  10. Memory-enhancing treatments reverse the impairment of inhibitory avoidance retention in sepsis-surviving rats

    PubMed Central

    Tuon, Lisiane; Comim, Clarissa M; Petronilho, Fabrícia; Barichello, Tatiana; Izquierdo, Ivan; Quevedo, João; Dal-Pizzol, Felipe

    2008-01-01

    Introduction Survivors from sepsis have presented with long-term cognitive impairment, including alterations in memory, attention, concentration, and global loss of cognitive function. Thus, we evaluated the effects of memory enhancers in sepsis-surviving rats. Methods The rats underwent cecal ligation and perforation (CLP) (sepsis group) with 'basic support' (saline at 50 mL/kg immediately and 12 hours after CLP plus ceftriaxone at 30 mg/kg and clindamycin at 25 mg/kg 6, 12, and 18 hours after CLP) or sham-operated (control group). After 10 or 30 days, rats were submitted to an inhibitory avoidance task. After task training, animals received injections of saline, epinephrine, naloxone, dexamethasone, or glucose. Twenty-four hours afterwards, animals were submitted to the inhibitory avoidance test. Results We demonstrated that memory enhancers reversed impairment in the sepsis group 10 and 30 days after sepsis induction. This effect was of lower magnitude when compared with sham animals 10 days, but not 30 days, after sepsis. Conclusions Using different pharmacologic approaches, we conclude that the adrenergic memory formation pathways are responsive in sepsis-surviving animals. PMID:18957125

  11. Escherichia coli counting using lens-free imaging for sepsis diagnosis

    NASA Astrophysics Data System (ADS)

    Moon, Sangjun; Manzur, Fahim; Manzur, Tariq; Klapperich, Catherine; Demirci, Utkan

    2009-09-01

    Sepsis causes 9.3% of overall deaths in United States. To diagnose sepsis, cell/bacteria capture and culturing methods have been widely investigated in the medical field. Escherichia Coli (E. Coli) is used as a model organism for sepsis in blood stream since wide variety of antibodies are established and the genetic modification process is well documented for fluorescent tagging. In point-of-care testing applications, the sepsis diagnostics require fast monitoring, inexpensive testing, and reliable results at resource limited settings, i.e. battle field, home care for dialysis. However, the cell/E.coli are hard to directly capture and see at the POCT because of the small size, 2 ?m long and 0.5 ?m in diameter, and the bacteria are rare in the blood stream in sepsis. Here, we propose a novel POCT platform to image and enumerate cell/E.coli on a microfluidic surface to diagnose sepsis at resource limited conditions. We demonstrate that target cells are captured from 5 ?l of whole blood using specific antibodies and E.coli are imaged using a lens-free imaging platform, 2.2 ?m pixel CMOS based imaging sensor. This POCT cell/bacteria capture and enumeration approach can further be used for medical diagnostics of sepsis. We also show approaches to rapidly quantify white blood cell counts from blood which can be used to monitor immune response.

  12. Electroacupuncture at Bilateral Zusanli Points (ST36) Protects Intestinal Mucosal Immune Barrier in Sepsis

    PubMed Central

    Zhu, Mei-fei; Xing, Xi; Lei, Shu; Wu, Jian-nong; Wang, Ling-cong; Huang, Li-quan; Jiang, Rong-lin

    2015-01-01

    Sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Acupuncture has also been used widely for many years in China to treat sepsis. However, the underlying mechanisms are not well-defined. We demonstrated here that EA preconditioning at ST36 obviously ameliorated CLP-induced intestinal injury and high permeability and reduced the mortality of CLP-induced sepsis rats. Moreover, electroacupuncture (EA) pretreatment exerted protective effects on intestinal mucosal immune barrier by increasing the concentration of sIgA and the percentage of CD3+, ?/?, and CD4+ T cells and the ratio of CD4+/CD8+ T cells. Although EA at ST36 treatments immediately after closing the abdomen in the CLP procedure with low-frequency or high-frequency could not reduce the mortality of CLP-induced sepsis in rats, these EA treatments could also significantly improve intestinal injury index in rats with sepsis and obviously protected intestinal mucosal immune barrier. In conclusion, our findings demonstrated that EA at ST36 could improve intestinal mucosal immune barrier in sepsis induced by CLP, while the precise mechanism underlying the effects needs to be further elucidated. PMID:26346309

  13. Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis

    PubMed Central

    Wynn, James L; Guthrie, Scott O; Wong, Hector R; Lahni, Patrick; Ungaro, Ricardo; Lopez, M Cecilia; Baker, Henry V; Moldawer, Lyle L

    2015-01-01

    Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ?3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age. PMID:26052715

  14. Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis.

    PubMed

    Wynn, James L; Guthrie, Scott O; Wong, Hector R; Lahni, Patrick; Ungaro, Ricardo; Lopez, M Cecilia; Baker, Henry V; Moldawer, Lyle L

    2015-01-01

    Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ?3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age. PMID:26052715

  15. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

    PubMed

    Malkin, Alexander D; Sheehan, Robert P; Mathew, Shibin; Federspiel, William J; Redl, Heinz; Clermont, Gilles

    2015-10-01

    Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8), a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5-24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment. PMID:26468651

  16. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis

    PubMed Central

    Malkin, Alexander D.; Sheehan, Robert P.; Mathew, Shibin; Federspiel, William J.; Redl, Heinz; Clermont, Gilles

    2015-01-01

    Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8), a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3–6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40–80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5–24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment. PMID:26468651

  17. Proven infection-related sepsis induces a differential stress response early after ICU admission

    PubMed Central

    2010-01-01

    Introduction Neuropeptides arginine-vasopressin (AVP), apelin (APL), and stromal-derived factor-1? (SDF-1?) are involved in the dysfunction of the corticotropic axis observed in septic ICU patients. Study aims were: (i) to portray a distinctive stress-related neuro-corticotropic systemic profile of early sepsis, (ii) to propose a combination data score, for aiding ICU physicians in diagnosing sepsis on admission. Methods This prospective one-center observational study was carried out in a medical intensive care unit (MICU), tertiary teaching hospital. Seventy-four out of 112 critically ill patients exhibiting systemic inflammatory response syndrome (SIRS) were divided into two groups: proven sepsis and non sepsis, based on post hoc analysis of microbiological criteria and final diagnosis, and compared to healthy volunteers (n = 14). A single blood sampling was performed on admission for measurements of AVP, copeptin, APL, SDF-1?, adrenocorticotropic hormone (ACTH), cortisol baseline and post-stimulation, and procalcitonin (PCT). Results Blood baseline ACTH/cortisol ratio was lower and copeptin higher in septic vs. nonseptic patients. SDF-1? was further increased in septic patients vs. normal patients. Cortisol baseline, ACTH, PCT, APACHE II and sepsis scores, and shock on admission, were independent predictors of sepsis diagnosis upon admission. Using the three first aforementioned categorical bio-parameters, a probability score for predicting sepsis yielded an area under the Receiver Operating Curve (ROC) curves better than sepsis score or PCT alone (0.903 vs 0.727 and 0.726: P = 0.005 and P < 0.04, respectively). Conclusions The stress response of early admitted ICU patients is different in septic vs. non-septic conditions. A proposed combination of variable score analyses will tentatively help in refining bedside diagnostic tools to efficiently diagnose sepsis after further validation. PMID:20615266

  18. Acute Bronchitis

    MedlinePLUS

    ... acute bronchitis can include: Sore throat Fever A cough that may bring up clear, yellow or green ... your doctor if: You continue to wheeze and cough for more than 2 weeks, especially at night ...

  19. Bronchitis - acute

    MedlinePLUS

    ... to breathe. Another symptom of bronchitis is a cough. Acute means the symptoms have been present only ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...

  20. The place of early haemoperfusion with polymyxin B fibre column in the treatment of sepsis

    PubMed Central

    Ronco, Claudio

    2005-01-01

    Direct haemoperfusion with polymyxin B-immobilized fibre (PMX-F) is a promising treatment for Gram-negative sepsis in critically ill patients. Indeed, it has been used routinely in Japan for a decade. Recent evidence presented in this journal suggests that PMX-F can have a positive impact on outcome in patients with sepsis, although other reports in the literature have presented confusing or even conflicting results. This commentary considers whether the available evidence allows us to establish an appropriate role for PMX-F treatment in sepsis and what further work is needed. PMID:16356251

  1. Eikenella corrodens Sepsis with Cerebrospinal Fluid Pleocytosis in a Very Low Birth Weight Neonate

    PubMed Central

    Sawyer, Christopher; Angelis, Dimitrios; Bennett, Robert

    2015-01-01

    We report a case of Eikenella corrodens sepsis associated with CSF pleocytosis in a very low birth weight neonate. A 1000-gram male neonate was born at 27-week gestation due to preterm labor. The patient presented with signs and symptoms of sepsis and was treated for suspected meningitis with intravenous ampicillin and gentamicin for 7 days, with cefotaxime added for three weeks. He had a normal brain MRI at discharge and normal development at 6 months of life. To our knowledge, this is the first case of E. corrodens sepsis and associated meningitis in a very low birth weight neonate. PMID:26635988

  2. Preoperative testing for sepsis before revision total knee arthroplasty.

    PubMed

    Della Valle, Craig J; Sporer, Scott M; Jacobs, Joshua J; Berger, Richard A; Rosenberg, Aaron G; Paprosky, Wayne G

    2007-09-01

    One hundred five consecutive painful knee arthroplasties were evaluated by a single surgeon for the presence of infection using a uniform protocol that included an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), perioperative aspiration with synovial fluid white blood cell (WBC) count and differential, intraoperative frozen section analysis, and culture. A synovial fluid WBC count of greater than 3000 was the most precise test with a sensitivity of 100%, specificity of 98%, and accuracy of 99%. The preoperative use of an ESR and CRP proved to be an excellent screening modality with only one infection identified with both values being normal. A rational approach to perioperative testing for sepsis includes a screening ESR and CRP, and if elevated, aspiration with synovial fluid WBC count or an intraoperative frozen section. PMID:17823024

  3. [Endotoxin adsortion as adjuvant therapy in gram negative severe sepsis].

    PubMed

    Candel, F J; Martínez-Sagasti, F; Borges, M; Maseda, E; Herrera-Gutiérrez, M; Garnacho-Montero, J; Maynar, F J; Zaragoza, R; Mensa, J; Azanza, J R

    2010-09-01

    The mortality rate of severe sepsis and septic shock remains still high. Within the last years a better knowledge of its physiopathology and the implementation of a group of measures addressed to a fast identification and early treatment of the septic patients have proved to reduce mortality rate. Likewise, it continues being investigated in modulating the inflammatory response and limiting the harmful action of the bacterial products on the immune system. As a result of this research some endotoxin adsorber devices have been designed to control one of the most important targets that start the inflammatory cascade when gram negative microorganisms are involved.The usefulness that these endotoxin removal devices might have as adjuvant treatment in the Septic Syndrome and its applicability are reviewed in this paper. Likewise a profile of patient that might be to the benefit of this therapy is suggested according to the current knowledge. PMID:20844841

  4. Neonatal Sepsis due to Coagulase-Negative Staphylococci

    PubMed Central

    Marchant, Elizabeth A.; Boyce, Guilaine K.; Sadarangani, Manish; Lavoie, Pascal M.

    2013-01-01

    Neonates, especially those born prematurely, are at high risk of morbidity and mortality from sepsis. Multiple factors, including prematurity, invasive life-saving medical interventions, and immaturity of the innate immune system, put these infants at greater risk of developing infection. Although advanced neonatal care enables us to save even the most preterm neonates, the very interventions sustaining those who are hospitalized concurrently expose them to serious infections due to common nosocomial pathogens, particularly coagulase-negative staphylococci bacteria (CoNS). Moreover, the health burden from infection in these infants remains unacceptably high despite continuing efforts. In this paper, we review the epidemiology, immunological risk factors, diagnosis, prevention, treatment, and outcomes of neonatal infection due to the predominant neonatal pathogen CoNS. PMID:23762094

  5. HIV and the kidney in the acute medical unit.

    PubMed

    Booth, John W; Post, Frank A

    2015-12-01

    Acute kidney injury (AKI) is encountered commonly in HIV-positive patients admitted to the acute medical unit. The spectrum of AKI has changed in the era of combination anti-retroviral therapy, and now includes adverse effects of commonly used anti-retroviral drugs in addition to traditional precipitants such as severe sepsis or exposure to nephrotoxic antimicrobials. An accurate diagnosis requires careful integration of clinical data including volume status, history of potentially nephrotoxic exposures and consideration of immuno-virological status. This article provides an overview of common causes of AKI in HIV and presents a framework by which the acute care physician may approach the finding of an elevated serum creatinine in a patient with HIV. PMID:26621951

  6. [Acute kidney injury in children].

    PubMed

    Amira-Peco-Anti?; Paripovi?, Dusan

    2014-01-01

    Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients. PMID:25033598

  7. Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome

    PubMed Central

    Richard, Kathleen R.; Lovvorn, Joshua J.; Oliver, Sara E.; Ross, Shannon A.; Benner, Kim W.; Kong, Michele Y.F.

    2015-01-01

    Patient: Male, 11 Final Diagnosis: Chromobacterium violaceum infection Symptoms: Abscess • fever • rash Medication: — Clinical Procedure: ECMO Specialty: Critical Care Medicine Objective: Rare disease Background: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. Case Report: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. Conclusions: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy. PMID:26477750

  8. Neuropathological Correlates of Hyperglycemia During Prolonged Polymicrobial Sepsis in Mice.

    PubMed

    Sonneville, Romain; Derese, Inge; Marques, Mirna Bastos; Langouche, Lies; Derde, Sarah; Chatre, Laurent; Chrétien, Fabrice; Annane, Djillali; Sharshar, Tarek; Van den Berghe, Greet; Vanhorebeek, Ilse

    2015-09-01

    Glucose toxicity may play a crucial role in evoking neurologic complications of critical illness. We studied whether the neuropathological alterations in fatal human critical illness observed under hyperglycemia are present and can be attenuated by maintaining normoglycemia in a mouse model of prolonged sepsis induced by cecal ligation and puncture. Mice were randomized to moderate hyperglycemia (>8.3 mmol/L, n = 8) or normoglycemia (4.4-6.7 mmol/L, n = 8). After 5 days, hippocampus and frontal cortex from septic mice were compared with those from healthy controls (n = 8). Blood glucose was 7.8 ± 1.3 mmol/L in hyperglycemic and 6.1 ± 0.7 mmol/L in normoglycemic critically ill mice (P = 0.007). The percentage of damaged neurons was twofold higher in frontal cortex (P = 0.01) and hippocampus (P = 0.06) of hyperglycemic ill mice than that of healthy mice. In frontal cortex, neuronal damage was attenuated under normoglycemia (P = 0.04). Critical illness reduced astrocyte density and activation status fourfold in hippocampus (P ? 0.02), but not in frontal cortex, irrespective of glycemic control. Microglia were twofold to fourfold more abundant in both brain areas of hyperglycemic critically ill mice (P ? 0.002), but only in frontal cortex were they reduced in number with normoglycemia (P = 0.0008). The density of apoptotic cells and abundance of carbonylated proteins were significantly higher than normal in frontal cortex of hyperglycemic ill mice only (P = 0.05). In a mouse model of prolonged polymicrobial sepsis, remarkable neuropathological changes develop with neuronal damage, impaired astrocyte activation, increased microglia, apoptosis, and accumulation of carbonylated proteins. These changes were partially prevented or attenuated when hyperglycemia was prevented with insulin. Frontal cortex appeared more vulnerable to hyperglycemic insults than hippocampus. PMID:26009823

  9. Landiolol, an ultra-short-acting ?1-blocker, is useful for managing supraventricular tachyarrhythmias in sepsis

    PubMed Central

    Okajima, Masaki; Takamura, Masayuki; Taniguchi, Takumi

    2015-01-01

    AIM: To investigate whether landiolol, an ultra-short-acting ?1-antagonist, can safely and effectively control heart rate in septic patients with supraventricular tachyarrhythmias. METHODS: We reviewed all patients with sepsis who admitted to our intensive care unit between January 2006 and December 2011. Sixty one septic patients suffered from supraventricular tachyarrhythmias (heart rate ? 120 bpm for > 1 h). Among 61 patients, 39 patients were treated with landiolol (landiolol group) and 22 patients were not treated with landiolol (control group). Arterial pressure, heart rate, cardiac rhythm, pulmonary arterial pressure and cardiac output (if a pulmonary arterial catheter was inserted) were compared between the 2 groups at 1, 8 and 24 h after the initiation of tachyarrhythmias. RESULTS: Mean age and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were similar between the 2 groups. Paroxysmal atrial fibrillation/flutter (87%), paroxysmal atrial tachycardia (10%), and paroxysmal supraventricular tachycardia (3%) were observed. The initial landiolol dose administered was 6.3 ± 5.8 g/kg per minute. Rapid and substantial reduction of heart rate was observed in the landiolol group without any deterioration of hemodynamics. Landiolol significantly reduced heart rate (from 145 ± 14 bpm to 90 ± 20 bpm) compared to the control group (from 136 ± 21 bpm to 109 ± 18 bpm, P < 0.05). The conversion to sinus rhythm was observed more frequently in the landiolol group than in the control group at every point (P < 0.01 at 8 h; P < 0.05 at 1 and 24 h). CONCLUSION: Landiolol safely reduced heart rate and, in part, converted to sinus rhythm in septic patients with supraventricular tachyarrhythmias. PMID:26261777

  10. Acute myelogenous leukemia (AML) - children

    MedlinePLUS

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  11. Improved Diagnostic Accuracy of Group A Streptococcal Pharyngitis Using Real-Time Biosurveillance

    PubMed Central

    Fine, Andrew M.; Nizet, Victor; Mandl, Kenneth D.

    2013-01-01

    Background Clinical prediction rules do not incorporate real time incidence data to adjust estimates of disease risk in symptomatic patients. Objective To measure the value of integrating local incidence data into a clinical decision rule for diagnosing group A streptococcal (GAS) pharyngitis in patients age 15 years and older. Design Retrospective analysis of clinical and biosurveillance predictors of GAS pharyngitis. Setting Large U.S.-based retail-health chain. Patients 82,062 patient visits for pharyngitis. Measurements Accuracy of the Centor score, was compared with that of a biosurveillance-responsive score, essentially an adjusted Centor score based on real-time GAS pharyngitis information from the 14 days prior to a patient’s visit – the recent local proportion positive (RLPP). Results Increased RLPP correlated with likelihood of GAS pharyngitis (r2 =0.79, p<0.001). Local incidence data enhanced diagnostic models. For example, when RLPP >0.30, managing patients with Centor scores of 1 as if scores were 2 would identify 62,537 previously missed patients annually while misclassifying 18,446 patients without GAS pharyngitis. Decreasing the score of patients with Centor values of 3 by one point for RLPP <0.20, would spare unnecessary antibiotics for 166,616 patients while missing 18,812 true positives. Limitations Analyses were conducted retrospectively. Real time regional GAS pharyngitis data are generally not yet available to clinicians. Conclusions Incorporating live biosurveillance data into clinical guidelines for GAS pharyngitis and other communicable diseases should be considered to reduce missed cases when the contemporaneous incidence is elevated and spare unnecessary antibiotics when the contemporaneous incidence is low. Delivering epidemiologic data to the point of care will enable the use of real-time pre-test probabilities in medical decision-making. Primary Funding Source The Mentored Public Health Research Scientist Development Award K01 HK000055 from the Centers for Disease Control and Prevention and R01 LM007677 from the National Library of Medicine, National Institutes of Health. PMID:21930851

  12. Mechanical ventilation and sepsis impair protein metabolism in the diaphragm of neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

  13. Sepsis progression to multiple organ dysfunction in carotid chemo/baro-denervated rats treated with lipopolysaccharide.

    PubMed

    Nardocci, Gino; Martin, Aldo; Abarzúa, Sebastián; Rodríguez, Jorge; Simon, Felipe; Reyes, Edison P; Acuña-Castillo, Claudio; Navarro, Cristina; Cortes, Paula P; Fernández, Ricardo

    2015-01-15

    Sepsis progresses to multiple organ dysfunction (MOD) due to the uncontrolled release of inflammatory mediators. Carotid chemo/baro-receptors could play a protective role during sepsis. In anesthetized male rats, we measured cardiorespiratory variables and plasma TNF-?, glucocorticoids, epinephrine, and MOD marker levels 90min after lipopolysaccharide (LPS) administration in control (SHAM surgery) and bilateral carotid chemo/baro-denervated (BCN) rats. BCN prior to LPS blunted the tachypneic response and enhanced tachycardia and hypotension. BCN-LPS rats also showed blunted plasma glucocorticoid responses, boosted epinephrine and TNF-? responses, and earlier MOD onset with a lower survival time compared with SHAM-LPS rats. Consequently, the complete absence of carotid chemo/baro-sensory function modified the neural, endocrine and inflammatory responses to sepsis. Thus, carotid chemo/baro-receptors play a protective role in sepsis. PMID:25595251

  14. Rational development of guidelines for management of neonatal sepsis in developing countries

    PubMed Central

    Seale, Anna C; Obiero, Christina W; Berkley, James A

    2015-01-01

    Purpose of review This review discusses the rational development of guidelines for the management of neonatal sepsis in developing countries. Recent findings Diagnosis of neonatal sepsis with high specificity remains challenging in developing countries. Aetiology data, particularly from rural, community based studies are very limited, but molecular tests to improve diagnostics are being tested in a community-based study in South Asia. Antibiotic susceptibility data are limited, but suggest reducing susceptibility to first and second line antibiotics in both hospital and community acquired neonatal sepsis. Results of clinical trials in South Asia and sub-Saharan Africa assessing feasibility of simplified antibiotic regimens are awaited. Summary Effective management of neonatal sepsis in developing countries is essential to reduce neonatal mortality and morbidity. Simplified antibiotic regimens are currently being examined in clinical trials, but reduced antimicrobial susceptibility threatens current empiric treatment strategies. Improved clinical and microbiological surveillance is essential, to inform current practice, treatment guidelines, and monitor implementation of policy changes. PMID:25887615

  15. Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In neonatal pigs, sepsis decreases protein synthesis in skeletal muscle by decreasing translation initiation. However, insulin stimulates muscle protein synthesis despite persistent repression of translation initiation signaling. To determine whether the insulin-induced increase in global rates of m...

  16. Lactoferrin and neonatology - role in neonatal sepsis and necrotizing enterocolitis: present, past and future.

    PubMed

    Sharma, Deepak; Shastri, Sweta

    2016-03-01

    Neonatal sepsis and necrotizing enterocolitis (NEC) are two most important neonatal problems in nursery which constitute the bulk of neonatal mortality and morbidity. Inflammatory mediators secondary to sepsis and NEC increases morbidity, by affecting various system of body like lung, brain and eye, thus causing long term implications. Lactoferrin (LF) is a component of breast milk and multiple actions that includes antimicrobial, antiviral, anti-fungal and anti-cancer and various other actions. Few studies have been completed and a number of them are in progress for evaluation of efficacy and safety of LF in the prevention of neonatal sepsis and NEC in field of neonatology. In future, LF prophylaxis and therapy may have a significant impact in improving clinical outcomes of vulnerable preterm neonates. This review analyse the role of lactoferrin in prevention of neonatal sepsis and NEC, with emphasis on mechanism of action, recent studies and current studies going on around the globe. PMID:25758631

  17. Anthracyclines Induce DNA Damage Response-Mediated Protection against Severe Sepsis

    PubMed Central

    Figueiredo, Nuno; Chora, Angelo; Raquel, Helena; Pejanovic, Nadja; Pereira, Pedro; Hartleben, Björn; Neves-Costa, Ana; Moita, Catarina; Pedroso, Dora; Pinto, Andreia; Marques, Sofia; Faridi, Hafeez; Costa, Paulo; Gozzelino, Raffaella; Zhao, Jimmy L.; Soares, Miguel P.; Gama-Carvalho, Margarida; Martinez, Jennifer; Zhang, Qingshuo; Döring, Gerd; Grompe, Markus; Simas, J. Pedro; Huber, Tobias B.; Baltimore, David; Gupta, Vineet; Green, Douglas R.; Ferreira, João A.; Moita, Luis F.

    2014-01-01

    Summary Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fancony Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis. PMID:24184056

  18. Validation and optimisation of an ICD-10-coded case definition for sepsis using administrative health data

    PubMed Central

    Jolley, Rachel J; Jetté, Nathalie; Sawka, Keri Jo; Diep, Lucy; Goliath, Jade; Roberts, Derek J; Yipp, Bryan G; Doig, Christopher J

    2015-01-01

    Objective Administrative health data are important for health services and outcomes research. We optimised and validated in intensive care unit (ICU) patients an International Classification of Disease (ICD)-coded case definition for sepsis, and compared this with an existing definition. We also assessed the definition's performance in non-ICU (ward) patients. Setting and participants All adults (aged ?18?years) admitted to a multisystem ICU with general medicosurgical ICU care from one of three tertiary care centres in the Calgary region in Alberta, Canada, between 1 January 2009 and 31 December 2012 were included. Research design Patient medical records were randomly selected and linked to the discharge abstract database. In ICU patients, we validated the Canadian Institute for Health Information (CIHI) ICD-10-CA (Canadian Revision)-coded definition for sepsis and severe sepsis against a reference standard medical chart review, and optimised this algorithm through examination of other conditions apparent in sepsis. Measures Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results Sepsis was present in 604 of 1001 ICU patients (60.4%). The CIHI ICD-10-CA-coded definition for sepsis had Sn (46.4%), Sp (98.7%), PPV (98.2%) and NPV (54.7%); and for severe sepsis had Sn (47.2%), Sp (97.5%), PPV (95.3%) and NPV (63.2%). The optimised ICD-coded algorithm for sepsis increased Sn by 25.5% and NPV by 11.9% with slightly lowered Sp (85.4%) and PPV (88.2%). For severe sepsis both Sn (65.1%) and NPV (70.1%) increased, while Sp (88.2%) and PPV (85.6%) decreased slightly. Conclusions This study demonstrates that sepsis is highly undercoded in administrative data, thus under-ascertaining the true incidence of sepsis. The optimised ICD-coded definition has a higher validity with higher Sn and should be preferentially considered if used for surveillance purposes. PMID:26700284

  19. Renal Presentation in Pediatric Acute Leukemia

    PubMed Central

    Sherief, Laila M.; Azab, Seham F.; Zakaria, Marwa M.; Kamal, M.; Elbasset Aly, Maha Abd; Ali, Adel; Alhady, Mohamed Abd

    2015-01-01

    Abstract Renal enlargement at time of diagnosis of acute leukemia is very unusual. We here in report 2 pediatric cases of acute leukemia who had their renal affection as the first presenting symptom with no evidences of blast cells in blood smear and none of classical presentation of acute leukemia. The first case is a 4-year-old girl who presented with pallor and abdominal enlargement. Magnetic resonance imaging showed bilateral symmetrical homogenous enlarged kidneys suggestive of infiltration. Complete blood picture (CBC) revealed white blood count 11?×?109/L, hemoglobin 8.7?g/dL and platelet count 197?×?109/L. Bone marrow aspiration was performed, and diagnosed precursor B-cell ALL was made. The child had an excellent response to modified CCG 1991 standard risk protocol of chemotherapy with sustained remission, but unfortunately relapsed 11 month after the end of therapy. The second child was 13-month old, presented with pallor, vomiting, abdominal enlargement, and oliguria 2 days before admission. Initial CBC showed bicytopenia, elevated blood urea, creatinine, and serum uric acid, while abdominal ultrasonography revealed bilateral renal enlargement. Bone marrow examination was done and showed 92% blast of biphenotypic nature. So, biphynotypic leukemia with bilateral renal enlargement and acute renal failure was subsequently diagnosed. The patients admitted to ICU and received supportive care and prednisolone. Renal function normalized and chemotherapy was started. The child achieved complete remission with marked reduction of kidney size but, unfortunately she died from sepsis in consolidation phase of therapy. This case demonstrates an unusual early renal enlargement in childhood acute leukemia. Renal involvement of acute leukemia should be considered in child presenting with unexplained bilateral renal enlargement with or without renal function abnormalities and bone marrow examination should be included in the workup. PMID:26376384

  20. M1 protein and protein H: IgGFc- and albumin-binding streptococcal surface proteins encoded by adjacent genes.

    PubMed Central

    Akesson, P; Schmidt, K H; Cooney, J; Björck, L

    1994-01-01

    M1 protein and Protein H are surface proteins simultaneously present at the surface of certain strains of Streptococcus pyogenes, important pathogenic bacteria in humans. The present study concerns the structure, protein-binding properties and relationship between these two molecules. The gene encoding M1 protein (emm1) was found immediately upstream of the Protein H gene (sph). Both genes were preceded by a promoter region. Comparison of the sequences revealed a high degree of similarity in the signal peptides, the C repeats located in the central parts of the molecules and in the C-terminal cell-wall-attached regions, whereas the N-terminal sequences showed no significant similarity. Protein H has affinity for the Fc region of IgG antibodies. Also M1 protein, isolated from streptococcal culture supernatants or from Escherichia coli expressing emm1, was found to bind human IgGFc. When tested against polyclonal IgG from eight other mammalian species, M1 protein and Protein H both showed affinity for baboon, rabbit and pig IgG. M1 protein also reacted with guinea-pig IgG, whereas both streptococcal proteins were negative in binding experiments with rat, mouse, bovine and horse IgG. The two proteins were also tested against other members of the immunoglobulin super family: human IgM, IgA, IgD, IgE, beta 2-microglobulin, and major histocompatibility complex (MHC) class-I and class-II antigens. M1 protein showed no affinity for any of these molecules whereas Protein H reacted with MHC class-II antigens. M1 protein is known to bind albumin and fibrinogen also. The binding sites for these two plasma proteins and for IgGFc were mapped to different sites on M1 protein. Thus albumin bound to the C repeats and IgGFc to a region (S) immediately N-terminal of the C repeats. Finally, fibrinogen bound further towards the N-terminus but close to the IgGFc-binding site. On the fibrinogen molecule, fragment D was found to mediate binding to M1 protein. The IgGFc-binding region of M1 protein showed no similarity to that of Protein H. Still, competitive binding experiments demonstrated that the two streptococcal proteins bound to overlapping sites on IgGFc. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 10 Figure 11 PMID:8010973

  1. Day 3 versus Day 1 disseminated intravascular coagulation score among sepsis patients: a prospective observational study.

    PubMed

    Park, J Y; Park, S; Park, S Y; Sim, Y S; Kim, J H; Hwang, Y I; Jang, S H; Jung, K S

    2016-01-01

    The role of disseminated intravascular coagulation (DIC) has not been extensively studied in patients with sepsis. A prospective study was performed in a single university hospital. The incidences of DIC at day 1 (<24 hours post-sepsis diagnosis) and day 3 (48 to 72 hours) were investigated among patients with sepsis. The International Society of Thrombosis and Haemostasis criteria for DIC were used. Among 381 patients initially screened, 219 were enrolled in this study and the incidences of overt DIC were 27.9% and 30.1% on day 1 and day 3, respectively. Patients with pneumonia had a lower incidence of DIC on day 1, but a higher hospital mortality rate compared to those with non-pneumonia sepsis. In multivariate models, although day 1 and day 3 DIC scores were not associated with hospital mortality after adjusting for existing severity scores, the change in DIC scores (odds ratio 1.862; 95% confidence interval 1.061 to 3.266) exhibited a significant association. Day 3 DIC scores were more accurate in predicting hospital mortality than day 1 DIC scores (P <0.001), especially in patients with non-pneumonia sepsis. However, DIC scores did not give additional discriminative power to the existing prognostic scores in predicting mortality of patients with sepsis. In conclusion, the change in DIC score was significantly associated with hospital mortality. Patients with pneumonia sepsis had a lower incidence of DIC on day 1, despite their higher disease severity and mortality rate, compared to those with other sources of sepsis. PMID:26673590

  2. Don't Go Chasing Waterfalls: Excessive Fluid Resuscitation in Severe Sepsis and Septic Shock.

    PubMed

    Chen, Leon

    2016-01-01

    Aggressive fluid resuscitation is the mainstay therapy in modern sepsis management. Its efficacy was demonstrated in the landmark study by Emmanuel Rivers in 2001. However, more recent evidence largely shows that a positive fluid balance increases mortality in critically ill patients with sepsis. This article examines the theoretical benefits of fluid resuscitation and physiological responses to it that may negatively affect patients' outcome. PMID:26633156

  3. Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach

    PubMed Central

    Su, Longxiang; Huang, Yingyu; Zhu, Ying; Xia, Lei; Wang, Rentao; Xiao, Kun; Wang, Huijuan; Yan, Peng; Wen, Bo; Cao, Lichao; Meng, Nan; Luan, Hemi; Liu, Changting; Li, Xin; Xie, Lixin

    2014-01-01

    Background To identify metabolic biomarkers that can be used to differentiate sepsis from systemic inflammatory response syndrome (SIRS), assess severity and predict outcomes. Methods 65 patients were involved in this study, including 35 patients with sepsis, 15 patients with SIRS and 15 normal patients. Small metabolites that were present in patient serum samples were measured by liquid chromatography mass spectrometry techniques and analysed using multivariate statistical methods. Results The metabolic profiling of normal patients and patients with SIRS or sepsis was markedly different. A significant decrease in the levels of lactitol dehydrate and S-phenyl-d-cysteine and an increase in the levels of S-(3-methylbutanoyl)-dihydrolipoamide-E and N-nonanoyl glycine were observed in patients with sepsis in comparison to patients with SIRS (p<0.05). Patients with severe sepsis and septic shock displayed lower levels of glyceryl-phosphoryl-ethanolamine, Ne, Ne dimethyllysine, phenylacetamide and d-cysteine (p<0.05) in their sera. The profiles of patients with sepsis 48?h before death illustrated an obvious state of metabolic disorder, such that S-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol (22:2 (13Z, 16Z)/0:0), glycerophosphocholine and S-succinyl glutathione were significantly decreased (p<0.05). The receiver operating characteristic curve of the differential expression of these metabolites was also performed. Conclusions The body produces significant evidence of metabolic disorder during SIRS or sepsis. Seven metabolites may potentially be used to diagnose sepsis. Trial registration number ClinicalTrial.gov identifier NCT01649440. PMID:25553245

  4. Catheter related line sepsis resulting from Mycobacterium chelonae infection in an immunocompromised host.

    PubMed

    Antony, Suresh J

    2015-01-01

    Almost any species of non tuberculosis mycobacterium [NTM], including M. chelonae may be associated with nosocomial infections including catheter related sepsis, pneumonia etc. We present a case of catheter related sepsis due to M. chelonae which was treated with appropriate therapy including removal of the catheter. This case serves as a reminder to include the NTM group in the differential diagnosis of these nosocomial infections. PMID:26205798

  5. The value of screening for diabetes in patients with skin sepsis.

    PubMed Central

    Baynes, C; Caplan, S; Hames, P; Swift, R; Poole, S; Wadsworth, J; Touquet, R; Elkeles, R S

    1993-01-01

    Four hundred and eighty-two patients with spontaneous skin and superficial sepsis and 291 controls of similar age and sex underwent random capillary blood glucose measurements in order to assess whether screening for diabetes in patients presenting with skin sepsis to an Accident & Emergency Department detects a greater number of cases than that present in the background population. All subjects with a concentration > 7.8 mmol/l were subsequently followed up with a 75 g oral glucose tolerance test. Forty-two (8.7%) of the 482 skin sepsis patients had a capillary blood glucose > 7.8 mmol/l compared to eight (2.7%) of the 291 without sepsis (chi 2 = 9.71, P < 0.002). Of these, 26 of the skin sepsis group and 7 of the control group attended for follow up. Of those who attended, 13 of the skin sepsis group had an abnormal glucose tolerance test (seven diabetes, six impaired glucose tolerance-IGT) compared to two (one diabetes, one IGT) of the control group (chi 2 = 2.87, P < 0.1). The difference in cases of frank diabetes between the two groups was not statistically significant. Of the total eight diabetic cases identified, five (on direct questioning) had symptoms of hyperglycaemia (thirst, polyuria and/or weight loss) and two of the others were obese, one of whom had documented ischaemic heart disease. Thus, while most cases of diabetes in patients with skin sepsis could be detected by specifically asking about hyperglycaemic symptoms and performing a blood glucose estimation when these are present, we suggest that the screening of patients with skin sepsis over 40 years of age provides an opportunistic method of screening. This strategy should yield clinically significant numbers of abnormal cases. PMID:8459378

  6. Energy Metabolism of Infants and Children with Systemic Inflammatory Response Syndrome and Sepsis

    PubMed Central

    Turi, Rosa A.; Petros, Andy J.; Eaton, Simon; Fasoli, Lorella; Powis, Mark; Basu, Rajat; Spitz, Lewis; Pierro, Agostino

    2001-01-01

    Objective To evaluate whether critically ill children with systemic inflammatory response syndrome (SIRS) or sepsis have altered resting energy expenditure (REE) and substrate utilization. Summary Background Data Studies in adults with sepsis have shown increased energy expenditure and mobilization of endogenous fat. In infants and children, energy metabolism and substrate utilization during sepsis have not been characterized. Methods Metabolic studies were performed in 21 critically ill children with SIRS or sepsis. Twenty-one stable control children, matched for weight, were also studied. Seven patients required inotropic support and 17 received mechanical ventilation. Fifteen patients with SIRS had evidence of bacterial, fungal, or viral infection and were considered septic. Respiratory gas exchange was measured by computerized indirect calorimetry for 1 to 2 hours continuously. Results The REE of patients with SIRS or sepsis was not different from that of controls. Similarly, there were no differences in carbon dioxide production and oxygen consumption. Resting energy metabolism was not different between patients with SIRS and patients with sepsis. In addition, the presence of low platelet count or inotropic support did not affect resting energy metabolism. The median respiratory quotient of patients with SIRS or sepsis was 0.88 (range 0.75–1.12), indicating mixed utilization of fat and carbohydrate; this was not significantly different from that of controls. The Pediatric Risk of Mortality Score was not significantly correlated with REE or respiratory quotient. Conclusions The energy requirements of children with SIRS or sepsis are not increased. Their resting metabolism is based on both carbohydrate and fat utilization. The authors speculate that these children divert the energy for growth into recovery processes. PMID:11303142

  7. Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL-dependent

    PubMed Central

    Gurung, Prajwal; Rai, Deepa; Condotta, Stephanie A.; Babcock, Jeffrey C.; Badovinac, Vladimir P.; Griffith, Thomas S.

    2011-01-01

    Sepsis is the leading cause of death in most ICU’s, and patients who survive the hyper-inflammation that develops early during sepsis later display severely compromised immunity. Not only is there apoptosis of lymphoid and myeloid cells during sepsis that depletes these critical cellular components of the immune system, but the remaining immune cells also show decreased function. Using a cecal-ligation and puncture (CLP) model to induce intra-abdominal polymicrobial peritonitis, we recently established a link between the apoptotic cells generated during sepsis and induction of sepsis-induced suppression of delayed-type hypersensitivity. The present study extends this earlier work to include a secondary heterologous bacterial infection (OVA-expressing Listeria monocytogenes; LM-OVA) subsequent to sepsis initiation to investigate sepsis-induced alterations in the control of this secondary infection and the associated naïve Ag-specific CD8 T cell response. We found that CLP-treated WT mice had a reduced ability to control the LM-OVA infection, which was paralleled by suppressed T cell responses, versus sham-treated WT mice. In contrast, CLP-treated Trail?/? and Dr5?/? mice were better able to control the secondary bacterial infection and the Ag-specific CD8 T cell response was similar to that seen in sham-treated mice. Importantly, administration of a blocking anti-TRAIL mAb to CLP-treated WT mice was able to restore the ability to control the LM-OVA infection and generate Ag-specific CD8 T cell responses like those seen in sham-treated mice. These data further implicate TRAIL-dependent immune suppression during sepsis, and suggest TRAIL neutralization may be a potential therapeutic target to restore cellular immunity in septic patients. PMID:21788440

  8. An integrated clinico-metabolomic model improves prediction of death in sepsis.

    PubMed

    Langley, Raymond J; Tsalik, Ephraim L; van Velkinburgh, Jennifer C; Glickman, Seth W; Rice, Brandon J; Wang, Chunping; Chen, Bo; Carin, Lawrence; Suarez, Arturo; Mohney, Robert P; Freeman, Debra H; Wang, Mu; You, Jinsam; Wulff, Jacob; Thompson, J Will; Moseley, M Arthur; Reisinger, Stephanie; Edmonds, Brian T; Grinnell, Brian; Nelson, David R; Dinwiddie, Darrell L; Miller, Neil A; Saunders, Carol J; Soden, Sarah S; Rogers, Angela J; Gazourian, Lee; Fredenburgh, Laura E; Massaro, Anthony F; Baron, Rebecca M; Choi, Augustine M K; Corey, G Ralph; Ginsburg, Geoffrey S; Cairns, Charles B; Otero, Ronny M; Fowler, Vance G; Rivers, Emanuel P; Woods, Christopher W; Kingsmore, Stephen F

    2013-07-24

    Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the following groups: fatty acid transport and ?-oxidation, gluconeogenesis, and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of five metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis. PMID:23884467

  9. The Presence of Hypothermia within 24 Hours of Sepsis Diagnosis Predicts Persistent Lymphopenia

    PubMed Central

    Drewry, Anne M.; Fuller, Brian M.; Skrupky, Lee P.; Hotchkiss, Richard S.

    2015-01-01

    Objective To determine whether hypothermia within 24 hours of sepsis diagnosis is associated with development of persistent lymphopenia, a feature of sepsis-induced immunosuppression Design Retrospective cohort study Setting 1200-bed university-affiliated tertiary care hospital Patients Adult patients diagnosed with bacteremia and sepsis within 5 days of hospital admission between January 1, 2010 and July 31, 2012 Interventions None Measurements and main results Leukocyte counts were recorded during the first four days following sepsis diagnosis. Persistent lymphopenia was defined as an absolute lymphocyte count less than 1.2 cells/?l x 103 present on the fourth day after diagnosis. Of the 445 septic patients included, 64 (14.4%) developed hypothermia (defined as a body temperature less than 36.0°C) within 24 hours of sepsis diagnosis. Hypothermia was a significant independent predictor of persistent lymphopenia (adjusted OR 2.70 [95% CI 1.10, 6.60], p =.03) after accounting for age, disease severity, comorbidities, source of bacteremia, and type of organism. Compared to the non-hypothermic patients, hypothermic patients had higher 28-day (50.0% vs. 24.9%, p < .001) and 1-year mortality (60.9% vs. 47.0%, p = .001). Conclusions Hypothermia is associated with higher mortality and an increased risk of persistent lymphopenia in septic patients, and it may be an early clinical predictor of sepsis-induced immunosuppression. PMID:25793436

  10. Procalcitonin, MR-Proadrenomedullin, and Cytokines Measurement in Sepsis Diagnosis: Advantages from Test Combination

    PubMed Central

    Angeletti, Silvia; Dicuonzo, Giordano; Fioravanti, Marta; De Cesaris, Marina; Fogolari, Marta; Lo Presti, Alessandra; Ciccozzi, Massimo; De Florio, Lucia

    2015-01-01

    Background. Elevated cytokines levels correlate with sepsis severity and mortality but their role in the diagnosis is controversial, whereas Procalcitonin (PCT) has been largely used. Recently, the mid-regional proadrenomedullin (MR-proADM) has been combined with PCT for diagnosis optimization. In this study the combined measurement of PCT, MR-proADM, and cytokines in patients with sepsis was evaluated. Methods. One hundred and four septic patients and 101 controls were enrolled. Receiver operating characteristic (ROC) analysis and multiple logistic regression were used to evaluate applicant markers for sepsis diagnosis. Markers with best Odds Ratio (OR) were combined, and the posttest probability and a composite score were computed. Results. Based upon ROC curves analysis, PCT, MR-proADM, IL-6, IL-10, TNF-?, and MCP-1 were considered applicant for sepsis diagnosis. Among these PCT, MR-proADM , IL-6, and TNF-? showed the best OR. A better posttest probability was found with the combination of PCT with MR-proADM and PCT with IL-6 or TNF-? compared to the single marker. A composite score of PCT, MR-proADM, and TNF-? showed the best ROC curve in the early diagnosis of sepsis. Conclusion. The combination of PCT with other markers should expedite diagnosis and treatment of sepsis optimizing clinical management. PMID:26635427

  11. HMGB1 as a therapeutic target for sepsis: it's all in the timing!

    PubMed

    Gentile, Lori F; Moldawer, Lyle L

    2014-03-01

    Morbidity and mortality from severe sepsis remain high, despite decades of research and improvements in intensive care unit (ICU) care. There have been over 100 failed clinical trials of biological response modifiers aimed at single therapeutic targets, mostly to suppress the early pro-inflammatory responses. In the last decade, extracellular HMGB1 has emerged as a late mediator of sepsis in murine sepsis models, whose blockade improves mortality and has a wider therapeutic window than previous efforts. Although this review promulgates the use of HMGB1 inhibitor as a therapeutic target, it should be recognized that it may not be an optimal approach to the early systemic inflammatory response syndrome (SIRS) response and cytokine storm, but rather for those patients who survive their cytokine storm and present with a persistent inflammatory, immunosuppressive and catabolism response (PICS). With earlier implementation of evidence-based best care principles for treating sepsis, fewer patients are dying from early septic shock, and there is an endemic increase in sepsis survivors with dismal long-term outcomes. These patients have ongoing inflammatory processes that may well be driven by the late and continued release of HMGB1 and other damage-associated molecular patterns receptors (DAMPRs). HMGB1 therapeutics, whether antibodies or natural herbal approaches, may be one novel approach for targeting not the early, but the late persistent inflammation of sepsis survivors. PMID:24479494

  12. Accuracy of serum interleukin (IL)-6 in sepsis diagnosis: a systematic review and meta-analysis

    PubMed Central

    Hou, Tieying; Huang, Dehong; Zeng, Rong; Ye, Zhiming; Zhang, Yu

    2015-01-01

    Objective: To systematic review and estimate the accuracy of Interleukin 6 assay in the diagnosis of sepsis by meta-analysis. Methods: With the aim to confirm this correlation, this paper performed a meta-analysis of 6 studies and the Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with corresponding 95% confidence intervals (CI) of each study were calculated and the pooled sensitivity was calculate using Random Effects Model and Summary receiver operating characteristic curves were constructed. Results: The pooled sensitivity for the diagnosis of sepsis was 80% (95% CI, 77% to 83%) and the specificity of 85% (95% CI, 81% to 88%). For sepsis versus health or infection, the area under the curve was 0.868. In neonate subgroup, IL-6 had a pooled sensitivity of 77.0% (95% CI, 73.0% to 81.0%) and specificity of 91.0% (95% CI, 86.0% to 94.0%) for sepsis diagnosis. In adult, IL-6 had a pooled sensitivity of 85.0% (95% CI, 80.0% to 88.0%) and specificity of 62.0% (95% CI, 55.0% to 68.0%) to identify sepsis. The AUC was 81.0%, and Q was 0.74. Conclusions: IL6 is a highly accurate diagnostic modality for the identification of sepsis, with promise for integration into routine imaging protocols for thyroid nodules.

  13. Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective

    PubMed Central

    2012-01-01

    Sepsis represents a dysregulated host response to infection, the extent of which determines the severity of organ dysfunction and subsequent outcome. All trialled immunomodulatory strategies to date have resulted in either outright failure or inconsistent degrees of success. Intravenous immunoglobulin (IVIg) therapy falls into the latter category with opinion still divided as to its utility. This article provides a narrative review of the biological rationale for using IVIg in sepsis. A literature search was conducted using the PubMed database (1966 to February 2011). The strategy included the following text terms and combinations of these: IVIg, intravenous immune globulin, intravenous immunoglobulin, immunoglobulin, immunoglobulin therapy, pentaglobin, sepsis, inflammation, immune modulation, apoptosis. Preclinical and extrapolated clinical data of IVIg therapy in sepsis suggests improved bacterial clearance, inhibitory effects upon upstream mediators of the host response (for example, the nuclear factor kappa B (NF-?B) transcription factor), scavenging of downstream inflammatory mediators (for example, cytokines), direct anti-inflammatory effects mediated via Fc? receptors, and a potential ability to attenuate lymphocyte apoptosis and thus sepsis-related immunosuppression. Characterizing the trajectory of change in immunoglobulin levels during sepsis, understanding mechanisms contributing to these changes, and undertaking IVIg dose-finding studies should be performed prior to further large-scale interventional trials to enhance the likelihood of a successful outcome. PMID:22424150

  14. A Systematic Review of Rhubarb (a Traditional Chinese Medicine) Used for the Treatment of Experimental Sepsis

    PubMed Central

    Lai, Fang; Zhang, Yan; Xie, Dong-ping; Mai, Shu-tao; Weng, Yan-na; Du, Jiong-dong; Wu, Guang-ping; Zheng, Jing-xia; Han, Yun

    2015-01-01

    Sepsis is a global major health problem in great need for more effective therapy. For thousands of years, Rhubarb had been used for various diseases including severe infection. Pharmacological studies and trials reported that Rhubarb may be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on Rhubarb for sepsis. The present study is the first systematic review of Rhubarb used for the treatment of experimental sepsis in both English and Chinese literatures by identifying 27 studies from 7 databases. It showed that Rhubarb might be effective in reducing injuries in gastrointestinal tract, lung, and liver induced by sepsis, and its potential mechanisms might include reducing oxidative stress and inflammation, ameliorating microcirculatory disturbance, and maintaining immune balance. Yet the positive findings should be interpreted with caution due to poor methodological quality. In a word, Rhubarb might be a promising candidate that is worth further clinical and experimental trials for sepsis therapy. PMID:26339264

  15. Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids.

    PubMed Central

    Tiao, G; Fagan, J; Roegner, V; Lieberman, M; Wang, J J; Fischer, J E; Hasselgren, P O

    1996-01-01

    Recent studies suggest that sepsis-induced increase in muscle proteolysis mainly reflects energy-ubiquitin-dependent protein breakdown. We tested the hypothesis that glucocorticoids activate the energy-ubiquitin-dependent proteolytic pathway in skeletal muscle during sepsis. Rats underwent induction of sepsis by cecal ligation and puncture or were sham-operated and muscle protein breakdown rates were measured 16 h later. The glucocorticoid receptor antagonist RU 38486 or vehicle was administered to groups of septic and sham-operated rats. In other experiments, dexamethasone (2.5 or 10 mg/kg) was injected subcutaneously in normal rats. Total and myofibrillar proteolysis was determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively. Energy-dependent proteolysis was determined in incubated muscles depleted of energy with 2-deoxyglucose and 2,4-dinitrophenol. Levels of muscle ubiquitin mRNA and free and conjugated ubiquitin were determined by Northern and Western blot, respectively. RU 38486 inhibited the sepsis-induced increase in total and myofibrillar energy-dependent protein breakdown rates and blunted the increase in ubiquitin mRNA levels and free ubiquitin. Some, but not all, sepsis-induced changes in ubiquitin protein conjugates were inhibited by RU 38486. Injection of dexamethasone in normal rats increased energy-dependent proteolysis and ubiquitin mRNA levels. The results suggest that glucocorticoids regulate the energy-ubiquitin-dependent proteolytic pathway in skeletal muscle during sepsis. PMID:8567953

  16. Effects of Rhubarb combined with ulinastatin on T-cell subsets in sepsis rats

    PubMed Central

    Tian, Huiyu; Zhang, Ming; Du, Chongbo; Li, Dongliang; Zhou, Qingming; Wu, Liping; Meng, Fulei; Song, Shaohua; Wang, Lai; Lu, Peng; Zhao, Zhitao; Yang, Xiufen

    2015-01-01

    Objective: The pathogenesis of sepsis, a systemic inflammatory response syndrome, is very complicated and not well understood. However, the importance of lymphocyte percentage and ratio is implicated. Rhubarb is a traditional Chinese medication and plays a role in protecting gastrointestinal mucous and controlling the SIRS damage. Ulinastatin is a protease inhibitor that prevents overproduction of inflammatory cytokines. Currently, despite numerous sepsis clinical researches, the study on the effects of combined drug therapy on sepsis is lacking. In this study, we studied Rhubarb and Ulinastatin combination treatment on T lymphocyte subsets in sepsis induced by the cecal ligation and perforation (CLP). Immunosuppression happened at the early stage of severe sepsis in the CLP rat models, as CD3+, CD4+, CD4+/CD8+ began to decline, dropped rapidly after 24 h and continuously decreased at 36 h. CD8+ T lymphocyte showed no significant change in all groups after CLP. The morality of CLP rats was increased with Rhubarb treatment in test dose (1.2 g/100 g). The immunosuppression state of CLP rats ameliorated with UTI treatment at early stage. The immunomodulatory properties were improved along with drug treatment, and immunities were obviously increased after 24 h, moreover, continuously increased at 36 h. The relief effect of immunosuppression after CLP showed much better in Rhubarb combined with UTI treatment than UTI monotherapy. In conclusion, the combination drug treatment facilitates the improvement of sepsis by modifying the lymphocyte percentage. PMID:25785118

  17. Invasive group B streptococcal disease in infants: a 19-year nationwide study. Serotype distribution, incidence and recurrent infection.

    PubMed Central

    Ekelund, K.; Konradsen, H. B.

    2004-01-01

    During the period 1984-2002, 472 cases of invasive group B streptococcal (GBS) disease in infants aged 0-90 days in Denmark were registered. The overall incidence was 0.4/1000 live births. Most infants (73%) had early-onset GBS infection with 53% registered within the first day. Serotype III predominated (59%) with other serotypes as follows: Ia (16%), Ib (8%), NT (7%), II (6%), other serotypes (5%). Recurrence of GBS infection was registered in six infants, and the interval with no antibiotic therapy varied from 2 to 39 days. The serotypes of the isolates obtained from first and second episodes were identical (serotype III in five, and serotype Ia in one infant). Paired isolates were indistinguishable by PFGE and antibiotic susceptibility testing. Invasive GBS infections in infants are still a problem in Denmark, and recurrent infections are registered in 1% of these infants. PMID:15635965

  18. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary ?-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  19. Amino Acid Derangements in Patients With Sepsis: Treatment With Branched Chain Amino Acid Rich Infusions

    PubMed Central

    Freund, Herbert R.; Ryan, John A.; Fischer, Josef E.

    1978-01-01

    Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, ?-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids. PMID:99098

  20. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes

    PubMed Central

    Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio

    2014-01-01

    Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney injury. PMID:25607268

  1. Recent knowledge on the pathophysiology of septic acute kidney injury: A narrative review.

    PubMed

    Shum, Hoi-Ping; Yan, Wing-Wa; Chan, Tak Mao

    2016-02-01

    Sepsis is the commonest cause of acute kidney injury in critically ill patients. Its pathophysiology is complex and not well understood. Until recently, it was believed that kidney hypoperfusion is the major contributor of septic acute kidney injury. However, recent publications have improved our understanding on this topic. We now know that its mechanisms included the following: (1) renal macrocirculatory and microcirculatory disturbance, (2) surge of inflammatory markers and oxidative stress, (3) coagulation cascade activation, and (4) bioenergetics adaptive response with controlled cell-cycle arrest aiming to prevent cell death. Uncovering these complicated mechanisms may facilitate the development of more appropriate therapeutic measures in the future. PMID:26475099

  2. [Recommendations for management of acute pharyngitis in adults].

    PubMed

    Cots, Josep M; Alós, Juan-Ignacio; Bárcena, Mario; Boleda, Xavier; Cañada, José L; Gómez, Niceto; Mendoza, Ana; Vilaseca, Isabel; Llor, Carles

    2015-10-01

    Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A ?-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy. PMID:26004567

  3. Recommendations for management of acute pharyngitis in adults.

    PubMed

    Cots, Josep M; Alós, Juan-Ignacio; Bárcena, Mario; Boleda, Xavier; Cañada, José L; Gómez, Niceto; Mendoza, Ana; Vilaseca, Isabel; Llor, Carles

    2015-01-01

    Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A ?-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy. PMID:25772389

  4. [Recommendations for management of acute pharyngitis in adults].

    PubMed

    Cots, Josep M; Alós, Juan-Ignacio; Bárcena, Mario; Boleda, Xavier; Cañada, José L; Gómez, Niceto; Mendoza, Ana; Vilaseca, Isabel; Llor, Carles

    2015-10-01

    Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A ?-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy. PMID:26025360

  5. Arginine and Citrulline and the Immune Response in Sepsis

    PubMed Central

    Wijnands, Karolina A.P.; Castermans, Tessy M.R.; Hommen, Merel P.J.; Meesters, Dennis M.; Poeze, Martijn

    2015-01-01

    Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO) and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target. PMID:25699985

  6. An extracorporeal blood-cleansing device for sepsis therapy.

    PubMed

    Kang, Joo H; Super, Michael; Yung, Chong Wing; Cooper, Ryan M; Domansky, Karel; Graveline, Amanda R; Mammoto, Tadanori; Berthet, Julia B; Tobin, Heather; Cartwright, Mark J; Watters, Alexander L; Rottman, Martin; Waterhouse, Anna; Mammoto, Akiko; Gamini, Nazita; Rodas, Melissa J; Kole, Anxhela; Jiang, Amanda; Valentin, Thomas M; Diaz, Alexander; Takahashi, Kazue; Ingber, Donald E

    2014-10-01

    Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin--mannose-binding lectin (MBL)--that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment. PMID:25216635

  7. Efficacy of Enrofloxacin in a Mouse Model of Sepsis

    PubMed Central

    Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A

    2014-01-01

    We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciprofloxacin were greater in the group treated by injection than in controls or the groups treated by administration in drinking water. Survival of the group treated with enrofloxacin injection was greater than that of controls and groups treated with enrofloxacin in the drinking water. Bioluminescence in the group treated with enrofloxacin injection was less than that in the groups treated with oral administration at 12 h and in the groups treated orally and the control group at 16 h. According to these findings, we recommend the use of injectable enrofloxacin at 5 mg/kg SC for mice with systemic infections. PMID:25199094

  8. Point of care optical device for sepsis diagnosis

    NASA Astrophysics Data System (ADS)

    Baldini, F.; Bolzoni, L.; Giannetti, A.; Porro, G.; Senesi, F.; Trono, C.

    2009-10-01

    The discrimination of viral and bacterial sepsis is an important issue in intensive care patients. For this purpose, the simultaneous measurements of different analytes are necessary. Among the possible candidates, C-reactive protein (CRP) and procalcitonin (PCT) are probably the most important ones. A novel optical platform was designed and realised for the implementation of fluorescence-based immunoassays. The core of the optical platform is a plastic biochip, constituted by 13 microchannels (50 ?m high, 600 ?m width, 10 mm long) through which the sample flows. The sensing layer, where the immunochemical reaction takes place, is located on the upper part of each microchannel. The chip is interrogated with a novel optoelectronic platform, based on fluorescence anisotropy. A line-shaped beam from a 635-nm laser-diode excites perpendicularly the sensing layer and great many of the emitted remains entrapped inside the chip. The particular shape of the top of the chip allows to guide the emitted fluorescence along the same direction of the microchannel. The fluorescence which comes out on the lateral side from the chip is collected by a single plastic optical fibre and sent to an amplified photodiode. The device was characterised by the implementation of the sandwich assay for CRP and PCT spiked in serum. Limit of quantifications of 4.5 and of 6 ?g L-1 in serum solution were achieved for CRP and PCT, respectively.

  9. Speciation of presumptive viridans streptococci from early onset neonatal sepsis.

    PubMed

    West, P W; Al-Sawan, R; Foster, H A; Electricwala, Q; Alex, A; Panigrahi, D

    1998-10-01

    Twenty isolates resembling viridans streptococci, 16 from blood and four from gastric aspirates, from 17 cases of early onset neonatal sepsis were identified by the API20 Strep, Rapid ID 32 Strep and conventional tests plus hydrolysis of methylumbelliferyl glycoside substrates. Nineteen of the isolates were identified as species of viridans streptococci and one as a Leuconostoc sp. Ten of the isolates were Streptococcus oralis, three S. mitis biotype 1, two S. mitis biotype 2 and one each of S. sanguis, S. vestibularis, S. salivarius and S. intermedius. The Rapid ID 32 Strep and conventional plus methylumbelliferyl tests gave the same species identity for 17 of the isolates. S. intermedius was identified by the Rapid ID 32 Strep as S. constellatus and S. salivarius as S. equinus, with S. salivarius at lower probability. The API20 Strep failed to identify S. vestibularis and identified S. salivarius as S. defectivus. The absence of certain critical tests, including urea hydrolysis, does not allow the API20 Strep to identify all the currently recognised species of viridans steptococci. The species distribution was unexpected and the incidence of S. oralis and other viridans streptococci in vaginal swabs from prenatal patients is being investigated further. PMID:9788817

  10. Epidemiology and Outcome of Severe Sepsis and Septic Shock in Surgical Intensive Care Units in Northern Taiwan.

    PubMed

    Huang, Chun-Ta; Tsai, Yi-Ju; Tsai, Pi-Ru; Yu, Chong-Jen; Ko, Wen-Je

    2015-11-01

    Severe sepsis remains the leading cause of mortality in the critically ill. Local epidemiological studies on sepsis are of paramount importance to increase our knowledge about sepsis features and to improve patient care and prognosis.Adult patients (?20 years) admitted to the surgical intensive care units with severe sepsis or septic shock from 2009 to 2010 were retrospectively retrieved and analyzed. The primary outcome of interest was 28-day mortality.Of 7795 admissions, 536 (6.9%) patients had severe sepsis. The most common sites of infection were the respiratory tract (38%) and abdomen (33%). Gram-negative bacteria, particularly Klebsiella pneumoniae (8.6%) and Escherichia coli (6.0%), were the major infecting micro-organisms, responsible for approximately two-thirds of the severe sepsis episodes. The overall 28-day mortality rate was 61%, and a higher sequential organ failure assessment score and the use of mechanical ventilation were independently associated with a worse outcome.Admissions with severe sepsis are not uncommon and are associated with substantial 28-day mortality in surgical intensive care units in northern Taiwan. Establishment and optimization of each institutional sepsis care standard to improve the outcome of sepsis are warranted. PMID:26632737

  11. Physical Inactivity and Long-Term Rates of Community-Acquired Sepsis

    PubMed Central

    Wang, Henry E.; Baddley, John; Griffin, Russell; Judd, Suzanne; Howard, George; Donnelly, John; Safford, Monika M.

    2014-01-01

    OBJECTIVE The authors sought to determine the association between physical inactivity (characterized by exercise and television watching levels) and long-term rates of community-acquired sepsis. METHODS Population-based cohort study of 30,183 adult (?45 years) community-dwelling participants. Subjects reported weekly exercise (low=none, medium=1-3 times/week, high= ?4 times/week) and daily television watching (low= <1 hour/day, medium= 1-3 hours/day, high= ?4 hours/day) levels. The authors evaluated the association between exercise, television watching and rates of sepsis, defined as hospital treatment for a serious infection with ?2 Systemic Inflammatory Response Syndrome (SIRS) criteria. RESULTS Among 30,183 participants, 1,500 experienced a sepsis event. Reported weekly exercise was: high 8,798 (29.2%), medium 10,695 (35.4%), and low 10,240 (33.9%). Where available, reported daily television watching was: low 4,615 (19.6%), medium 11,587 (49.3%) and high 7,317 (31.1%). Decreased weekly exercise was associated with increased adjusted sepsis rates (high – referent; medium HR 1.02, 95% CI 0.96-1.20; low 1.33, 1.13-1.56). Daily television watching was not associated with sepsis rates. Sepsis rates were highest among those with both low exercise and high television watching levels (HR 1.49, 95% CI: 1.10-2.01). CONCLUSIONS Physical inactivity may be associated with increased long-term rates of community-acquired sepsis. PMID:24768917

  12. Toll-like receptors expression and interferon-? production by NK cells in human sepsis

    PubMed Central

    2012-01-01

    Introduction During the course of infection, natural killer (NK) cells contribute to innate immunity by producing cytokines, particularly interferon-gamma (IFN-?). In addition to their beneficial effects against infection, NK cells may play a detrimental role during systemic inflammation, causing lethality during sepsis. Little is known on the immune status of NK cells in patients with systemic inflammatory response syndrome (SIRS) or sepsis in terms of cell surface markers expression and IFN-? production. Methods We investigated 27 sepsis patients and 11 patients with non-infectious SIRS. CD56bright and CD56dim NK cell subsets were identified by flow cytometry and Toll-like receptor (TLR)2, TLR4, TLR9, CX3CR1, CD16 and CD69 expression were analyzed, as well as ex vivo IFN-? production by NK cells in whole blood samples. Results We first showed that in NK cells from healthy controls, TLR2 and TLR4 expression is mainly intracellular, similarly to TLR9. Intracellular levels of TLR2 and TLR4, in both CD56bright and CD56dim NK cell subsets from sepsis patients, were increased compared to healthy subjects. In addition, the percentage of CD69+ cells was higher among NK cells of sepsis patients. No difference was observed for TLR9, CX3CR1, and CD16 expression. The ex vivo stimulation by TLR4 or TLR9 agonists, or whole bacteria in synergy with accessory cytokines (IL-15+IL-18), resulted in significant production of IFN-? by NK cells of healthy controls. In contrast, for SIRS and sepsis patients this response was dramatically reduced. Conclusions This study reports for the first time an intracellular expression of TLR2 and TLR4 in human NK cells. Surface TLR4 expression allows discriminating sepsis and SIRS. Furthermore, during these pathologies, NK cells undergo an alteration of their immune status characterized by a profound reduction of their capacity to release IFN-?. PMID:23098236

  13. Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

    PubMed Central

    Guitton, Christophe; Gérard, Nathalie; Sébille, Véronique; Bretonnière, Cédric; Zambon, Olivier; Villers, Daniel; Charreau, Béatrice

    2011-01-01

    Purpose The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble (s)EPCR are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established. Methods We investigated the time-course of plasma sEPCR upon the 5 first days (D) of severe sepsis in 40 patients. Résults Firstly, no significant difference was observed when comparing sEPCR at admission (D1) to healthy volunteers and to patients with vasculitis. We report that the kinetic profile of plasma sEPCR in patients was almost stable at the onset of sepsis with no change from D1 to D4 and then a significant decrease at D5. This pattern of release was consistently observed whatever the level of sEPCR at D1. Characteristics of patients or of infections (except Gram negative) had no or poor critical influence on sEPCR profile. However, we found that sEPCR kinetic was clearly influenced by patient’s outcome (D28 survival). We demonstrate that a significant but moderate (< 15% of basal level) and transient increase in sEPCR level at Day2 associates with poor outcome at Day28. Conclusion Severe sepsis, at the onset, only triggers moderate quantitative changes in plasma sEPCR levels. Our findings suggest that in severe sepsis, an early (at D2), transient but significant increase in circulating sEPCR may be detrimental suggesting that sEPCR could provide an early biological marker of sepsis outcome. PMID:21394629

  14. Increased incidence of sepsis at birth in neutropenic infants of mothers with preeclampsia.

    PubMed

    Doron, M W; Makhlouf, R A; Katz, V L; Lawson, E E; Stiles, A D

    1994-09-01

    Neutropenia is often found at birth in infants born to mothers with preeclampsia, and is most likely present in utero. To determine whether this neutropenia is associated with an increased incidence of early-onset sepsis, we reviewed the hospital records of 301 low birth weight infants of mothers with preeclampsia. Early-onset sepsis was proved if the result of a culture of blood or cerebrospinal fluid in the first 48 hours of life was positive, or presumed if culture results were negative but two or more clinical signs of sepsis were present and the attending neonatologist believed that an infant was infected and needed at least 7 days of antibiotic therapy. Forty-eight percent of low birth weight infants of mothers with preeclampsia had neutropenia at less than 12 hours of age. Infants with neutropenia had mothers with more severe preeclampsia, were more premature (30 weeks vs 32 weeks), weighed less (1097 gm vs 1615 gm), and were more likely to be small for gestational age. Although maternal and obstetric risk factors for infection were less common in the group with neutropenia, rates of proven or presumed early-onset sepsis were higher (14% vs 2%; p < 0.001). Sepsis was proved in 6% of infants with neutropenia and in none of the infants without neutropenia (p = 0.03). A logistic regression analysis of the relative effects of birth weight, gestational age, and absolute neutrophil count on the incidence of sepsis revealed that only a low absolute neutrophil count correlated significantly with an increased risk of early-onset sepsis in infants with neutropenia. PMID:8071757

  15. Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset.

    PubMed

    Jiang, Jia-Horng; Chiu, Nan-Chang; Huang, Fu-Yang; Kao, Hsin-An; Hsu, Chyong-Hsin; Hung, Han-Yang; Chang, Jui-Hsing; Peng, Chun-Chih

    2004-10-01

    Neonatal sepsis is a major cause of death in newborns despite sophisticated neonatal intensive care. This retrospective study reviewed the clinical characteristics of cases of culture-proven sepsis in a neonatal intensive care unit from January 1992 to December 2001. Patients were divided into those with onset of sepsis in the first 7 days of life (early-onset group) and those with onset after the seventh day of life (late-onset group). A total of 270 cases with 325 episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late onset occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%). Coagulase-negative staphylococci (20.1%) was the most common organism isolated, but infection with Pseudomonas aeruginosa was associated with the highest morality rate (55.0%). Late-onset sepsis was significantly more common in very low birth weight and premature infants. The most frequently encountered pathogens in the early-onset group were group B streptococci (GBS) and Escherichia coli, while in the late-onset group, the organisms were coagulase-negative staphylococci and Enterobacteriaceae, including E. coli, Klebsiella pneumoniae, and Acinetobacter baumannii. GBS infection resulted in the highest mortality when the onset of sepsis was within the first 24 hours of life. PMID:15497012

  16. The dynamics of acute inflammation

    NASA Astrophysics Data System (ADS)

    Kumar, Rukmini

    The acute inflammatory response is the non-specific and immediate reaction of the body to pathogenic organisms, tissue trauma and unregulated cell growth. An imbalance in this response could lead to a condition commonly known as "shock" or "sepsis". This thesis is an attempt to elucidate the dynamics of acute inflammatory response to infection and contribute to its systemic understanding through mathematical modeling and analysis. The models of immunity discussed use Ordinary Differential Equations (ODEs) to model the variation of concentration in time of the various interacting species. Chapter 2 discusses three such models of increasing complexity. Sections 2.1 and 2.2 discuss smaller models that capture the core features of inflammation and offer general predictions concerning the design of the system. Phase-space and bifurcation analyses have been used to examine the behavior at various parameter regimes. Section 2.3 discusses a global physiological model that includes several equations modeling the concentration (or numbers) of cells, cytokines and other mediators. The conclusions drawn from the reduced and detailed models about the qualitative effects of the parameters are very similar and these similarities have also been discussed. In Chapter 3, the specific applications of the biologically detailed model are discussed in greater detail. These include a simulation of anthrax infection and an in silico simulation of a clinical trial. Such simulations are very useful to biologists and could prove to be invaluable tools in drug design. Finally, Chapter 4 discusses the general problem of extinction of populations modeled as continuous variables in ODES is discussed. The average time to extinction and threshold are estimated based on analyzing the equivalent stochastic processes.

  17. Complete genome sequencing and analysis of a Lancefield group G Streptococcus dysgalactiae subsp. equisimilis strain causing streptococcal toxic shock syndrome (STSS)

    PubMed Central

    2011-01-01

    Background Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes invasive streptococcal infections, including streptococcal toxic shock syndrome (STSS), as does Lancefield group A Streptococcus pyogenes (GAS). We sequenced the entire genome of SDSE strain GGS_124 isolated from a patient with STSS. Results We found that GGS_124 consisted of a circular genome of 2,106,340 bp. Comparative analyses among bacterial genomes indicated that GGS_124 was most closely related to GAS. GGS_124 and GAS, but not other streptococci, shared a number of virulence factor genes, including genes encoding streptolysin O, NADase, and streptokinase A, distantly related to SIC (DRS), suggesting the importance of these factors in the development of invasive disease. GGS_124 contained 3 prophages, with one containing a virulence factor gene for streptodornase. All 3 prophages were significantly similar to GAS prophages that carry virulence factor genes, indicating that these prophages had transferred these genes between pathogens. SDSE was found to contain a gene encoding a superantigen, streptococcal exotoxin type G, but lacked several genes present in GAS that encode virulence factors, such as other superantigens, cysteine protease speB, and hyaluronan synthase operon hasABC. Similar to GGS_124, the SDSE strains contained larger numbers of clustered, regularly interspaced, short palindromic repeats (CRISPR) spacers than did GAS, suggesting that horizontal gene transfer via streptococcal phages between SDSE and GAS is somewhat restricted, although they share phage species. Conclusion Genome wide comparisons of SDSE with GAS indicate that SDSE is closely and quantitatively related to GAS. SDSE, however, lacks several virulence factors of GAS, including superantigens, SPE-B and the hasABC operon. CRISPR spacers may limit the horizontal transfer of phage encoded GAS virulence genes into SDSE. These findings may provide clues for dissecting the pathological roles of the virulence factors in SDSE and GAS that cause STSS. PMID:21223537

  18. Proteolytic processing of the streptococcal IgG endopeptidase IdeS modulates the functional properties of the enzyme and results in reduced immunorecognition.

    PubMed

    Persson, Helena; Söderberg, Jenny Johansson; Vindebro, Reine; Johansson, Björn P; von Pawel-Rammingen, Ulrich

    2015-12-01

    The important human gram positive bacterial pathogen Streptococcus pyogenes employs various virulence factors to promote inflammation and to facilitate invasive disease progression. In this study we explored the relation of the secreted streptococcal cysteine proteases IdeS and SpeB, and neutrophil (PMN) proteases. We found that SpeB is resistant to proteolytic attack in an inflammatory environment, emphasizing the importance of SpeB for streptococcal pathogenicity, while PMN enzymes and SpeB itself process the IgG degrading endopeptidase IdeS. Processing occurs as NH2-terminal cleavage of IdeS resulting in reduced immunorecognition of the protease by specific antibodies. While the endopeptidase retains IgG cleaving activity, its ability to suppress the generation of reactive oxygen species is abolished. We suggest that the cleavage of NH2-terminal peptides by SpeB and/or neutrophil proteases is a mechanism evolved to prevent early inactivation of this important streptococcal virulence factor, albeit at the cost of impaired functionality. PMID:26343448

  19. Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis syndrome. AMCC Sepsis Project Working Group.

    PubMed

    Bates, D W; Parsonnet, J; Ketchum, P A; Miller, E B; Novitsky, T J; Sands, K; Hibberd, P L; Graman, P S; Lanken, P N; Schwartz, J S; Kahn, K; Snydman, D R; Moore, R; Black, E; Platt, R

    1998-09-01

    Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was > or = 0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection. PMID:9770160

  20. Prevention and treatment strategy in pregnant women with group B streptococcal infection.

    PubMed

    Tevdorashvili, G; Tevdorashvili, D; Andghuladze, M; Tevdorashvili, M

    2015-04-01

    Group B streptococcus (GBS; Streptococcus agalactiae) are encapsulated gram-positive cocci belonging to Lancefield group B, that frequently colonizes the human genital and gastrointestinal tracts. It is an important cause of illness in three categories of population: infants, pregnant women, and adults with underlying medical conditions. In pregnant women and postpartum women, GBS is a frequent cause of asymptomatic bacteriuria, urinary tract infection, upper genital tract infection (i.e. intraamniotic infection or chorioamnionitis), postpartum endometritis (8%), pneumonia (2%), puerperal sepsis (2%), and bacteremia without a focal site (31%). It also can cause focal infections such as pneumonia, meningitis, and endocarditis, albeit rarely. Invasive maternal infection with GBS is associated with pregnancy loss and preterm delivery. Prior to the widespread use of maternal intrapartum chemoprophylaxis, maternal colonization with GBS conferred an increased risk of chorioamnionitis, and early postpartum infection. The serotype distribution of invasive GBS infection in pregnant women is similar to that of early-onset neonatal disease. The most common GBS serotypes causing invasive disease in adults and neonates are Ia, Ib, III, and V. Vaccination of adolescent women is considered an ideal solution. However, recent reports (April 2015) have shown that serotype IV GBS is emerging in pregnant carriers and causing infections in neonates and adults. This emergence is of concern because GBS conjugate vaccines that are being developed to prevent invasive disease may protect only against serotypes Ia, Ib, II, III, and V, or combinations thereof. Though research for the development of such a vaccine is underway, a good candidate vaccine has yet to surface. PMID:25953932

  1. Intrauterine group A streptococcal infections are exacerbated by prostaglandin E2.

    PubMed

    Mason, Katie L; Rogers, Lisa M; Soares, Elyara M; Bani-Hashemi, Tara; Erb Downward, John; Agnew, Dalen; Peters-Golden, Marc; Weinberg, Jason B; Crofford, Leslie J; Aronoff, David M

    2013-09-01

    Streptococcus pyogenes (Group A Streptococcus; GAS) is a major cause of severe postpartum sepsis, a re-emerging cause of maternal morbidity and mortality worldwide. Immunological alterations occur during pregnancy to promote maternofetal tolerance, which may increase the risk for puerperal infection. PGE2 is an immunomodulatory lipid that regulates maternofetal tolerance, parturition, and innate immunity. The extent to which PGE2 regulates host immune responses to GAS infections in the context of endometritis is unknown. To address this, both an in vivo mouse intrauterine (i.u.) GAS infection model and an in vitro human macrophage-GAS interaction model were used. In C57BL/6 mice, i.u. GAS inoculation resulted in local and systemic inflammatory responses and triggered extensive changes in the expression of eicosanoid pathway genes. The i.u. administration of PGE2 increased the mortality of infected mice, suppressed local IL-6 and IL-17A levels, enhanced neutrophilic inflammation, reduced uterine macrophage populations, and increased bacterial dissemination. A role for endogenous PGE2 in the modulation of antistreptococcal host defense was suggested, because mice lacking the genes encoding the microsomal PGE2 synthase-1 or the EP2 receptor were protected from death, as were mice treated with the EP4 receptor antagonist, GW627368X. PGE2 also regulated GAS-macrophage interactions. In GAS-infected human THP-1 (macrophage-like) cells, PGE2 inhibited the production of MCP-1 and TNF-? while augmenting IL-10 expression. PGE2 also impaired the phagocytic ability of human placental macrophages, THP-1 cells, and mouse peritoneal macrophages in vitro. Exploring the targeted disruption of PGE2 synthesis and signaling to optimize existing antimicrobial therapies against GAS may be warranted. PMID:23913961

  2. Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study

    PubMed Central

    Rautanen, Anna; Mills, Tara C; Gordon, Anthony C; Hutton, Paula; Steffens, Michael; Nuamah, Rosamond; Chiche, Jean-Daniel; Parks, Tom; Chapman, Stephen J; Davenport, Emma E; Elliott, Katherine S; Bion, Julian; Lichtner, Peter; Meitinger, Thomas; Wienker, Thomas F; Caulfield, Mark J; Mein, Charles; Bloos, Frank; Bobek, Ilona; Cotogni, Paolo; Sramek, Vladimir; Sarapuu, Silver; Kobilay, Makbule; Ranieri, V Marco; Rello, Jordi; Sirgo, Gonzalo; Weiss, Yoram G; Russwurm, Stefan; Schneider, E Marion; Reinhart, Konrad; Holloway, Paul A H; Knight, Julian C; Garrard, Chris S; Russell, James A; Walley, Keith R; Stüber, Frank; Hill, Adrian V S; Hinds, Charles J

    2015-01-01

    Summary Background Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival. Methods We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1–3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died. Findings In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1–3), common variants in the FER gene were strongly associated with survival (p=9·7?×?10?8). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5·6?×?10?8 (odds ratio 0·56, 95% CI 0·45–0·69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0·56, 95% CI 0·45–0·69; likelihood ratio test p=3·4 × 10?9, after adjustment for age and stratification by cohort). Mortality was 9·5% in patients carrying the CC genotype, 15·2% in those carrying the TC genotype, and 25·3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined. Interpretation We have identified common variants in the FER gene that associate with a reduced risk of death from sepsis due to pneumonia. The FER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification. Funding European Commission and the Wellcome Trust. PMID:25533491

  3. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis

    PubMed Central

    Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank

    2008-01-01

    Introduction In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. Methods In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. Results In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). Conclusions In early severe sepsis a gene expression pattern with induction of the pro-apoptotic Bcl-2 family members Bim, Bid and Bak and a downregulation of the anti-apoptotic Bcl-2 and Bcl-xl proteins was observed in peripheral blood. This constellation may affect cellular susceptibility to apoptosis and complex immune dysfunction in sepsis. PMID:18925930

  4. Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation

    NASA Astrophysics Data System (ADS)

    Herrmann, I. K.; Bertazzo, S.; O'Callaghan, D. J. P.; Schlegel, A. A.; Kallepitis, C.; Antcliffe, D. B.; Gordon, A. C.; Stevens, M. M.

    2015-08-01

    Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions. Electronic supplementary information (ESI) available: Fig. S1: Markers of inflammation and microvesicle characteristics in patient plasma samples, Fig. S2: Experimental sepsis model, Table S1: Patient characteristics. Table S2: Inclusion/exclusion criteria. See DOI: 10.1039/c5nr01851j

  5. Neonatal sepsis with multi-organ failure and treated with a new dialysis device specifically designed for newborns.

    PubMed

    Peruzzi, Licia; Bonaudo, Roberto; Amore, Alessandro; Chiale, Federica; Donadio, Maria Elena; Vergano, Luca; Coppo, Rosanna

    2014-05-01

    Neonatal sepsis due to E. coli is often complicated by multiple organ failure (MOF) and a high mortality risk. We report the case of a term newborn discharged in good condition who suddenly fell into septic shock after 11 days and required immediate resuscitation, volume expansion and a high-dosage amine infusion. Extremely severe metabolic acidosis, disseminated intravascular coagulation (DIC) with diffuse bleeding, and unstable hemodynamic status with oliguria turned into strict anuria, and the patient became anuric. The presence of DIC, with gastric and intestinal bleeding, rendered peritoneal dialysis impossible. Continuous renal replacement therapy (CRRT) was started with the new dialysis machine CARPEDIEM(®) (Cardio-Renal Pediatric Dialysis Emergency Machine), available on a trial-basis in our center, after the surgical placement of jugular double-lumen central venous catheters. A 'ready to use' neonatal kit with a low-priming volume of the extracorporeal circuit allowed a prompt hemofiltration start. The filtration CRRT was continuously performed for 48 h, then intermittently (12 h/day) for 2 more days and interrupted on day 5 for diuresis reprisal. Acute kidney injury and multi-organ failure resolved after 5 days. The child survived without neurological damage, with a normal renal function and a normal development at 9 months follow-up. In conclusion, a prompt CRRT start with this specifically designed neonatal device allowed a progressive stabilization of hemodynamics, a better control of acidosis, a reduction of amine requirement, a gradual control of fluid overload and a rapid improvement of MOF, DIC as well as a resolution of the acute kidney injury. The device also allowed the extension of CRRT in the neonatal age. PMID:25028585

  6. Defective cytokine production early after multiple traumas: Modulation in severe sepsis.

    PubMed

    Paraschos, Michael D; Patrani, Maria; Pistiki, Aikaterini; Katsenos, Chrysostomos; Tsaganos, Thomas; Netea, Mihai G; Giamarellos-Bourboulis, Evangelos J; Mandragos, Konstantinos

    2015-12-01

    The exact time frame of multiple trauma-induced immunosuppression and the immune mechanisms mediating transition to severe sepsis are largely unknown. Peripheral blood mononuclear cells were isolated from 69 patients with multiple injuries within the first 24h from injury and from 36 healthy volunteers and stimulated for cytokine production. Circulating endotoxins were measured by the kinetic LAL assay. Measurements were repeated the first 24h of sepsis onset. Patients had defective responses for tumour necrosis factor-alpha (TNF?), interleukin (IL)-10, IL-17 and interferon-gamma (IFN?) using a broad-panel of bacterial stimuli. Production of IFN? was pronounced for patients with trauma-related multiple organ failure (MOF). Thirty-six patients developed severe sepsis. At that time, production of TNF? was increased compared to baseline. The increase was greater among non-survivors than among survivors. Enhanced TNF? production on sepsis onset was a main finding of patients without endotoxemia. Immunosuppression of both innate and adaptive cytokine responses appears as early as the first 24h from injury. Transition into severe sepsis due to bacterial superinfection is accompanied by enhanced production of TNF? and this is linked with unfavorable outcome. PMID:26082021

  7. The Effect of Ghrelin upon the Early Immune Response in Lean and Obese Mice during Sepsis

    PubMed Central

    Siegl, Daniel; Midura, Emily F.; Annecke, Thorsten; Conzen, Peter; Caldwell, Charles C.; Tschoep, Johannes

    2015-01-01

    Introduction It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis. Methods In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis. Results In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-? concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement. Conclusion In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice. PMID:25844479

  8. Soluble ST2 Has a Prognostic Role in Patients With Suspected Sepsis

    PubMed Central

    Hur, Mina; Kim, Hanah; Kim, Hyun Jeong; Yang, Hyun Suk; Magrini, Laura; Marino, Rossella; Cardelli, Patrizia

    2015-01-01

    Background Soluble suppression of tumorigenicity 2 (sST2) has emerged as a novel biomarker for heart failure, and serum sST2 concentrations could be increased in inflammatory diseases. We explored whether sST2 is related to cardiac dysfunction/failure and has a prognostic role in patients with suspected sepsis. Methods In a total of 397 patients with suspected sepsis, sST2 concentrations were measured by using the Presage ST2 Assay (Critical Diagnostics, USA). sST2 concentrations were analyzed according to procalcitonin (PCT) concentrations, cardiovascular subscores of the sepsis-related organ failure assessment (SOFA) score, and clinical outcomes. Results sST2 concentrations were increased significantly according to the five groups of PCT concentrations and cardiovascular subscores of the SOFA score (P<0.000001 and P=0.036, respectively). In-hospital mortality was significantly higher among patients with sST2 concentrations above 35 ng/mL (P=0.0213) and among patients with increased concentrations of both sST2 and PCT (P=0.0028). Conclusions sST2 seems to be related to both cardiac dysfunction/failure and severity in sepsis. Measurement of sST2 and PCT in combination would be useful for risk stratification and prognosis prediction in patients with suspected sepsis. PMID:26354344

  9. Sepsis and mechanisms of inflammatory response: is exercise a good model?

    PubMed Central

    Shephard, R

    2001-01-01

    Objectives—The immune changes induced by a bout of prolonged and vigorous exercise have been suggested to be a useful experimental model of sepsis and the inflammatory response. Available literature was reviewed to evaluate this hypothesis. Methods—Literature describing the immune response to various patterns of exercise was compared with data on the immune changes observed during sepsis and inflammation. Results—Although there are qualitative similarities between the immune responses to exercise and sepsis, the magnitude of the changes induced by most forms of exercise remains much smaller than in a typical inflammatory response. Indeed, the exercise induced changes in some key elements such as plasma cytokine concentrations are too small to be detected reliably by current technology. Conclusions—If exercise is to provide a valid model of sepsis and the inflammatory response, it will be necessary to focus on subjects who are willing to exercise extremely hard, to use the pattern of exercise that has the greatest effect on the immune system, and to combine this stimulus with other psychological, environmental, or nutritional stressors. Key Words: sepsis; inflammatory response; exercise; cytokines; endorphins; immune function PMID:11477013

  10. Effects of sodium butyrate on aversive memory in rats submitted to sepsis.

    PubMed

    Steckert, Amanda V; Comim, Clarissa M; Igna, Dhébora M Dall; Dominguini, Diogo; Mendonça, Bruna P; Ornell, Felipe; Colpo, Gabriela D; Gubert, Carolina; Kapczinski, Flávio; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

    2015-05-19

    Epigenetic mechanisms are involved in normal behavior and are implicated in several brain neurodegenerative conditions, psychiatric and inflammatory diseases as well. Moreover, it has been demonstrated that sepsis lead to an imbalance in acetylation of histones and that histone deacetylase inhibitors (HDACi) can reverse this condition. In the present study, we evaluated the effects of a microinjection of sodium butyrate (SB, HDACi) into cerebral ventricle on aversive memory in rats submitted to the sepsis. Rats were given a single intraventricular injection of artificial cerebrospinal fluid (ACSF) or SB and immediately after the stereotaxic surgery and the drug infusion, the animals were subjected to cecal ligation and perforation (CLP). The animals were killed twenty four hours or ten days after sepsis induction and the prefrontal cortex, hippocampus, striatum and cortex were obtained to the determination of histone deacetylase activity. In a separate cohort of animals 10 days after sepsis induction, it was performed the inhibitory avoidance task. SB administration was able to reverse the impairment in aversive memory and inhibited the HDAC activity in prefrontal cortex and hippocampus 10 days after CLP. These support a role for an epigenetic mechanism in the long-term cognitive impairments observed in sepsis survivors animals. PMID:25888815

  11. Epidemiology of Neonatal Sepsis and Implicated Pathogens: A Study from Egypt

    PubMed Central

    Shehab El-Din, Eman M. Rabie; El-Sokkary, Mohamed M. Adel; Bassiouny, Mohamed Reda; Hassan, Ramadan

    2015-01-01

    Prospective analytic study was conducted in NICUs of three Egyptian Neonatal Network (EGNN) participants in Mansoura Hospitals in Egypt over a period of 18 months from March 2011 to August 2012. By using EGNN 28-day discharge form, all demographic, clinical, and laboratory data were recorded and studied. During the study period, 357 neonates were diagnosed as suspected sepsis with an incidence of 45.9% (357/778) among the admitted neonates at the three neonatal intensive care units. 344 neonates (sex ratio = 1.3:1) were enrolled in the study in which 152 (44.2%) were classified as early onset sepsis EOS (?72 hr) and 192 (55.8%) as late onset sepsis LOS (>72 hr). Among the LOS cases, 33.9% (65/192) were caused by nosocomial infections. In 40.7% (140/344), sepsis was confirmed by positive blood culture. The total mortality rate for the proven neonatal sepsis was 51% (25/49) and 42.9% (39/91) for EOS and LOS, respectively. Coagulase negative staphylococci were predominant isolates in both EOS and LOS, followed by Klebsiella pneumoniae. Most of the bacterial isolates had low sensitivity to the commonly used empiric antibiotics. However, 70.1% (89/127) exhibited multidrug resistance. Best sensitivities among Gram-positive isolates were found against imipenem, ciprofloxacin, vancomycin, and amikacin. PMID:26146621

  12. CD1d- and MR1-Restricted T Cells in Sepsis.

    PubMed

    Szabo, Peter A; Anantha, Ram V; Shaler, Christopher R; McCormick, John K; Haeryfar, S M Mansour

    2015-01-01

    Dysregulated immune responses to infection, such as those encountered in sepsis, can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis. These cell types are typified by invariant natural killer T (iNKT) cells, variant NKT (vNKT) cells, and mucosa-associated invariant T (MAIT) cells. iNKT and vNKT cells are CD1d-restricted, lipid-reactive cells with remarkable immunoregulatory properties. MAIT cells participate in antimicrobial defense, and are restricted by major histocompatibility complex-related protein 1 (MR1), which displays microbe-derived vitamin B metabolites. Importantly, NKT and MAIT cells are rapid and potent producers of immunomodulatory cytokines. Therefore, they may be considered attractive targets during the early hyperinflammatory phase of sepsis when immediate interventions are urgently needed, and also in later phases when adjuvant immunotherapies could potentially reverse the dangerous state of immunosuppression. We will highlight recent findings that point to the significance or the therapeutic potentials of NKT and MAIT cells in sepsis and will also discuss what lies ahead in research in this area. PMID:26322041

  13. CD1d- and MR1-Restricted T Cells in Sepsis

    PubMed Central

    Szabo, Peter A.; Anantha, Ram V.; Shaler, Christopher R.; McCormick, John K.; Haeryfar, S.M. Mansour

    2015-01-01

    Dysregulated immune responses to infection, such as those encountered in sepsis, can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis. These cell types are typified by invariant natural killer T (iNKT) cells, variant NKT (vNKT) cells, and mucosa-associated invariant T (MAIT) cells. iNKT and vNKT cells are CD1d-restricted, lipid-reactive cells with remarkable immunoregulatory properties. MAIT cells participate in antimicrobial defense, and are restricted by major histocompatibility complex-related protein 1 (MR1), which displays microbe-derived vitamin B metabolites. Importantly, NKT and MAIT cells are rapid and potent producers of immunomodulatory cytokines. Therefore, they may be considered attractive targets during the early hyperinflammatory phase of sepsis when immediate interventions are urgently needed, and also in later phases when adjuvant immunotherapies could potentially reverse the dangerous state of immunosuppression. We will highlight recent findings that point to the significance or the therapeutic potentials of NKT and MAIT cells in sepsis and will also discuss what lies ahead in research in this area. PMID:26322041

  14. The top cited clinical research articles on sepsis: a bibliometric analysis

    PubMed Central

    2012-01-01

    Introduction The objective of this study was to identify and characterize the most highly cited clinical research articles published on sepsis. Methods A comprehensive list of citation classics in sepsis was generated by searching the database of Web of Science-Expanded (1970 to present) using keywords 'sepsis' or 'septic shock'. The top 50 cited clinical research papers were retrieved by reading the abstract or full text if needed. Each eligible article was reviewed for basic information, including country of origin, article type, journals, authors, and funding sources. Results A total of 2,151 articles were cited more than 100 times; the 50 top-cited clinical articles were published between 1974 and 2008. The number of citations ranged from 372 to 2,932, with a mean of 678 citations per article. These citation classics came from nine countries, of which 26 articles came from the United States. Rush University and the University of Pittsburgh lead the list of classics with six papers each. The 50 top-cited articles were published in 17 journals, with the New England Journal of Medicine and Journal of the American Medical Association topping the list. The top 50 articles consisted of 21 clinical trials and 29 observational studies. Conclusions Our bibliometric analysis provides a historical perspective on the progress of clinical research on sepsis. Articles originating from the United States and published in high-impact journals are most likely to be cited in the field of sepsis research. PMID:22731930

  15. Linezolid therapy in a perinatal late-onset Staphylococcus aureus sepsis complicated by spondylodiscitis and endophthalmitis.

    PubMed

    Krzysztofiak, Andrzej; Bozzola, Elena; Lancella, Laura; Boccuzzi, Elena; Vittucci, Anna Chiara; Marchesi, Alessandra; Villani, Alberto

    2015-12-01

    We report the case of a two-month-old immunocompetent girl affected by Staphylococcus aureus sepsis complicated with pneumonia and pleural effusion, spondylodiscitis and endophthalmitis treated with linezolid. She developed a S. aureus sepsis in the neonatal period antibiotically treated with clinical resolution. Ten days after therapy discontinuation, the infant experienced a new S. aureus sepsis complicated by pneumonia with pleural effusion. Due to the presence of dorsal swelling, a pulmonary computer tomography was performed that showed a dorsal D5-D6 spondylodiscitis. Since the sepsis was scarcely responsive to several appropriate antibiotics, we finally decided to treat the patient with linezolid. A few weeks after changing antibiotics, the child underwent an ophthalmologic visit. Due to the finding of ocular lesions, imaging examinations were performed. The diagnosis was compatible with retinoblastoma, such that the eye was enucleated. Nevertheless, histological and microbiological investigations did not confirm the tumour hypothesis, but revealed a S. aureus abscess with retinal detachment. The child completed antibiotic therapy with linezolid and was visited periodically at the Infectious Disease Unit for a follow-up. She underwent progressive resolution of discitis and did not present any further flare of sepsis. Nevertheless, she still has a replacement device in her right eye and a D5-D6 severe kyphosis with spinal fusion. PMID:26700087

  16. Acute Kidney Injury in Lymphoma: A Single Centre Experience

    PubMed Central

    Khalil, Muhammad Abdul Mabood; Rehman, Abdur; Kashif, Waqar Uddin; Awan, Safia; Khalil, Zarghona; Mushtaq, Uziar; Ahmad, Maria; Khalil, Muhammad Ashhad Ullah; Ranga Sami, Manickam; Tan, Jackson

    2014-01-01

    Background. Acute kidney injury (AKI) is a common but least studied complication of lymphoma. Objective. To determine the frequency and predictors of AKI in lymphoma and to study the impact of AKI on hospital stay and mortality. Methods. Retrospective review of medical records of hospitalized lymphoma patients aged ?14 years between January 2008 and December 2011 was done. Results. Out of 365 patients, AKI was present in 31.8% (116/365). Multivariate logistic regression analysis showed that independent predictors for AKI included sepsis (odds ratio (OR) 3.76; 95% CI 1.83–7.72), aminoglycosides (OR 4.75; 95% CI 1.15–19.52), diuretics (OR 2.96; 95% CI 1.31–6.69), tumor lysis syndrome (OR 3.85; 95% CI 1.54–9.59), and R-CVP regimen (OR 4.70; 95% CI 1.20–18.36). AKI stages 2 and 3 was associated with increased hospital stay (OR 2.01; 95% CI 1.19–3.40). Conclusion. AKI was significantly associated with sepsis, aminoglycoside, diuretics, presence of tumor lysis syndrome, and use of R-CVP regimen. Presence of AKIN (Acute Kidney Injury Network) stages 2 and 3 AKI had increased hospital stay. AKI was also associated with increased mortality. PMID:24639896

  17. Unrecognized clozapine-related constipation leading to fatal intra-abdominal sepsis – a case report

    PubMed Central

    Oke, Vikram; Schmidt, Frances; Bhattarai, Bikash; Basunia, Md; Agu, Chidozie; Kaur, Amrit; Enriquez, Danilo; Quist, Joseph; Salhan, Divya; Gayam, Vijay; Mungikar, Prajakta

    2015-01-01

    Clozapine is the preferred antipsychotic used for the treatment of resistant schizophrenia with suicidal ideation. The drug is started at a low dose and gradually increased to a target dose of 300–450 mg/day. It is well known to cause agranulocytosis and neutropenia. Several cases of fatal sepsis have been reported in neutropenic patients and emphasis is placed on monitoring for agranulocytosis; however, clozapine also causes intestinal hypomotility and constipation, which if unrecognized can lead to intestinal obstruction, bowel necrosis, and intra-abdominal sepsis. Reduced behavioral pain reactivity in schizophrenics may alter the ability to express pain, potentially leading to a delay in the presentation for medical attention. We report a case of fatal intra-abdominal sepsis secondary to an unrecognized case of clozapine-related constipation. PMID:26392790

  18. Neonatal infected subgaleal hematoma: an unusual complication of early-onset E. coli sepsis.

    PubMed

    Chang, Hung-Yang; Cheng, Kun-Shan; Liu, Yu-Peng; Hung, Hsiao-Fang; Fu, Hua-Wen

    2015-04-01

    Subgaleal hematoma (SGH) is an uncommon but potentially lethal medical emergency in newborns. Delay in diagnosis may lead to mortality and morbidity. Infection of an SGH is extremely rare. We report an infected SGH with abscess formation as a complication of early-onset Escherichia coli sepsis in a term neonate. The patient was discovered to have SGH soon after birth. Early-onset E. coli sepsis developed on Day 3 of life. The SGH became infected, with abscess formation 1 week later. The infected SGH was probably due to direct hematogenous spreading of sepsis. The patient was successfully treated without complications. Clinicians should be aware that SGH is a potential site of infection and infection may be caused either by direct hematogenous extension or from traumatic scalp lesions. Appropriate antibiotic treatment and surgical debridement are necessary when an infected SGH occurs. PMID:23597516

  19. Pathophysiology of Sepsis-Related Cardiac Dysfunction: Driven by Inflammation, Energy Mismanagement, or Both?

    PubMed Central

    Lymperopoulos, Anastasios; Kennel, Peter Johannes; Pollak, Nina; Schulze, P. Christian; Goldberg, Ira J.

    2015-01-01

    Sepsis is a systemic inflammatory response that follows bacterial infection. Cardiac dysfunction is an important consequence of sepsis that affects mortality and has been attributed to either elevated inflammation or suppression of both fatty acid and glucose oxidation and eventual ATP depletion. Moreover, cardiac adrenergic signaling is compromised in septic patients and this aggravates further heart function. While anti-inflammatory therapies are important for the treatment of the disease, administration of anti-inflammatory drugs did not improve survival in septic patients. This review article summarizes findings on inflammatory and other mechanisms that are triggered in sepsis and affect cardiac function and mortality. Particularly, it focuses on the effects of the disease in metabolic pathways, as well as in adrenergic signaling and the potential interplay of the latter with inflammation. It is suggested that therapeutic approaches should include combination of anti-inflammatory treatments, stimulation of energy production, and restoration of adrenergic signaling in the heart. PMID:25475180

  20. A novel natural compound from garlic (Allium sativum L.) with therapeutic effects against experimental polymicrobial sepsis.

    PubMed

    Lee, Sung Kyun; Park, Yoo Jung; Ko, Min Jung; Wang, Ziyu; Lee, Ha Young; Choi, Young Whan; Bae, Yoe-Sik

    2015-08-28

    Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-?, interleukin-1? (IL-1?) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-? and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm. PMID:26166823

  1. Perirectal sepsis after rubber band ligation of haemorrhoids : a case report.

    PubMed

    Duchateau, A; Huyghe, M

    2014-01-01

    Rubber band ligation (Barron ligation, RBL) is a widely used method for the treatment of symptomatic -haemorrhoids. In general, it is considered as a safe, effective and easily performed way of treating second and third -degree haemorrhoids. Perineal and pelvic sepsis was already known to be a rare, but possible complication after stapled haemorrhoidopexy. However, there have been some reports of severe sepsis after rubber band ligation as well. We -present a patient who was treated twice for haemorrhoids with rubber band ligation and attended the emergency department 10 days later. He was diagnosed with perirectal sepsis and aggressive antibiotic treatment was the first attempt of treatment. Because of further deterioration under medical therapy, our patient required extensive surgery. PMID:26021540

  2. Sepsis survivors monitoring and coordination in outpatient health care (SMOOTH): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Sepsis sequelae include critical illness polyneuropathy, myopathy, wasting, neurocognitive deficits, post-traumatic stress disorder, depression and chronic pain. Little is known howlong-term sequelae following hospital discharge are treated. The aim of our study is to determine the effect of a primary care-based, long-term program on health-related quality of life in sepsis survivors. Methods/Design In a two-armed randomized multicenter interventional study, patients after sepsis (n?=?290) will be assessed at 6, 12 and 24 months. Patients are eligible if severe sepsis or septic shock (ICD-10), at least two criteria of systemic inflammatory response syndrome (SIRS), at least one organ dysfunction and sufficient cognitive capacity are present. The intervention comprises 1) discharge management, 2) training of general practitioners and patients in evidence-based care for sepsis sequelae and 3) telephone monitoring of patients. At six months, we expect an improved primary outcome (health-related quality of life/SF-36) and improved secondary outcomes such as costs, mortality, clinical-, psycho-social- and process-of-care measures in the intervention group compared to the control group. Discussion This study evaluates a primary care-based, long-term program for patients after severe sepsis. Study results may add evidence for improved sepsis care management. General practitioners may contribute efficiently to sepsis aftercare. Trial registration U1111-1119-6345. DRKS00000741, CCT-NAPN-20875 (25 February 2011). PMID:25015838

  3. Non-hematopoietic TLR2 contributes to neutrophil and cardiac function impairment during polymicrobial sepsis1

    PubMed Central

    Zou, Lin; Feng, Yan; Zhang, Ming; Li, Yan; Chao, Wei

    2011-01-01

    Toll-like receptor 2 (TLR2) has been implicated in neutrophil and cardiac dysfunction during sepsis. Here we tested the hypothesis that non-hematopoietic (parenchymal) and hematopoietic TLR2 play distinct roles in sepsis pathogenesis. To achieve this, we generated two groups of chimeric mice with TLR2 deletions either in non-hematopoietic cells (KO mice with WT-bone marrow, BM) or in BM cells (WT mice with KO-BM). Polymicrobial sepsis was created by cecum ligation and puncture (CLP). Neutrophil functions, cytokine production, and bacterial clearance were investigated following CLP or sham procedures. Cardiac contractile function was measured in a Langendorff apparatus. Intracellular reactive oxygen species were measured using redox-sensitive dye and flow cytometry. CLP mice had markedly increased peritoneal neutrophil recruitment compared with the sham-operated mice. TLR2 KO mice, regardless their TLR2 phenotypes (WT vs. KO) in their BM-derived hematopoietic cells, had markedly increased neutrophil migration as well as phagocytosis, and reduced cytokine productions compared to TLR2 WT mice following polymicrobial peritonitis. These changes in the chimeric TLR2 KO mice were associated with enhanced blood bacterial clearance and markedly improved cardiac contractile function. Moreover, CLP induced a robust ROS production in the peritoneal leukocytes isolated from WT mice but not from TLR2 KO mice. Taken together, these data indicate that TLR2, particularly that of non-hematopoietic cells, plays a major role in sepsis pathogenesis by impairing neutrophil migratory and phagocytic function, promoting cytokine production, and mediating cardiac contractile dysfunction during polymicrobial sepsis. TLR2 also mediates critical ROS production during polymicrobial sepsis. PMID:21701420

  4. Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma

    PubMed Central

    Tudor, S; Giza, D E; Lin, H Y; Fabris, L; Yoshiaki, K; D'Abundo, L; Toale, K M; Shimizu, M; Ferracin, M; Challagundla, K B; Angelica Cortez, M; Fuentes-Mattei, E; Tulbure, D; Gonzalez, C; Henderson, J; Row, M; Rice, T W; Ivan, C; Negrini, M; Fabbri, M; Morris, J S; Yeung, S-C J; Vasilescu, C; Calin, G A

    2014-01-01

    Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation. PMID:25476907

  5. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction.

    PubMed

    Essandoh, Kobina; Yang, Liwang; Wang, Xiaohong; Huang, Wei; Qin, Dongze; Hao, Jiukuan; Wang, Yigang; Zingarelli, Basilia; Peng, Tianqing; Fan, Guo-Chang

    2015-11-01

    Sepsis is an infection-induced severe inflammatory disorder that leads to multiple organ failure. Amongst organs affected, myocardial depression is believed to be a major contributor to septic death. While it has been identified that large amounts of circulating pro-inflammatory cytokines are culprit for triggering cardiac dysfunction in sepsis, the underlying mechanisms remain obscure. Additionally, recent studies have shown that exosomes released from bacteria-infected macrophages are pro-inflammatory. Hence, we examined in this study whether blocking the generation of exosomes would be protective against sepsis-induced inflammatory response and cardiac dysfunction. To this end, we pre-treated RAW264.7 macrophages with GW4869, an inhibitor of exosome biogenesis/release, followed by endotoxin (LPS) challenge. In vivo, we injected wild-type (WT) mice with GW4869 for 1h prior to endotoxin treatment or cecal ligation/puncture (CLP) surgery. We observed that pre-treatment with GW4869 significantly impaired release of both exosomes and pro-inflammatory cytokines (TNF-?, IL-1?, IL-6) in RAW264.7 macrophages. At 12h after LPS treatment or CLP surgery, WT mice pre-treated with GW4869 displayed lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminished the sepsis-induced cardiac inflammation, attenuated myocardial depression and prolonged survival. Together, our findings indicate that blockade of exosome generation in sepsis dampens the sepsis-triggered inflammatory response and thereby, improves cardiac function and survival. PMID:26300484

  6. Managing Deep Postanal Space Sepsis via an Intersphincteric Approach: Our Early Experience

    PubMed Central

    Tan, Ker-Kan; Koh, Dean C.

    2013-01-01

    Purpose Managing deep postanal (DPA) sepsis often involves multiple procedures over a long time. An intersphincteric approach allows adequate drainage to be performed while tackling the primary pathology at the same sitting. The aim of our study was to evaluate this novel technique in managing DPA sepsis. Methods A retrospective review of all patients who underwent this intersphincteric technique in managing DPA sepsis from February 2008 to October 2010 was performed. All surgeries were performed by the same surgeon. Results Seventeen patients with a median age of 43 years (range, 32 to 71 years) and comprised of 94.1% (n = 16) males formed the study group. In all patients, an internal opening in the posterior midline with a tract leading to the deep postanal space was identified. This intersphincteric approach operation was adopted as the primary procedure in 12 patients (70.6%) and was successful in 11 (91.7%). In the only failure, the sepsis recurred, and a successful advancement flap procedure was eventually performed. Five other patients (29.4%) underwent this same procedure as a secondary procedure after an initial drainage operation. Only one was successful. In the remaining four patients, one had a recurrent abscess that required drainage while the other three patients had a tract between the internal opening and the intersphincteric incision. They subsequently underwent a drainage procedure with seton insertion and advancement flap procedures. Conclusion Managing DPA space sepsis via an intersphincteric approach is successful in 70.6% of patients. This single-staged technique allows for effective drainage of the sepsis and removal of the primary pathology in the intersphincteric space. PMID:23700571

  7. Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

    PubMed Central

    Zhou, Jianfang; Qian, Chuanyun; Zhao, Mingyan; Yu, Xiangyou; Kang, Yan; Ma, Xiaochun; Ai, Yuhang; Xu, Yuan; Liu, Dexin; An, Youzhong; Wu, Dawei; Sun, Renhua; Li, Shusheng; Hu, Zhenjie; Cao, Xiangyuan; Zhou, Fachun; Jiang, Li; Lin, Jiandong; Mao, Enqiang; Qin, Tiehe; He, Zhenyang; Zhou, Lihua; Du, Bin

    2014-01-01

    Introduction Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. Methods We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. Results A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n?=?365) or septic shock (n?=?119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n?=?139) and 33.5% (n?=?162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality. Conclusions Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients. PMID:25226033

  8. Antibiotics Before Removal of Percutaneously Inserted Central Venous Catheters Reduces Clinical Sepsis in Premature Infants

    PubMed Central

    Reynolds, Gail E.; Tierney, Sarah B.

    2015-01-01

    OBJECTIVES: Evaluate the incidence of postcatheter removal clinical sepsis when antibiotics were infused prior to the removal of percutaneously inserted central venous catheters (PICCs). METHODS: A retrospective chart review of premature neonates (n = 196) weighing ?1250 g at birth with 218 PICC line removals in the presence or absence of antibiotics at a tertiary level neonatal intensive care unit (NICU) between January 1, 2010, and May 31, 2012. Charts were reviewed looking for the presence of clinical sepsis defined as a sepsis workup including white blood cell count, differential, C-reactive protein, blood and/or cerebral spinal fluid (CSF), and urine cultures along with at least 48 hours of antibiotic therapy given within 72 hours after removal of a PICC line. Antibiotics were considered present at line removal if given within 12 hours before catheter removal either electively or at completion of a planned course. RESULTS: When antibiotics were given within 12 hours before PICC line removal, only 2% of the line removal episodes (1/48) resulted in a neonate developing clinical sepsis versus 13% (21/165) when no antibiotics were given prior to removal (p = 0.03, Fisher's exact test). Despite the increased use of elective antibiotics with line removal, there was no increase in total antibiotic usage due to the overall decrease in episodes of clinical sepsis or changes in antibiogram susceptibility patterns. CONCLUSIONS: There was an 11% absolute decrease and a 6-fold relative decrease in postcatheter removal clinical sepsis events in premature neonates who received antibiotics prior to PICC line removal. PMID:26170772

  9. Survival advantage of heterozygous fV Leiden carriers in murine sepsis

    PubMed Central

    Kerschen, Edward; Hernandez, Irene; Zogg, Mark; Maas, Matthias; Weiler, Hartmut

    2015-01-01

    Summary Background The high allelic frequency of the prothrombotic Leiden polymorphism in human blood coagulation factor V (fV) has been speculated to reflect positive selection during evolution. Heterozygous Leiden carriers enrolled in the placebo arm of the PROWESS sepsis trial, and heterozygous Leiden mice challenged with endotoxin both showed reduced mortality, whereas homozygous Leiden mice were not protected from lethal endotoxemia. Follow-up analyses of clinical outcomes, and of mouse models of infection with various pathogens remained inconclusive. Objective To establish whether aPC-resistance of fV Leiden modifies the outcome of bacterial infection in murine sepsis models. Methods Homozygous and heterozygous fV Leiden mice were subjected to gram-positive (S.aureus) or gram-negative (Y.pestis; E.coli) septic peritonitis, or polymicrobial, focal septic peritonitis induced by cecal ligation and puncture (CLP); and the effect of fV Leiden on 7-day survival and bacterial dissemination was assessed. Outcomes were compared to the sepsis survival of mice with genetically impaired hemostasis (hemophilia A, thrombocytopenia, thrombin receptor PAR4 deficiency, protein C receptor ProcR/EPCR-deficiency). Results Heterozygous, but not homozygous Leiden mice were protected from lethal infection with highly virulent S.aureus and Y.pestis strains. FV Leiden did not affect the outcome of sepsis induced by CLP, staphylokinase-deficient S.aureus, Pla-deficient Y.pestis, or E.coli. Thrombocytopenia, deficiency of PAR1 or PAR4 did not affect S.aureus sepsis survival, whereas hemophilia A increased mortality. ProcR-deficiency selectively abolished the survival advantage of heterozygous Leiden mice. Conclusions In mice, heterozygous fV Leiden carriers are protected from sepsis mortality after infection with clinically relevant human bacterial pathogens. PMID:25690763

  10. Sepsis Induces Specific Changes in Histone Modification Patterns in Human Monocytes

    PubMed Central

    Lichtenstern, Christoph; Siegler, Benedikt H.; Bhuju, Sabin; Jarek, Michael; Bartkuhn, Marek; Weigand, Markus A.

    2015-01-01

    Background Sepsis is a global burden and the primary cause of death in intensive care units worldwide. The pathophysiological changes induced by the host’s systemic inflammatory response to infection are not yet fully understood. During sepsis, the immune system is confronted with a variety of factors, which are integrated within the individual cells and result in changes of their basal state of responsiveness. Epigenetic mechanisms like histone modifications are known to participate in the control of immune reactions, but so far the situation during sepsis is unknown. Methods and Findings In a pilot approach, we performed combined chromatin immunoprecipitation followed by high-throughput sequencing to assess the genome-wide distribution of the chromatin modifications histone 3 lysine 4 and 27 trimethylation and lysine 9 acetylation in monocytes isolated from healthy donors (n = 4) and patients with sepsis (n = 2). Despite different underlying causes for sepsis, a comparison over promoter regions shows a high correlation between the patients for all chromatin marks. These findings hold true also when comparing patients to healthy controls. Despite the global similarity, differential analysis reveals a set of distinct promoters with significant enrichment or depletion of histone marks. Further analysis of overrepresented GO terms show an enrichment of genes involved in immune function. To the most prominent ones belong different members of the HLA family located within the MHC cluster together with the gene coding for the major regulator of this locus—CIITA. Conclusions We are able to show for the first time that sepsis in humans induces selective and precise changes of chromatin modifications in distinct promoter regions of immunologically relevant genes, shedding light on basal regulatory mechanisms that might be contributing to the functional changes occurring in monocytes. PMID:25793379

  11. Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

    PubMed Central

    McMaken, Sara; Exline, Matthew C.; Mehta, Payal; Piper, Melissa; Wang, Yijie; Fischer, Sara N.; Newland, Christie A.; Schrader, Carrie A.; Balser, Shannon R.; Sarkar, Anasuya; Baran, Christopher P.; Marsh, Clay B.; Cook, Charles H.; Phillips, Gary S.; Ali, Naeem A.

    2011-01-01

    Background Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGF?1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. Methodology/Principal Findings We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E.coli injection (IP E.coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1?/? animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGF?1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1?/? mice after CLP. The survival advantage for TSP-1?/? animals persisted when IP E.coli injections were p