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Sample records for acute streptococcal sepsis

  1. Acute streptococcal necrotising fasciitis.

    PubMed

    Frankish, P D; Mason, G H; Allen, P R; Milsom, F P; Christmas, T I

    1988-10-12

    Two cases of acute streptococcal necrotising fasciitis are reported. Both patients were taking nonsteroidal antiinflammatory drugs when they developed this infection. Urgent surgical debridement was undertaken and resulted in a successful outcome in both patients. The clinical and histopathological features of this condition are reviewed.

  2. Prevention of neonatal group B streptococcal sepsis: is routine antenatal screening appropriate.

    PubMed

    Gilbert, G L; Isaacs, D; Burgess, M A; Garland, S M; Grimwood, K; Hogg, G G; McIntyre, P

    1995-05-01

    Four strategies for prevention of early onset neonatal group B streptococcal (GBS) sepsis were considered: A: routine antenatal screening for GBS vaginal carriage at 26-28 weeks' gestation and intrapartum antibiotic prophylaxis for all carriers; B: screening as above and prophylaxis only for carriers with risk factors for sepsis; C: prophylaxis for all women with risk factors; D: as for C plus screening at 37 weeks' gestation and prophylaxis for carriers. The outcomes considered for each option were: the proportion of women given prophylaxis; the risk of anaphylaxis; cases of neonatal GBS sepsis and deaths prevented; costs of screening, prophylaxis and of acute care of remaining cases. Published local and overseas studies of neonatal GBS sepsis, effectiveness of antenatal screening and prophylaxis and estimated costs were evaluated. Any of the proposed strategies can prevent a significant proportion of cases of neonatal GBS sepsis and a strategy for prevention of neonatal group B streptococcal sepsis should be part of routine obstetric practice. Strategy C is simple, effective, inexpensive and avoids unnecessary antibiotic use; it is recommended particularly when antenatal care is provided mainly in community or private practice. Strategy A (using vaginal and rectal swabs for screening) could prevent more cases, but at greater cost which could be justified only if protocols can be properly implemented and monitored.

  3. Incidence and Outcome of Group B Streptococcal Sepsis in Infants in Switzerland.

    PubMed

    Giannoni, Eric; Berger, Christoph; Stocker, Martin; Agyeman, Philipp; Posfay-Barbe, Klara M; Heininger, Ulrich; Konetzny, Gabriel; Niederer-Loher, Anita; Kahlert, Christian; Donas, Alex; Leone, Antonio; Hasters, Paul; Relly, Christa; Baer, Walter; Aebi, Christoph; Schlapbach, Luregn J

    2016-02-01

    The incidence and outcome of group B streptococcal (GBS) sepsis were assessed prospectively between September 2011 and February 2015 in all tertiary care pediatric hospitals of Switzerland. We describe a low incidence of GBS early-onset sepsis (0.12/1000 livebirths) and a predominance of GBS late-onset sepsis (0.36/1000 livebirths), a pattern that has not been reported in other countries.

  4. The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis.

    PubMed

    Reglinski, Mark; Sriskandan, Shiranee

    2014-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide range of pathologies ranging from mild pharyngitis and impetigo to severe invasive soft tissue infections. Despite the continuing susceptibility of the bacterium to β-lactam antibiotics there has been an unexplained resurgence in the prevalence of invasive GAS infection over the past 30 years. Of particular importance was the emergence of a GAS-associated sepsis syndrome that is analogous to the systemic toxicosis associated with TSST-1 producing strains of Staphylococcus aureus. Despite being recognized for over 20 years, the etiology of GAS associated sepsis and the streptococcal toxic shock syndrome remains poorly understood. Here we review the virulence factors that contribute to the etiology of GAS associated sepsis with a particular focus on coagulation system interactions and the role of the superantigens in the development of streptococcal toxic shock syndrome. PMID:24157731

  5. The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis

    PubMed Central

    Reglinski, Mark; Sriskandan, Shiranee

    2014-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide range of pathologies ranging from mild pharyngitis and impetigo to severe invasive soft tissue infections. Despite the continuing susceptibility of the bacterium to β-lactam antibiotics there has been an unexplained resurgence in the prevalence of invasive GAS infection over the past 30 years. Of particular importance was the emergence of a GAS-associated sepsis syndrome that is analogous to the systemic toxicosis associated with TSST-1 producing strains of Staphylococcus aureus. Despite being recognized for over 20 years, the etiology of GAS associated sepsis and the streptococcal toxic shock syndrome remains poorly understood. Here we review the virulence factors that contribute to the etiology of GAS associated sepsis with a particular focus on coagulation system interactions and the role of the superantigens in the development of streptococcal toxic shock syndrome. PMID:24157731

  6. Delayed onset of right congenital diaphragmatic hernia associated with Group B streptococcal sepsis in a neonate

    PubMed Central

    Parida, Lalit

    2016-01-01

    A full-term male neonate was initially managed for respiratory distress which developed few hours after birth. His initial chest radiograph was normal, and blood culture revealed Group B streptococcal (GBS) sepsis. He subsequently developed progressive right chest opacification that did not improve with medical management. Imaging done few days later revealed right-sided diaphragmatic hernia. The 12-day-old neonate underwent primary repair of the diaphragmatic defect and had an uneventful recovery. This case report intends to highlight this unique association between early onset GBS sepsis and delayed onset of the right congenital diaphragmatic hernia. PMID:27046983

  7. An Unbiased Systems Genetics Approach to Mapping Genetic Loci Modulating Susceptibility to Severe Streptococcal Sepsis

    PubMed Central

    Abdeltawab, Nourtan F.; Aziz, Ramy K.; Kansal, Rita; Rowe, Sarah L.; Su, Yin; Gardner, Lidia; Brannen, Charity; Nooh, Mohammed M.; Attia, Ramy R.; Abdelsamed, Hossam A.; Taylor, William L.; Lu, Lu; Williams, Robert W.; Kotb, Malak

    2008-01-01

    Striking individual differences in severity of group A streptococcal (GAS) sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL) on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%–30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases. PMID:18421376

  8. Sepsis-induced acute kidney injury.

    PubMed

    Majumdar, Arghya

    2010-01-01

    Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit. It is being suggested that sepsis-induced AKI may have a distinct pathophysiology and identity. Availability of biomarkers now enable us to detect AKI as early as four hours after it's inception and may even help us to delineate sepsis-induced AKI. Protective strategies such as preferential use of vasopressin or prevention of intra-abdominal hypertension may help, in addition to the other global management strategies of sepsis. Pharmacologic interventions have had limited success, may be due to their delayed usage. Newer developments in extracorporeal blood purification techniques may proffer effects beyond simple replacement of renal function, such as metabolic functions of the kidney or modulation of the sepsis cascade.

  9. Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis.

    PubMed

    Leung, D Y; Travers, J B; Giorno, R; Norris, D A; Skinner, R; Aelion, J; Kazemi, L V; Kim, M H; Trumble, A E; Kotb, M

    1995-11-01

    Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis. Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection. This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens. Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families. Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05). The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets. Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response. All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion. These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s).

  10. Rapid group A streptococcal antigen detection kit: effect on antimicrobial therapy for acute pharyngitis.

    PubMed

    Redd, S C; Facklam, R R; Collin, S; Cohen, M L

    1988-10-01

    Newly introduced rapid diagnostic tests for group A streptococcal pharyngitis should facilitate appropriate antimicrobial use in patients with group A streptococcal pharyngitis. Because of high rates of acute pharyngitis in Tuba City, AZ, at the Navajo Indian reservation, the use of rapid diagnostic test was prospectively evaluated. The sensitivity and specificity of the test was measured and changes in physician prescribing patterns attributable to use of the test were correlated. Of 320 patients with pharyngitis enrolled during the present 3-week study, 86 met the study's definition of a patient with streptococcal pharyngitis and 163 met the study's definition of a patient with nonstreptococcal pharyngitis. The rapid test was 62.8% sensitive and 96.9% specific in identifying patients from whom group A streptococci were isolated. Although treatment of patients with streptococcal pharyngitis at the time of the first visit increased from 36.5% in a retrospective sample to 72.5% during the study, treatment of patients in whom cultures were negative remained the same. Further analyses showed that physicians tended to treat patients with signs characteristic of streptococcal pharyngitis and, as the study progressed, to rely less on negative rapid test results as a reason to withhold antimicrobial agents. It was concluded that rapid tests with good specificity but limited sensitivity may improve treatment of patients with streptococcal pharyngitis by allowing earlier specific therapy. A more sensitive test with a higher negative predictive value would be necessary to prevent treatment of persons with nonstreptococcal pharyngitis. PMID:3050865

  11. 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

  12. Post–Acute Care Use and Hospital Readmission after Sepsis

    PubMed Central

    Jones, Tiffanie K.; Fuchs, Barry D.; Small, Dylan S.; Halpern, Scott D.; Hanish, Asaf; Umscheid, Craig A.; Baillie, Charles A.; Kerlin, Meeta Prasad; Gaieski, David F.

    2015-01-01

    Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P < 0.001), with the highest rate observed after severe sepsis. Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001). Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the increased readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Conclusions: Post–acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with

  13. Sepsis and Acute Respiratory Distress Syndrome: Recent Update.

    PubMed

    Kim, Won-Young; Hong, Sang-Bum

    2016-04-01

    Severe sepsis or septic shock is characterized by an excessive inflammatory response to infectious pathogens. Acute respiratory distress syndrome (ARDS) is a devastating complication of severe sepsis, from which patients have high mortality. Advances in treatment modalities including lung protective ventilation, prone positioning, use of neuromuscular blockade, and extracorporeal membrane oxygenation, have improved the outcome over recent decades, nevertheless, the mortality rate still remains high. Timely treatment of underlying sepsis and early identification of patients at risk of ARDS can help to decrease its development. In addition, further studies are needed regarding pathogenesis and novel therapies in order to show promising future treatments of sepsis-induced ARDS. PMID:27066082

  14. The Dynamics of Platelet Activation during the Progression of Streptococcal Sepsis

    PubMed Central

    Hurley, Sinead M.; Lutay, Nataliya; Holmqvist, Bo; Shannon, Oonagh

    2016-01-01

    Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5, 12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet-neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection. PMID:27656898

  15. Effect of an interleukin-1 receptor antagonist on the hemodynamic manifestations of group B streptococcal sepsis.

    PubMed

    Vallette, J D; Goldberg, R N; Suguihara, C; Del Moral, T; Martinez, O; Lin, J; Thompson, R C; Bancalari, E

    1995-11-01

    IL-1 is purported to be a proximal mediator in the cascade leading to septic shock. To characterize its hemodynamic effects and to ascertain whether its blockade would ameliorate the deleterious consequences of sepsis, an IL-1 receptor antagonist (IL-1ra) was administered to 16 anesthetized, mechanically ventilated piglets that received a continuous infusion of group B streptococci (GBS) (7.5 x 10(7) colony-forming units/kg/min). Systemic (Psa), pulmonary artery (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and every 30 min during GBS infusion. After 15 min of bacterial infusion the control group received normal saline, whereas the treatment group received a bolus of IL-1ra (40 mg/kg) followed by a continuous infusion of IL-1ra (60 micrograms/kg/min). In comparing IL-1ra-treated animals with controls from the 15-min GBS baseline to the succeeding septic study period (45-120 min), the following treatment effects were noted (120-min values shown): mean Psa remained elevated in treatment compared with control animals (12.7 +/- 2.5 versus 9 +/- 3.5 kPa; p < 0.001) as did CO (0.21 +/- 0.07 versus 0.13 +/- 0.08 L/min/kg; p < 0.001). Pwp decreased in the treatment compared to the control group over the study period (1 +/- 0.3 versus 1.6 +/- 0.7 kPa; p < 0.02). Mean Ppa and mean Pra were not different between groups over time. Median length of survival was significantly longer (p = 0.04) in treated (226 min) compared with control animals (150 min). These data suggest that IL-1 plays an important role in GBS sepsis and septic shock, and that IL-1ra may in part ameliorate the cardiovascular alterations associated with GBS sepsis in the neonate.

  16. Improving Sepsis Management in the Acute Admissions Unit.

    PubMed

    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.

  17. A Pediatric Case of Acute Generalized Pustular Eruption without Streptococcal Infection.

    PubMed

    Tabata, Nobuko; Yoshizawa, Hideka

    2016-01-01

    Generalized pustular lesions characterized by acute onset with fever occur in pustulosis acuta generalisata, acute generalized exanthematous pustulosis, and generalized pustular psoriasis. In the present report, we describe a pediatric case of generalized pustular eruption that was not completely consistent with clinical features. Our patient had no evidence of a post-streptococcal infection. We observed scattered symmetric eruption of discrete pustules with an inflammatory halo on normal skin. The eruption was absent on her palms and soles of the feet. To the best of our knowledge, there are no reports in the English literature of cases with clinical features similar to those of our patient. PMID:27462226

  18. Platelets promote bacterial dissemination in a mouse model of streptococcal sepsis.

    PubMed

    Kahn, Fredrik; Hurley, Sinead; Shannon, Oonagh

    2013-01-01

    Platelets have been reported to contribute to inflammation and inflammatory disorders. In the present study, we demonstrate that platelets contribute to the acute response to bacterial infection in a mouse model of invasive Streptococcus pyogenes infection. Thrombocytopenia occurred rapidly in infected animals and this was associated with platelet activation, formation of platelet-neutrophil complexes and neutrophil activation. In order to assess the role of platelets during infection, platelets were depleted prior to infection. Platelet-depleted animals had significantly decreased platelet-neutrophil complex formation and neutrophil activation in response to infection. Importantly, significantly fewer bacteria disseminated to the blood, lungs, and spleen of platelet-depleted animals. Platelet-depleted animals did not decrease as significantly in weight as the infected control animals. The results demonstrate a previously unappreciated role for platelets during the pathophysiological response to infection, whereby S. pyogenes bacteria bind to platelets and platelets facilitate bacterial dissemination.

  19. Sepsis

    MedlinePlus

    ... the episode 3 , 4 . What is the economic cost of sepsis? Treatment for sepsis often involves a ... care unit and complex therapies, which incur high costs. The Agency for Healthcare Research and Quality lists ...

  20. Dress syndrome with sepsis, acute respiratory distress syndrome and pneumomediastinum.

    PubMed

    Giri, Prabhas Prasun; Roy, Swapan; Bhattyacharya, Sukanta; Pal, Priyankar; Dhar, Sandipan

    2011-11-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, and is characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause DRESS syndrome. We report a case of a 10-year-old girl who developed clinical manifestations of fever, rash, lymphadenopathy, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis) after taking phenobarbital for seizures, with subsequent development of sepsis, acute respiratory distress syndrome (ARDS) and spontaneous air leak syndrome (pnemothorax and pneumomediastinum). She was put on steroids and various antibiotics and was ventilated, but ultimately succumbed to sepsis and pulmonary complications. PMID:22345792

  1. CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.

    PubMed

    Wang, Chao-Yung; Hsieh, Ming-Jer; Hsieh, I-Chang; Shie, Shian-Sen; Ho, Ming-Yun; Yeh, Jih-Kai; Tsai, Ming-Lung; Yang, Chia-Hung; Hung, Kuo-Chun; Wang, Chun-Chieh; Wen, Ming-Shien

    2016-09-16

    Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications. PMID:27520377

  2. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease

    PubMed Central

    Bouchard, Josée; Soroko, Sharon B.; Ikizler, T. Alp; Paganini, Emil P.; Chertow, Glenn M.; Himmelfarb, Jonathan

    2010-01-01

    Purpose Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI. Methods We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis. Results We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI. Conclusions Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis. PMID:21152901

  3. Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

    PubMed Central

    Fialkow, Léa; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, João C; Vachon, Eric; Downey, Gregory P

    2006-01-01

    Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of

  4. Sepsis-induced acute kidney injury in patients with cirrhosis.

    PubMed

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  5. Update in sepsis and acute kidney injury 2014.

    PubMed

    Schortgen, Frédérique; Asfar, Pierre

    2015-06-01

    Sepsis and acute kidney injury (AKI) represent an important burden in intensive care unit clinical practices. The Journal published important contributions in sepsis for novel therapeutic approaches suggesting that combined molecular targets (e.g., dual inhibition of IL-1β and IL-18, and coadministration of endothelial progenitor cells and stromal cell-derived factor-1α analog) could perform better. The clinical effectiveness of 1,25-dihydroxyvitamin D was reported in a double-blind, randomized, placebo-controlled trial. Although its experimental properties appeared favorable in the pro- and antiinflammatory cytokine balance, 1,25-dihydroxyvitamin D failed to improve survival. Strategies for decreasing antimicrobial resistances are of particular importance. Effective (aerosolized antibiotics for ventilator-associated pneumonia) and ineffective (procalcitonin algorithm for antibiotic deescalation) approaches were published. In 2014, several publications raised an important point shared by survivors from sepsis and/or AKI. The increased number of survivors over time brought out long-term sequelae, leading to a poor outcome after hospital discharge. Among them, cardiovascular events and chronic kidney disease may explain the significant increase in the risk of death, which can persist up to 10 years and significantly increases the use of health care. Postdischarge survival represents a new target for future research in sepsis and AKI to find how we can prevent and manage long-term sequelae. A milestone of the year was the Ebola outbreak. The Journal contributed to our better understanding of Ebola virus disease with a paper underlying the crucial role of a large implementation of pragmatic supportive care, including fluid infusion and correction of metabolic abnormalities, to save more lives. PMID:26029837

  6. Sepsis.

    PubMed

    Dean, Erin

    2016-09-01

    Essential facts Sepsis, a clinical syndrome caused by the body's immune and coagulation systems being switched on by an infection, is believed to cause about 44,000 deaths a year. If not recognised early and treated promptly, sepsis can lead to shock, multiple organ failure and death. Major reports (UK parliamentary and health service ombudsman enquiry in 2013 and the UK National Confidential Enquiry into Patient Outcome and Death in 2015) have highlighted sepsis as being a leading cause of avoidable death that kills more people than breast, bowel and prostate cancer combined. PMID:27581906

  7. Sepsis.

    PubMed

    Dean, Erin

    2016-09-01

    Essential facts [Figure: see text] Sepsis, a clinical syndrome caused by the body's immune and coagulation systems being switched on by an infection, is believed to cause about 44,000 deaths a year. If not recognised early and treated promptly, sepsis can lead to shock, multiple organ failure and death. Major reports (UK parliamentary and health service ombudsman enquiry in 2013 and the UK National Confidential Enquiry into Patient Outcome and Death in 2015) have highlighted sepsis as being a leading cause of avoidable death that kills more people than breast, bowel and prostate cancer combined. PMID:27615338

  8. Sepsis

    MedlinePlus

    ... oxygen. In severe cases, one or more organs fail. In the worst cases, blood pressure drops and the heart weakens, leading to septic shock. Anyone can get sepsis, but the risk is higher in People with weakened immune systems Infants and children The elderly People with chronic ...

  9. Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury.

    PubMed

    Umbro, Ilaria; Gentile, Giuseppe; Tinti, Francesca; Muiesan, Paolo; Mitterhofer, Anna Paola

    2016-02-01

    Sepsis is a complex clinical syndrome characterized by a systemic inflammatory response to an infective insult. This process often leads to widespread tissue injury and multiple organ dysfunction. In particular, the development of acute kidney injury (AKI) is one of the most frequent complications, which increases the complexity and cost of care, and is an independent risk factor for mortality. Previous suggestions highlighting systemic hypotension, renal vasoconstriction and ischaemia-reperfusion injury as the primary pathophysiological mechanisms involved in sepsis-induced AKI have been challenged. Recently it has been shown that sepsis-induced AKI occurs in the setting of microvascular dysfunction with release of microparticles, inflammation and energetic adaptation of highly metabolic organs to cellular stress. The intolerable high mortality rate associated with sepsis-induced AKI is partially explained by an incomplete understanding of its pathophysiology and a delay in diagnosis. The aim of this review is to focus on advances in understanding the sepsis pathophysiology, with particular attention to the fundamental mechanisms of sepsis-induced AKI and the potential diagnostic and prognostic markers involved.

  10. Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury.

    PubMed

    Umbro, Ilaria; Gentile, Giuseppe; Tinti, Francesca; Muiesan, Paolo; Mitterhofer, Anna Paola

    2016-02-01

    Sepsis is a complex clinical syndrome characterized by a systemic inflammatory response to an infective insult. This process often leads to widespread tissue injury and multiple organ dysfunction. In particular, the development of acute kidney injury (AKI) is one of the most frequent complications, which increases the complexity and cost of care, and is an independent risk factor for mortality. Previous suggestions highlighting systemic hypotension, renal vasoconstriction and ischaemia-reperfusion injury as the primary pathophysiological mechanisms involved in sepsis-induced AKI have been challenged. Recently it has been shown that sepsis-induced AKI occurs in the setting of microvascular dysfunction with release of microparticles, inflammation and energetic adaptation of highly metabolic organs to cellular stress. The intolerable high mortality rate associated with sepsis-induced AKI is partially explained by an incomplete understanding of its pathophysiology and a delay in diagnosis. The aim of this review is to focus on advances in understanding the sepsis pathophysiology, with particular attention to the fundamental mechanisms of sepsis-induced AKI and the potential diagnostic and prognostic markers involved. PMID:26702738

  11. First report of acute cholecystitis with sepsis caused by Cellulomonas denverensis.

    PubMed

    Ohtaki, Hirofumi; Ohkusu, Kiyofumi; Sawamura, Haruki; Ohta, Hirotoshi; Inoue, Rina; Iwasa, Junpei; Ito, Hiroyasu; Murakami, Nobuo; Ezaki, Takayuki; Moriwaki, Hisataka; Seishima, Mitsuru

    2009-10-01

    Cellulomonas denverensis is a small and thin gram-positive rod-shaped bacterium that was proposed as a new species in 2005. Here we report a female case of acute cholecystitis and sepsis in which C. denverensis was determined to be causative.

  12. First Report of Acute Cholecystitis with Sepsis Caused by Cellulomonas denverensis▿

    PubMed Central

    Ohtaki, Hirofumi; Ohkusu, Kiyofumi; Sawamura, Haruki; Ohta, Hirotoshi; Inoue, Rina; Iwasa, Junpei; Ito, Hiroyasu; Murakami, Nobuo; Ezaki, Takayuki; Moriwaki, Hisataka; Seishima, Mitsuru

    2009-01-01

    Cellulomonas denverensis is a small and thin gram-positive rod-shaped bacterium that was proposed as a new species in 2005. Here we report a female case of acute cholecystitis and sepsis in which C. denverensis was determined to be causative. PMID:19656981

  13. Streptococcal superantigens: categorization and clinical associations.

    PubMed

    Commons, Robert J; Smeesters, Pierre R; Proft, Thomas; Fraser, John D; Robins-Browne, Roy; Curtis, Nigel

    2014-01-01

    Superantigens are key virulence factors in the immunopathogenesis of invasive disease caused by group A streptococcus. These protein exotoxins have also been associated with severe group C and group G streptococcal infections. A number of novel streptococcal superantigens have recently been described with some resulting confusion in their classification. In addition to clarifying the nomenclature of streptococcal superantigens and proposing guidelines for their categorization, this review summarizes the evidence supporting their involvement in various clinical diseases including acute rheumatic fever.

  14. Renal artery thrombosis secondary to sepsis-induced disseminated intravascular coagulation in acute pyelonephritis

    PubMed Central

    Lee, Jayoung; Chul Nam, Hee; Gyoung Kim, Boo; Gyung Kim, Hyun; Chan Jung, Hee; Hee Kim, Ji; Seok Yang, Geun; Jeong Park, Youn; Young Kim, Ka; Yun, Yu-Seon; Ok Kim, Young; Yu, Jihan

    2012-01-01

    There are some reports of renal vein thrombosis associated with acute pyelonephritis, but a case of renal artery thrombosis in acute pyelonephritis has not been reported yet. Here we report a case of renal artery thrombosis which developed in a patient with acute pyelonephritis complicated with sepsis-induced disseminated intravascular coagulation (DIC). A 65-year-old woman with diabetes was diagnosed with acute pyelonephritis complicated with sepsis. Escherichia coli was isolated from both blood and urine cultures. When treated with antibiotics, her condition gradually improved. She suddenly complained of severe right flank pain without fever in the recovery phase. A computed tomography scan revealed right renal artery thrombosis with concomitant renal infarction. Prophylactic anticoagulation therapy was not suggested because of sustained thrombocytopenia and increased risk of bleeding. Flank pain resolved with conservative treatment and perfusion of infarcted kidney improved at the time of discharge. To our knowledge, this is the first case of renal artery thrombosis related to acute pyelonephritis with sepsis-induced DIC. PMID:26889428

  15. Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome.

    PubMed

    Dickson, Robert P; Singer, Benjamin H; Newstead, Michael W; Falkowski, Nicole R; Erb-Downward, John R; Standiford, Theodore J; Huffnagle, Gary B

    2016-01-01

    Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here, we report culture-independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecological analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut-specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture and correlated with the intensity of systemic inflammation. Alveolar TNF-α, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases. PMID:27670109

  16. Acute kidney injury in sepsis: transient or intrinsic?

    PubMed

    Jörres, Achim

    2013-11-20

    The negative prediction of intrinsic versus transient acute kidney injury (AKI) in septic patients may be facilitated by combined assessment of fractional excretion of sodium and urea. If both excretions are high this would signal the presence of transient AKI and suggest that successful restoration of diuresis by conservative therapy is likely, thus supporting a wait-and-watch approach regarding the initiation of acute renal replacement therapy.

  17. Urgent endoscopic ultrasound-guided choledochoduodenostomy for acute obstructive suppurative cholangitis-induced sepsis

    PubMed Central

    Minaga, Kosuke; Kitano, Masayuki; Imai, Hajime; Yamao, Kentaro; Kamata, Ken; Miyata, Takeshi; Omoto, Shunsuke; Kadosaka, Kumpei; Yoshikawa, Tomoe; Kudo, Masatoshi

    2016-01-01

    Acute obstructive suppurative cholangitis (AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis. PMID:27122677

  18. Neonatal sepsis: an old problem with new insights.

    PubMed

    Shah, Birju A; Padbury, James F

    2014-01-01

    Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW<1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount.

  19. Designing phase 3 sepsis trials: application of learned experiences from critical care trials in acute heart failure.

    PubMed

    Mebazaa, Alexandre; Laterre, Pierre François; Russell, James A; Bergmann, Andreas; Gattinoni, Luciano; Gayat, Etienne; Harhay, Michael O; Hartmann, Oliver; Hein, Frauke; Kjolbye, Anne Louise; Legrand, Matthieu; Lewis, Roger J; Marshall, John C; Marx, Gernot; Radermacher, Peter; Schroedter, Mathias; Scigalla, Paul; Stough, Wendy Gattis; Struck, Joachim; Van den Berghe, Greet; Yilmaz, Mehmet Birhan; Angus, Derek C

    2016-01-01

    Substantial attention and resources have been directed to improving outcomes of patients with critical illnesses, in particular sepsis, but all recent clinical trials testing various interventions or strategies have failed to detect a robust benefit on mortality. Acute heart failure is also a critical illness, and although the underlying etiologies differ, acute heart failure and sepsis are critical care illnesses that have a high mortality in which clinical trials have been difficult to conduct and have not yielded effective treatments. Both conditions represent a syndrome that is often difficult to define with a wide variation in patient characteristics, presentation, and standard management across institutions. Referring to past experiences and lessons learned in acute heart failure may be informative and help frame research in the area of sepsis. Academic heart failure investigators and industry have worked closely with regulators for many years to transition acute heart failure trials away from relying on dyspnea assessments and all-cause mortality as the primary measures of efficacy, and recent trials have been designed to assess novel clinical composite endpoints assessing organ dysfunction and mortality while still assessing all-cause mortality as a separate measure of safety. Applying the lessons learned in acute heart failure trials to severe sepsis and septic shock trials might be useful to advance the field. Novel endpoints beyond all-cause mortality should be considered for future sepsis trials. PMID:27034779

  20. Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature.

    PubMed

    Marshall, Catherine S; Cheng, Allen C; Markey, Peter G; Towers, Rebecca J; Richardson, Leisha J; Fagan, Peter K; Scott, Lesley; Krause, Vicki L; Currie, Bart J

    2011-10-01

    Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0-54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6-94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed.

  1. Extracorporeal lung assist for sepsis and acute respiratory distress syndrome.

    PubMed

    Iwashita, Yoshiaki; Imai, Hiroshi

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is one of the major causes of ICU deaths. Extracorporeal lung assist (ECLA) has been used as a rescue therapy for most severe form of ARDS. However, its survival benefit had not been shown until CESAR trial in 2009. This has been because the concept of lung protective ventilation strategy had not yet known. Since CESAR trial, the clinical application of ECLA for ARDS as a method to achieve lung rest has wide spread. The effectiveness is further appreciated during the 2009 H1N1 influenza pandemic. The succeeded countries achieved building the transportation systems to collect ECLA patients. With the accumulating evidences of survival benefit, the long-term outcome such as pulmonary function and quality of life are in concern. PumplessECLA which is a newly developed form of ECLA is also reviewed. In this essay we will firstly review the basics of ARDS and ECLA. Then the historical development of ECLA evidences for ARDS are reviewed. PMID:25567336

  2. Alkaline phosphatase: a possible treatment for sepsis-associated acute kidney injury in critically ill patients.

    PubMed

    Peters, Esther; Heemskerk, Suzanne; Masereeuw, Rosalinde; Pickkers, Peter

    2014-06-01

    Acute kidney injury (AKI) is a common disease in the intensive care unit and accounts for high morbidity and mortality. Sepsis, the predominant cause of AKI in this setting, involves a complex pathogenesis in which renal inflammation and hypoxia are believed to play an important role. A new therapy should be aimed at targeting both these processes, and the enzyme alkaline phosphatase, with its dual mode of action, might be a promising candidate. First, alkaline phosphatase is able to reduce inflammation through dephosphorylation and thereby detoxification of endotoxin (lipopolysaccharide), which is an important mediator of sepsis. Second, adenosine triphosphate, released during cellular stress caused by inflammation and hypoxia, has detrimental effects but can be converted by alkaline phosphatase into adenosine with anti-inflammatory and tissue-protective effects. These postulated beneficial effects of alkaline phosphatase have been confirmed in animal experiments and two phase 2a clinical trials showing that kidney function improved in critically ill patients with sepsis-associated AKI. Because renal inflammation and hypoxia also are observed commonly in AKI induced by other causes, it would be of interest to investigate the therapeutic effect of alkaline phosphatase in these nephropathies as well.

  3. Artificial organ treatment for multiple organ failure, acute renal failure, and sepsis: recent new trends.

    PubMed

    Tetta, C; Bellomo, R; Ronco, C

    2003-03-01

    Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the nonselective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extracorporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials that lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. Additionally, we will review novel information related to other blood purification techniques using large pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

  4. Growth arrest-specific protein 6 attenuates neutrophil migration and acute lung injury in sepsis.

    PubMed

    Giangola, Matthew D; Yang, Weng-Lang; Rajayer, Salil R; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2013-12-01

    Sepsis is an acute inflammatory condition that can result in multiple organ failure and acute lung injury. Growth arrest-specific protein 6 (Gas6) is a broad regulator of the innate immune response involved with the nuclear factor κB signaling pathway. We hypothesized that Gas6 could have a protective role in attenuating the severity of acute lung injury and sepsis. Male mice were subjected to sepsis by cecal ligation and puncture (CLP) after which recombinant murine Gas6 (rmGas6; 5 μg/mouse) or normal saline (vehicle) was administered intravenously. Blood and lung tissues were collected at 20 h after CLP for various measurements. Treatment with rmGas6 significantly reduced serum levels of the injury markers aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as proinflammatory cytokines interleukin 6 (IL-6) and IL-17, compared with the vehicle group (P < 0.05). The parenchyma of the lungs damaged by CLP was attenuated by rmGas6 treatment. Lung mRNA levels of tumor necrosis factor α, IL-1β, IL-6, IL-17, and macrophage inflammatory protein 2 (MIP-2) were decreased by 60%, 86%, 82%, 93%, and 82%, respectively, with rmGas6 treatment as determined by real-time reverse transcriptase-polymerase chain reaction (P < 0.05). The degradation of IκB-α induced by CLP in the lungs was inhibited by rmGas6 treatment. The number of neutrophils and myeloperoxidase activity in the lungs were significantly reduced in the rmGas6 group. Moreover, rmGas6 reduced the in vitro migration of differentiated human promyelocytic HL60 cells by 64%. Finally, the 10-day survival rate of mice subjected to CLP was increased from 31% in the vehicle group to 67% in the rmGas6 group (P < 0.05). Thus, Gas6 has potential to be developed as a novel therapeutic agent to treat patients with sepsis and acute lung injury.

  5. A case of acute post-streptococcal glomerulonephritis that developed posterior reversible encephalopathy syndrome.

    PubMed

    Kasap, Belde; Çarman, Kürşat Bora; Yiş, Uluç

    2014-12-01

    A 10-year male patient presented with swelling in the face, legs and scrotal area which developed 8 days after tonsillitis treatment. Acute post-sterotococcal glomerulonephritis (APSGN) was considered in the patient whose urinalysis revealed hematuria and proteinuria at nephrotic level, whose urea, creatinine, lipid profile and anti-streptolysine O antibody levels were increased, albumin and C3 value were decreased and whose 24-hour urine test revealed proteinuria. Renal biopsy was found to be compatible with APSGN. In the follow-up, severe headache, vomiting and convulsion were observed under antihypertensive and diuretic treatment and when the blood pressure was 130/80 mmHg (the 99(th) percentile for the patient: 129/88 mmHg). During the follow-up, the blood pressure values increased to 160/90 mmHg. The electroencephalogram (EEG) performed was found to be normal and magnetic resonance imaging (MRI) findings were compatible with posterior reversible encephalopathy syndrome (PRES). MRI was found to be normal at the first month following antihypertensive and anticonvulsive treatment. In the first year of the follow-up, the blood pressure, neurological examination and urinalysis findings were found to be normal. This patient was presented to draw attention to the fact that PRES can also present with a blood pressure tending to increase and with blood pressure values which are not so high. PMID:26078688

  6. 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-α and IL-1β, 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-α and IL-1β 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

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

    PubMed

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

    2015-08-31

    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-α and IL-1β, 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-α and IL-1β 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.

  8. Accelerated Cellular Uptake and Metabolism of L-Thyroxine during Acute Salmonella typhimurium Sepsis

    PubMed Central

    DeRubertis, Frederick R.; Woeber, Kenneth A.

    1973-01-01

    The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T4) distribution and metabolism and on serum total and free T4 concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T4 from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T4 disposal. In the infected monkeys, serum total T4 and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T4 were enhanced by 4 h after inoculation of monkeys with either heat-killed or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T4 kinetics could neither be correlated with changes in the binding of T4 in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T4 disappearance was also observed during Escherichia coli and Diplococcus pucumoniae bacteremias. Our findings are consistent with a primary increase in the cellular uptake and metabolism of T4 during bacterial sepsis, possibly related to phagocytic cell function in the host. PMID:4629910

  9. 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.

  10. Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

    PubMed Central

    2010-01-01

    Background Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. Methods We studied nineteen neonates (27.3 ± 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO2 and VCO2 measured by gas chromatography. Results REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO2 (7.4 ± 1.9 vs 10 ± 1.5 ml/kg/min) and VCO2 (5.1 ± 1.7 vs 7.4 ± 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01). Conclusion REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities. PMID:20653967

  11. 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 AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle. Similarly, the expressions of TNF-α, IL-1β, 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 AMPKα2 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

  12. Effect on extrapulmonary sepsis-induced acute lung injury by hemoperfusion with neutral microporous resin column.

    PubMed

    Huang, Zhao; Wang, Si-rong; Yang, Zi-li; Liu, Ji-yun

    2013-08-01

    The aim of this study was to investigate the effect of neutral microporous resin hemoperfusion on oxygenation improvement, removal of inflammatory cytokines in plasma and bronchoalveolar lavage, and mortality in acute lung injury induced by extrapulmonary sepsis. Forty-six patients with acute lung injury induced by extrapulmonary sepsis were randomized to HA type hemoperfusion treatment (N=25) or standard therapy (N=21). Those undergoing hemoperfusion treatment received HA330 hemoperfusion. We measured the plasma and bronchoalveolar lavage concentrations of TNF-α and IL-1, and the following parameters were compared between the control group and the hemoperfusion group on days 0, 3 and 7: lung injury measurements (arterial oxygen tension/fractional inspired oxygen ratio, lung injury score, chest X-ray score); interstitial edema of lung (extravascular lung water). Duration of mechanical ventilation, hospital, 28-day, and intensive care unit mortality were also observed. Patients treated with HA hemoperfusion showed a significant removal of plasma and bronchoalveolar lavage TNF-α and IL-1 over time while in the study. Patients in the HA group also demonstrated not only significant improvement of PaO2 /FiO2 , but also decreased Lung Injury Score and chest X-ray score at days 3 and 7. Furthermore, the measurements of the arterial oxygen tension/fractional inspired oxygen ratio, lung injury score and extravascular lung water (EVLWI) significantly correlated with and the concentration of cytokines in the plasma (all P<0.05). The HA hemoperfusion treatment group had a significant reduction in duration of mechanical ventilation, length of intensive care unit stay, and intensive care unit mortality. Significant removal of inflammatory cytokines from circulation and lung by hemoperfusion treatment using the HA type cartridge may contribute to the improvement of lung injury and intensive care unit outcome in extrapulmonary septic patients. PMID:23931889

  13. Effect of induced mild hypothermia on two pro-inflammatory cytokines and oxidative parameters during experimental acute sepsis.

    PubMed

    Léon, Karelle; Moisan, Christine; Amérand, Aline; Poupon, Gwladys; L'Her, Erwan

    2013-01-01

    This study aimed to determine the effect of induced mild hypothermia (34°C) on the production of two cytokines (interleukin (IL-6) and tumor necrosis factor (TNF)alpha) and reactive nitrogen and oxygen species in plasma and the heart of acutely septic rats. After anesthesia and in conditions of normothermia (38°C) or mild hypothermia (34°C), acute sepsis was induced by cecal ligation and perforation. For each temperature three groups were formed: (1) baseline (blood sample collected at T0 hour), (2) sham (blood sample at T4 hours) and (3) septic (blood sample at T4 hours). At either temperature sepsis induced a significant increase in plasma IL-6, TNF-alpha and HO• concentration, compared with the sham groups (P≤0.016). Compared with the normothermic septic group, septic rats exposed to mild hypothermia showed a mild decrease in TNF-alpha concentration (104±50 pg/ml vs. 215±114 pg/ml; P>0.05) and a significant decrease in IL-6 (1131±402 pg/ml vs. 2494±691 pg/ml, P=0.038). At either temperature sepsis induced no enhancement within the heart of lipoperoxidation (malondialdehyde content) or antioxidant activities (superoxide dismutase and catalase). In conclusion, during acute sepsis, induced mild hypothermia appears to reduce some pro-inflammatory and oxidative responses. This may, in part, explain the beneficial effect of hypothermia on survival duration of septic rats. PMID:23746123

  14. Diuretics induced uremia and nonrecovery of renal function in a patient with acute renal failure caused by sepsis

    PubMed Central

    Sahu, P. K.; Pal, A.; Panda, J.; Patnaik, S.

    2011-01-01

    Sepsis is a clinical syndrome related to severe infection and is characterized by systemic inflammation and injury to multiple organs and functional systems. Sepsis is one of the main causes of acute renal failure (ARF). Diuretics are frequently administered during ARF. However, there is scant evidence that diuretics provide any benefit to the patients with ARF. This case report highlights the occurrence of uremia and nonrecovery of renal function after administration of diuretics in a patient with ARF caused by sepsis. It is suggested that physicians should be cautious in prescribing diuretics to patients with ARF due to septicemia. Diuretics cause uremia and may lead to false diagnosis of chronic renal failure and nonrecovery of renal function. The patient may unnecessarily require prolonged dialysis. PMID:22022011

  15. Cervical insufficiency: a new issue for guidelines on prevention of perinatal group B streptococcal disease?

    PubMed

    Natale, Fabio; Brunelli, Roberto; Bizzarri, Bianca; Castronovo, Antonella; De Curtis, Mario

    2013-02-01

    The updated Guidelines on Prevention of Perinatal Group B Streptococcal Disease, issued by the Centers for Disease Control and Prevention, actually represent the mainstay in the prevention of neonatal early-onset group B streptococcal (GBS) sepsis. According to these guidelines, patients with possible preterm delivery are screened for GBS colonization and offered intrapartum prophylaxis only if they enter preterm labor or experience preterm premature rupture of the membranes. Nonetheless, the fulfillment of these recommendations seems to be suboptimal in clinical practice, as it is heavily influenced by the knowledge of the colonization status. We report here 2 cases of blood culture-proven, early-onset neonatal GBS sepsis involving preterm infants delivered by mothers who had midtrimester cervical insufficiency and bulging membranes. Midtrimester acute cervical insufficiency strongly predicts preterm delivery. These women are liable to miss intrapartum antibiotic prophylaxis because they typically have shorter labor, and the test results for GBS status are unlikely to be available before delivery. We believe that women with midtrimester cervical insufficiency and bulging membranes should be screened for GBS infection soon after hospital admittance if the gestational age is close to the threshold of fetal viability. A timely diagnosis of GBS colonization may not only increase the number of patients receiving targeted intrapartum antibiotic prophylaxis but would also allow consideration of the administration of antepartum antibiotic prophylaxis. Indeed, as further outlined in this report, GBS intraamniotic infection may dramatically occur before the onset of preterm labor or preterm premature rupture of the membranes.

  16. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury.

    PubMed

    Wang, Zhen; Holthoff, Joseph H; Seely, Kathryn A; Pathak, Elina; Spencer, Horace J; Gokden, Neriman; Mayeux, Philip R

    2012-02-01

    Acute kidney injury is a frequent and serious complication of sepsis. To better understand the development of sepsis-induced acute kidney injury, we performed the first time-dependent studies to document changes in renal hemodynamics and oxidant generation in the peritubular microenvironment using the murine cecal ligation and puncture (CLP) model of sepsis. CLP caused an increase in renal capillary permeability at 2 hours, followed by decreases in mean arterial pressure, renal blood flow (RBF), and renal capillary perfusion at 4 hours, which were sustained through 18 hours. The decline in hemodynamic parameters was associated with hypoxia and oxidant generation in the peritubular microenvironment and a decrease in glomerular filtration rate. The role of oxidants was assessed using the superoxide dismutase mimetic/peroxynitrite scavenger MnTMPyP [Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin]. At 10 mg/kg administered 6 hours after CLP, MnTMPyP did not alter blood pressure, but blocked superoxide and peroxynitrite generation, reversed the decline in RBF, capillary perfusion, and glomerular filtration rate, preserved tubular architecture, and increased 48-hour survival. However, MnTMPyP administered at CLP did not prevent capillary permeability or the decrease in RBF and capillary perfusion, which suggests that these early events are not mediated by oxidants. These data demonstrate that renal hemodynamic changes occur early after sepsis and that targeting the later oxidant generation can break the cycle of injury and enable the microcirculation and renal function to recover.

  17. Serotype distribution in pneumococcal acute otitis media with ruptured tympanic membrane or sepsis in Germany.

    PubMed

    van der Linden, M; Reinert, R R

    2010-07-01

    This retrospective analysis examined the pneumococcal serotype distribution of acute otitis media in Germany from 1995 to 2007. Data from the German National Reference Centre for Streptococci included 512 cases of pneumococcal otitis media in children and adults. Infections were mainly seen in children aged <5 years, who represented 67.0% of all reported cases. Most isolates (86.7%) were from spontaneous ruptures of the tympanum; 11.1% of the isolates were from otogenic sepsis or meningitis. Serotype 19F was the leading serotype (21.5%); serotype 3 (13.9%) was also often encountered. In children aged <5 years, the 7-valent, 10-valent, and 13-valent pneumococcal conjugate vaccines covered 54.3%, 60.2%, and 84.6% of the serotypes, respectively. Reduced penicillin susceptibility (minimum inhibitory concentration >or=0.1 mg/l) was seen in 11.0% of strains; 22.4% of strains were resistant to macrolides. Although based on a very limited selection of acute otitis media isolates, this analysis provides an estimate of the pneumococcal serotypes responsible for otitis media in Germany and underscores the need for future prospective studies.

  18. Awareness and knowledge of sepsis in the general Korean population: comparison with the awareness and knowledge of acute myocardial infarction and stroke

    PubMed Central

    Park, Minji; Kim, Kyuseok; Lee, Jae Hyuk; Kang, Changwoo; Jo, You Hwan; Kim, Dong Hoon; Kang, Kyeong Won; Lee, Soo Hoon; Park, Chanjong; Kim, Joonghee; Chung, Heajin; Park, Hyunmi; Jang, Sujin

    2014-01-01

    Objective Patients with severe sepsis or septic shock require timely, aggressive management to improve their outcomes, and early presentation of patients to the hospital may also be important. Thus, public awareness about sepsis may be important for improved outcomes. However, there are no studies regarding the public awareness of sepsis in the general Korean population. Therefore, the objective of this survey was to gain insight into the public awareness of sepsis. Methods Prospective paper-based and web-based surveys were issued between May and June 2013 to adults aged ≥18 years. Results A total of 1,081 participants responded to the survey (394 paper-based and 687 web-based). Mean age was 38.7±11.4 years, and 541 participants (50%) were men. Of the 1,081 participants, 831 (76.9%) had heard of the term “sepsis.” Of these participants, only 295 (35%) responded correctly regarding the definition of sepsis. However, 1,019 participants (94.3%) had heard of acute myocardial infarction, and 817 of these (80%) correctly defined acute myocardial infarction. Regarding stroke, 1,047 (96.9%) had heard of stroke, and 975 of these responded (93.1%) correctly to the definition of stroke. Conclusion There is poor public awareness about sepsis compared with that of acute myocardial infarction and stroke. This may limit the timely management of severe sepsis and septic shock. PMID:27752551

  19. Effect of ulinastatin on HMGB1 expression in rats with acute lung injury induced by sepsis.

    PubMed

    Wang, S Y; Li, Z J; Wang, X; Li, W F; Lin, Z F

    2015-04-30

    The aim of this study was to investigate the influence of ulinastatin (UTI) on high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression in acute lung injury (ALI) rats with sepsis caused by cecal ligation and puncture (CLP) surgery, as well as to examine the underlying biological mechanism. Thirty rats were randomly and evenly divided into sham (control), CLP, and CLP + UTI groups. Thirty minutes after the surgery, the rats in the CLP + UTI group received UTI via the caudal vein, while normal saline was administered to rats in the other groups. Blood, lung tissues, and bronchoalveolar lavage fluid (BALF) were collected at different time points (6, 12, 24, and 48 h) after surgery for determination of related indicators. Compared with the CLP group, rats in the CLP + UTI group exhibited higher seven day survival rates, less lung injury, and decreased HMGB1 expression in the lung tissue, serum, and BALF. In addition, the levels of TNF-α and IL-6 at 24 h in the CLP + UTI group were markedly lower than those in the CLP group. These results suggest that by deregulation, UTI might decrease the lung injury and increase the survival time of ALI rats by downregulating HMGB1 expression as well as by inhibiting TNF-α and IL-6 levels in serum and BALF.

  20. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury.

    PubMed

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD(+) dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  1. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

    PubMed Central

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD+ dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  2. 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

  3. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    PubMed Central

    Peng, Qian-Yi; Zou, Yu; Zhang, Li-Na; Ai, Mei-Lin; Liu, Wei; Ai, Yu-Hang

    2016-01-01

    Background: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. Methods: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. Results: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-α and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. Conclusions: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI. PMID:27411462

  4. Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis

    PubMed Central

    2014-01-01

    Background Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission. Methods This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission. Results Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001). Conclusions The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes. PMID:24593040

  5. 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.

  6. Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design.

    PubMed

    Prescott, Hallie C; Calfee, Carolyn S; Thompson, B Taylor; Angus, Derek C; Liu, Vincent X

    2016-07-15

    Both quality improvement and clinical research efforts over the past few decades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness," we highlight promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis. We then discuss how this information can be leveraged to improve the success and translatability of clinical trials by using predictive enrichment and other design strategies. Last, we discuss the challenges and limitations to identifying biomarkers and endotypes and incorporating them into routine clinical practice. PMID:27244481

  7. Comparison of serum creatinine and serum cystatin C as biomarkers to detect sepsis-induced acute kidney injury and to predict mortality in CD-1 mice.

    PubMed

    Leelahavanichkul, Asada; Souza, Ana Carolina P; Street, Jonathan M; Hsu, Victor; Tsuji, Takayuki; Doi, Kent; Li, Lingli; Hu, Xuzhen; Zhou, Hua; Kumar, Parag; Schnermann, Jürgen; Star, Robert A; Yuen, Peter S T

    2014-10-15

    Acute kidney injury (AKI) dramatically increases sepsis mortality, but AKI diagnosis is delayed when based on serum creatinine (SCr) changes, due in part, to decreased creatinine production. During experimental sepsis, we compared serum cystatin C (sCysC), SCr, and blood urea nitrogen (BUN) to inulin glomerular filtration rate (iGFR) before or 3-18 h after cecal ligation and puncture (CLP)-induced sepsis in CD-1 mice. sCysC had a faster increase and reached peak levels more rapidly than SCr in both sepsis and bilateral nephrectomy (BiNx) models. sCysC was a better surrogate of iGFR than SCr during sepsis. Combining sCysC with SCr values into a composite biomarker improved correlation with iGFR better than any biomarker alone or any other combination. We determined the renal contribution to sCysC handling with BiNx. sCysC and SCr were lower post-BiNx/CLP than post-BiNx alone, despite increased inflammatory and nonrenal organ damage biomarkers. Sepsis decreased CysC production in nephrectomized mice without changing body weight or CysC space. Sepsis decreased sCysC production and increased nonrenal clearance, similar to effects of sepsis on SCr. sCysC, SCr, and BUN were measured 6 h postsepsis to link AKI with mortality. Mice with above-median sCysC, BUN, or SCr values 6 h postsepsis died earlier than mice with below-median values, corresponding to a substantial AKI association with sepsis mortality in this model. sCysC performs similarly to SCr in classifying mice at risk for early mortality. We conclude that sCysC detects AKI early and better reflects iGFR in CLP-induced sepsis. This study shows that renal biomarkers need to be evaluated in specific contexts.

  8. Serum Neutrophil Gelatinase-Associated Lipocalin in Infants and Children with Sepsis-Related Conditions with or without Acute Renal Dysfunction

    PubMed Central

    Afify, Mohammed Farouk M.; Maher, Sheren Esam; Ibrahim, Nora Mohamed; El-Hamied, Waleed Mahamoud Abd

    2016-01-01

    PURPOSE To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury (AKI) in sepsis-related conditions and its predictive and prognostic values. PATIENTS AND METHODS This study included 65 patients, who were clinically evaluated for sepsis, severe sepsis, or septic shock, and 20 apparently healthy served as controls. Patients were divided into two groups: Group I (AKI-sepsis): 65 newly admitted patients diagnosed as sepsis, who were further divided into three subgroups according to the severity: systemic inflammatory response syndrome, severe sepsis, and septic shock, and Group II (control group): 20 apparently healthy subjects matched for age and sex, serum creatinine and serum NGAL concentrations were estimated initially within 24 hours of admission and after 72 hours of admission in all patients and control groups. RESULTS Serum NGAL increased significantly with increasing severity of renal impairment. Receiver-operating characteristic analysis suggested that serum NGAL cutoff value of 40 ng/mL within the first 24 hours of admission is highly specific and sensitive for predicting AKI, with sensitivity of 90.9% and specificity of 75.8%. CONCLUSION We concluded that early measurement of serum NGAL level in sepsis can serve as a clinically useful marker for early prediction of AKI and for grading of its severity. PMID:27547045

  9. Urine sTREM-1 may be a valuable biomarker in diagnosis and prognosis of sepsis-associated acute kidney injury.

    PubMed

    Su, Longxiang; Xie, Lixin; Liu, Dawei

    2015-07-14

    Urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) has been reported in sepsis diagnosis and prediction of sepsis-associated acute kidney injury (AKI). However, the mechanisms of the role of sTREM-1 for AKI remain unclear. It may be that topical inflammatory response of kidney, not just systemic inflammation, contributes to the elevated secretion of urine sTREM-1 in the process of sepsis-associated AKI. To further evaluate the role of sTREM-1 in this process, a larger-cohort multicenter study and the relevant basic research should be performed to reveal the diagnostic value and mechanism of sTREM-1 during the sepsis-associated AKI process. If successful, then urine sTREM-1 would be a good marker for sepsis and its associated AKI and could contribute to non-invasive diagnosis and monitoring in the clinical setting. Additionally, owing to the complexity of the pathogenesis of sepsis, it is necessary to combine some biomarkers to improve diagnostic performance in the diagnosis of sepsis-associated AKI rather than relying on a single marker.

  10. The anti-MAP and anti-group A carbohydrate antibodies response in streptococcal human infections.

    PubMed

    Mihalcu, F; Stefãnescu, M

    1975-01-01

    The streptococcal infection cases from two outbreaks were serologically examined against two components of the streptococcal cellular wall; the M associated protein (MAP), by a latex agglutination test and the group A carbohydrate (A-CHO), by passive hemagglutination technique. Many positive cases with high levels of both antibodies were found, in rheumatic fever and glomerulo-nephritis, comparatively with the acute streptococcal infections. The differences were statistically significant. The results were correlated with the ASO titres and with the dermic cellular response.

  11. [Sepsis in Emergency Medicine].

    PubMed

    Christ, Michael; Geier, Felicitas; Bertsch, Thomas; Singler, Katrin

    2016-07-01

    Sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host-response to infection". Presence of organ dysfunction is associated with a mortality of 10% and higher in hospitalized sepsis patients.Introduction of standards in diagnosis and treatment of sepsis in intensive care units has not considerably reduced sepsis mortality. About 80% of patients with sepsis are transferred to intensive care units from usual care wards and emergency departments. Thus, it is tempting to speculate whether opportunities for further improvement of sepsis management exist outside of intensive care units. Performing a "quick sequential organ assessment" (qSOFA; two of following criteria have to be present: respiratory rate >22/min; sytolic blood pressure <100mmHg; altered mental status) supports to identify patients with suspicion of an infection and an increased risk of death within the hospital. Subsequent treatment according to current guidelines on sepsis management will reduce in-hospital mortality of sepsis patients. Indeed, we were able to show a substantial decrease of in-hospital mortality of about 20% in patients presenting with community acquired pneumonia to the emergency department.In summary, decision of further management of sepsis patients has to be done outside intensive care units at the time of initial presentation to professional care givers. Sepsis management in acute care settings should include a structured and standardized protocol to further improve survival in affected patients with even mild organ dysfunction.

  12. Immunoblotting of streptococcal antigens in guttate psoriasis.

    PubMed

    Wilson, A G; Clark, I; Heard, S R; Munro, D D; Kirby, J D

    1993-02-01

    Guttate psoriasis may be precipitated by acute streptococcal infection, usually of the upper respiratory tract. We have studied the immune response to streptococci in 26 patients presenting with a first or recurrent episode of acute guttate psoriasis (AGP), using immunoblotting. Eighteen of 26 patients studied had a demonstrable response to a wide range of streptococcal antigens using this approach, compared with 14 of 26 patients who demonstrated a response using more conventional antistreptococcal antibody tests. Patients with AGP had a significantly higher antibody detection score using immunoblotting than did control subjects (P < 0.005). We conclude that immunoblotting is a useful technique in studying this condition and may be of benefit in exploring the immunopathogenesis of AGP.

  13. Post-streptococcal reactive arthritis: where are we now

    PubMed Central

    Pathak, Himanshu; Marshall, Tarnya

    2016-01-01

    A 35-year-old man presented with polyarthritis and constitutional symptoms, and a recent history of multiple tick bites and skin rash on trekking holiday. He did not respond to oral doxycycline and cephalexine for presumed Lyme's disease. Further investigation confirmed strongly positive streptococcal serology. There was absence of clinical or echocardiography evidence of heart involvement and immunological screening for inflammatory arthritis was negative. In the absence of other major Jones criteria for acute rheumatic fever, besides polyarthritis and the serological evidence of a recent streptococcal infection, a diagnosis of post-streptococcal reactive arthritis (PSRA) was also made. He responded well to penicillin therapy and has been started on oral penicillin prophylaxis as per available guidance. As streptococcal infections in the adult population are increasingly reported, it is a timely opportunity to revisit PSRA, and develop comprehensive treatment and antibiotic prophylaxis guidelines. PMID:27520996

  14. Post-streptococcal reactive arthritis: where are we now.

    PubMed

    Pathak, Himanshu; Marshall, Tarnya

    2016-01-01

    A 35-year-old man presented with polyarthritis and constitutional symptoms, and a recent history of multiple tick bites and skin rash on trekking holiday. He did not respond to oral doxycycline and cephalexine for presumed Lyme's disease. Further investigation confirmed strongly positive streptococcal serology. There was absence of clinical or echocardiography evidence of heart involvement and immunological screening for inflammatory arthritis was negative. In the absence of other major Jones criteria for acute rheumatic fever, besides polyarthritis and the serological evidence of a recent streptococcal infection, a diagnosis of post-streptococcal reactive arthritis (PSRA) was also made. He responded well to penicillin therapy and has been started on oral penicillin prophylaxis as per available guidance. As streptococcal infections in the adult population are increasingly reported, it is a timely opportunity to revisit PSRA, and develop comprehensive treatment and antibiotic prophylaxis guidelines. PMID:27520996

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

    PubMed

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

    2014-01-01

    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 permselectivity. 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-α 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.

  16. Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

    PubMed Central

    Wernly, Bernhard; Lichtenauer, Michael; Franz, Marcus; Kabisch, Bjoern; Muessig, Johanna; Masyuk, Maryna; Kelm, Malte; Hoppe, Uta C.; Jung, Christian

    2016-01-01

    Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient

  17. Predictors of Acute Hemodynamic Decompensation in Early Sepsis: An Observational Study

    PubMed Central

    Lee, Young Im; Smith, Robert L.; Gartshteyn, Yevgeniya; Kwon, Sophia; Caraher, Erin J.; Nolan, Anna

    2016-01-01

    Background The study of sepsis is hindered by its heterogeneous time course and evolution. A subgroup of patients with severe sepsis develops shock soon after the initiation of treatment while others present hypotensive. We sought to determine the incidence of hypotension after the initiation of treatment for sepsis, and characterize their clinical features and course. Methods A retrospective review of electronic medical record of all septic patients (n = 542) that met the definition of septic shock within 24 hours of admission (2011 - 2012) at an urban Veteran Affairs Hospital was performed. Subjects either had 1) initial normotension (INT) with hypotension developing within 24 hours or 2) initial hypotension (IH). Logistic regression was used to model associated factors of INT/IH. Results INT occurred in 62 patients (11%) with average initial blood pressure of 120/71 mm Hg and developed hypotension to 79/48 mm Hg. IH was identified in 52 patients (10%) with average presenting blood pressure of 81/46 mm Hg. INT showed evidence of increased sympathetic tone with significantly higher heart rate, blood pressure and temperature. INT patients were younger, more frequently on alpha-blockers, and more likely septic from pneumonia compared to IH patients. INT and IH patients had similar timing of antibiotic initiation, amount of 24-hour fluid resuscitation, vasopressor use, organ dysfunction and mortality at 28 days. Using alpha-blockers, being Caucasian, and having higher temperatures were independent predictors of INT. Conclusion INT is a distinctive presentation of septic shock characterized by rapid deterioration during early treatment. By further studying this subgroup, mediators of septic shock may be identified that clarify pathophysiology and provide timely targeted treatment. PMID:27429677

  18. Functional Characterization of Streptococcal Pyrogenic Exotoxin J, a Novel Superantigen

    PubMed Central

    McCormick, John K.; Pragman, Alexa A.; Stolpa, John C.; Leung, Donald Y. M.; Schlievert, Patrick M.

    2001-01-01

    Streptococcal toxic shock syndrome (STSS) is a highly lethal, acute-onset illness that is a subset of invasive streptococcal disease. The majority of clinical STSS cases have been associated with the pyrogenic toxin superantigens (PTSAgs) streptococcal pyrogenic exotoxin A or C (SPE A or C), although cases have been reported that are not associated with either of these exotoxins. Recent genome sequencing projects have revealed a number of open reading frames that potentially encode proteins with similarity to SPEs A and C and to other PTSAgs. Here, we describe the cloning, expression, purification, and functional characterization of a novel exotoxin termed streptococcal pyrogenic exotoxin J (SPE J). Purified recombinant SPE J (rSPE J) expressed from Escherichia coli stimulated the expansion of both rabbit splenocytes and human peripheral blood lymphocytes, preferentially expanded human T cells displaying Vβ2, -3, -12, -14, and -17 on their T-cell receptors, and was active at concentrations as low as 5 × 10−6 μg/ml. Furthermore, rSPE J induced fevers in rabbits and was lethal in two models of STSS. Biochemically, SPE J had a predicted molecular weight of 24,444 and an isoelectric point of 7.7 and lacked the ability to form the cystine loop structure characteristic of many PTSAgs. SPE J shared 19.6, 47.1, 38.8, 18.1, 19.6, and 24.4% identity with SPEs A, C, G, and H, streptococcal superantigen, and streptococcal mitogenic exotoxin Z-2, respectively, and was immunologically cross-reactive with SPE C. The characterization of a seventh functional streptococcal PTSAg raises important questions relating to the evolution of the streptococcal superantigens. PMID:11179302

  19. 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-α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) 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

  20. Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria. Comparison between sepsis and trauma.

    PubMed

    Kushimoto, Shigeki; Gando, Satoshi; Saitoh, Daizoh; Ogura, Hiroshi; Mayumi, Toshihiko; Koseki, Kazuhide; Ikeda, Toshiaki; Ishikura, Hiroyasu; Iba, Toshiaki; Ueyama, Masashi; Eguchi, Yutaka; Otomo, Yasuhiro; Okamoto, Kohji; Endo, Shigeatsu; Shimazaki, Shuji

    2008-12-01

    The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) study group recently announced new diagnostic criteria for DIC. These criteria have been prospectively validated and demonstrated to progress to overt DIC as defined by the International Society on Thrombosis and Haemostasis (ISTH). Although an underlying condition is essential for the development of DIC, it has never been clarified if patients with different underlying disorders have a similar course. Among 329 patients with DIC diagnosed by the JAAM criteria, those with underlying sepsis (n = 98) or trauma (n = 95) were compared. The 28-day mortality rate was significantly higher in sepsis patients than trauma patients (34.7% vs. 10.5%, p < 0.0001). Within three days of fulfilling the JAAM criteria, sepsis patients had a lower platelet count, higher prothrombin time ratio, higher systemic inflammatory response syndrome score, and higher Sequential Organ Failure Assessment score compared with trauma patients. On day 3, a significantly higher percentage of trauma patients than sepsis patients showed improvement of DIC (64.2% vs. 30.6%, p < 0.001). These differences were mainly due to patients with lower JAAM DIC scores. More than 50% of the JAAM DIC patients with sepsis who died within 28 days could not be detected by ISTH DIC criteria during the initial three days. In contrast, most trauma patients who died within 28 days had DIC simultaneously diagnosed by JAAM and ISTH criteria, except for those with brain death. These findings suggest that coagulation abnormalities, organ dysfunction, and the outcome of JAAM DIC differ between patients with sepsis and trauma.

  1. Streptococcal diseases worldwide: present status and prospects*

    PubMed Central

    Rotta, J.; Tikhomirov, E.

    1987-01-01

    Infections caused by streptococci pathogenic for man are some of the most common bacterial diseases in temperate zones and occur very frequently in tropical and subtropical countries. The highest morbidity occurs from infections caused by group A streptococci; these infections can lead to rheumatic fever and acute glomerulonephritis. The incidence of rheumatic fever and the prevalence of rheumatic heart disease are several times higher in tropical countries than temperate countries. Recent developments in fundamental and applied research are throwing light on various aspects of the problem, e.g., the rapid (non-culture) identification of group A streptococcal infection. Analyses of the chemical structure of the M-protein molecule of group A streptococcus and of the biological properties of the epitopes of the M-protein have provided encouraging results. Furthermore, synthetic analogues of the protective immunodominant polypeptides of the M-protein have been prepared. The prospect of a streptococcal vaccine for preventing group A streptococcal diseases is thus more realistic. The control of infections caused by group B streptococci is important for the health of neonates. The identification of the chemical structure of the major group B streptococcal types may lead to development of a vaccine in the future. An alternative approach would entail the use of anti-group-B immunoglobulins, but a number of questions have to be answered before the new control measures can be introduced. The streptococci causing bacterial pneumonia, subacute bacterial endocarditis and possibly dental caries have been widely studied and promising advances have been made towards the introduction of better control of the diseases caused by these pathogens. PMID:3325183

  2. Streptococcal diseases worldwide: present status and prospects.

    PubMed

    Rotta, J; Tikhomirov, E

    1987-01-01

    Infections caused by streptococci pathogenic for man are some of the most common bacterial diseases in temperate zones and occur very frequently in tropical and subtropical countries. The highest morbidity occurs from infections caused by group A streptococci; these infections can lead to rheumatic fever and acute glomerulonephritis. The incidence of rheumatic fever and the prevalence of rheumatic heart disease are several times higher in tropical countries than temperate countries.Recent developments in fundamental and applied research are throwing light on various aspects of the problem, e.g., the rapid (non-culture) identification of group A streptococcal infection. Analyses of the chemical structure of the M-protein molecule of group A streptococcus and of the biological properties of the epitopes of the M-protein have provided encouraging results. Furthermore, synthetic analogues of the protective immunodominant polypeptides of the M-protein have been prepared. The prospect of a streptococcal vaccine for preventing group A streptococcal diseases is thus more realistic.The control of infections caused by group B streptococci is important for the health of neonates. The identification of the chemical structure of the major group B streptococcal types may lead to development of a vaccine in the future. An alternative approach would entail the use of anti-group-B immunoglobulins, but a number of questions have to be answered before the new control measures can be introduced. The streptococci causing bacterial pneumonia, subacute bacterial endocarditis and possibly dental caries have been widely studied and promising advances have been made towards the introduction of better control of the diseases caused by these pathogens. PMID:3325183

  3. TAT-SNAP-23 treatment inhibits the priming of neutrophil functions contributing to shock and/or sepsis-induced extra-pulmonary acute lung injury.

    PubMed

    Bai, Jianwen; Tang, Lunxian; Lomas-Neira, Joanne; Chen, Yaping; McLeish, Kenneth R; Uriarte, Silvia M; Chung, Chun-Shiang; Ayala, Alfred

    2015-01-01

    Respiratory burst function of neutrophils is thought to play a pivotal role in the development of pathologies such as indirect (extra-pulmonary) acute lung injury (iALI), as well as sepsis. The current study was conducted to determine the effect of an HIV transactivator of transcription (TAT)-fusion protein containing a soluble N-ethylmaleimide-sensitive factor attachment protein receptor domain from synaptosome-associated protein-23 (SNAP-23) on the shock/sepsis- and sepsis-enhanced neutrophil burst capacity using the clinical relevant two-hit iALI mouse model and the classical cecal ligation and puncture (CLP) septic model. TAT-SNAP-23 significantly decreased the blood neutrophil respiratory burst in vitro, and also in vivo in CLP and hemorrhaged mice. We found that the neutrophil influx to the lung tissue, as measured by myeloperoxidase levels and neutrophil-specific esterase(+) cells, was also decreased in the TAT-SNAP-23-treated group. Consistent with this, treatment of TAT-SNAP-23 significantly reduced the disruption of lung tissue architecture and protein concentration of bronchoalveolar lavage fluid in iALI mice compared with vehicle-treated iALI mice. In addition, although TAT-SNAP-23 did not alter the extent of local cytokine/chemokine expression, the in vitro migration capacity of neutrophils was blunted from septic and hemorrhagic mice. These data support our hypothesis that TAT-SNAP-23 reduces neutrophil dysfunction in iALI and sepsis by inhibiting neutrophil respiratory burst.

  4. Group A Streptococcal Infection in Pregnancy and the Puerperium.

    PubMed

    Sosa, Mary Ellen Burke

    2016-01-01

    There has been an increasing incidence worldwide of invasive group A streptococcal disease in pregnancy and the puerperal period over the past 30 years. Group A Streptococcus (GAS) was identified as the major cause of maternal morbidity and mortality from sepsis before the identification that hand washing techniques could prevent the transmission of the bacteria. Hand washing remains the cornerstone of prevention as transmission can occur directly from an asymptomatic colonized healthcare provider, other patients, or a community-acquired source. Pregnancy and the puerperal period are associated with significant maternal physiologic changes that must be identified and clarified to identify signs and symptoms of GAS so that treatment can be initiated at the earliest moment. Treatment of group A streptococcal sepsis follows the guidelines developed under the Surviving Sepsis Campaign model. Maternal outcomes are improved by identifying risk factors and working with the perinatal team to implement rapid intervention. Even with prompt treatment of invasive group A Streptococcus, it remains the most common cause of infection that results in severe maternal morbidity and death in the world. PMID:27104603

  5. Effect of Fluconazole on Phagocytic Response of Polymorphonuclear Leukocytes in a Rat Model of Acute Sepsis

    PubMed Central

    Khan, Haseeb Ahmad

    2005-01-01

    Recently, fluconazole (FLZ) has been shown to improve survival and reduce multiorgan failure in experimental and clinical septic shock. The mechanism by which FLZ affords protection against sepsis remains obscure. This study examines the effect of FLZ on phagocytic activity of polymorphonuclear leukocytes (PMNs) in a rat model of septic shock by inducing fecal peritonitis in male Wistar rats using intraperitoneal instillation (1 mL/kg) of fecal suspension in saline (1:1 w/v). Sham control rats received sterile fecal suspension and vehicle treatment. FLZ was administered in the doses of 0, 3, 10, and 30 mg/kg by gavage 30 minutes before fecal instillation. The samples of peritoneal fluid were collected 8 hours following fecal inoculation for the evaluation of phagocytic response of PMNs using zymosan-induced luminol-dependent chemiluminescence (CL). Fecal peritonitis caused massive infiltration of PMNs in the peritoneal cavity (ANOVA F4.45 = 6.322, P < .001). Although FLZ reduced the infiltration of PMNs, this effect was neither significant nor dose dependent. The actual CL response was significantly higher in the peritoneal fluid of rats subjected to peritonitis, which was significantly and dose-dependently attenuated by FLZ treatment (ANOVA F4.45 = 11.048, P < .001). Normalization of CL response for 1000 PMNs revealed that FLZ dose-dependently albeit insignificantly reduced the activity of PMNs. The high dose of FLZ caused 2.29-fold decrement in the area under curve (AUC) pertaining to cumulative CL response. The findings of this study suggest that FLZ protects rats against septic shock by inhibiting PMN-mediated inflammatory cascade without compromising their phagocytic activity. PMID:15770061

  6. Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

    PubMed

    Schaalan, Mona F; Mohamed, Walid A

    2016-09-01

    The antimicrobial β-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1α, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFα (4.4-times) and TGFβ1 (3.2-times) compared to controls (p < 0.05). Further, HEPC and HIF-1α levels were also increased (8.8- and 3.6-times control levels), while EPO levels were decreased (77.8%) from control levels. After 12 weeks of antibiotic therapy, all septic AKI patients showed significant improvement of the altered markers of kidney dysfunction. In line with significant reductions in serum TNFα and TGFβ1 (25.5% and 26.2%, respectively), HEPC and HIF-1α levels were significantly decreased (31.6% and 19.3%), and EPO levels increased (1.9-fold) compared to pretreatment values. There was a significant positive correlation between HEPC levels and kidney function markers (SCr and BUN), inflammatory TNFα and TGFβ1 and serum HIF-1α and pAKT in septic AKI patients before and after treatment. Based on the results here, we conclude that HEPC, EPO and HIF-1α are involved in the pathogenesis of sepsis-induced AKI and confirm the dominating effects of inflammatory determinants over hypoxia

  7. Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

    PubMed

    Schaalan, Mona F; Mohamed, Walid A

    2016-09-01

    The antimicrobial β-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1α, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFα (4.4-times) and TGFβ1 (3.2-times) compared to controls (p < 0.05). Further, HEPC and HIF-1α levels were also increased (8.8- and 3.6-times control levels), while EPO levels were decreased (77.8%) from control levels. After 12 weeks of antibiotic therapy, all septic AKI patients showed significant improvement of the altered markers of kidney dysfunction. In line with significant reductions in serum TNFα and TGFβ1 (25.5% and 26.2%, respectively), HEPC and HIF-1α levels were significantly decreased (31.6% and 19.3%), and EPO levels increased (1.9-fold) compared to pretreatment values. There was a significant positive correlation between HEPC levels and kidney function markers (SCr and BUN), inflammatory TNFα and TGFβ1 and serum HIF-1α and pAKT in septic AKI patients before and after treatment. Based on the results here, we conclude that HEPC, EPO and HIF-1α are involved in the pathogenesis of sepsis-induced AKI and confirm the dominating effects of inflammatory determinants over hypoxia

  8. A Multicentre Study of Acute Kidney Injury in Severe Sepsis and Septic Shock: Association with Inflammatory Phenotype and HLA Genotype

    PubMed Central

    Legrand, Matthieu; Gayat, Etienne; Faivre, Valérie; Megarbane, Bruno; Azoulay, Elie; Fieux, Fabienne; Charron, Dominique; Loiseau, Pascale; Busson, Marc

    2012-01-01

    Background To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis. Methodology/Principal Findings Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004). Conclusions AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT. PMID:22701553

  9. Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.

    PubMed

    Zielske, Joerg; Bohne, Silvia; Brunkhorst, Frank M; Axer, Hubertus; Guntinas-Lichius, Orlando

    2014-11-01

    Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs.

  10. Ulinastatin is a novel candidate drug for sepsis and secondary acute lung injury, evidence from an optimized CLP rat model.

    PubMed

    Wang, Ning; Liu, Xin; Zheng, Xinchuan; Cao, Hongwei; Wei, Guo; Zhu, Yuanfeng; Fan, Shijun; Zhou, Hong; Zheng, Jiang

    2013-11-01

    Ulinastatin is a potent multivalent serine protease inhibitor, which was recently found with therapeutic potentials in treating sepsis, and the most life-threatening complication of critically ill population. However, the pharmacological features and possible mechanisms need to be further elucidated in reliable and clinical relevant sepsis models. As known, sepsis induced by surgery of cecal ligation and puncture (CLP) is widely accepted as the gold standard animal model, but the inconsistency of outcomes is the most obvious problem. In the present experiments, we reported an improved rat CLP model with much more consistent outcomes using self-made three edged puncture needles in our lab. Results from this optimized model revealed that ulinastatin improved survivals of CLP rats, attenuated proinflammatory response and prevented systemic disorder and organ dysfunction. Ulinastatin was also found to be effective in ameliorating sepsis-related ALI, a syndrome most frequent and fatal in sepsis. The molecular mechanism investigation showed that ulinastatin's protection against ALI was probably related to the down-regulation of NF-κB activity and inhibition of TNF-α, IL-6 and elastase expressions in the lung tissue. In conclusion, based on a successful establishment of optimized rat CLP model ulinastatin is proved to be an effective candidate for sepsis treatment, due to its anti-inflammation and anti-protease activities that ameliorate systemic disorders, prevent organ injuries and thus improve the survival outcomes of sepsis in animals.

  11. T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis

    PubMed Central

    Anantha, R V; Mazzuca, D M; Xu, S X; Porcelli, S A; Fraser, D D; Martin, C M; Welch, I; Mele, T; Haeryfar, S M M; McCormick, J K

    2014-01-01

    Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis. PMID:24965554

  12. 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.

  13. 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

  14. Streptococcal Infection-related Nephritis (SIRN) Manifesting Membranoproliferative Glomerulonephritis Type I.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Yamamoto, Yasutaka; Kobayashi, Naoto; Oda, Takashi; Yamaguchi, Yutaka; Shibata, Takanori

    2016-01-01

    We herein report the case of an 18-year-old boy who developed nephrotic syndrome and hypertension after upper airway inflammation. Post-streptococcal acute glomerulonephritis was diagnosed on the basis of a high antistreptolysin O titer, hypocomplementemia, proteinuria, and microscopic hematuria. A renal biopsy was performed due to persistent proteinuria, and the pathological diagnosis was membranoproliferative glomerulonephritis (MPGN) type I. Glomeruli showed positive staining for nephritis-associated plasmin receptor (NAPlr), a nephritogenic group A streptococcal antigen, and plasmin activity was found in a similar distribution as NAPlr deposition. This rare case of streptococcal infection-related nephritis (SIRN) manifesting MPGN type I supports the histological diversity of SIRN. PMID:26984084

  15. 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

    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 β-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

  16. 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

  17. Treatment of sepsis and ARDS with extracorporeal membrane oxygenation and interventional lung assist membrane ventilator in a patient with acute lymphoblastic leukemia.

    PubMed

    Gorjup, Vojka; Fister, Misa; Noc, Marko; Rajic, Vladan; Ribaric, Suada Filekovic

    2012-07-01

    We report an 18-year-old ice skater with acute lymphoblast leukemia. She developed Staphylococcus epidermidis bacteremia, severe sepsis, septic shock, and ARDS following chemotherapy-induced severe bone marrow failure. She was successfully treated with extraordinary life support measures, which included extracorporeal membrane oxygenation, double lumen lung ventilation for management of hemoptysis, and lung assist membrane ventilation. After 57 days of ICU treatment and a year of rehabilitation, the patient has fully regained her functional status, is now finishing high school, and is ice skating again.

  18. High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

    PubMed Central

    2011-01-01

    Background To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses. Methods Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured. Results Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed. Conclusions During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators. PMID:22204611

  19. Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting NF-κB and upregulating endothelial nitric oxide synthase.

    PubMed

    Souza, Ana Carolina C Pessoa de; Volpini, Rildo A; Shimizu, Maria Heloísa; Sanches, Talita Rojas; Camara, Niels Olsen Saraiva; Semedo, Patrícia; Rodrigues, Camila Eleutério; Seguro, Antonio Carlos; Andrade, Lúcia

    2012-04-15

    The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-κB activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP+EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-l-arginine methyl ester (l-NAME) simultaneously with EPO administration (CLP+EPO+l-NAME). A fifth group (CLP+EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP+EPO rats presented significantly higher inulin clearance than did CLP and CLP+EPO+l-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP+EPO rats; and inulin clearance was significantly higher in CLP+EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP+EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-α activation, NF-κB activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-κB downregulation.

  20. Effects of Fluid Resuscitation With 0.9% Saline Versus a Balanced Electrolyte Solution on Acute Kidney Injury in a Rat Model of Sepsis*

    PubMed Central

    Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V.; Cove, Matthew E.; Singbartl, Kai; Kellum, John A.

    2014-01-01

    Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short

  1. Evaluation of short-term clinical efficacy of 3-day therapy with azithromycin in comparison with 5-day cefcapene-pivoxyl for acute streptococcal tonsillopharyngitis in primary care.

    PubMed

    Koga, Takeharu; Rikimaru, Toru; Tokunaga, Naoto; Higashi, Toshihiro; Nakamura, Masahiro; Ichikawa, Yoichiro; Matsuo, Kazuhiko

    2011-08-01

    Group A streptococcal (GAS) tonsillopharyngitis is one of the few conditions for which antibiotics are advocated among common upper respiratory infections. Although a 3-day course of azithromycin is attracting attention as a treatment of choice for the condition, it is not clear if the efficacy of the treatment is comparable with that of treatment with cephalosporins. A prospective, randomized, comparative multicenter study was conducted to compare the efficacy of azithromycin (AZM) given once daily for 3 days with that of cefcapene-pivoxyl (CFPN-PI) divided into three daily doses for 5 days. 88 patients (male: 38, mean age: 16.5) were treated with AZM and 69 (male: 34, mean age: 16.9) with CFPN-PI. The symptoms of all but 5 (2 for AZM and 3 for CFPN-PI) of the patients were resolved by the 8th day of the treatment. By the 4th day of the treatment, criteria for clinical efficacy were fulfilled in 71 (80.7%) subjects who were treated with AZM and in 48 (67.6%) of those treated with CFPN-PI (p = 0.07). The same figures on the 8th day of the treatment were 86 (97.7%) and 68 (95.8%), respectively (p = 0.66), confirming there was no significant difference in clinical efficacy between the two treatments. Mild adverse reactions were reported by two patients treated with AZM and by none treated with CFPN-PI. The clinical efficacy of a 3-day course with AZM was comparable with that of a 5-day course of CFPN-PI for GAS tonsillopharyngitis.

  2. Streptococcal infections of skin and PANDAS.

    PubMed

    Carelli, Rosanna; Pallanti, Stefano

    2014-01-01

    Group A streptococcal infections are associated with a variety of infections and a subset of obsessive-compulsive disorder and/or tic disorders. Screening of obsessive-compulsive symptoms and tics in patient with streptococcal infection of skin must be effective in identifying subjects who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). PMID:24502308

  3. Streptococcal infections of skin and PANDAS.

    PubMed

    Carelli, Rosanna; Pallanti, Stefano

    2014-01-01

    Group A streptococcal infections are associated with a variety of infections and a subset of obsessive-compulsive disorder and/or tic disorders. Screening of obsessive-compulsive symptoms and tics in patient with streptococcal infection of skin must be effective in identifying subjects who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

  4. Removal of regulatory T cells prevents secondary chronic infection but increases the mortality of subsequent sub-acute infection in sepsis mice

    PubMed Central

    Wang, Xiaoya; Zhao, Yong; Wang, Yi; Zhao, Xiaomin; Chang, Lingling; Liu, Shan-lu; Tong, Dewen; Zhang, Hai; Huang, Yong

    2016-01-01

    The immunosuppression following initial septic insult impairs resistance to secondary infection. Modulation of lymphocytes population may help to develop an effective therapeutic strategy. In this study, lipopolysaccharide (LPS)-induced endotoxemia was employed as the initial septic insult. 24 hours later, mice underwent cecal ligation and puncture to induce chronic or sub-acute peritonitis. Potential usefulness of T regs deletion antibody (anti-CD25) in improving LPS-induced immunosuppression and the survival of subsequent different infections were evaluated. LPS injection induced lymphocyte loss and led to decreased IL-6, TNF-α and IFN-γ, and weakened bacteria clearance upon chronic peritonitis at 24 h post-LPS, whereas reconstitution with lymphocytes reversed these changes. LPS-induced T regs expansion contributed to T and NK cells decrease in number and activity during sepsis. Depletion of T regs using anti-CD25 antibodies partly prevented lymphocyte loss and increased the responses of T and NK cells to subsequent stimulation, resulting in significantly increased bacterial clearance and survival in a 2-hit model of chronic peritonitis, but which significantly increased early mortality upon subsequently sub-acute infection. Yet, using lower dosage of anti-CD25 antibodies to moderate down-regulate T regs levels could partly improve bacterial clearance and survival in either chronic or sub-acute infection. These results demonstrate that using anti-CD25 antibodies to deplete T regs can ameliorate immunosuppression through increasing T cells and NK cells responses in sepsis, which is beneficial for preventing subsequently chronic infection, but will probably bring some deleterious effects for subsequent sub-acute infection. PMID:26918357

  5. STUDIES ON STREPTOCOCCAL FIBRINOLYSIS

    PubMed Central

    1947-01-01

    A method for the measurement of fibrinolysin production by beta hemolytic streptococci is described. The test was shown to be highly accurate in that repeated determinations showed only small variations. A study of 766 strains of beta hemolytic streptococci isolated from normal soldiers and patients with respiratory disease showed that fibrinolysin was produced by Lancefield groups A, C, and G, and, in addition, by a few strains of groups B and F. Group A streptococci produced more fibrinolysin on the average than the other groups. The median titers were 117 for group A, 61 for group C, and 20 for group G streptococci. In a study of 388 typed group A streptococci from different subjects the fibrinolytic capacity of an organism was shown to be related to the serological type. The importance of this observation in relation to the role of streptococcal fibrinolysis in infections is discussed. Finally, it was demonstrated that strains of streptococci which produced large amounts of fibrinolysin were capable of stimulating antifibrinolysin formation in patients whereas strains that produced small amounts only occasionally caused antibody formation. PMID:19871628

  6. 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-1β and TNFα) 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

  7. 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

  8. Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury

    PubMed Central

    2012-01-01

    Background Recent studies showed that overwhelming inflammatory response mediated by the toll-like receptor (TLR)-related pathway was important in the development of acute lung injury (ALI). The aim of this study was to determine whether common genetic variation in four genes of the TLR signaling pathway were associated with sepsis-induced ALI susceptibility and risk of death in Chinese Han population. Methods Fourteen tag single nucleotide polymorphisms (tagSNPs) in MyD88, IRAK1, IRAK4 and TRAF6 were genotyped in samples of sepsis-induced ALI (n = 272) and sepsis alone patients (n = 276), and tested for association in this case-control collection. Then, we investigated correlation between the associated SNP and the mRNA expression level of the corresponding gene. And we also investigated correlation between the associated SNP and tumor necrosis factor alpha (TNF-α) as well as interleukin-6 (IL-6) concentrations in peripheral blood mononuclear cells (PBMCs) exposed to lipopolysaccharides (LPS) ex vivo. The mRNA expression level was determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Results The association analysis revealed that rs4755453, an intronic SNP of TRAF6, was significantly associated with susceptibility to sepsis-induced ALI. The C allele frequency of rs4755453 in the sepsis alone group was significantly higher than that in the sepsis-induced ALI group (P = 0.00026, odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.37–0.74). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. TRAF6 mRNA expression levels in PBMCs from homozygotes of the rs4755453G allele were significantly higher than that in heterozygotes and homozygotes of the rs4755453C allele at baseline (P = 0.012 and P = 0.003, respectively) as well as after

  9. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

    PubMed Central

    2013-01-01

    Introduction Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis. Methods We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis. Results Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI. Conclusions The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis. PMID:24330815

  10. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  11. Group A streptococcal pharyngitis and immune-mediated complications: from diagnosis to management.

    PubMed

    Shulman, Stanford T; Tanz, Robert R

    2010-02-01

    Group A streptococcal pharyngitis remains the most important bacterial pharyngitis because of its frequency and potential complications. Group A streptococcal pharyngitis is most common in children 5-11 years of age in winter-spring, and a rapid test or culture is necessary for accurate diagnosis. We propose a management strategy for those geographic areas with very low acute rheumatic fever rates, emphasizing selective testing that avoids testing those patients with viral-like features (e.g., rhinorrhea and cough). Acute rheumatic fever is the most important immune-mediated sequela and has become rare in most areas of the USA and Western Europe, most probably due to decreased circulation of highly rheumatogenic group A streptococcal strains.

  12. Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score

    PubMed Central

    Zhang, Zhongheng; Ji, Xuqing

    2016-01-01

    Oxygen therapy is widely used in emergency and critical care settings, while there is little evidence on its real therapeutic effect. The study aimed to explore the impact of arterial oxygen partial pressure (PaO2) on clinical outcomes in patients with sepsis. A large clinical database was employed for the study. Subjects meeting the diagnostic criteria of sepsis were eligible for the study. All measurements of PaO2 were extracted. The primary endpoint was death from any causes during hospital stay. Survey data analysis was performed by using individual ICU admission as the primary sampling unit. Quadratic function was assumed for PaO2 and its interaction with other covariates were explored. A total of 199,125 PaO2 samples were identified for 11,002 ICU admissions. Each ICU stay comprised 18 PaO2 samples in average. The fitted multivariable model supported our hypothesis that the effect of PaO2 on mortality risk was in quadratic form. There was significant interaction between PaO2 and SAPS-I (p = 0.007). Furthermore, the main effect of PaO2 on SOFA score was nonlinear. The study shows that the effect of PaO2 on mortality risk is in quadratic function form, and there is significant interaction between PaO2 and severity of illness. PMID:27734905

  13. Neutropenic sepsis.

    PubMed

    Jones, Tracie

    2016-09-28

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The article discussed the causes, signs and symptoms of neutropenic sepsis in adult patients after cancer treatment. It also explored the prevention and management of this condition. PMID:27682569

  14. Improving management of sepsis in the community.

    PubMed

    Culligan, Fiona

    2016-08-31

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Pathological changes in the circulation reduce the blood supply to major organs, causing them to fail. This may lead to death, therefore rapid recognition and treatment of sepsis is vital. Sepsis research has focused on patients in acute hospital settings. However, most cases of sepsis originate in the community, suggesting that the identification of sepsis and delivery of timely care is necessary before hospital admission. Therefore, it is essential that nurses practising in the community are provided with appropriate sepsis guidelines that can be implemented immediately. The UK Sepsis Trust has developed the General Practice Sepsis Decision Support Tool, which has been designed specifically for use in the community. This article provides an overview of how the tool is used in the community and how it works in conjunction with the 'Sepsis Six' care bundle and care bundles for hospital settings. Changes to the terminology used in relation to sepsis and recent guidelines are also explained. PMID:27577313

  15. Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression.

    PubMed

    Meng, L; Lv, Z; Yu, Z Z; Xu, D; Yan, X

    2016-07-29

    This study aimed to explore the protective effect of quercetin on acute lung injury (ALI) in rats with sepsis and the related mechanism. Rats were administered different doses of quercetin intraperitoneally, and blood samples and lung tissue were collected at 24 h after treatment. Arterial blood gases, lung water content, protein content, and cell counts in bronchoalveolar lavage fluid (BALF) were measured. Morphological changes in lung tissue pathology were observed under a light microscope. Serum intercellular adhesion molecule (ICAM)-1 and macrophage inflammatory protein 2 (MIP-2) levels were detected and ICAM-1 and MIP-2 mRNA expression in lung tissue was determined. Compared with that in the control model group, arterial blood gases, lung water content, protein content, and cell counts in BALF improved in the high- and low-dose quercetin groups (P < 0.05), with maximal improvement observed for the high-dose quercetin (P < 0.05). Lesions on the lungs improved in the high- and low-dose quercetin groups than those in the control model group, and the high-dose quercetin group showed better improvement than the low-dose group (P < 0.05). Compared with that in the sham-operated group, both serum and lung tissue ICAM-1 and MIP-2 expression increased significantly in the model group (P < 0.05). The quercetin groups presented lower ICAM-1 and MIP-2 expression than the control model group, with the lowest expression observed in the high-dose group (P < 0.05). Quercetin may protect against ALI in rats with sepsis by inhibiting ICAM-1 and MIP-2 expression.

  16. 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.

  17. Group B Streptococcal Endocarditis in Obstetric and Gynecologic Practice

    PubMed Central

    Crespo, Antonio; Retter, Avi S.

    2003-01-01

    Background: We describe a case and review ten other instances of group B streptococcal endocarditis in the setting of obstetric and gynecologic practice reported since the last review in 1985. Case: Abortion remains a common antecedent event, but in contrast to earlier reports, most patients did not have underlying valvular disease, the tricuspid valve was most often involved, and mortality was low. Patients with tricuspid valve infection tended to have a subacute course, whereas those with aortic or mitral involvement typically had a more acute, fulminant course. Conclusion: Despite an improvement in mortality, morbidity remains high, with 8 of 11 patients having clinically significant emboli. PMID:14627217

  18. The immune cellular response tested by lymphocyte transformation in the streptococcal infections.

    PubMed

    Mihalcu, F; Stefănescu, ? M; Teodorescu, ? M

    1975-01-01

    Thirty-five children between 6 and 17 years treated in the clinic for scarlet fever, rheumatic fever and other non-streptococcal infections as controls, were tested by lymphocyte transformation to four streptococcal antigens. In all cases of scarlet fever and especially of rheumatic fever the lymphocytes were better stimulated by streptococcal products than in the control group. The SO and the MAP fraction showed a good stimulating activity. The response in the rheumatic fever patients was not influenced by the steroid treatment, nor by the stage of the illness. A parallelism with high humoral and cellular responses to SO at the beginning of the acute rheumatic fever was observed, followed by a dissociation of both responses during the evolution with the maintenance of the cellular one and the decrease of the ASO titre.

  19. Sepsis Induced by Cecal Ligation and Puncture

    PubMed Central

    Wen, Haitao

    2014-01-01

    Summary Despite advances in intensive care unit interventions, including the use of specific antibiotics and anti-inflammation treatment, sepsis with concomitant multiple organ failure is the most common cause of death in many acute care units. In order to understand the mechanisms of clinical sepsis and develop effective therapeutic modalities, there is a need to use effective experimental models that faithfully replicate what occurs in patients with sepsis. Several models are commonly used to study sepsis, including intravenous endotoxin challenge, injection of live organisms into the peritoneal cavity, establishing abscesses in the extremities, and the induction of polymicrobial peritonitis via cecal ligation and puncture (CLP). Here, we describe the surgery procedure of CLP in mice, which has been proposed to closely replicate the nature and course of clinical sepsis in humans. PMID:23824895

  20. Sepsis biomarkers.

    PubMed

    Prucha, Miroslav; Bellingan, Geoff; Zazula, Roman

    2015-02-01

    Sepsis is the most frequent cause of death in non-coronary intensive care units (ICUs). In the past 10 years, progress has been made in the early identification of septic patients and in their treatment and these improvements in support and therapy mean that the mortality is gradually decreasing but it still remains unacceptably high. Leaving clinical diagnosis aside, the laboratory diagnostics represent a complex range of investigations that can place significant demands on the system given the speed of response required. There are hundreds of biomarkers which could be potentially used for diagnosis and prognosis in septic patients. The main attributes of successful markers would be high sensitivity, specificity, possibility of bed-side monitoring, and financial accessibility. Only a fraction is used in routine clinical practice because many lack sufficient sensitivity or specificity. The following review gives a short overview of the current epidemiology of sepsis, its pathogenesis and state-of-the-art knowledge on the use of specific biochemical, hematological and immunological parameters in its diagnostics. Prospective approaches towards discovery of new diagnostic biomarkers have been shortly mentioned.

  1. An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients. Methods/Design This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg-1.min-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients

  2. Henoch-Schönlein nephritis associated with streptococcal infection and persistent hypocomplementemia: a case report

    PubMed Central

    2010-01-01

    Introduction Henoch-Schönlein purpura is a systemic disease with frequent renal involvement, characterized by IgA mesangial deposits. Streptococcal infection can induce an abnormal IgA immune response like Henoch-Schönlein purpura, quite similar to typical acute post-infectious glomerulonephritis. Indeed, hypocomplementemia that is typical of acute glomerulonephritis has also been described in Henoch-Schönlein purpura. Case presentation We describe a 14-year-old Caucasian Spanish girl who developed urinary abnormalities and cutaneous purpura after streptococcal infection. Renal biopsy showed typical findings from Henoch-Schönlein purpura nephritis. In addition, she had low serum levels of complement (C4 fraction) that persisted during follow-up, in spite of her clinical evolution. She responded to treatment with enalapril and steroids. Conclusion The case described has, at least, three points of interest in Henoch-Schönlein purpura: 1) Initial presentation was preceded by streptococcal infection; 2) There was a persistence of low serum levels of complement; and 3) There was response to steroids and angiotensin-converting enzyme inhibitor in the presence of nephrotic syndrome. There are not many cases described in the literature with these characteristics. We conclude that Henoch-Schönlein purpura could appear after streptococcal infection in patients with abnormal complement levels, and that steroids and angiotensin-converting enzyme inhibitor could be successful treatment for the disease. PMID:20181224

  3. The role of platelets in sepsis.

    PubMed

    de Stoppelaar, Sacha F; van 't Veer, Cornelis; van der Poll, Tom

    2014-10-01

    Platelets are small circulating anucleate cells that are of crucial importance in haemostasis. Over the last decade, it has become increasingly clear that platelets play an important role in inflammation and can influence both innate and adaptive immunity. Sepsis is a potentially lethal condition caused by detrimental host response to an invading pathogen. Dysbalanced immune response and activation of the coagulation system during sepsis are fundamental events leading to sepsis complications and organ failure. Platelets, being major effector cells in both haemostasis and inflammation, are involved in sepsis pathogenesis and contribute to sepsis complications. Platelets catalyse the development of hyperinflammation, disseminated intravascular coagulation and microthrombosis, and subsequently contribute to multiple organ failure. Inappropriate accumulation and activity of platelets are key events in the development of sepsis-related complications such as acute lung injury and acute kidney injury. Platelet activation readouts could serve as biomarkers for early sepsis recognition; inhibition of platelets in septic patients seems like an important target for immune-modulating therapy and appears promising based on animal models and retrospective human studies. PMID:24966015

  4. The role of platelets in sepsis.

    PubMed

    de Stoppelaar, Sacha F; van 't Veer, Cornelis; van der Poll, Tom

    2014-10-01

    Platelets are small circulating anucleate cells that are of crucial importance in haemostasis. Over the last decade, it has become increasingly clear that platelets play an important role in inflammation and can influence both innate and adaptive immunity. Sepsis is a potentially lethal condition caused by detrimental host response to an invading pathogen. Dysbalanced immune response and activation of the coagulation system during sepsis are fundamental events leading to sepsis complications and organ failure. Platelets, being major effector cells in both haemostasis and inflammation, are involved in sepsis pathogenesis and contribute to sepsis complications. Platelets catalyse the development of hyperinflammation, disseminated intravascular coagulation and microthrombosis, and subsequently contribute to multiple organ failure. Inappropriate accumulation and activity of platelets are key events in the development of sepsis-related complications such as acute lung injury and acute kidney injury. Platelet activation readouts could serve as biomarkers for early sepsis recognition; inhibition of platelets in septic patients seems like an important target for immune-modulating therapy and appears promising based on animal models and retrospective human studies.

  5. Purification and characterization of streptococcal proliferative factor.

    PubMed

    Rasmussen, E O; Wuepper, K D

    1981-08-01

    Group A streptococcal infections are often associated with scarlet fever and flares of guttate psoriasis. Previous investigation has demonstrated the presence of a factor in streptococcal culture filtrates capable of stimulating proliferation of rabbit keratinocytes in vivo and human lymphocytes in vitro. This report outlines an in vivo method for the production of streptococcal proliferation factor, its purification, and characterization of its physical properties. We cultured Group A streptococci (Type 12, Strain NY5) in synthetic media by in vivo incubation within dialysis casing surgically implanted in rabbit peritoneum. Streptococcal exoproteins were isolated by centrifugation of the bacteria and millipore filtration. Purification of streptococcal proliferative factor was accomplished by differential solubility and molecular sieve was discovered in the resulting product. The relative by SDS gels and molecular sieve chromatography. The sedimentation coefficient determined by sucrose gradient ultracentrifugation is 2.7S. Isoelectric focusing showed minimal microheterogeneity with the pI of the major band being 5.0. Thus, streptococcal proliferative factor can be produced by in vivo incubation of streptococci in synthetic media. Purification entails a rapid 2-step process. The relative molecular weight, sedimentation coefficient and isoelectric points have been established.

  6. Superantigenicity of streptococcal M protein

    PubMed Central

    1990-01-01

    M proteins that define the serotypes of group A streptococci are powerful blastogens for human T lymphocytes. The mechanism by which they activate T cells was investigated and compared with the conventional T cell mitogen phytohemagglutinin, and the known superantigen staphylococcal enterotoxin B. Although major histocompatibility complex (MHC) class II molecules are required for presentation, there is no MHC restriction, since allogeneic class II molecules presented the bacterial protein to human T cells. Type 5 M protein appears to bind class II molecules on the antigen-presenting cells and stimulate T cells bearing V beta 8 sequences. Our results indicate that this streptococcal M protein is a superantigen and suggest a possible mechanism of its role in the pathogenesis of the postinfectious autoimmune sequelae. PMID:2358781

  7. 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

  8. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6.

    PubMed

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    The Sepsis 6 is an internationally accepted management bundle that, when initiated within one hour of identifying sepsis, can reduce morbidity and mortality. This management bundle was advocated by the Scottish Patient Safety Programme as part of its Acute Adult campaign launched in 2008 and adopted by NHS Tayside in 2012. Despite this, the Emergency Department (ED) of Ninewells Hospital, a tertiary referral centre and major teaching hospital in Scotland, was displaying poor success in the Sepsis 6. We therefore set out to improve compliance by evaluating the application of all aspects of the NHS Tayside Sepsis 6 bundle within one hour of ED triage time, to identify what human factors may influence achieving the one hour The Sepsis 6 bundle. This allowed us to tailor a number of specific interventions including educational sessions, regular audit and personal feedback and check list Sepsis 6 sticker. These interventions promoted a steady increase in compliance from an initial rate of 51.0% to 74.3%. The project highlighted that undifferentiated patients create a challenge in initiating the Sepsis 6. Pyrexia is a key human factor-trigger for recognising sepsis with initial nursing assessment being vital in recognition and identifying the best area (resus) of the department to manage severely septic patients. EDs need to recognise these challenges and develop educational and feedback plans for staff and utilise available resources to maximise the Sepsis 6 compliance. PMID:27239303

  9. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6

    PubMed Central

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    The Sepsis 6 is an internationally accepted management bundle that, when initiated within one hour of identifying sepsis, can reduce morbidity and mortality. This management bundle was advocated by the Scottish Patient Safety Programme as part of its Acute Adult campaign launched in 2008 and adopted by NHS Tayside in 2012. Despite this, the Emergency Department (ED) of Ninewells Hospital, a tertiary referral centre and major teaching hospital in Scotland, was displaying poor success in the Sepsis 6. We therefore set out to improve compliance by evaluating the application of all aspects of the NHS Tayside Sepsis 6 bundle within one hour of ED triage time, to identify what human factors may influence achieving the one hour The Sepsis 6 bundle. This allowed us to tailor a number of specific interventions including educational sessions, regular audit and personal feedback and check list Sepsis 6 sticker. These interventions promoted a steady increase in compliance from an initial rate of 51.0% to 74.3%. The project highlighted that undifferentiated patients create a challenge in initiating the Sepsis 6. Pyrexia is a key human factor-trigger for recognising sepsis with initial nursing assessment being vital in recognition and identifying the best area (resus) of the department to manage severely septic patients. EDs need to recognise these challenges and develop educational and feedback plans for staff and utilise available resources to maximise the Sepsis 6 compliance. PMID:27239303

  10. Pulmonary Renal Syndrome After Streptococcal Pharyngitis

    PubMed Central

    Mara-Koosham, Gopi; Stoltze, Karl; Aday, Jeffrey; Rendon, Patrick

    2016-01-01

    Pulmonary renal syndrome is a class of small vessel vasculitides that are characterized by the dual presentation of diffuse alveolar hemorrhage (DAH) and glomerulonephritis. Pulmonary renal syndrome has multiple etiologies, but its development has been rarely reported following infection with group A streptococcus. We present the case of a 36-year-old Native American male who was transferred to our facility due to refractory hypoxic respiratory failure. He had been diagnosed with streptococcal pharyngitis 2 weeks prior to admission. Given the presence of hemoptysis, bronchoscopy was performed and was consistent with DAH. Urinalysis demonstrated hematuria and proteinuria, in the setting of elevated creatinine and blood urea nitrogen. Additionally, antistreptolysin O titer was positive. Given the constellation of laboratory findings and history of streptococcal pharyngitis, the patient was diagnosed with PRS secondary to streptococcal infection. High-dose methylprednisolone was initiated with concomitant plasmapheresis. He was extubated successfully after his respiratory status improved and was eventually discharged home after making a full recovery within 2 weeks after admission. This case illustrates the importance of clinically relevant sequelae of streptococcal infection as well as the appropriate treatment of PRS secondary to streptococcal pharyngitis with plasmapheresis and intravenous corticosteroids. PMID:27231692

  11. Sepsis Questions and Answers

    MedlinePlus

    ... has kidney problems, sepsis can lead to kidney failure that requires lifelong dialysis. Top of Page How ... to prevent healthcare-associated infections. Recently, CDC has projects specifically focused on sepsis prevention so that we ...

  12. Common Questions About Streptococcal Pharyngitis.

    PubMed

    Kalra, Monica G; Higgins, Kim E; Perez, Evan D

    2016-07-01

    Group A beta-hemolytic streptococcal (GABHS) infection causes 15% to 30% of sore throats in children and 5% to 15% in adults, and is more common in the late winter and early spring. The strongest independent predictors of GABHS pharyngitis are patient age of five to 15 years, absence of cough, tender anterior cervical adenopathy, tonsillar exudates, and fever. To diagnose GABHS pharyngitis, a rapid antigen detection test should be ordered in patients with a modified Centor or FeverPAIN score of 2 or 3. First-line treatment for GABHS pharyngitis includes a 10-day course of penicillin or amoxicillin. Patients allergic to penicillin can be treated with firstgeneration cephalosporins, clindamycin, or macrolide antibiotics. Nonsteroidal anti-inflammatory drugs are more effective than acetaminophen and placebo for treatment of fever and pain associated with GABHS pharyngitis; medicated throat lozenges used every two hours are also effective. Corticosteroids provide only a small reduction in the duration of symptoms and should not be used routinely. PMID:27386721

  13. Lymphocyte activation by streptococcal antigens in psoriasis.

    PubMed

    Gross, W L; Packhäuser, U; Hahn, G; Westphal, E; Christophers, E; Schlaak, M

    1977-11-01

    Cell-mediated immune responses in 28 hospitalized patients with psoriasis and in 36 healthy controls were studied using the two-step leukocyte migration agarose test. Specific cell-mediated immunity to A-streptococcal cell wall and cell membrane antigens occurred significantly more often in patients with psoriasis than in the control group. A statistically significant correlation between psoriasis-associated antigens of the HLA-B locus and cellular immune reactivity to A-streptococcal antigens or clinical course was not found. When patients with guttate psoriasis were compared separately with the control group, leukocyte migration inhibition induced by cell-free supernatants of A-streptococcal antigen-exposed mononuclear cell cultures was found to be more frequent than in other forms of psoriasis.

  14. Discovery of the gene signature for acute lung injury in patients with sepsis Address for reprint requests and other correspondence: J. A. Howrylak, UPMC Montefiore NW 628, 3459 5th Ave., Pittsburgh, PA 15213 (e-mail: howrylakj@upmc.edu).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    PubMed Central

    Howrylak, Judie A.; Dolinay, Tamas; Lucht, Lorrie; Wang, Zhaoxi; Christiani, David C.; Sethi, Jigme M.; Xing, Eric P.; Donahoe, Michael P.; Choi, Augustine M. K.

    2009-01-01

    The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was described 30 yr ago, yet making a definitive diagnosis remains difficult. The identification of biomarkers obtained from peripheral blood could provide additional noninvasive means for diagnosis. To identify gene expression profiles that may be used to classify patients with ALI, 13 patients with ALI + sepsis and 20 patients with sepsis alone were recruited from the Medical Intensive Care Unit of the University of Pittsburgh Medical Center, and microarrays were performed on peripheral blood samples. Several classification algorithms were used to develop a gene signature for ALI from gene expression profiles. This signature was validated in an independently obtained set of patients with ALI + sepsis (n = 8) and sepsis alone (n = 1). An eight-gene expression profile was found to be associated with ALI. Internal validation found that the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 100% accuracy, corresponding to a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. In the independently obtained external validation set, the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 88.9% accuracy. The use of classification models to develop a gene signature from gene expression profiles provides a novel and accurate approach for classifying patients with ALI. PMID:19174476

  15. [Clinical aspects of streptococcal and staphylococcal toxinic diseases].

    PubMed

    Floret, D

    2001-09-01

    however, a cutaneous or soft tissue infection is at the origin. Necrotizing fasciitis complicating varicella is a classic cause in children. Bacteremia is often observed. The mortality rate is as high as 60%. The streptococcal strains involved in north america use to produce the toxin erythrogenic A, the european cases seem to be more related to strains secreting the B toxin with a dysregulation of the mechanisms which control the secretion of the toxin. Staphylococcus strains producing the Panton and Valentine leucocidin are responsible for chronic or relapsing furonculosis and above all for a very severe necrotizing pneumonia observed in children and young adults presenting as an acute respiratory distress syndrome with leucopenia, hemoptysis and shock carrying a heavy mortality rate. Besides these specific diseases, staphylococcal and streptococcal toxins may be involved in some syndromes of unknown origin, in which the intervention of superantigens seems very likely. Kawasaki syndrome is among them as strains producing staphylococcal and streptococcal toxins have been grown from patients with Kawasaki syndrome. In the same way, the intervention of toxins is suspected in the determination of sudden infant death syndrome and atopic eczema.

  16. Plantar Purpura as the Initial Presentation of Viridians Streptococcal Shock Syndrome Secondary to Streptococcus gordonii Bacteremia

    PubMed Central

    Liao, Chen-Yi; Su, Kuan-Jen; Lin, Cheng-Hui; Huang, Shu-Fang; Chin, Hsien-Kuo; Chang, Chin-Wen; Kuo, Wu-Hsien; Ben, Ren-Jy; Yeh, Yen-Cheng

    2016-01-01

    Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality. PMID:27366188

  17. The doripenem serum concentrations in intensive care patients suffering from acute kidney injury, sepsis, and multi organ dysfunction syndrome undergoing continuous renal replacement therapy slow low-efficiency dialysis.

    PubMed

    Wieczorek, Andrzej; Tokarz, Andrzej; Gaszynski, Wojciech; Gaszynski, Tomasz

    2014-01-01

    Doripenem is a novel wide-spectrum antibiotic, and a derivate of carbapenems. It is an ideal antibiotic for treatment of serious nosocomial infections and severe sepsis for its exceptionally high efficiency and broad antibacterial spectrum of action. Doripenem is eliminated mainly by the kidneys. In cases of acute kidney injury, dosing of doripenem depends on creatinine clearance and requires adjustments. Doripenem is eliminated during hemodialysis because its molecular weight is 300-400 Da. The aim of this study was to establish the impact of continuous renal replacement therapy (CRRT) slow low-efficiency dialysis (SLED) on doripenem serum concentrations in a population of intensive-therapy patients with life-threatening infections and severe sepsis. Ten patients were enrolled in this observational study. Twelve blood samples were collected during the first administration of doripenem in a 1-hour continuous infusion while CRRT SLED was provided. Fluid chromatography was used for measurement of the concentration of doripenem in serum. In all collected samples, concentration of doripenem was above the minimum inhibition concentration of this antibiotic. Based on these results, we can draw the conclusion that doripenem concentration is above the minimum inhibition concentration throughout all of CRRT. The dosing pattern proposed by the manufacturer can be used in patients receiving CRRT SLED without necessary modifications.

  18. Early management of sepsis

    PubMed Central

    Vincent, Jean-Louis; Pereira, Adriano José; Gleeson, James; Backer, Daniel De

    2014-01-01

    Increased awareness of the signs and symptoms of sepsis and an emphasis on the importance of early treatment have helped to improve survival rates from this serious and frequent condition in recent years. With no specific, effective anti-sepsis therapies available, management focuses on early source control with adequate and appropriate antibiotics and removal of any source of infection, rapid resuscitation, hemodynamic stabilization and organ support. Use of dedicated teams to care for patients with sepsis can help optimize early management.

  19. Study protocol for a multicentre randomised controlled trial: Safety, Tolerability, efficacy and quality of life Of a human recombinant alkaline Phosphatase in patients with sepsis-associated Acute Kidney Injury (STOP-AKI)

    PubMed Central

    Peters, Esther; Mehta, Ravindra L; Murray, Patrick T; Hummel, Jürgen; Joannidis, Michael; Kellum, John A; Arend, Jacques; Pickkers, Peter

    2016-01-01

    Introduction Acute kidney injury (AKI) occurs in 55–60% of critically ill patients, and sepsis is the most common underlying cause. No pharmacological treatment options are licensed to treat sepsis-associated AKI (SA-AKI); only supportive renal replacement therapy (RRT) is available. One of the limited number of candidate compounds in clinical development to treat SA-AKI is alkaline phosphatase (AP). The renal protective effect of purified bovine intestinal AP has been demonstrated in critically ill sepsis patients. To build on these observations, a human recombinant AP (recAP) was developed, of which safety and efficacy in patients with SA-AKI will be investigated in this trial. Methods This is a randomised, double-blind, placebo-controlled, 4-arm, proof-of-concept, dose-finding adaptive phase IIa/IIb study, conducted in critically ill patients with SA-AKI. A minimum of 290 patients will be enrolled at ∼50 sites in the European Union and North America. The study involves 2 parts. Patients enrolled during Part 1 will be randomly assigned to receive either placebo (n=30) or 1 of 3 different doses of recAP (n=30 per group) once daily for 3 days (0.4, 0.8 or 1.6 mg/kg). In Part 2, patients will be randomly assigned to receive the most efficacious dose of recAP (n=85), selected during an interim analysis, or placebo (n=85). Treatment must be administered within 24 hours after SA-AKI is first diagnosed and within 96 hours from first diagnosis of sepsis. The primary end point is the area under the time-corrected endogenous creatinine clearance curve from days 1 to 7. The key secondary end point is RRT incidence during days 1–28. Ethics and dissemination This study is approved by the relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this

  20. Exogenous arginine in sepsis.

    PubMed

    Luiking, Yvette C; Deutz, Nicolaas E P

    2007-09-01

    Sepsis is a severe condition in critically ill patients and is considered an arginine deficiency state. The rationale for arginine deficiency in sepsis is mainly based on the reduced arginine levels in sepsis that are associated with the specific changes in arginine metabolism related to endothelial dysfunction, severe catabolism, and worse outcome. Exogenous arginine supplementation in sepsis shows controversial results with only limited data in humans and variable results in animal models of sepsis. Since in these studies the severity of sepsis varies but also the route, timing, and dose of arginine, it is difficult to draw a definitive conclusion for sepsis in general without considering the influence of these factors. Enhanced nitric oxide production in sepsis is related to suggested detrimental effects on hemodynamic instability and enhanced oxidative stress. Potential mechanisms for beneficial effects of exogenous arginine in sepsis include enhanced (protein) metabolism, improved microcirculation and organ function, effects on immune function and antibacterial effects, improved gut function, and an antioxidant role of arginine. We recently performed a study indicating that arginine can be given to septic patients without major effects on hemodynamics, suggesting that more studies can be conducted on the effects of arginine supplementation in septic patients.

  1. Pediatric sepsis: challenges and adjunctive therapies

    PubMed Central

    Hanna, William; Wong, Hector R.

    2012-01-01

    SYNOPSIS Sepsis remains an important challenge in pediatric critical care medicine. The current review intends to provide an appraisal of adjunctive therapies for sepsis and to highlight opportunities for meeting selected challenges in the field. Future clinical studies should address long-term and functional outcomes, as well as acute outcomes. Potential adjunctive therapies such as corticosteroids, hemofiltration, hemoadsorption, and plasmapheresis may have important roles, but still require formal and more rigorous testing by way of clinical trials. Finally, the design of future clinical trials should consider novel approaches for stratifying outcome risks as a means of improving the risk to benefit ratio of experimental therapies. PMID:23537672

  2. Prevention of Sepsis in Children: A New Paradigm for Public Policy

    PubMed Central

    Riley, Carley; Wheeler, Derek S.

    2012-01-01

    Sepsis is one of the leading causes of death worldwide. While the management of critically ill patients with sepsis is certainly better now compared to 20 years ago, sepsis-associated mortality remains unacceptably high. Annual deaths from sepsis in both children and adults far surpass the number of deaths from acute myocardial infarction (AMI), stroke, or cancer. Given the substantial toll that sepsis takes worldwide, prevention of sepsis remains a global priority. Multiple effective prevention strategies exist. Antibiotic prophylaxis, immunizations, and healthcare quality improvement initiatives are important means through which we may reduce the morbidity and mortality from sepsis around the world. Inclusion of these strategies in a coordinated and thoughtful campaign to reduce the global burden of sepsis is necessary for the improvement of pediatric health worldwide. PMID:22216408

  3. 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.

  4. 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.

  5. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children

    PubMed Central

    Di Pierro, Francesco; Colombo, Maria; Zanvit, Alberto; Risso, Paolo; Rottoli, Amilcare S

    2014-01-01

    Background Streptococcus salivarius K12 is an oral probiotic strain releasing two lantibiotics (salivaricin A2 and salivaricin B) that antagonize the growth of S. pyogenes, the most important bacterial cause of pharyngeal infections in humans also affected by episodes of acute otitis media. S. salivarius K12 successfully colonizes the oral cavity, and is endowed with an excellent safety profile. We tested its preventive role in reducing the incidence of both streptococcal and viral pharyngitis and/or tonsillitis in children. Materials and methods We enrolled 61 children with a diagnosis of recurrent oral streptococcal disorders. Thirty-one of them were enrolled to be treated daily for 90 days with a slow-release tablet for oral use, containing no less than 1 billion colony-forming units/tablet of S. salivarius K12 (Bactoblis®), and the remaining 30 served as the untreated control group. During treatment, they were all examined for streptococcal infection. Twenty children (ten per group) were also assessed in terms of viral infection. Secondary end points in both groups were the number of days under antibiotic and antipyretic therapy and the number of days off school (children) and off work (parents). Results The 30 children who completed the 90-day trial with Bactoblis® showed a significant reduction in their episodes of streptococcal pharyngeal infection (>90%), as calculated by comparing the infection rates of the previous year. No difference was observed in the control group. The treated group showed a significant decrease in the incidence (80%) of oral viral infections. Again, there was no difference in the control group. With regard to secondary end points, the number of days under antibiotic treatment of the treated and control groups were 30 and 900 respectively, days under antipyretic treatment 16 and 228, days of absence from school 16 and 228, and days of absence from work 16 and 228. The product was well tolerated by the subjects, with no side effects

  6. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    PubMed

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  7. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children

    PubMed Central

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-01-01

    Abstract Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness. A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression. HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05). Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  8. Sepsis-induced myopathy

    PubMed Central

    Callahan, Leigh Ann; Supinski, Gerald S.

    2014-01-01

    Sepsis is a major cause of morbidity and mortality in critically ill patients, and despite advances in management, mortality remains high. In survivors, sepsis increases the risk for the development of persistent acquired weakness syndromes affecting both the respiratory muscles and the limb muscles. This acquired weakness results in prolonged duration of mechanical ventilation, difficulty weaning, functional impairment, exercise limitation, and poor health-related quality of life. Abundant evidence indicates that sepsis induces a myopathy characterized by reductions in muscle force-generating capacity, atrophy (loss of muscle mass), and altered bioenergetics. Sepsis elicits derangements at multiple subcellular sites involved in excitation contraction coupling, such as decreasing membrane excitability, injuring sarcolemmal membranes, altering calcium homeostasis due to effects on the sarcoplasmic reticulum, and disrupting contractile protein interactions. Muscle wasting occurs later and results from increased proteolytic degradation as well as decreased protein synthesis. In addition, sepsis produces marked abnormalities in muscle mitochondrial functional capacity and when severe, these alterations correlate with increased death. The mechanisms leading to sepsis-induced changes in skeletal muscle are linked to excessive localized elaboration of proinflammatory cytokines, marked increases in free-radical generation, and activation of proteolytic pathways that are upstream of the proteasome including caspase and calpain. Emerging data suggest that targeted inhibition of these pathways may alter the evolution and progression of sepsis-induced myopathy and potentially reduce the occurrence of sepsis-mediated acquired weakness syndromes. PMID:20046121

  9. Neurology of Sepsis.

    PubMed

    Sweis, Rochelle; Ortiz, Jorge; Biller, José

    2016-03-01

    Sepsis is a systemic inflammatory response syndrome occurring secondary to infection and labeled severe when end organ dysfunction or tissue hypoperfusion transpires. Sepsis-associated mortality remains high among critically ill patients, with chronic disease and immunosuppression being the most common risk factors. Studies demonstrate that early recognition and treatment are vital to decreasing mortality. Some of the least understood effects of sepsis are the associated neurologic complications. The peripheral nervous system (PNS) has gained most consideration and thought, largely due to dependence on mechanical ventilation. Central nervous system (CNS) complications related to sepsis have only more recently gained attention but continue to go unnoticed. Aside from the clinical examination, electroencephalography (EEG) is a sensitive tool for prognostication or uncovering non-convulsive seizures in encephalopathic patients. Further studies are needed to further define the urgency of a prevention and treatment plan for the deleterious effects of sepsis on the PNS and CNS. PMID:26820754

  10. Implementing sepsis bundles

    PubMed Central

    Jozwiak, Mathieu; Monnet, Xavier

    2016-01-01

    Sepsis bundles represent key elements of care regarding the diagnosis and treatment of patients with septic shock and allow ones to convert complex guidelines into meaningful changes in behavior. Sepsis bundles endorsed the early goal-directed therapy (EGDT) and their implementation resulted in an improved outcome of septic shock patients. They induced more consistent and timely application of evidence-based care and reduced practice variability. These benefits mainly depend on the compliance with sepsis bundles, highlighting the importance of dedicated performance improvement initiatives, such as multifaceted educational programs. Nevertheless, the interest of early goal directed therapy in septic shock patients compared to usual care has recently been questioned, leading to an update of sepsis bundles in 2015. These new sepsis bundles may also exhibit, as the previous bundles, some limits and pitfalls and the effects of their implementation still needs to be evaluated. PMID:27713890

  11. Plasma arginine correlations in trauma and sepsis.

    PubMed

    Chiarla, C; Giovannini, I; Siegel, J H

    2006-02-01

    , transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

  12. 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

  13. THE INCIDENCE AND PATHOGENESIS OF MYOCARDITIS IN RABBITS AFTER GROUP A STREPTOCOCCAL PHARYNGEAL INFECTIONS

    PubMed Central

    Glaser, Robert J.; Thomas, Wilbur A.; Morse, Stephen I.; Darnell, James E.

    1956-01-01

    Rabbits subjected to single pharyngeal infections with group A streptococci developed cardiac lesions characterized by myofiber necrosis and a non-granulocytic cellular reaction with histiocytes, lymphocytes, and Anitschkow myocytes. The histopathologic changes were demonstrable in some animals within 24 hours of inoculation, apparently were maximal 72 hours after induction of infection (at which time they were seen in the hearts of all nine rabbits studied), and thereafter healed in the course of the following 2 weeks. The extent of involvement was variable, and with healing the necrotic areas were replaced by fibrous tissue. When intradermal infections with the same organisms were produced in rabbits, cardiac lesions, indistinguishable from those observed in the pharyngeally infected group, appeared in a much smaller number of animals. The hearts of five of six rabbits sacrificed a month or more following the last of a series of streptococcal pharyngeal infections exhibited lesions characterized chiefly by fibrosis, although mononuclear cellular infiltrations were also noted. In these repetitively infected animals the presence of occasional multinucleated giant cells and a few small foci of calcification were features not encountered in the single infection group. In a second series of rabbits sacrificed 3 days after the last of three pharyngeal infections with different strains of streptococci, acute as well as more chronic changes were observed. In none of the lesions in rabbits subjected to single or multiple streptococcal infections were bacteria demonstrable, either in histologic sections or in cultures of myocardial tissue. A large number of control animals was studied concomitantly, and in only one instance was a lesion, considered comparable to those described in the streptococcal series, encountered. The implications of these findings, particularly in terms of the non-suppurative sequelae of streptococcal infections in man, are discussed. PMID:13278463

  14. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010.

    PubMed

    Verani, Jennifer R; McGee, Lesley; Schrag, Stephanie J

    2010-11-19

    Despite substantial progress in prevention of perinatal group B streptococcal (GBS) disease since the 1990s, GBS remains the leading cause of early-onset neonatal sepsis in the United States. In 1996, CDC, in collaboration with relevant professional societies, published guidelines for the prevention of perinatal group B streptococcal disease (CDC. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR 1996;45[No. RR-7]); those guidelines were updated and republished in 2002 (CDC. Prevention of perinatal group B streptococcal disease: revised guidelines from CDC. MMWR 2002;51[No. RR-11]). In June 2009, a meeting of clinical and public health representatives was held to reevaluate prevention strategies on the basis of data collected after the issuance of the 2002 guidelines. This report presents CDC's updated guidelines, which have been endorsed by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the American College of Nurse-Midwives, the American Academy of Family Physicians, and the American Society for Microbiology. The recommendations were made on the basis of available evidence when such evidence was sufficient and on expert opinion when available evidence was insufficient. The key changes in the 2010 guidelines include the following: • expanded recommendations on laboratory methods for the identification of GBS, • clarification of the colony-count threshold required for reporting GBS detected in the urine of pregnant women, • updated algorithms for GBS screening and intrapartum chemoprophylaxis for women with preterm labor or preterm premature rupture of membranes, • a change in the recommended dose of penicillin-G for chemoprophylaxis, • updated prophylaxis regimens for women with penicillin allergy, and • a revised algorithm for management of newborns with respect to risk for early-onset GBS disease. Universal screening at 35-37 weeks' gestation for maternal GBS

  15. The older adult experiencing sepsis.

    PubMed

    Englert, Nadine C; Ross, Carl

    2015-01-01

    Sepsis is a potentially fatal response to infection affecting patients across the life span. Sepsis can progress from systemic inflammatory response to severe sepsis and septic shock if not recognized promptly and managed effectively. Risk factors for sepsis include age, gender, the presence of invasive devices (eg, urinary catheters), and chronic medical conditions (eg, chronic obstructive pulmonary disease). Sepsis awareness is essential and includes identification of population-focused risk factors, recognition of clinical signs and symptoms, and timely implementation of interventions. The purpose of this article was to examine sepsis in older adults, including prevalence, atypical presentation of the condition, and considerations for sepsis management in the elderly population.

  16. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis.

    PubMed

    Zheng, Yijun; Zhu, Duming

    2016-01-01

    Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis. PMID:27413421

  17. The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis

    PubMed Central

    Koczera, Patrick

    2016-01-01

    Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The endothelial glycocalyx is one of the earliest sites involved during sepsis. This fragile layer is a complex network of cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining the luminal side of endothelial cells with a thickness of about 1 to 3 μm. Sepsis-associated alterations of its structure affect endothelial permeability and result in the liberation of endogenous damage-associated molecular patterns (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating consequences of the proinflammatory cascades in sepsis and septic shock. In this way, the injury to the glycocalyx with the consecutive release of DAMPs contributes to a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the extent of glycocalyx degradation serves as a marker of endothelial dysfunction and sepsis severity. In this review, we highlight the crucial role of the glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis-associated multiple organ failures. PMID:27699168

  18. Late mortality after sepsis: propensity matched cohort study

    PubMed Central

    Osterholzer, John J; Langa, Kenneth M; Angus, Derek C; Iwashyna, Theodore J

    2016-01-01

    Objectives To determine whether late mortality after sepsis is driven predominantly by pre-existing comorbid disease or is the result of sepsis itself. Deign Observational cohort study. Setting US Health and Retirement Study. Participants 960 patients aged ≥65 (1998-2010) with fee-for-service Medicare coverage who were admitted to hospital with sepsis. Patients were matched to 777 adults not currently in hospital, 788 patients admitted with non-sepsis infection, and 504 patients admitted with acute sterile inflammatory conditions. Main outcome measures Late (31 days to two years) mortality and odds of death at various intervals. Results Sepsis was associated with a 22.1% (95% confidence interval 17.5% to 26.7%) absolute increase in late mortality relative to adults not in hospital, a 10.4% (5.4% to 15.4%) absolute increase relative to patients admitted with non-sepsis infection, and a 16.2% (10.2% to 22.2%) absolute increase relative to patients admitted with sterile inflammatory conditions (P<0.001 for each comparison). Mortality remained higher for at least two years relative to adults not in hospital. Conclusions More than one in five patients who survives sepsis has a late death not explained by health status before sepsis. PMID:27189000

  19. The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis

    PubMed Central

    Koczera, Patrick

    2016-01-01

    Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The endothelial glycocalyx is one of the earliest sites involved during sepsis. This fragile layer is a complex network of cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining the luminal side of endothelial cells with a thickness of about 1 to 3 μm. Sepsis-associated alterations of its structure affect endothelial permeability and result in the liberation of endogenous damage-associated molecular patterns (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating consequences of the proinflammatory cascades in sepsis and septic shock. In this way, the injury to the glycocalyx with the consecutive release of DAMPs contributes to a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the extent of glycocalyx degradation serves as a marker of endothelial dysfunction and sepsis severity. In this review, we highlight the crucial role of the glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis-associated multiple organ failures.

  20. Perianal streptococcal dermatitis associated with guttate psoriasis and/or balanoposthitis: a study of five cases.

    PubMed

    Patrizi, A; Costa, A M; Fiorillo, L; Neri, I

    1994-06-01

    Perianal streptococcal dermatitis (PSD) is a recently described cutaneous entity caused by group A beta-hemolytic streptococci. It is characterized by perianal erythema, sometimes associated with functional disturbances. We describe four children (2 boys, 2 girls) who had acute guttate psoriasis and also PSD. One of these patients also had balanoposthitis. A fifth patient experienced an association of PSD and balanoposthitis without psoriasis. To our knowledge, the association between guttate psoriasis and PSD has only been reported in five children, and the one with balanitis has not been previously reported.

  1. 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.

  2. Animal models of sepsis

    PubMed Central

    Fink, Mitchell P

    2014-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism. PMID:24022070

  3. The Surviving Sepsis Campaign: Where have we been and where are we going?

    PubMed

    Dellinger, R Phillip

    2015-04-01

    The Surviving Sepsis Campaign develops and promotes evidence-based guidelines and performance-improvement practices aimed at reducing deaths from sepsis worldwide. The most recent guidelines, published in 2013, provide detailed management strategies for acute care, fluid resuscitation, and vasopressor use. In addition, the campaign has developed simple, short protocols for what to do within 3 and 6 hours of recognition of sepsis. These protocols are associated with reduced mortality rates.

  4. Platelet depletion and severity of streptococcal endocarditis

    PubMed Central

    Dall, Lawrence; Miller, Todd; Herndon, Betty; Diez, Ireneo; Dew, Michelle

    1998-01-01

    OBJECTIVE: To evaluate the importance of thrombocytopenia in streptococcal endocarditis using an animal model. DESIGN: A model of human septic endocarditis was established in rats (polyethylene catheters across the aortic valve and administration of Streptococcus sanguis, 5×107 colony forming units [cfu] intravenous). Thrombocytopenia at four levels was produced by antiplatelet serum. Secondary methods of producing thrombocytopenia were also evaluated. At sacrifice (96 h after platelet depletion and 72 h after infection), vegetations were removed, weighed, diluted, plated and counted. Potential mechanisms of the dose-response relationship between vegetation density and platelet count were evaluated. SETTING: Controlled research laboratory experiments. POPULATION STUDIED: Animal models of streptococcal endocarditis. MAIN RESULTS: The bacterial density of the aortic valve vegetations significantly increased as the platelet count decreased (P=0.0007). In severely thrombocytopenic animals (two-dose antiplatelet serum), data suggest increased vegetation embolism. Platelet depletion, which was minimal with chemical methods, was produced most effectively by antithrombocyte serum. Platelet surfaces in endocarditis were found to express elevated CD62p proteins (72.7% endocarditis, 34.7% control). Platelet protein fractions were evaluated in vitro by both streptocidal (P=0.19) and phagocytosis-stimulating assays. Platelet presence in mature aortic valve vegetations averaged only about 2%. CONCLUSIONS: In platelet depletion experiments using a rat model, a dose-response relationship of peripheral circulating platelet depletion to aortic valve vegetation density was found. The mechanism relating thrombocytopenia to endocarditis severity remains unresolved. PMID:22346555

  5. Laboratory identification and epidemiology of streptococcal hospital isolates.

    PubMed

    Hardy, M A; Dalton, H P; Allison, M J

    1978-11-01

    A total of 343 streptococcal strains were identified to species on the basis of the progressive method of bacterial identification as advocated by Cowan & Steel's Manual for the Identification of Medical Bacteria. Comparative studies were also performed with these strains to determine the accuracy and feasibility of using various types of blood, differential media, and biochemical tests in conjunction with the progressive method of identification. The streptococcal species were then correlated with the type of specimen, sex, and age of hospitalized patients to obtain some insight into the epidemiology of hospital streptococcal isolates.

  6. Factors Associated with Streptococcal Bacteremia in Diarrheal Children under Five Years of Age and Their Outcome in an Urban Hospital in Bangladesh

    PubMed Central

    Shahid, Abu Sadat Mohammad Sayeem Bin; Ahmed, Tahmeed; Shahunja, K. M.; Kabir, Senjuti; Chowdhury, Fahmida; Faruque, Abu Syeed Golam; Das, Sumon Kumar; Sarker, Mohammad Habibur Rahman; Bardhan, Pradip Kumar; Chisti, Mohammod Jobayer

    2016-01-01

    Background Although Streptococcal bacteremia is common in diarrheal children with high morbidity and mortality, no systematic data are available on Streptococcal bacteremia in diarrheal children. We sought to evaluate the factors associated with Streptococcal bacteremia in diarrheal children under five years of age and their outcome. Methods We used an unmatched case-control design to investigate the associated factors with Streptococcal bacteremia in all the diarrheal children under five years of age through electronic medical record system of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. We had simultaneously used a retrospective cohort design to further evaluate the outcome of our study children. All the enrolled children had their blood culture done between January 2010 and December 2012. Comparison was made among the children with (cases = 26) and without Streptococcal bacteremia (controls = 78). Controls were selected randomly from hospitalized diarrheal children under five years of age. Results Cases had proportionately higher deaths compared to controls, but it was statistically insignificant (15% vs. 10%, p = 0.49). The cases more often presented with severe dehydration, fever, respiratory distress, severe sepsis, and abnormal mental status compared to the controls (for all p<0.05). In the logistic regression analysis, after adjusting for potential confounders, it has been found that Streptococcal bacteremia in diarrheal children under five years of age was independently associated with nutritional edema (OR: 5.86, 95% CI = 1.28–26.80), hypoxemia (OR: 19.39, 95% CI = 2.14–175.91), fever (OR: 4.44, 95% CI = 1.13–17.42), delayed capillary refill time (OR: 7.00, 95% CI = 1.36–35.93), and respiratory distress (OR: 2.69, 95% CI = 1.02–7.12). Conclusions and Significance The results of our analyses suggest that diarrheal children under five years of age presenting with nutritional edema, hypoxemia, fever, delayed

  7. Vanishing Venous Coronary Artery Bypass Grafts after Sepsis

    PubMed Central

    Park, Soo Jin; Park, Ji Ye; Jung, Joonho; Hong, You Sun; Lee, Cheol Joo; Lim, Sang Hyun

    2016-01-01

    The dehiscence of saphenous vein grafts (SVGs) is a rare, often fatal, complication of coronary artery bypass grafting (CABG). We present the case of a 57-year-old man who underwent hemiarch graft interposition and CABG for a Stanford type A aortic dissection. Five months after discharge, the patient developed streptococcal sepsis caused by a hemodialysis catheter. Complete rupture of the proximal anastomoses of the saphenous veins and containment by the obliterated pericardial cavity was observed 25 months after the initial operation. The patient was successfully treated surgically. This report describes a patient who developed potentially fatal dehiscence of SVGs secondary to infection and outlines preventive and management strategies for this complication. PMID:27734001

  8. 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-α 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

  9. Immunomodulation during sepsis in organ transplanted children.

    PubMed

    Angele, M K; Loehe, F; Faist, E

    2005-10-01

    Newer immunosuppressive agents have dramatically reduced the rates of acute graft rejection over the last decade but may have exacerbated the problem of post-transplant infections. Causes of early mortality include graft dysfunction and sepsis. Late mortality occurs mainly due to sepsis. An excessive inflammatory response followed with a dramatic paralysis of cell-mediated immunity has been documented in septic patients. In transplanted individuals the pathophysiological changes of the immune response are further complicated by immunosuppressive agents. This article will focus on the effect of immunosuppressive agents and sepsis on cell-mediated immune responses. Moreover, potentially promising immunomodulatory approaches, i.e. human activated protein C, immunomodulatory diets containing L-arginine and fish oil, selective cytokine blockade, platelet-activating factor receptor antagonist, LPS receptor CD14 blockade and G-CSF, for the treatment of immunodysfunction in septic patients will be outlined in this review article. Most of them, however, have not been tested in the clinical arena in transplanted patients. Thus, the main part of the article, immunomodulation during sepsis in organ transplanted children is quite speculative and based on immunomodulatory strategies in other non-transplanted septic patients.

  10. Short-term Gains with Long-term Consequences: The Evolving Story of Sepsis Survivorship.

    PubMed

    Maley, Jason H; Mikkelsen, Mark E

    2016-06-01

    Sepsis is an acute, life-threatening condition that afflicts millions of patients annually. Advances in care and heightened awareness have led to substantial declines in short-term mortality. An expanding body of literature describes the long-term impact of sepsis, revealing long-term cognitive and functional impairments, sustained inflammation and immune dysfunction, increased healthcare resource use, reduced health-related quality of life, and increased mortality. The evidence challenges the notion that sepsis is an acute, transient illness, revealing rather that sepsis is an acute illness with lingering consequences. This article provides a state-of-the-art review of the emerging literature of the long-term consequences of sepsis. PMID:27229651

  11. Sepsis-Associated Encephalopathy

    PubMed Central

    Cotena, Simona; Piazza, Ornella

    2012-01-01

    Summary Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole. PMID:23905041

  12. Sepsis in critical care.

    PubMed

    King, Joan E

    2007-03-01

    Sepsis is a syndrome produced by the accelerated activity of the inflammatory immune response, the clotting cascade, and endothelial damage. It is a systematic process that can progress easily into septic shock and MODS. The chemical mediators or cytokines produce a complex self-perpetuating process that impacts all body systems. It is critical for the nurse first to identify patients at risk for developing sepsis and to assess patients who have SIRS and sepsis continually for signs and symptoms of organ involvement and organ dysfunction. Once sepsis has been diagnosed, evidence-based practice indicates initiation of fluid resuscitation. Vasopressor therapy, positive inotropic support, and appropriate antibiotic therapy should be started within the first hour. Within a 6-hour timeframe the goal is stabilization of the CVP, MAP, and UOP to prevent further organ damage. The challenge for nurses caring for septic patients is to support the treatment goals, to prevent added complications including stress ulcers, DVTs, aspiration pneumonia, and the progression to MODS, and to address the patient's and the family's psychosocial needs. As complex as the pathophysiology of sepsis is, the nursing care is equally complex but also rewarding. Patients who previously might have died now recover as vigilant nursing care combines forces with new drug therapies and evidence-based practice guidelines.

  13. Angiopoietin-2 associations with the underlying infection and sepsis severity.

    PubMed

    Lymperopoulou, Korina; Velissaris, Dimitrios; Kotsaki, Antigone; Antypa, Elli; Georgiadou, Sara; Tsaganos, Thomas; Koulenti, Despina; Paggalou, Evgenia; Damoraki, Georgia; Karagiannidis, Napoleon; Orfanos, Stylianos E

    2015-05-01

    Angiopoietin-2 (Ang-2) is an important mediator in sepsis. We have previously shown that endotoxemia levels are related to the underlying infection and affect septic patients' outcome. Based on this background we now investigated if circulating Ang-2 (cAng-2) and monocyte Ang-2 expression in septic patients are associated with the underlying infection and organ failure. We measured cAng-2 in 288 septic patients (121 with sepsis, 167 with severe sepsis/septic shock) at less than 24h post study inclusion (day 1) and on days 3 and 7. Peripheral blood mononuclear cells (PBMCs) were additionally isolated; Ang-2 gene expression was estimated by means of real-time PCR. Levels of cAng-2 were higher under severe sepsis and septic shock, as compared to uncomplicated sepsis; PBMC Ang-2 copies were higher in severe sepsis. On day 1, cAng-2 and Ang-2 gene copies were greater under severe sepsis/septic shock in sufferers from all types of infections with the exception of community-acquired pneumonia and ventilator-associated pneumonia. cAng-2 increased proportionally to the number of failing organs, and was higher under metabolic acidosis and acute coagulopathy as compared to no failing organ. On day 1, copies of Ang-2 were higher in survivors, whereas cAng-2 was higher in non-survivors. In a large cohort of septic patients, cAng-2 kinetics appears associated with the underlying infection and organ failure type.

  14. 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)

  15. FIBROGEN PRECIPITATION BY STREPTOCOCCAL M PROTEIN. II. RENAL LESIONS INDUCED BY INTRAVENOUS INJECTION OF M PROTEIN INTO MICE AND RATS.

    PubMed

    KANTOR, F S

    1965-05-01

    Intravenous injection of Type 1 streptococcal M protein into mice and rats produced lesions confined to renal glomeruli. Thrombi of eosinophilic amorphous material, seen to occlude glomerular capillaries, were shown to contain M protein and fibrinogen. Gradual regression of the morphological lesions was observed during the 3 weeks following injection. Initial abnormal proteinuria and azotemia returned to control levels by the end of the 1st week; a second rise in urinary protein excretion and urea retention was demonstrated in some rats coincident with appearance of anti-M antibodies. The mechanism of renal localization of streptococcal M protein by means of a complex with fibrinogen was suggested, which may comprise an initial phase in the pathogenesis of acute poststreptococcal glomerulonephritis.

  16. A one-year study of streptococcal infections and their complications among Ethiopian children.

    PubMed Central

    Tewodros, W.; Muhe, L.; Daniel, E.; Schalén, C.; Kronvall, G.

    1992-01-01

    Post-streptococcal complications are known to be common among Ethiopian children. Little is known, however, about the epidemiology of beta-haemolytic streptococci in Ethiopia. A total of 816 children were studied during a one-year period: 24 cases of acute rheumatic fever (ARF), 44 chronic rheumatic heart disease (CRHD), 44 acute post streptococcal glomerulonephritis (APSGN), 143 tonsillitis, 55 impetigo, and 506 were apparently healthy children. Both ARF and APSGN occurred throughout the year with two peaks during the rainy and cold seasons. The female:male ratio among ARF patients was 1.4:1 and 1:1.9 among APSGN. The monthly carrier rate of beta-haemolytic streptococci group A varied from 7.5-39%, average being 17%. T type 2 was the most frequent serotype. Marked seasonal fluctuations were noted in the distribution of serogroups among apparently healthy children. Beta-haemolytic streptococci group A dominated during the hot and humid months of February-May. Strains were susceptible to commonly used antibiotics, except for tetracycline. PMID:1397112

  17. A plethora of angiopoietin-2 effects during clinical sepsis

    PubMed Central

    2010-01-01

    The interesting study by Davis and colleagues in the current issue of Critical Care expands on the increasingly recognized role of angiopoietins in human sepsis but raises a number of questions, which are discussed in this commentary. The authors describe an association between elevated angiopoietin (ang)-2 levels and impaired vascular reactivity, measured by the partly nitric oxide-dependent finger hyperemic response to forearm vascular occlusion, in patients with sepsis. This suggests that the ang-1/2-Tie2 system is involved in a number of pathophysiologic, phenotypic and perhaps prognostic alterations in human sepsis, on top of the effect on pulmonary endothelial barrier function. The novel inflammatory route may be a target for future therapeutic studies in human sepsis and acute lung injury, including those with activated protein C. PMID:20587077

  18. Essentials of sepsis management.

    PubMed

    Green, John M

    2015-04-01

    Despite remarkable advances in the knowledge of infection and human response to it, sepsis continues to be one of the most common challenges surgeons and critical care providers face. Surgeons confront the problem of infection every day, in treating established infections or reacting to a consequence of surgical intervention. Infections after surgery continue to be a problem despite massive efforts to prevent them. Patients rely on the surgeon's ability to recognize infection and treat it. Also, preventing nosocomial infection and antibiotic resistance is a primary responsibility. This article describes diagnostic and therapeutic measures for sepsis in the perioperative surgical patient.

  19. 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

  20. Hospital Case Volume and Outcomes among Patients Hospitalized with Severe Sepsis

    PubMed Central

    Wiener, Renda Soylemez

    2014-01-01

    Rationale: Processes of care are potential determinants of outcomes in patients with severe sepsis. Whether hospitals with more experience caring for patients with severe sepsis also have improved outcomes is unclear. Objectives: To determine associations between hospital severe sepsis caseload and outcomes. Methods: We analyzed data from U.S. academic hospitals provided through University HealthSystem Consortium. We used University HealthSystem Consortium’s sepsis mortality model (c-statistic, 0.826) for risk adjustment. Validated International Classification of Disease, 9th Edition, Clinical Modification algorithms were used to identify hospital severe sepsis case volume. Associations between risk-adjusted severe sepsis case volume and mortality, length of stay, and costs were analyzed using spline regression and analysis of covariance. Measurements and Main Results: We identified 56,997 patients with severe sepsis admitted to 124 U.S. academic hospitals during 2011. Hospitals admitted 460 ± 216 patients with severe sepsis, with median length of stay 12.5 days (interquartile range, 11.1–14.2), median direct costs $26,304 (interquartile range, $21,900–$32,090), and average hospital mortality 25.6 ± 5.3%. Higher severe sepsis case volume was associated with lower unadjusted severe sepsis mortality (R2 = 0.10, P = 0.01) and risk-adjusted severe sepsis mortality (R2 = 0.21, P < 0.001). After further adjustment for geographic region, number of beds, and long-term acute care referrals, hospitals in the highest severe sepsis case volume quartile had an absolute 7% (95% confidence interval, 2.4–11.6%) lower hospital mortality than hospitals in the lowest quartile. We did not identify associations between case volume and resource use. Conclusions: Academic hospitals with higher severe sepsis case volume have lower severe sepsis hospital mortality without higher costs. PMID:24400669

  1. The resuscitation package in sepsis.

    PubMed

    Demertzis, Lee M; Kollef, Marin H

    2010-09-01

    Sepsis and its attendant complications are commonly encountered in the intensive care unit. Early recognition of sepsis is critical because it allows for rapid deployment of a multifaceted resuscitation package. The cornerstones of sepsis management are antibiotic therapy, source control, and hemodynamic resuscitation. In select patients, ancillary therapies are indicated, such as activated protein C, corticosteroids, and glycemic control. Given the complexity of sepsis management, optimal care can be delivered as a bundle-a protocol encompassing the above interventions. The evidence behind the various components of sepsis management are reviewed here.

  2. Revisiting caspases in sepsis.

    PubMed

    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

  3. Nutrition and sepsis.

    PubMed

    Cohen, Jonathan; Chin, w Dat N

    2013-01-01

    The effect of nutritional support in critically ill patients with sepsis has received much attention in recent years. However, many of the studies have produced conflicting results. As for all critically ill patients, nutritional support, preferably via the enteral route, should be commenced once initial resuscitation and adequate perfusion pressure is achieved. Where enteral feeding is impossible or not tolerated, parenteral nutrition (either as total or complimentary therapy) may safely be administered. Most positive studies relating to nutritional support and sepsis have been in the setting of sepsis prevention. Thus, the administration of standard nutrition formulas to critically ill patients within 24 h of injury or intensive care unit admission may decrease the incidence of pneumonia. Both arginine-supplemented enteral diets, given in the perioperative period, and glutamine-supplemented parenteral nutrition have been shown to decrease infections in surgical patients. Parenteral fish oil lipid emulsions as well as probiotics given in the perioperative period may also reduce infections in patients undergoing major abdominal operations, such as liver transplantation. There is little support at the present time for the positive effect of specific pharmaconutrients, in particular fish oil, probiotics, or antioxidants, in the setting of established sepsis. More studies are clearly required on larger numbers of more homogeneous groups of patients. PMID:23075593

  4. 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

  5. Nutrition and sepsis.

    PubMed

    Cohen, Jonathan; Chin, w Dat N

    2013-01-01

    The effect of nutritional support in critically ill patients with sepsis has received much attention in recent years. However, many of the studies have produced conflicting results. As for all critically ill patients, nutritional support, preferably via the enteral route, should be commenced once initial resuscitation and adequate perfusion pressure is achieved. Where enteral feeding is impossible or not tolerated, parenteral nutrition (either as total or complimentary therapy) may safely be administered. Most positive studies relating to nutritional support and sepsis have been in the setting of sepsis prevention. Thus, the administration of standard nutrition formulas to critically ill patients within 24 h of injury or intensive care unit admission may decrease the incidence of pneumonia. Both arginine-supplemented enteral diets, given in the perioperative period, and glutamine-supplemented parenteral nutrition have been shown to decrease infections in surgical patients. Parenteral fish oil lipid emulsions as well as probiotics given in the perioperative period may also reduce infections in patients undergoing major abdominal operations, such as liver transplantation. There is little support at the present time for the positive effect of specific pharmaconutrients, in particular fish oil, probiotics, or antioxidants, in the setting of established sepsis. More studies are clearly required on larger numbers of more homogeneous groups of patients.

  6. Sepsis Associated Encephalopathy.

    PubMed

    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.

  7. [Sepsis management -- antibiotic therapy].

    PubMed

    Welte, T

    2004-11-26

    Sepsis is one of the most frequent infectious problems at Intensive Care Units, and sepsis is associated with significant mortality. The latter could not be markedly reduced in the last years, despite a number of advances in the field of volume substitution, catecholamines, and endocrinologic therapy. The reason might be that important steps towards overcoming of sepsis are the surgical resection of infectious foci and an adequate antibiotic treatment. A critical role plays the growing resistance of pathogens against the common antibiotics. Since no major progress in the development of new antibiotics can be expected for the next years, sepsis treatment must be focused on prevention of infection, and on an optimised application of current antibiotic substances. The key factors are a broad and high dose initial treatment, a de-escalation strategy according to the clinical course, and -with exceptions- a limitation of treatment to 7 to 10 days. Rotation of antibiotics should be performed, if problems with resistances exist or no specialist for infectious diseases is available on the Intensive Care Unit.

  8. Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever

    PubMed Central

    1989-01-01

    The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined. The data indicate that the majority of serotypes fall into two major classes. Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein. The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site. In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site. Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules. Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor. These two groups closely parallel our current definition of Class I and Class II serotypes. Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface. Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype. Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever. PMID:2642529

  9. Sepsis-associated renal salt wasting: how much is too much?

    PubMed Central

    Saleh, Mohamed

    2014-01-01

    We report the case of a patient who presented with an extremely high level of glomerular filtration rate and renal salt wasting during acute severe sepsis. Clinical implications for resuscitation and antibiotics dosage regimens are discussed. PMID:24408942

  10. 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-κB, 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

  11. Pulmonary Renal Syndrome After Streptococcal Pharyngitis: A Case Report.

    PubMed

    Mara-Koosham, Gopi; Stoltze, Karl; Aday, Jeffrey; Rendon, Patrick

    2016-01-01

    Pulmonary renal syndrome is a class of small vessel vasculitides that are characterized by the dual presentation of diffuse alveolar hemorrhage (DAH) and glomerulonephritis. Pulmonary renal syndrome has multiple etiologies, but its development has been rarely reported following infection with group A streptococcus. We present the case of a 36-year-old Native American male who was transferred to our facility due to refractory hypoxic respiratory failure. He had been diagnosed with streptococcal pharyngitis 2 weeks prior to admission. Given the presence of hemoptysis, bronchoscopy was performed and was consistent with DAH. Urinalysis demonstrated hematuria and proteinuria, in the setting of elevated creatinine and blood urea nitrogen. Additionally, antistreptolysin O titer was positive. Given the constellation of laboratory findings and history of streptococcal pharyngitis, the patient was diagnosed with PRS secondary to streptococcal infection. High-dose methylprednisolone was initiated with concomitant plasmapheresis. He was extubated successfully after his respiratory status improved and was eventually discharged home after making a full recovery within 2 weeks after admission. This case illustrates the importance of clinically relevant sequelae of streptococcal infection as well as the appropriate treatment of PRS secondary to streptococcal pharyngitis with plasmapheresis and intravenous corticosteroids. PMID:27231692

  12. Functional outcomes of general medical patients with severe sepsis

    PubMed Central

    2013-01-01

    Background Severe sepsis is a common cause for admission to the general medical ward. Previous work has demonstrated substantial new long-term disability in patients with severe sepsis, but the short-term functional outcomes of patients admitted to the general medical floor -- where the majority of severe sepsis is treated -- are largely unknown. Methods A retrospective cohort study was performed of patients initially admitted to non-ICU medical wards at a tertiary care academic medical center. Severe sepsis was confirmed by three physician reviewers, using the International Consensus Conference definition of sepsis. Baseline functional status, disposition location, and receipt of post-acute skilled care were recorded using a structured abstraction instrument. Results 3,146 discharges had severe sepsis by coding algorithm; from a random sample of 111 patients, 64 had the diagnosis of severe sepsis confirmed by reviewers. The mean age of the 64 patients was 63.5 years +/- 18.0. Prior to admission, 80% of patients lived at home and 50.8% of patients were functionally independent. Inpatient mortality was 12.5% and 37.5% of patients were discharged to a nursing facility. Of all patients in the cohort, 50.0% were discharged home, and 66.7% of patients who were functionally independent at baseline were discharged to home. Conclusions New physical debility is a common feature of severe sepsis in patients initially cared for on the general medical floor. Debility occurs even in those with good baseline physical function. Interventions to improve the poor functional outcomes of this population are urgently needed. PMID:24330544

  13. The encephalopathy of sepsis.

    PubMed

    Jackson, A C; Gilbert, J J; Young, G B; Bolton, C F

    1985-11-01

    Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.

  14. 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

  15. Sepsis-associated hyperlactatemia.

    PubMed

    Garcia-Alvarez, Mercedes; Marik, Paul; Bellomo, Rinaldo

    2014-01-01

    There is overwhelming evidence that sepsis and septic shock are associated with hyperlactatemia (sepsis-associated hyperlactatemia (SAHL)). SAHL is a strong independent predictor of mortality and its presence and progression are widely appreciated by clinicians to define a very high-risk population. Until recently, the dominant paradigm has been that SAHL is a marker of tissue hypoxia. Accordingly, SAHL has been interpreted to indicate the presence of an 'oxygen debt' or 'hypoperfusion', which leads to increased lactate generation via anaerobic glycolysis. In light of such interpretation of the meaning of SAHL, maneuvers to increase oxygen delivery have been proposed as its treatment. Moreover, lactate levels have been proposed as a method to evaluate the adequacy of resuscitation and the nature of the response to the initial treatment for sepsis. However, a large body of evidence has accumulated that strongly challenges such notions. Much evidence now supports the view that SAHL is not due only to tissue hypoxia or anaerobic glycolysis. Experimental and human studies all consistently support the view that SAHL is more logically explained by increased aerobic glycolysis secondary to activation of the stress response (adrenergic stimulation). More importantly, new evidence suggests that SAHL may actually serve to facilitate bioenergetic efficiency through an increase in lactate oxidation. In this sense, the characteristics of lactate production best fit the notion of an adaptive survival response that grows in intensity as disease severity increases. Clinicians need to be aware of these developments in our understanding of SAHL in order to approach patient management according to biological principles and to interpret lactate concentrations during sepsis resuscitation according to current best knowledge. PMID:25394679

  16. Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants

    PubMed Central

    Kaufman, David; Fairchild, Karen D.

    2004-01-01

    Twenty percent of very-low-birth-weight (<1500 g) preterm infants experience a serious systemic infection, and despite advances in neonatal intensive care and antimicrobials, mortality is as much as threefold higher for these infants who develop sepsis than their counterparts without sepsis during their hospitalization. Outcomes may be improved by preventative strategies, earlier and accurate diagnosis, and adjunct therapies to combat infection and protect the vulnerable preterm infant during an infection. Earlier diagnosis on the basis of factors such as abnormal heart rate characteristics may offer the ability to initiate treatment prior to the onset of clinical symptoms. Molecular and adjunctive diagnostics may also aid in diagnosing invasive infection when clinical symptoms indicate infection but no organisms are isolated in culture. Due to the high morbidity and mortality, preventative and adjunctive therapies are needed. Prophylaxis has been effective in preventing early-onset group B streptococcal sepsis and late-onset Candida sepsis. Future research in prophylaxis using active and passive immunization strategies offers prevention without the risk of resistance to antimicrobials. Identification of the differences in neonatal intensive care units with low and high infection rates and implementation of infection control measures remain paramount in each neonatal intensive care unit caring for preterm infants. PMID:15258097

  17. Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection

    PubMed Central

    2010-01-01

    Introduction Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time. Methods The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer. Results Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis. Conclusions Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics. PMID:20504311

  18. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept

    PubMed Central

    Macerollo, Antonella; Martino, Davide

    2013-01-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham’s chorea (SC)—the prototypical post-streptococcal neuropsychiatric disorder—and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo’s criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo’s criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been

  19. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

    PubMed

    Macerollo, Antonella; Martino, Davide

    2013-01-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by

  20. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

    PubMed

    Macerollo, Antonella; Martino, Davide

    2013-01-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by

  1. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePlus

    ... disclaimer . Subscribe Surviving Sepsis Taming a Deadly Immune Response Many people have never heard of sepsis, or ... tract infection) and then a powerful and harmful response by your body’s own immune system . “With sepsis, ...

  2. Group A β-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 β-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 β-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 β-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out.

  3. Group A β-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 β-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 β-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 β-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

  4. Group A β-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 β-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 β-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 β-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

  5. Synergistic inhibition of Streptococcal biofilm by ribose and xylitol.

    PubMed

    Lee, Heon-Jin; Kim, Se Chul; Kim, Jinkyung; Do, Aejin; Han, Se Yeong; Lee, Bhumgey David; Lee, Hyun Ho; Lee, Min Chan; Lee, So Hui; Oh, Taejun; Park, Sangbin; Hong, Su-Hyung

    2015-02-01

    Streptococcus mutans and Streptococcus sobrinus are the major causative agents of human dental caries. Therefore, the removal or inhibition of these streptococcal biofilms is essential for dental caries prevention. In the present study, we evaluated the effects of ribose treatment alone or in combination with xylitol on streptococcal biofilm formation for both species. Furthermore, we examined the expression of genes responsible for dextran-dependent aggregation (DDAG). In addition, we investigated whether ribose affects the biofilm formation of xylitol-insensitive streptococci, which results from long-term exposure to xylitol. The viability of streptococci biofilms formed in a 24-well polystyrene plate was quantified by fluorescent staining with the LIVE/DEAD bacterial viability and counting kit, which was followed by fluorescence activated cell sorting analysis. The effects of ribose and/or xylitol on the mRNA expression of DDAG-responsible genes, gbpC and dblB, was evaluated by RT-qPCR. Our data showed that ribose and other pentose molecules significantly inhibited streptococcal biofilm formation and the expression of DDAG-responsible genes. In addition, co-treatment with ribose and xylitol decreased streptococcal biofilm formation to a further extent than ribose or xylitol treatment alone in both streptococcal species. Furthermore, ribose attenuated the increase of xylitol-insensitive streptococcal biofilm, which results in the reduced difference of biofilm formation between S. mutans that are sensitive and insensitive to xylitol. These data suggest that pentose may be used as an additive for teeth-protective materials or in sweets. Furthermore, ribose co-treatment with xylitol might help to increase the anti-cariogenic efficacy of xylitol.

  6. [A study on early-onset group "B" streptococcal neonatal infection].

    PubMed

    Vacheva, R; Todorova, M; Decheva, A; Yarakova, N; Kraleva, I; Takova, Ts; Dimitrova, N; Dobreva, A

    2012-01-01

    The results achieved with 80% reduction in the incidence of early-onset neonatal group B streptococcal (GBS) sepsis following the implementation of the preliminary (1996, 2002) and subsequently the revised (2010) guidelines for intrapartum antibiotic prophylaxis imposed the discussion on a large scale of the updated:--algorithms for GBS screening (35-37 weeks of gestation) with the recommended dosage of penicillin-G for intrapartum antibiotic prophylaxis for women having normal labor and delivery;--algorithms for GBS screening and intrapartum antibiotic prophylaxis for women with preterm labor (PPROM) or premature rupture of membranes (PROM);--intrapartum antibiotic prophylaxis regimens for women with penicillin allergy;--algorithm for management of newborns with respect to risk of early-onset GBS disease. The present study is aimed at studying the distribution of the early-onset GBS disease in our country based on the data of leading obstetrics & gynecology clinics and wards. The aim is to diferrentiate clinically the cases and investigate the influence of the known risk factors on the part of the mother. A special accent is put over the microbiological diagnostics of cases in view of CDC expanded recommendations on the laboratory methods for identification of GBS. As a final conclusion the necessity for introduction of an official registration of the early- and late-onset GBS disease in the country is emphasized.

  7. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    PubMed

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. PMID:27229649

  8. Group A streptococcal meningitis in a patient with palmoplantar pustulosis.

    PubMed

    Hagiya, Hideharu; Otsuka, Fumio

    2013-01-01

    A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality.

  9. Programmed cell death receptor ligand 1 modulates the regulatory T cells' capacity to repress shock/sepsis-induced indirect acute lung injury by recruiting phosphatase SRC homology region 2 domain-containing phosphatase 1.

    PubMed

    Tang, Lunxian; Bai, Jianwen; Chung, Chun-Shiang; Lomas-Neira, Joanne; Chen, Yaping; Huang, Xin; Ayala, Alfred

    2015-01-01

    We recently reported that adoptively transferred (AT) exogenous CD4+ CD25+ regulatory T cells (Tregs) to wild-type (WT) mice can directly act to repress shock/sepsis-induced experimental indirect acute lung injury (iALI), and this is mediated in part by programmed cell death receptor 1 (PD-1). In this study, we further determine whether recipient mouse lacking PD-L1, one of the primary ligands for PD-1, contributes to the manipulation of the Tregs' capacity to repress lung injury. To do this, Tregs isolated from the spleen of WT mice were AT into PD-L1 mice subjected to hemorrhagic shock and subsequent to cecal ligation and puncture to induce iALI. Samples were collected for analyses 24 h after cecal ligation and puncture. We found that in PD-L1-recipient mice, AT WT-Tregs lost the ability to reverse the development of iALI seen in WT recipient mice (i.e., no reduction of lung injury indices assessed by histology and vascular leakage, failure to decrease the lung neutrophil influx [myeloperoxidase activity], or the rise in lung apoptosis [caspase 3 activity]). Also, a significant increase in interleukin 1β (IL-1β) and keratinocyte-derived chemokine, but no changes in IL-6, IL-10, and IL-17A levels in lung tissues were seen in these mice compared with iALI mice without AT of Tregs. Furthermore, we noted that the lung tissue tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1), but not SHP-2, was activated with the AT of Tregs in PD-L1(-/-) iALI mice. Finally, through local depletion of CD4+ T cells or CD25+ (Tregs) in the lung, prior to inducing iALI, we found that SHP-1 activation was associated with the loss of Tregs' protective effects in vivo. Collectively, our data reveal that PD-L1 is a critical modulator of Tregs' ability to suppress iALI, and this appears to involve SHP-1 activation.

  10. Muscle regeneration after sepsis.

    PubMed

    Bouglé, Adrien; Rocheteau, Pierre; Sharshar, Tarek; Chrétien, Fabrice

    2016-01-01

    Severe critical illness is often complicated by intensive care unit-acquired weakness (ICU-AW), which is associated with increased ICU and post-ICU mortality, delayed weaning from mechanical ventilation and long-term functional disability. Several mechanisms have been implicated in the pathophysiology of ICU-AW, but muscle regeneration has not been investigated to any extent in this context, even though its involvement is suggested by the protracted functional consequences of ICU-AW. Recent data suggest that muscle regeneration could be impaired after sepsis, and that mesenchymal stem cell treatment could improve the post-injury muscle recovery. PMID:27193340

  11. Functional and histopathologic changes in the liver during sepsis.

    PubMed

    Caruana, J A; Montes, M; Camara, D S; Ummer, A; Potmesil, S H; Gage, A A

    1982-05-01

    Although liver failure from sepsis is a frequent occurrence in serious ill, hospitalized patients, little information is available on the histologic changes of the liver. We examined the histopathology of the liver of 19 patients who died of clinical sepsis and attempted to relate certain features of the illness or treatment to the observed histopathologic changes. The most striking finding was midzonal and peripheral necrosis of a moderate to marked degree in 11 of 19 patients. Other important changes were acute inflammation and cholestasis. The severity of hepatocellular necrosis did not appear to be influenced by the premortem circulating pathogen, by the nutritional support administered or by the arterial blood pressure. It is suggested that hepatocellular necrosis is characteristic of sepsis and may be caused by loss of specific factors which normally maintain liver function and structure. PMID:6803371

  12. Streptococcal Histone Induces Murine Macrophages To Produce Interleukin-1 and Tumor Necrosis Factor Alpha

    PubMed Central

    Zhang, Liping; Ignatowski, Tracey A.; Spengler, Robert N.; Noble, Bernice; Stinson, Murray W.

    1999-01-01

    The histone-like protein (HlpA) is highly conserved among streptococci. After lysis of streptococci in infected tissues, HlpA can enter the bloodstream and bind to proteoglycans in the glomerular capillaries of kidneys, where it can react with antibodies or stimulate host cell receptors. Deposits of streptococcal antigens in tissues have been associated with localized acute inflammation. In this study, we measured the ability of purified HlpA (5 to 100 μg/ml), from Streptococcus mitis, to induce the production of proinflammatory cytokines by cultured, murine peritoneal macrophages. The release of tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) was time and concentration dependent and was not diminished by the presence of polymyxin B. Exposure of macrophages to a mixture of HlpA and lipoteichoic acid resulted in a synergistic response in the production of both TNF-α and IL-1. Stimulation with a mixture of HlpA and heparin resulted in reduced cytokine production (50% less IL-1 and 76% less TNF-α) compared to that by cells incubated with HlpA alone. The inclusion of antibodies specific to HlpA in macrophage cultures during stimulation with HlpA did not affect the quantity of TNF-α or IL-1 produced. These observations suggest that streptococcal histone may contribute to tissue injury at infection sites by promoting monocytes/macrophages to synthesize and release cytokines that initiate and exacerbate inflammation. Streptococcus pyogenes, which can infect tissues in enormous numbers, may release sufficient amounts of HlpA to reach the kidneys and cause acute poststreptococcal glomerulonephritis. PMID:10569765

  13. Rationale and design of the African group A streptococcal infection registry: the AFROStrep study

    PubMed Central

    Barth, Dylan D; Engel, Mark E; Whitelaw, Andrew; Alemseged, Abdissa; Sadoh, Wilson E; Ali, Sulafa K M; Sow, Samba O; Dale, James; Mayosi, Bongani M

    2016-01-01

    Introduction Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, also known as Streptococcus pyogenes, causes pyoderma, pharyngitis and invasive disease. Repeated GAS infections may lead to autoimmune diseases such as acute post-streptococcal glomerulonephritis, acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Invasive GAS (iGAS) disease is an important cause of mortality and morbidity worldwide. The burden of GAS infections is, however, unknown in Africa because of lack of surveillance systems. Methods and analysis The African group A streptococcal infection registry (the AFROStrep study) is a collaborative multicentre study of clinical, microbiological, epidemiological and molecular characteristics for GAS infection in Africa. The AFROStrep registry comprises two components: (1) active surveillance of GAS pharyngitis cases from sentinel primary care centres (non-iGAS) and (2) passive surveillance of iGAS disease from microbiology laboratories. Isolates will also be subjected to DNA isolation to allow for characterisation by molecular methods and cryopreservation for long-term storage. The AFROStrep study seeks to collect comprehensive data on GAS isolates in Africa. The biorepository will serve as a platform for vaccine development in Africa. Ethics and dissemination Ethics approval for the AFROStrep registry has been obtained from the Human Research Ethics Committee at the University of Cape Town (HREC/REF: R006/2015). Each recruiting site will seek ethics approval from their local ethics’ committee. All participants will be required to provide consent for inclusion into the registry as well as for the storage of isolates and molecular investigations to be conducted thereon. Strict confidentiality will be applied throughout. Findings and updates will be disseminated to collaborators, researchers, health planners and colleagues through peer-reviewed journal articles, conference publications and proceedings. PMID:26916694

  14. Model for predicting short-term mortality of severe sepsis

    PubMed Central

    Adrie, Christophe; Francais, Adrien; Alvarez-Gonzalez, Antonio; Mounier, Roman; Azoulay, Elie; Zahar, Jean-Ralph; Clec'h, Christophe; Goldgran-Toledano, Dany; Hammer, Laure; Descorps-Declere, Adrien; Jamali, Samir; Timsit, Jean-Francois

    2009-01-01

    Introduction To establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number. Methods In this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training cohort (n = 1458) and a validation cohort (n = 810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset. Results Independent predictors of death were logistic organ dysfunction (odds ratio (OR), 1.22 per point, P < 10-4), septic shock (OR, 1.40; P = 0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; P = 0.10 ≥ 3: OR, 2.64; P < 10-3), multiple sources of infection (OR; 1.45, P = 0.03), simplified acute physiology score II (OR, 1.02 per point; P < 10-4), McCabe score ([greater than or equal to]2) (OR, 1.96; P < 10-4), and number of chronic co-morbidities (1: OR, 1.75; P < 10-3, ≥ 2: OR, 2.24, P < 10-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI, 0.74 to 0.79; and HL Chi-square: 15.3 (P = 0.06) for all episodes pooled). Conclusions In ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection. PMID:19454002

  15. Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

    PubMed

    Haytac, M Cenk; Oz, I Attila

    2007-01-01

    Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

  16. Streptococcal Meningitis Resulting from Contact with an Infected Horse

    PubMed Central

    Downar, James; Willey, Barbara M.; Sutherland, Jeffrey W.; Mathew, Kelly; Low, Donald E.

    2001-01-01

    We report a case of group C streptococcal meningitis in a woman with a history of close animal contact as well as head trauma as a result of a kick by a horse. Blood and cerebrospinal fluid cultures grew Streptococcus equi subsp. zooepidemicus, as did a throat culture taken from the colt that had kicked her 2 weeks prior to admission. PMID:11376093

  17. Autoimmune neurological disorders associated with group-A beta-hemolytic streptococcal infection.

    PubMed

    Hachiya, Yasuo; Miyata, Rie; Tanuma, Naoyuki; Hongou, Kazuhisa; Tanaka, Keiko; Shimoda, Konomi; Kanda, Sachiko; Hoshino, Ai; Hanafusa, Yukiko; Kumada, Satoko; Kurihara, Eiji; Hayashi, Masaharu

    2013-08-01

    Although central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham's chorea is a well-recognized disease that can arise following infection. Children may develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement subsequent to GABHS infection. These disorders have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). Herein we report one case each of acute disseminated encephalomyelitis (ADEM), PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the pathogenesis of the CNS disorders associated with GABHS infection, we measured levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and performed immunohistochemistry using patient sera to stain human brain sections. All three cases showed psychiatric behavioral disorders. Immunotherapy was effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were elevated at the acute stage in all three cases. In each case of ADEM and PANDAS, immunohistochemistry demonstrated neuronal impairment in the basal ganglia during the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex at the acute stage in the case of subacute encephalitis. There was no direct correlation between immunoreactivity of patient sera on the brain sections and positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest that autoimmune responses may modulate neurotransmission, and the use of patient serum for immunohistochemistry is a sensitive screening method for the detection of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection. PMID:23142103

  18. Learning a Severity Score for Sepsis: A Novel Approach based on Clinical Comparisons

    PubMed Central

    Dyagilev, Kirill; Saria, Suchi

    2015-01-01

    Sepsis is one of the leading causes of death in the United States. Early administration of treatment has been shown to decrease sepsis-related mortality and morbidity. Existing scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment scores (SOFA) achieve poor sensitivity in distinguishing between the different stages of sepsis. Recently, we proposed the Disease Severity Score Learning (DSSL) framework that automatically derives a severity score from data based on clinical comparisons – pairs of disease states ordered by their severity. In this paper, we test the feasibility of using DSSL to develop a sepsis severity score. We show that the learned score significantly outperforms APACHE-II and SOFA in distinguishing between the different stages of sepsis. Additionally, the learned score is sensitive to changes in severity leading up to septic shock and post treatment administration. PMID:26958288

  19. Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).

    PubMed

    Leonard, H L; Swedo, S E

    2001-06-01

    The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise

  20. Glycocalyx and sepsis-induced alterations in vascular permeability.

    PubMed

    Chelazzi, Cosimo; Villa, Gianluca; Mancinelli, Paola; De Gaudio, A Raffaele; Adembri, Chiara

    2015-01-28

    Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

  1. Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.

    PubMed

    Hayakawa, Mineji; Saito, Shinjiro; Uchino, Shigehiko; Yamakawa, Kazuma; Kudo, Daisuke; Iizuka, Yusuke; Sanui, Masamitsu; Takimoto, Kohei; Mayumi, Toshihiko; Azuhata, Takeo; Ito, Fumihito; Yoshihiro, Shodai; Hayakawa, Katsura; Nakashima, Tsuyoshi; Ogura, Takayuki; Noda, Eiichiro; Nakamura, Yoshihiko; Sekine, Ryosuke; Yoshikawa, Yoshiaki; Sekino, Motohiro; Ueno, Keiko; Okuda, Yuko; Watanabe, Masayuki; Tampo, Akihito; Saito, Nobuyuki; Kitai, Yuya; Takahashi, Hiroki; Kobayashi, Iwao; Kondo, Yutaka; Matsunaga, Wataru; Nachi, Sho; Miike, Toru; Takahashi, Hiroshi; Takauji, Shuhei; Umakoshi, Kensuke; Todaka, Takafumi; Kodaira, Hiroshi; Andoh, Kohkichi; Kasai, Takehiko; Iwashita, Yoshiaki; Arai, Hideaki; Murata, Masato; Yamane, Masahiro; Shiga, Kazuhiro; Hori, Naoto

    2016-01-01

    Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

  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

  3. The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats

    PubMed Central

    Li, Guofu; Jia, Jia; Ji, Kaiqiang; Gong, Xiaoying; Wang, Rui; Zhang, Xiaoli; Wang, Haiyuan; Zang, Bin

    2016-01-01

    Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury. PMID:27430552

  4. Heparanase mediates renal dysfunction during early sepsis in mice

    PubMed Central

    Lygizos, Melissa I; Yang, Yimu; Altmann, Christopher J; Okamura, Kayo; Hernando, Ana Andres; Perez, Mario J; Smith, Lynelle P; Koyanagi, Daniel E; Gandjeva, Aneta; Bhargava, Rhea; Tuder, Rubin M; Faubel, Sarah; Schmidt, Eric P

    2013-01-01

    Heparanase, a heparan sulfate-specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced polymicrobial sepsis in mice using cecal ligation and puncture (CLP) in the presence or absence of competitive heparanase inhibitors (heparin or nonanticoagulant N-desulfated re-N-acetylated heparin [NAH]). Four hours after surgery, we collected serum and urine for measurement of renal function and systemic inflammation, invasively determined systemic hemodynamics, harvested kidneys for histology/protein/mRNA, and/or measured glomerular filtration by inulin clearance. CLP-treated mice demonstrated early activation of glomerular heparanase with coincident loss of glomerular filtration, as indicated by a >twofold increase in blood urea nitrogen (BUN) and a >50% decrease in inulin clearance (P < 0.05) in comparison to sham mice. Administration of heparanase inhibitors 2 h prior to CLP attenuated sepsis-induced loss of glomerular filtration rate, demonstrating that heparanase activation contributes to early septic renal dysfunction. Glomerular heparanase activation was not associated with renal neutrophil influx or altered vascular permeability, in marked contrast to previously described effects of pulmonary heparanase on neutrophilic lung injury during sepsis. CLP induction of renal inflammatory gene (IL-6, TNF-α, IL-1β) expression was attenuated by NAH pretreatment. While serum inflammatory indices (KC, IL-6, TNF-α, IL-1β) were not impacted by NAH pretreatment, heparanase inhibition attenuated the CLP-induced increase in serum IL-10. These findings demonstrate that glomerular heparanase is active during sepsis and contributes to septic renal dysfunction via mechanisms disparate from heparanase-mediated lung injury. PMID:24400155

  5. Reduced Immunocompetent B Cells and Increased Secondary Infection in Elderly Patients With Severe Sepsis.

    PubMed

    Suzuki, Kodai; Inoue, Shigeaki; Kametani, Yoshie; Komori, Yukako; Chiba, Sayuri; Sato, Takehito; Inokuchi, Sadaki; Ogura, Shinji

    2016-09-01

    Lymphocyte exhaustion was recently recognized as a mechanism of immunosuppression in sepsis. While B cells are known to play pivotal roles in bacterial infection and sepsis, changes in B-cell-mediated humoral immunity have not been evaluated in critically ill septic patients. We aimed to investigate changes in humoral immunity caused by defective B-cell function during severe sepsis. Thirty-three severe sepsis patients and 44 healthy subjects were prospectively enrolled. Blood was collected from patients within 72 h of and 8 to 11 h after sepsis onset to measure B-cell subtypes, serum immunoglobulin M concentration, and CpG-B oligodeoxynucleotide-induced immunoglobulin M (IgM) production ex vivo. Participants were divided into two age groups: adults (18-64 years) and elderly (≥65 years). The fraction of CD21 exhausted B cells in acute sepsis patients (3.18%) was higher than that observed in healthy donors (0.77%, respectively, P <0.01). Significantly, serum IgM in elderly septic patients (≥65 years) was negatively correlated with acute physiology and chronic health evaluation II score (r = -0.57, P <0.05). Consistently, in B cells stimulated ex vivo, both aging and sepsis induced significant reductions in supernatant IgM (P <0.01). This finding was clinically relevant, as elderly patients with decreased IgM production might be more susceptible to infection by Gram-negative bacteria and fungi. Reduced immunocompetent B cells may be related to increased secondary infection after sepsis, especially in the elderly. Finally, impaired humoral immunity with increased CD21 exhausted B cells and insufficient immunoglobulin M production may be a critical immunological change in sepsis. PMID:27172158

  6. 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

  7. 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

  8. Streptococcal tonsillitis and its association with psoriasis: a review.

    PubMed

    England, R J; Strachan, D R; Knight, L C

    1997-12-01

    Lancefield group A streptococcal upper respiratory tract infections are well known to be precursors of a number of disease processes. That they frequently herald a first attack of guttate psoriasis or a reactivation of chronic plaque psoriasis is well recognized, though this is perhaps more true among dermatologists than otolaryngologists. This paper briefly summarizes the historical background, recent research into, and current understanding of the connection between the two pathological phenomena.

  9. Rapid rewarming after therapeutic hypothermia worsens outcome in sepsis

    PubMed Central

    Jo, You Hwan; Kim, Kyuseok; Lee, Jae Hyuk; Rim, Kwang Pil; Cho, In Soo

    2014-01-01

    Objective This study was performed to investigate the effect of the rewarming rate on survival and acute lung injury in sepsis. Methods Male Sprague-Dawley rats underwent cecal ligation and incision. After 1 hour of sepsis induction, normothermia (37°C±0.5°C, NT group) or hypothermia (32°C±0.5°C) was induced. Hypothermia was maintained for 4 hours and rats were divided into two groups according to the rewarming rate: RW1 group, 1 hour of rewarming; and RW2 group, 2 hours of rewarming. In the survival study, rats were observed for 12 hours after sepsis induction (n=6 per group). In the second experiment, rats were sacrificed 7 hours after sepsis induction, and lung tissues and plasma were harvested (n=10 per group). Results In the survival study, the RW2 group survived longer than the RW1 group (P<0.05), but the RW1 and NT groups showed no significant difference in survival duration (P>0.05). The histological lung injury score and malondialdehyde concentrations in the lung tissues were significantly higher in the RW1 group than in the RW2 group (P<0.05). Plasma interleukin (IL)-6 concentration and the ratio of IL-6 to IL-10 were higher in the RW1 group than in the RW2 group (P<0.05). Conclusion Rapid rewarming after therapeutic hypothermia results in a shorter survival period and acute lung injury in sepsis, which could be associated with the inflammatory responses.

  10. Surviving sepsis in the critical care environment.

    PubMed

    Benedict, Lara

    2015-01-01

    The management of sepsis and septic shock in the intensive care environment is a complex task requiring the cooperation of a multidisciplinary team. The Surviving Sepsis Campaign provides systematic guidelines for the recognition, early intervention, and supportive management of sepsis. Critical care nurses are instrumental in ensuring that these guidelines and other sources of evidence-based practice are used for patients with severe sepsis or septic shock. This article discusses the pathophysiologic processes in severe sepsis and septic shock and discusses the appropriate interventions as recommended by the Surviving Sepsis Campaign. Recommended early treatments are reviewed along with interventions related to hemodynamics, perfusion, and supportive care in the critical care environment.

  11. Molecular markers for the study of streptococcal epidemiology.

    PubMed

    McMillan, David J; Sanderson-Smith, Martina L; Smeesters, Pierre Robert; Sriprakash, Kadaba S

    2013-01-01

    Diseases caused by Streptococcus pyogenes (Group A streptococcus, GAS) range from superficial infections such as pharyngitis and impetigo to potentially fatal rheumatic heart disease and invasive disease. Studies spanning emm-typing surveillance to population genomics are providing new insights into the epidemiology, pathogenesis, and biology of this organism. Such studies have demonstrated the differences that exist in the epidemiology of streptococcal disease between developing and developed nations. In developing nations, where streptococcal disease is endemic, the diversity of GAS emm-types circulating is much greater than that found in developed nations. An association between emm-type and disease, as observed in developed countries is also lacking. Intriguingly, comparative genetic studies suggest that emm-type is not always a good predictor of the evolutionary relatedness of geographically distant isolates. A view of GAS as a highly dynamic organism, in possession of a core set of virulence genes that contribute to host niche specialization and common pathogenic processes, augmented by accessory genes that change the relative virulence of specific lineages is emerging. Our inability to definitively identify genetic factors that contribute to specific disease outcome underscores the complex nature of streptococcal diseases. PMID:23179674

  12. 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

  13. Sepsis-associated encephalopathy.

    PubMed

    Gofton, Teneille E; Young, G Bryan

    2012-10-01

    Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed.

  14. 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

  15. 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-1β (IL-1β) 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-1β, IL-6, and tumor necrosis factor-α (TNFα) 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

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

    PubMed

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

    2013-07-01

    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-1β (IL-1β) 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 h. Finally, mRNA and protein for IL-1β, IL-6, and tumor necrosis factor-α (TNFα) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6h to 72 h 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

  17. Soluble Suppression of Tumorigenicity 2 and Echocardiography in Sepsis.

    PubMed

    Yang, Hyun Suk; Hur, Mina; Kim, Hanah; Magrini, Laura; Marino, Rossella; Di Somma, Salvatore

    2016-11-01

    Soluble suppression of tumorigenicity 2 (sST2) has emerged as a biomarker of cardiac stretch or remodeling, and has demonstrated a role in acutely decompensated heart failure. However, its role in sepsis-induced cardiac dysfunction is still unknown. We explored whether sST2 serum concentration reflects either systolic or diastolic dysfunction as measured by Doppler echocardiography. In a total of 127 patients with sepsis, correlations between sST2 and blood pressure, left ventricular (LV) ejection fraction, LV diastolic filling (ratio of early transmitral flow velocity to early diastolic mitral annulus velocity), and resting pulmonary arterial pressure were evaluated. Correlations between sST2 and other sepsis biomarkers (high-sensitivity C-reactive protein [hs-CRP] and procalcitonin) were also examined. sST2 showed a moderate correlation with mean arterial pressure (r=-0.3499) but no correlation with LV ejection fraction, diastolic filling, or resting pulmonary hypertension. It showed moderate correlations with hs-CRP and procalcitonin (r=0.2608 and r=0.3829, respectively). sST2 might have a role as a biomarker of shock or inflammation, but it cannot reflect echocardiographic findings of LV ejection fraction or diastolic filling in sepsis. PMID:27578513

  18. Sepsis and pregnancy: do we know how to treat this situation?

    PubMed Central

    Cordioli, Ricardo Luiz; Cordioli, Eduardo; Negrini, Romulo; Silva, Eliezer

    2013-01-01

    Sepsis is defined as an acute inflammatory response syndrome secondary to an infectious focus. It has a high incidence, morbidity and mortality, causing substantial financial costs, especially due to complications such as septic shock and multiple organ dysfunction. The pathogen toxins associated with individual susceptibility culminate with cytokine release, which promotes a systemic inflammatory response that can progress to multiple organ dysfunction and eventual patient death. Specifically, sepsis incidence, morbidity and mortality are lower in pregnant women, as this group is typically younger with fewer comorbidities having a polymicrobial etiology resulting in sepsis. Pregnant women exhibit physiological characteristics that may confer specific clinical presentation and laboratory patterns during the sepsis course. Thus, a better understanding of these changes is critical for better identification and management of these patients. The presence of a fetus also requires unique approaches in a pregnant woman with sepsis. Sepsis treatment is based on certain guidelines that were established after major clinical trials, which, unfortunately, all classified pregnancy as a exclusion criteria. Thus, the treatment of sepsis in the general population has been extrapolated to the pregnant population, with the following main goals: maintenance of tissue perfusion with fluid replacement and vasoactive drugs (initial resuscitation), adequate oxygenation, control of the infection source and an early start of antibiotic therapy, corticosteroid infusion and blood transfusion when properly indicated, prophylaxis, and specifically monitoring and maintenance of fetal heath. PMID:24553516

  19. Diagnostic utility of biomarkers for neonatal sepsis--a systematic review.

    PubMed

    Hedegaard, Sofie Sommer; Wisborg, Kirsten; Hvas, Anne-Mette

    2015-03-01

    Neonatal sepsis is a major cause of morbidity and mortality. Early diagnosis and treatment of the neonate with suspected sepsis are essential to prevent life-threatening complications. Diagnosis of neonatal sepsis is a challenge due to non-specific clinical signs and the fact that infection markers are difficult to interpret in the first and critical phase of neonatal sepsis. The objective of the present study was to systematically evaluate existing evidence of the diagnostic utility of biomarkers for prediction of sepsis in neonates. We conducted a systematic literature search performed in PubMed and Embase. The study population was neonates with gestation age > 24 weeks in their first 28 days of life with suspected sepsis. The included manuscripts were rated due to criteria from a modified rating scale developed by Douglas Altman. Of 292 potentially relevant manuscripts, 77 fulfilled the inclusion and exclusion criteria; 16 (21%) were rated as high-quality studies. C-reactive protein (CRP) was the most extensively studied biomarker evaluated. The high-quality studies indicated that the acute phase protein serum amyloid A had high sensitivity, both at onset of symptoms and 2 days after. The studies evaluating serum amyloid A presented a variable positive predictive value (PPV, 0.67 and 0.92) with a high negative predictive value (NPV, 0.97 and 1.00). The existing evidence of the diagnostic value of serum amyloid A for neonatal sepsis showed promising results, and should be further investigated in clinical settings.

  20. Sepsis and pregnancy: do we know how to treat this situation?

    PubMed

    Cordioli, Ricardo Luiz; Cordioli, Eduardo; Negrini, Romulo; Silva, Eliezer

    2013-01-01

    Sepsis is defined as an acute inflammatory response syndrome secondary to an infectious focus. It has a high incidence, morbidity and mortality, causing substantial financial costs, especially due to complications such as septic shock and multiple organ dysfunction. The pathogen toxins associated with individual susceptibility culminate with cytokine release, which promotes a systemic inflammatory response that can progress to multiple organ dysfunction and eventual patient death. Specifically, sepsis incidence, morbidity and mortality are lower in pregnant women, as this group is typically younger with fewer comorbidities having a polymicrobial etiology resulting in sepsis. Pregnant women exhibit physiological characteristics that may confer specific clinical presentation and laboratory patterns during the sepsis course. Thus, a better understanding of these changes is critical for better identification and management of these patients. The presence of a fetus also requires unique approaches in a pregnant woman with sepsis. Sepsis treatment is based on certain guidelines that were established after major clinical trials, which, unfortunately, all classified pregnancy as a exclusion criteria. Thus, the treatment of sepsis in the general population has been extrapolated to the pregnant population, with the following main goals: maintenance of tissue perfusion with fluid replacement and vasoactive drugs (initial resuscitation), adequate oxygenation, control of the infection source and an early start of antibiotic therapy, corticosteroid infusion and blood transfusion when properly indicated, prophylaxis, and specifically monitoring and maintenance of fetal heath.

  1. Streptococcal lung abscesses from a dental focus following tocilizumab: a case report.

    PubMed

    de Kruif, Martijn D; van Gorp, Eric C M; Bel, Elisabeth H; Gerlag, Danielle M; Kunst, Peter W

    2012-01-01

    Patients suffering from dental infections and concurrently using immunosuppressive medication are at increased risk of developing systemic streptococcal infections. Tocilizumab is a novel therapeutic agent targeting interleukin-6. We describe a case of streptococcal lung abscesses from a dental focus after use of tocilizumab for treatment of Takayasu arteritis.

  2. 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…

  3. Current epidemiology of sepsis in mainland China

    PubMed Central

    Liao, Xuelian; Du, Bin; Lu, Meizhu; Wu, Minming

    2016-01-01

    The disease burden of sepsis is a global issue. Most of the large-scale epidemiological investigations on sepsis have been carried out in developed countries. The population of 1.3 billion in mainland China accounts for approximately 1/5th of the whole world population. Thus, the knowledge of the incidence and mortality of sepsis in mainland China is vital before employing measures for its improvement. However, most of the epidemiological data of sepsis in mainland China was obtained from ICU settings, and thus lacks the population-based incidence and mortality of sepsis. In the present review, we summarized the limited literature encompassing the incidence, mortality, long-term outcome, and pathogens of sepsis in mainland China. Therefore, it might provide some valuable information regarding the sepsis disease burden and current issues in the management of sepsis in mainland China. PMID:27713882

  4. Fast Action Can Prevent Sepsis Death: CDC

    MedlinePlus

    ... fullstory_160574.html Fast Action Can Prevent Sepsis Death: CDC Know the signs of extreme response to ... treated long before it causes severe illness or death, U.S. health officials report. Sepsis, or septicemia, occurs ...

  5. T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein

    PubMed Central

    1991-01-01

    M proteins, the major virulence factor of group A streptococci, have been implicated in the pathogenesis of acute rheumatic fever (ARF) and other streptococcal related autoimmune diseases. A 22-kD fragment of M type 5 protein is a potent stimulant of human T cells and has recently been shown by our laboratory to belong to the newly designated family of superantigens. Using flow cytometry and the polymerase chain reaction, we demonstrate that this molecule reacts with subsets of human T cells expressing specific T cell receptor (TCR) V beta elements, namely V beta 2, 4, and 8. We employed similar techniques to analyze the TCR V alpha usage of pep M5-stimulated T cells. These studies revealed that the preferential usage of particular V alpha elements is not specific for the superantigen; rather, it may reflect the repertoire of the individual being tested. The expansion of a large number of T cells bearing specific TCR V beta sequences by M protein may account for its role in mediating the pathogenesis of post- streptococcal diseases. Furthermore, the preferential usage of TCR V alpha elements in certain individuals may be an important factor that predisposes them to development of self-reactivity. PMID:1711564

  6. Severe sepsis management are we doing enough?

    PubMed

    Ahrens, Tom; Vollman, Kathleen

    2003-10-01

    For the first time in medical history, a drug has been shown to reduce the mortality associated with sepsis, the leading cause of death in many ICUs. Optimal use by appropriate selection of patients and early recognition of sepsis could save thousands of lives. Nurses play a major role in recognizing severe sepsis. By using the concepts introduced here, nurses can play a direct role in saving the lives of patients with sepsis.

  7. Sepsis caused by Flavimonas oryzihabitans.

    PubMed

    Lucas, K G; Kiehn, T E; Sobeck, K A; Armstrong, D; Brown, A E

    1994-07-01

    Previous reports of F. oryzihabitans sepsis involving central venous access devices reveal a relatively high rate of complications, including device removal, despite a course of broad-spectrum anti-microbials with compatible in vitro susceptibility results. In the present report of 22 cases of F. oryzihabitans sepsis treated at Memorial Sloan-Kettering Cancer Center from February 1986 through September 1993, the majority of CVAD-related infections with F. oryzihabitans were successfully treated with a 14-day course of antimicrobials with antipseudomonal activity, and removal of the device was usually not required. Factors that may complicate successful treatment of CVAD-related sepsis caused by F. oryzihabitans include polymicrobial infections and premature discontinuation of antibiotic therapy.

  8. Sepsis caused by Flavimonas oryzihabitans.

    PubMed

    Lucas, K G; Kiehn, T E; Sobeck, K A; Armstrong, D; Brown, A E

    1994-07-01

    Previous reports of F. oryzihabitans sepsis involving central venous access devices reveal a relatively high rate of complications, including device removal, despite a course of broad-spectrum anti-microbials with compatible in vitro susceptibility results. In the present report of 22 cases of F. oryzihabitans sepsis treated at Memorial Sloan-Kettering Cancer Center from February 1986 through September 1993, the majority of CVAD-related infections with F. oryzihabitans were successfully treated with a 14-day course of antimicrobials with antipseudomonal activity, and removal of the device was usually not required. Factors that may complicate successful treatment of CVAD-related sepsis caused by F. oryzihabitans include polymicrobial infections and premature discontinuation of antibiotic therapy. PMID:8041243

  9. Transfusion-associated bacterial sepsis.

    PubMed Central

    Wagner, S J; Friedman, L I; Dodd, R Y

    1994-01-01

    The incidence of sepsis caused by transfusion of bacterially contaminated blood components is similar to or less than that of transfusion-transmitted hepatitis C virus infection, yet significantly exceeds those currently estimated for transfusion-associated human immunodeficiency and hepatitis B viruses. Outcomes are serious and may be fatal. In addition, transfusion of sterile allogenic blood can have generalized immunosuppressive effects on recipients, resulting in increased susceptibility to postoperative infection. This review examines the frequency of occurrence of transfusion-associated sepsis, the organisms implicated, and potential sources of bacteria. Approaches to minimize the frequency of sepsis are discussed, including the benefits and disadvantages of altering the storage conditions for blood. In addition, the impact of high levels of bacteria on the gross characteristics of erythrocyte and platelet concentrates is described. The potentials and limitations of current tests for detecting bacteria in blood are also discussed. PMID:7923050

  10. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis.

    PubMed

    Lobo, Leandro A; Benjamim, Claudia F; Oliveira, Ana Carolina

    2016-07-01

    Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation. PMID:27525063

  11. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis.

    PubMed

    Lobo, Leandro A; Benjamim, Claudia F; Oliveira, Ana Carolina

    2016-07-01

    Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation.

  12. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis

    PubMed Central

    Lobo, Leandro A; Benjamim, Claudia F; Oliveira, Ana Carolina

    2016-01-01

    Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation. PMID:27525063

  13. Epidemiologic trends of sepsis in western countries

    PubMed Central

    Suarez De La Rica, Alejandro; Gilsanz, Fernando

    2016-01-01

    Since the American College of Chest Physicians (ACCP) and the Society of Critical care Medicine (SCCM) published the first consensus definition of syndromes related to sepsis in 1992, the knowledge of epidemiology of sepsis has clearly improved, although no prospective studies have been performed to analyse the incidence of sepsis in general population. There are differences in epidemiologic trends in sepsis between western countries and low-income and middle-income countries. In the United States (US), most of epidemiologic studies have been based on large, administrative databases, reporting an increase in the incidence of severe sepsis over years. In general, studies describing epidemiology of sepsis outside the US use clinical definitions and intensive care unit (ICU) observational cohort designs instead of administrative databases and definitions. Incidence of sepsis has increased over years, probably due to progressive aging of population, the existence of more comorbidities and maybe the liberal use of sepsis codification, by including patients with less severity. Notwithstanding, mortality due to sepsis is clearly decreasing over years, probably to improvement in ICU care, although absolute mortality is growing on account of the raise in incidence. Risk factors for sepsis are the two ends of life, male sex, US black race, presence of comorbidities and certain genetic variants. Respiratory tract infections are the most common source of sepsis, and, nowadays, Gram-positive infections are more frequent that Gram-negative sepsis in most prospective studies. PMID:27713883

  14. Neonatal sepsis of nosocomial origin: an epidemiological study from the "Grupo de Hospitales Castrillo".

    PubMed

    López Sastre, J B; Coto Cotallo, D; Fernández Colomer, B

    2002-01-01

    A prospective multicenter study was designed to assess the frequency, etiology, and mortality of nosocomial neonatal sepsis diagnosed between 1996 and 1997 in the neonatology services of 27 acute-care hospitals in Spain ("Grupo de Hospitales Castrillo"). Nosocomial sepsis is defined in the literature using chronological criteria (> 3-7 days of life at the onset of symptoms); accordingly, there is the possibility of including late-onset maternally acquired sepsis or of excluding early-onset nosocomial sepsis (< 3-7 days of life). For these reasons, in this study, cases of nosocomial sepsis that developed at < or = 3-7 days after birth (early onset) were also recorded and maternally acquired sepsis diagnosed beyond 3-7 days of life were excluded. Using these criteria in a total of 30,993 admissions to the neonatal units of the participating hospitals, the nosocomial sepsis rate was 2.1% with an incidence density of 0.89 per 1000 patient days. Sepsis rate was significantly more frequent among very low birth weight (VLBW) infants (15.6%) than among those weighing > or = 1500 g (1.16%) (P < 0.001). Fifty-eight percent of all isolates were Gram-positive organisms, mainly Staphylococcus epidermidis (42%). Gram-negative organisms were isolated in 29.5% of cases (Escherichia coli and Klebsiella spp. were the most commonly isolated pathogens) and fungal infections in 12%, with absolute predominance of Candida spp. The overall mortality rate was 11.8% and the following subgroups had significantly higher (P < 0.001) mortality rates: sepsis caused by Gram-negative organisms (19% vs. 5.1% in Gram-positive pathogens) and sepsis caused by Pseudomonas aeruginosa (33.3% vs. 9.4% for the total number of sepsis caused by the remaining causative pathogens). Sepsis caused by S. epidermidis showed a significantly lower mortality rate (5.5%) compared with overall sepsis for the remaining etiologies (14.2%) (P < 0.001). In VLBW infants, the mortality rate was significantly higher than in

  15. Prevalence and incidence of severe sepsis in Dutch intensive care units

    PubMed Central

    van Gestel, Aukje; Bakker, Jan; Veraart, Christiaan PWM; van Hout, Ben A

    2004-01-01

    Introduction Severe sepsis is a dreaded consequence of infection and necessitates intensive care treatment. Severe sepsis has a profound impact on mortality and on hospital costs, but recent incidence data from The Netherlands are not available. The purpose of the present study was to determine the prevalence and incidence of severe sepsis occurring during the first 24 hours of admission in Dutch intensive care units (ICUs). Methods Forty-seven ICUs in The Netherlands participated in a point prevalence survey and included patients with infection at the time of ICU admission. Clinical symptoms of severe sepsis during the first 24 hours of each patient's ICU stay were recorded and the prevalence of severe sepsis was calculated. Then, the annual incidence of severe sepsis in The Netherlands was estimated, based on the prevalence, the estimated length of stay, and the capacity of the participating ICUs relative to the national intensive care capacity. Results The participating ICUs had 442 beds available for admissions, which was estimated to be 42% of the national ICU capacity. At the time of the survey, 455 patients were currently admitted and 151 were included in the analysis; 134 (29.5%) patients met criteria for severe sepsis. The most common failing organ system was the respiratory system (90%), and most patients were admitted following surgery (37%) and were admitted because of acute infection (62%). The most prevalent source of infection was the lung (47%). The estimated duration of ICU stay for severe sepsis patients was 13.3 ± 1.1 days. Conclusion The annual number of admissions for severe sepsis in Dutch ICUs was calculated at 8643 ± 929 cases/year, which is 0.054% of the population, 0.61% of hospital admissions and 11% of ICU admissions. PMID:15312213

  16. Therapeutic effects of compound hypertonic saline on rats with sepsis.

    PubMed

    Dong, Fang; Chen, Wei; Xu, Liang; Wang, Huabing; Lu, Huizhi

    2014-01-01

    Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

  17. Chlorhexidine susceptibilities of mutans streptococcal serotypes and ribotypes.

    PubMed Central

    Grönroos, L; Mättö, J; Saarela, M; Luoma, A R; Luoma, H; Jousimies-Somer, H; Pyhälä, L; Asikainen, S; Alaluusua, S

    1995-01-01

    The susceptibilities of 379 clinical mutans streptococcal isolates to chlorhexidine (CHX) were tested by agar dilution according to the standards of the National Committee for Clinical Laboratory Standards. Isolates were obtained from saliva samples of 34 young mothers who had high or moderate salivary levels of mutans streptococci at baseline. Samples were collected on three occasions, before childbirth, when each child was 6 months old, and 1 year later. Of these isolates, 50% were inhibited at 1 microgram of CHX per ml, 90% were inhibited at 2.0 micrograms/ml, and all were inhibited at 4.0 micrograms/ml. The MICs for Streptococcus mutans isolates (serotypes c, e, and f) were lower than those for Streptococcus sobrinus isolates (serotypes d and g). In some subjects, the MICs for isolates of the same serotype were different. This phenomenon was studied by ribotyping isolates (n = 45) from selected subjects (n = 7). It was found that if there were intraindividual differences in the MICs for isolates of the same serotype, then the ribotypes of these isolates were different. In order to decrease the mutans streptococcal infection risk for children, 24 mothers (test group) brushed their teeth periodically with a gel that contained 0.3% CHX digluconate and 0.2% NaF, pH 5.8, between the second and third sampling occasions. The gel was used twice a day for the first 10 days of each month. Development of resistant strains during CHX-NaF gel use was not detected. The serotype distribution of isolates from the test group after 1 year of periodic CHX-NaF gel use did not differ from that at baseline. Periodic CHX-NaF gel brushing did not lead to lower salivary mutans streptococcal counts. PMID:7785991

  18. [Necrotising fasciitis caused by streptococcal toxic shock syndrome].

    PubMed

    Wedler, V; Meuli-Simmen, C; Künzi, W; Giovanoli, P; Meyer, V E

    2002-03-01

    Between 1994 and 1997, sixteen patients suffering from necrotising soft tissue infection were treated at the burn centre of the Division of Reconstructive Surgery, University of Zurich. The case of a 47 year old man is presented: He suffered from a necrotising fasciitis caused by Streptococcal induced Toxic Shock Syndrome (STSS). This example emphasizes the necessity of early diagnosis, priority of surgical intervention, and the antibiotic strategy. Necrotising fasciitis is a serious disease, caused by a variety of bacteria, which shows a high mortality rate, and its frequency was increasing over the last years.

  19. Outcomes and Resource Use of Sepsis-associated Stays by Presence on Admission, Severity, and Hospital Type

    PubMed Central

    Ashton, Carol M.; Kiehne, Lisa B.; Nicolas, Juan C.; Rose, Alexis L.; Shirkey, Beverly A.; Masud, Faisal; Wray, Nelda P.

    2016-01-01

    Objective: To establish a baseline for the incidence of sepsis by severity and presence on admission in acute care hospital settings before implementation of a broad sepsis screening and response initiative. Methods: A retrospective cohort study using hospital discharge abstracts of 5672 patients, aged 18 years and above, with sepsis-associated stays between February 2012 and January 2013 at an academic medical center and 5 community hospitals in Texas. Results: Sepsis was present on admission in almost 85% of cases and acquired in-hospital in the remainder. The overall inpatient death rate was 17.2%, but was higher in hospital-acquired sepsis (38.6%, medical; 29.2%, surgical) and Stages 2 (17.6%) and 3 (36.4%) compared with Stage 1 (5.9%). Patients treated at the academic medical center had a higher death rate (22.5% vs. 15.1%, P<0.001) and were more costly ($68,050±184,541 vs. $19,498±31,506, P<0.001) versus community hospitals. Conclusions: Greater emphasis is needed on public awareness of sepsis and the detection of sepsis in the prehospitalization and early hospitalization period. Hospital characteristics and case mix should be accounted for in cross-hospital comparisons of sepsis outcomes and costs. PMID:26759980

  20. Immunoconglutinin and complement changes in children with acute nephritis

    PubMed Central

    Ngu, J. L.; Soothill, J. F.

    1969-01-01

    Immunoconglutinin and electrophoretically altered forms of complement are detectable only after the fall in complement levels in acute nephritis, and may occur even when the fall is not noted. The delay between the postulated initiating streptococcal infection and the development of immunoconglutinin is longer than would be expected. The immunopathological significance of these findings is discussed. PMID:4189125

  1. A retrospective review of streptococcal infections in pediatric atopic dermatitis.

    PubMed

    Sugarman, Jeffrey L; Hersh, Adam L; Okamura, Tessie; Howard, Renee; Frieden, Ilona J

    2011-01-01

    In order to assess the clinical characteristics and impact of group A streptococcal infection in children with atopic dermatitis, a retrospective review was performed in children diagnosed with atopic dermatitis who had a skin culture. Culture results and clinical characteristics of those with group A streptococcus were compared with those with Staphlococcus aureus. Infection with group A streptococcus was present in 16%; infection with Staphlococcus aureus was present in 72%, and 14% had mixed cultures. Patients infected with group A streptococcus were more likely to be febrile, to have facial and periorbital involvement, and to be hospitalized compared with those infected with Staphlococcus aureus alone (p ≤ 0.01 for all comparisons). Bacteremia and cellulitis were significantly more common in those infected with group A streptococcus than in those infected with Staphlococcus aureus. Retrospective design and review of only those patients receiving bacterial cultures may select for greater severity than in the general atopic dermatitis population. Group A streptococcus appears to be a significant skin pathogen infecting children with atopic dermatitis. Children with atopic dermatitis and group A streptococcal infection are more likely to have invasive disease and complications than those infected with Staphlococcus aureus alone.

  2. Streptococcal C5a peptidase is a highly specific endopeptidase.

    PubMed Central

    Cleary, P P; Prahbu, U; Dale, J B; Wexler, D E; Handley, J

    1992-01-01

    Compositional analysis of streptococcal C5a peptidase (SCPA) cleavage products from a synthetic peptide corresponding to the 20 C-terminal residues of C5a demonstrated that the target cleavage site is His-Lys rather than Lys-Asp, as previously suggested. A C5a peptide analog with Lys replaced by Gln was also subject to cleavage by SCPA. This confirmed that His-Lys rather than Lys-Asp is the scissile bond. Cleavage at histidine is unusual but is the same as that suggested for a peptidase produced by group B streptococci. Native C5 protein was also resistant to SCPA, suggesting that the His-Lys bond is inaccessible prior to proteolytic cleavage by C5 convertase. These experiments showed that the streptococcal C5a peptidase is highly specific for C5a and suggest that its function is not merely to process protein for metabolic consumption but to act primarily to eliminate this chemotactic signal from inflammatory foci. Images PMID:1452354

  3. A link between perianal strep and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS).

    PubMed

    Toufexis, Megan; Deoleo, Caroline; Elia, Josephine; Murphy, Tanya K

    2014-04-01

    Perianal streptococcal dermatitis is an infection caused by group A streptococcus (GAS). Children with a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) phenotype may have tics or obsessive compulsive symptoms secondary to a systemic immune activation by GAS infecting perianal areas. In this retrospective case series, the authors describe three children with symptoms consistent with PANDAS and a confirmed perianal streptococcal dermatitis as the likely infectious trigger. Concomitant perianal dermatitis and new-onset obsessive-compulsive symptoms and/or tics are strong indications for perianal culture and rapid antigen detection test in young children. PMID:24763762

  4. A link between perianal strep and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS).

    PubMed

    Toufexis, Megan; Deoleo, Caroline; Elia, Josephine; Murphy, Tanya K

    2014-04-01

    Perianal streptococcal dermatitis is an infection caused by group A streptococcus (GAS). Children with a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) phenotype may have tics or obsessive compulsive symptoms secondary to a systemic immune activation by GAS infecting perianal areas. In this retrospective case series, the authors describe three children with symptoms consistent with PANDAS and a confirmed perianal streptococcal dermatitis as the likely infectious trigger. Concomitant perianal dermatitis and new-onset obsessive-compulsive symptoms and/or tics are strong indications for perianal culture and rapid antigen detection test in young children.

  5. Diagnosing sepsis - The role of laboratory medicine.

    PubMed

    Fan, Shu-Ling; Miller, Nancy S; Lee, John; Remick, Daniel G

    2016-09-01

    Sepsis is the host response to microbial pathogens resulting in significant morbidity and mortality. An accurate and timely diagnosis of sepsis allows prompt and appropriate treatment. This review discusses laboratory testing for sepsis because differentiating systemic inflammation from infection is challenging. Procalcitonin (PCT) is currently an FDA approved test to aid in the diagnosis of sepsis but with questionable efficacy. However, studies support the use of PCT for antibiotic de-escalation. Serial lactate measurements have been recommended for monitoring treatment efficacy as part of sepsis bundles. The 2016 sepsis consensus definitions include lactate concentrations >2mmol/L (>18mg/dL) as part of the definition of septic shock. Also included in the 2016 definitions are measuring bilirubin and creatinine to determine progression of organ failure indicating worse prognosis. Hematologic parameters, including a simple white blood cell count and differential, are frequently part of the initial sepsis diagnostic protocols. Several new biomarkers have been proposed to diagnose sepsis or to predict mortality, but they currently lack sufficient sensitivity and specificity to be considered as stand-alone testing. If sepsis is suspected, new technologies and microbiologic assays allow rapid and specific identification of pathogens. In 2016 there is no single laboratory test that accurately diagnoses sepsis. PMID:27387712

  6. 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

  7. Early PREdiction of Severe Sepsis (ExPRES-Sepsis) study: protocol for an observational derivation study to discover potential leucocyte cell surface biomarkers

    PubMed Central

    Antonelli, Jean; Warner, Noel; Brown, Kenneth Alun; Wright, John; Simpson, A John; Rennie, Jillian; Hulme, Gillian; Lewis, Sion Marc; Mare, Tracey Anne; Cookson, Sharon; Weir, Christopher John; Dimmick, Ian; Keenan, Jim; Rossi, Adriano Giorgio; Shankar-Hari, Manu; Walsh, Timothy S

    2016-01-01

    Introduction Sepsis is an acute illness resulting from infection and the host immune response. Early identification of individuals at risk of developing life-threatening severe sepsis could enable early triage and treatment, and improve outcomes. Currently available biomarkers have poor predictive value for predicting subsequent clinical course in patients with suspected infection. Circulating leucocytes provide readily accessible tissues that reflect many aspects of the complex immune responses described in sepsis. We hypothesise that measuring cellular markers of immune responses by flow cytometry will enable early identification of infected patients at risk of adverse outcomes. We aim to characterise leucocyte surface markers (biomarkers) and their abnormalities in a population of patients presenting to the hospital emergency department with suspected sepsis, and explore their ability to predict subsequent clinical course. Methods and analysis We will conduct a prospective, multicentre, clinical, exploratory, cohort observational study. To answer our study question, 3 patient populations will be studied. First, patients with suspected sepsis from the emergency department (n=300). To assess performance characteristics of potential tests, critically ill patients with established sepsis, and age and gender matched patients without suspicion of infection requiring hospital admission (both n=100) will be recruited as comparator populations. In all 3 groups, we plan to assess circulating biomarker profiles using flow cytometry. We will select candidate biomarkers by cross-cohort comparison, and then explore their predictive value for clinical outcomes within the cohort with suspected sepsis. Ethics and dissemination The study will be carried out based on the principles in the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice. Ethics approval has been granted from the Scotland A Research Ethics Committee (REC) and Oxford C

  8. Evaluation of procalcitonin for diagnosis of neonatal sepsis of vertical transmission

    PubMed Central

    López Sastre, José B; Solís, David Pérez; Serradilla, Vicente Roqués; Colomer, Belén Fernández; Cotallo, Gil D Coto

    2007-01-01

    Background The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission. Methods PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results. Results 169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%). Conclusion Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life. PMID:17324267

  9. Disseminated intravascular coagulation in sepsis.

    PubMed

    Zeerleder, Sacha; Hack, C Erik; Wuillemin, Walter A

    2005-10-01

    Disseminated intravascular coagulation is a frequent complication of sepsis. Coagulation activation, inhibition of fibrinolysis, and consumption of coagulation inhibitors lead to a procoagulant state resulting in inadequate fibrin removal and fibrin deposition in the microvasculature. As a consequence, microvascular thrombosis contributes to promotion of organ dysfunction. Recently, three randomized, double-blind, placebo-controlled trials investigated the efficacy of antithrombin, activated protein C (APC), and tissue factor pathway inhibitor, respectively, in sepsis patients. A significant reduction in mortality was demonstrated in the APC trial. In this article, we first discuss the physiology of coagulation and fibrinolysis activation. Then, the pathophysiology of coagulation activation, consumption of coagulation inhibitors, and the inhibition of fibrinolysis leading to a procoagulant state are described in more detail. Moreover, therapeutic concepts as well as the three randomized, double-blind, placebo-controlled studies are discussed.

  10. Sepsis: Medical errors in Poland.

    PubMed

    Rorat, Marta; Jurek, Tomasz

    2016-01-01

    Health, safety and medical errors are currently the subject of worldwide discussion. The authors analysed medico-legal opinions trying to determine types of medical errors and their impact on the course of sepsis. The authors carried out a retrospective analysis of 66 medico-legal opinions issued by the Wroclaw Department of Forensic Medicine between 2004 and 2013 (at the request of the prosecutor or court) in cases examined for medical errors. Medical errors were confirmed in 55 of the 66 medico-legal opinions. The age of victims varied from 2 weeks to 68 years; 49 patients died. The analysis revealed medical errors committed by 113 health-care workers: 98 physicians, 8 nurses and 8 emergency medical dispatchers. In 33 cases, an error was made before hospitalisation. Hospital errors occurred in 35 victims. Diagnostic errors were discovered in 50 patients, including 46 cases of sepsis being incorrectly recognised and insufficient diagnoses in 37 cases. Therapeutic errors occurred in 37 victims, organisational errors in 9 and technical errors in 2. In addition to sepsis, 8 patients also had a severe concomitant disease and 8 had a chronic disease. In 45 cases, the authors observed glaring errors, which could incur criminal liability. There is an urgent need to introduce a system for reporting and analysing medical errors in Poland. The development and popularisation of standards for identifying and treating sepsis across basic medical professions is essential to improve patient safety and survival rates. Procedures should be introduced to prevent health-care workers from administering incorrect treatment in cases.

  11. Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters

    PubMed Central

    Goldman, John; Cheriyath, Pramil; Nookala, Vinod

    2014-01-01

    Introduction. Aeromonas hydrophila is a gram negative bacillus that is native to aquatic environments that is increasingly reported in humans. This case is remarkable for A. hydrophila with an initial presentation of acute pancreatitis. Case Presentation. A 61-year-old male presented to the emergency department with nausea, vomiting, and abdominal pain for two days. His past medical history was significant for alcohol abuse. Initial laboratory examination showed an elevated white blood cell count, elevated lipase, and elevated liver function tests (LFT). Computer tomography (CT) showed peripancreatic inflammatory changes and retroperitoneal free fluid, suggestive of acute pancreatitis. The patient was treated with intravenous (IV) fluids and IV meropenem. After two days, the patient developed sepsis and respiratory failure and was intubated. Blood cultures were positive for Aeromonas hydrophila sensitive to ciprofloxacin which was added to his treatment. Additionally, it was discovered that this patient had recently vacationed in Florida where he consumed raw oysters. He was discharged home on the eighth day of the hospital admission. Conclusion. This is a rare case of A. hydrophila sepsis in an elderly patient with acute pancreatitis and a history of consumption of raw oysters. This case suggests that A. hydrophila can cause disseminated infection in immunocompetent individuals. PMID:25506003

  12. Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters.

    PubMed

    Nikiforov, Ivan; Goldman, John; Cheriyath, Pramil; Vyas, Anix; Nookala, Vinod

    2014-01-01

    Introduction. Aeromonas hydrophila is a gram negative bacillus that is native to aquatic environments that is increasingly reported in humans. This case is remarkable for A. hydrophila with an initial presentation of acute pancreatitis. Case Presentation. A 61-year-old male presented to the emergency department with nausea, vomiting, and abdominal pain for two days. His past medical history was significant for alcohol abuse. Initial laboratory examination showed an elevated white blood cell count, elevated lipase, and elevated liver function tests (LFT). Computer tomography (CT) showed peripancreatic inflammatory changes and retroperitoneal free fluid, suggestive of acute pancreatitis. The patient was treated with intravenous (IV) fluids and IV meropenem. After two days, the patient developed sepsis and respiratory failure and was intubated. Blood cultures were positive for Aeromonas hydrophila sensitive to ciprofloxacin which was added to his treatment. Additionally, it was discovered that this patient had recently vacationed in Florida where he consumed raw oysters. He was discharged home on the eighth day of the hospital admission. Conclusion. This is a rare case of A. hydrophila sepsis in an elderly patient with acute pancreatitis and a history of consumption of raw oysters. This case suggests that A. hydrophila can cause disseminated infection in immunocompetent individuals. PMID:25506003

  13. 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-γ), and tumor necrosis factor alpha (TNF-α), 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

  14. Biosensor of endotoxin and sepsis

    NASA Astrophysics Data System (ADS)

    Shao, Yang; Wang, Xiang; Wu, Xi; Gao, Wei; He, Qing-hua; Cai, Shaoxi

    2001-09-01

    To investigate the relation between biosensor of endotoxin and endotoxin of plasma in sepsis. Method: biosensor of endotoxin was designed with technology of quartz crystal microbalance bioaffinity sensor ligand of endotoxin were immobilized by protein A conjugate. When a sample soliton of plasma containing endotoxin 0.01, 0.03, 0.06, 0.1, 0.5, 1.0Eu, treated with perchloric acid and injected into slot of quartz crystal surface respectively, the ligand was released from the surface of quartz crystal to form a more stable complex with endotoxin in solution. The endotoxin concentration corresponded to the weight change on the crystal surface, and caused change of frequency that occurred when desorbed. The result was biosensor of endotoxin might detect endotoxin of plasma in sepsis, measurements range between 0.05Eu and 0.5Eu in the stop flow mode, measurement range between 0.1Eu and 1Eu in the flow mode. The sensor of endotoxin could detect the endotoxin of plasm rapidly, and use for detection sepsis in clinically.

  15. Early-onset neonatal sepsis.

    PubMed

    Simonsen, Kari A; Anderson-Berry, Ann L; Delair, Shirley F; Davies, H Dele

    2014-01-01

    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-γ), and tumor necrosis factor alpha (TNF-α), 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.

  16. Sepsis: From Bench to Bedside

    PubMed Central

    Silva, Eliézer; Passos, Rogério Da Hora; Ferri, Maurício Beller; de Figueiredo, Luiz Francisco Poli

    2008-01-01

    Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on “early-goal” directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible. PMID:18297215

  17. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an indication for tonsillectomy.

    PubMed

    Alexander, Alan A Z; Patel, Nitin J; Southammakosane, Cathy A; Mortensen, Melissa M

    2011-06-01

    Children with obsessive compulsive disorder or tic disorders that are associated with streptococcal infections (Group A beta-hemolytic) in the oro-pharyngeal region are given the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Tonsillectomy has been reported to resolve the neuro-psychiatric symptoms in these children. We have a case of a 9-year-old boy who was seen in our clinic with multiple recurrent streptococcal infections of the oro-pharyngeal cavity. He also exhibited neuro-psychiatric symptoms including agitation, hyperactivity, and tics. These symptoms followed his recurrent infections. Tonsillectomy was performed and in one year follow-up the patient did not have any recurrent streptococcal infections, and his neuro-psychiatric symptoms resolved completely. Guidelines for medical and surgical management of recurrent strep infections in the face of PANDAS are reviewed.

  18. Protective effect of Aloe vera on polymicrobial sepsis in mice.

    PubMed

    Yun, Nari; Lee, Chan-Ho; Lee, Sun-Mee

    2009-06-01

    Sepsis is an acute life-threatening clinical condition and remains the major cause of death in intensive care units. The primary pathophysiologic event central to the septic response is an overwhelming activation of the inflammatory system and countervailing response from the anti-inflammatory system. However, the cause of this perturbation has yet to be elucidated. In this study, we report that Aloe vera therapeutically reverses the lethality induced by cecal ligation and puncture (CLP), a clinically relevant model of sepsis. The administration of Aloe vera ameliorated the multiple organ dysfunction syndrome, as evidenced by the serum levels of biochemical parameters and histological changes. In order to investigate the pharmacological mechanism of Aloe vera, the levels of the cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined by ELISA at various time points. The increases in the levels of TNF-alpha, IL-1beta, and IL-6 were attenuated by Aloe vera.In vivo administration of Aloe vera also markedly enhanced bacterial clearance. Our findings suggest that Aloe vera could be a potential therapeutic agent for the clinical treatment of sepsis. PMID:19298839

  19. Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

    PubMed Central

    Dahdah, Albert; Gautier, Gregory; Attout, Tarik; Fiore, Frédéric; Lebourdais, Emeline; Msallam, Rasha; Daëron, Marc; Monteiro, Renato C.; Benhamou, Marc; Charles, Nicolas; Davoust, Jean; Blank, Ulrich; Malissen, Bernard; Launay, Pierre

    2014-01-01

    Controlling the overwhelming inflammatory reaction associated with polymicrobial sepsis remains a prevalent clinical challenge with few treatment options. In septic peritonitis, blood neutrophils and monocytes are rapidly recruited into the peritoneal cavity to control infection, but the role of resident sentinel cells during the early phase of infection is less clear. In particular, the influence of mast cells on other tissue-resident cells remains poorly understood. Here, we developed a mouse model that allows both visualization and conditional ablation of mast cells and basophils to investigate the role of mast cells in severe septic peritonitis. Specific depletion of mast cells led to increased survival rates in mice with acute sepsis. Furthermore, we determined that mast cells impair the phagocytic action of resident macrophages, thereby allowing local and systemic bacterial proliferation. Mast cells did not influence local recruitment of neutrophils and monocytes or the release of inflammatory cytokines. Phagocytosis inhibition by mast cells involved their ability to release prestored IL-4 within 15 minutes after bacterial encounter, and treatment with an IL-4–neutralizing antibody prevented this inhibitory effect and improved survival of septic mice. Our study uncovers a local crosstalk between mast cells and macrophages during the early phase of sepsis development that aggravates the outcome of severe bacterial infection. PMID:25180604

  20. Imaging in sepsis-associated encephalopathy--insights and opportunities.

    PubMed

    Stubbs, Daniel J; Yamamoto, Adam K; Menon, David K

    2013-10-01

    Sepsis-associated encephalopathy (SAE) refers to a clinical spectrum of acute neurological dysfunction that arises in the context of sepsis. Although the pathophysiology of SAE is incompletely understood, it is thought to involve endothelial activation, blood-brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance. SAE is associated with a high risk of mortality. Imaging studies using MRI and CT have demonstrated changes in the brains of patients with SAE that are also seen in disorders such as stroke. Next-generation imaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and PET, as well as experimental imaging modalities, provide options for early identification of patients with SAE, and could aid in identification of pathophysiological processes that represent possible therapeutic targets. In this Review, we explore the recent literature on imaging in SAE, relating the findings of these studies to pathological data and experimental studies to obtain insights into the pathophysiology of sepsis-associated neurological dysfunction. Furthermore, we suggest how novel imaging technologies can be used for early-stage proof-of-concept and proof-of-mechanism translational studies, which may help to improve diagnosis in SAE.

  1. [Albumin in sepsis].

    PubMed

    Tamion, F

    2010-09-01

    Human serum albumin is a small (66kD) globular protein representing over 60 % of the total plasma protein content. It is made up of 585 amino 6 acids and contains 35 cysteine residues forming disulfide bridges that contribute to its overall tertiary structure. It has a free cysteine-derived thiol group at Cys-34, which accounts for 80 % of its redox activity. Physiologically, serum albumin exists in a reduced form with a free thiol contributing to its antioxidant properties. It is synthesized primarily in the liver and is an acute-phase protein. It is a multifunctional plasma protein ascribed ligand-binding and transport properties as well as antioxidants and enzymatic functions. It maintains colloid osmotic pressure, modulates inflammatory response and may influence oxidative damage. Hypoalbuminemia is common in the intensive care unit and may be due to decreased synthesis by the liver and/or to increased losses or increased proteolysis and clearance. Although albumin was long used to control vascular collapse in critically ill patients, the evidence suggests that it does not offer a benefit over crystalloid solutions in vascular collapse. However, human serum albumin is an important circulating antioxidant and it may be beneficial in critically ill patients to limit oxidative damage. A number of studies suggest that in specific groups of hypoalbuminemic critically ill patients, albumin administration may have beneficial effects on organ function, although the exact mechanisms remain undefined. Further trials are needed to confirm theses observations and to clearly demonstrate whether albumin should be administered in critically ill patients with hypoalbuminemia. PMID:20675098

  2. Invasive Group B Streptococcal Disease in South Africa: Importance of Surveillance Methodology

    PubMed Central

    Cohen, Cheryl; von Gottberg, Anne; Meiring, Susan; Cutland, Clare L.; Schrag, Stephanie J.; Madhi, Shabir A.

    2016-01-01

    Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7–89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06–1.43] vs. 1.50 [95%CI 1.30–1.71], respectively, rate ratio 0.82 [95%CI 0.67–1.01]; LOD 1.04 [95% CI 0.90–1.23] vs. 1.22 [95%CI 1.05–1.42], rate ratio 0.85 [95% CI 0.68–1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a

  3. Invasive Group B Streptococcal Disease in South Africa: Importance of Surveillance Methodology.

    PubMed

    Quan, Vanessa; Verani, Jennifer R; Cohen, Cheryl; von Gottberg, Anne; Meiring, Susan; Cutland, Clare L; Schrag, Stephanie J; Madhi, Shabir A

    2016-01-01

    Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7-89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06-1.43] vs. 1.50 [95%CI 1.30-1.71], respectively, rate ratio 0.82 [95%CI 0.67-1.01]; LOD 1.04 [95% CI 0.90-1.23] vs. 1.22 [95%CI 1.05-1.42], rate ratio 0.85 [95% CI 0.68-1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a probe to better

  4. Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin

    PubMed Central

    López Sastre, José B; Pérez Solís, David; Roqués Serradilla, Vicente; Fernández Colomer, Belén; Coto Cotallo, Gil D; Krauel Vidal, Xavier; Narbona López, Eduardo; García del Río, Manuel; Sánchez Luna, Manuel; Belaustegui Cueto, Antonio; Moro Serrano, Manuel; Urbón Artero, Alfonso; Álvaro Iglesias, Emilio; Cotero Lavín, Ángel; Martínez Vilalta, Eduardo; Jiménez Cobos, Bartolomé

    2006-01-01

    Background It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. Results The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%). Conclusion Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be

  5. Sepsis management in the deployed field hospital.

    PubMed

    Johnston, Andrew McD; Easby, D; Ewington, I

    2013-09-01

    Sepsis, a syndrome caused by severe infection, affects a small proportion of military casualties but has a significant effect in increasing morbidity and mortality, including causing some preventable deaths. Casualties with abdominal trauma and those with significant tissue loss appear to be at a greater risk of sepsis. In this article, the diagnosis and management of sepsis in military casualties with reference to the Surviving Sepsis Campaign guidelines are examined. We discuss the management considerations specific to military casualties in the deployed setting and also discuss factors affecting evacuation by the UK Royal Air Force Critical Care Air Support Team. PMID:24109139

  6. 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

  7. Autophagy in sepsis: Degradation into exhaustion?

    PubMed

    Ho, Jeffery; Yu, Jun; Wong, Sunny H; Zhang, Lin; Liu, Xiaodong; Wong, Wai T; Leung, Czarina C H; Choi, Gordon; Wang, Maggie H T; Gin, Tony; Chan, Matthew T V; Wu, William K K

    2016-07-01

    Autophagy is one of the innate immune defense mechanisms against microbial challenges. Previous in vitro and in vivo models of sepsis demonstrated that autophagy was activated initially in sepsis, followed by a subsequent phase of impairment. Autophagy modulation appears to be protective against multiple organ injuries in these murine sepsis models. This is achieved in part by preventing apoptosis, maintaining a balance between the productions of pro- and anti-inflammatory cytokines, and preserving mitochondrial functions. This article aims to discuss the role of autophagy in sepsis and the therapeutic potential of autophagy enhancers.

  8. Sepsis management in the deployed field hospital.

    PubMed

    Johnston, Andrew McD; Easby, D; Ewington, I

    2013-09-01

    Sepsis, a syndrome caused by severe infection, affects a small proportion of military casualties but has a significant effect in increasing morbidity and mortality, including causing some preventable deaths. Casualties with abdominal trauma and those with significant tissue loss appear to be at a greater risk of sepsis. In this article, the diagnosis and management of sepsis in military casualties with reference to the Surviving Sepsis Campaign guidelines are examined. We discuss the management considerations specific to military casualties in the deployed setting and also discuss factors affecting evacuation by the UK Royal Air Force Critical Care Air Support Team.

  9. [Prevention of neonatal group B streptococcal sepsis in Hungary in 2012. Preliminary data of a nation-wide survey].

    PubMed

    Sziller, István; Szabó, Miklós; Valek, Andrea; Rigó, Barbara; Ács, Nándor

    2014-07-20

    Bevezetés: Magyarországon jelenleg nincs kötelező útmutató a korai kezdetű újszülöttkori B csoportú Streptococcus-szepszis megelőzésére. Célkitűzés: A szerzők a szülészeti intézetekben spontán szerveződő prevenciós módszerek megismerését tűzték ki célul. Módszer: Az országban működő 71 szülészeti intézettől érdeklődtek a 2012. évben folytatott gyakorlatukról. Eredmények: Megkeresésükre 20 intézetből (27,4%) érkezett válasz. A felmérésben részt vevő intézetekből összesen 36 092 szülésről és 36 588 újszülöttről kaptak adatokat, miközben 2012-ben Magyarországon összesen 90 269 szülést tartottak nyilván. A választ küldő intézetekben a 2012. évi országos szülésszám 39,9%-a zajlott. Valamennyi választ küldő intézet rendelkezett saját stratégiával az újszülöttek korai kezdetű szepszisének megelőzésére. A profilaxisra szoruló terhesek azonosítása az esetek 95%-ában bakteriológiai tenyésztéssel, 5%-ában kizárólag kockázatelemzéssel történt. A bakteriológiai módszert alkalmazó intézetek 58%-a a tenyésztést a 36. hét után végezte. A profilaxisra elsőnek választott antibiotikum minden intézetben penicillinszármazék volt (100%). Az intrapartum antibiotikumprofilaxis többszöri adagolásból állt az intézetek 80%-ában. Kötelező érvényű népegészségügyi előírások hiányában is a hazai szülészeti intézetekben proaktív stratégiával foglalkoztak a korai kezdetű újszülöttkori szepszis megelőzésének kérdésével. Következtetések: A vizsgálatban részt vevő intézetek több mint felében a profilaxis módszere az elfogadott nemzetközi gyakorlatnak felelt meg. Az önkéntes felmérésben a részvételi hajlandóság alacsony volt. Orv. Hetil., 2014, 155(29), 1167–1172.

  10. Sepsis in Buraidah Central Hospital, Qassim, Kingdom of Saudi Arabia

    PubMed Central

    Gasim, Gasim I.; Musa, Imad R; Yassin, Taha; Al Shobaili, Hani A.; Adam, Ishag

    2016-01-01

    Objectives Severe sepsis is a major public health concern and a frequent cause of intensive care unit (ICU) admission with a high fatality rate. Higher (Sequential Organ Failure Assessment score) SOFA score and co-morbidity of acute renal failure (ARF) are risk factors contributing to fatal outcome. This work was meant to study the epidemiology of sepsis in Buraidah central hospital. Methods This is a descriptive study conducted in the period from January 1, 2012, to June 29, 2012 to determine the epidemiology (incidence, clinical characteristics) and the outcome of sepsis in Buraidah hospital, Saudi Arabia. Results Out of 387 patients admitted to ICU, 62 (16%) patients had sepsis, their mean (SD) age was 62.7 (21.3) years. Three quarters of them 47 (75.8%) presented with septic shock. The median APACHE II score was 26.5 (8 to 48) and SOFA score 11 (5 to 21). The mean of duration of hospital stay was 11.95 days. The most frequent infection site was the pulmonary (69.5%). There were 37 isolated organism, gram-negative organisms (13; 35.13%) were the predominant isolates. There were 25 (40.3%) deaths; the majority of the deaths were due to septic shock 20(80%). There was a significant difference between deaths and the survivors, in the APACHI II score, SOFA score), and whether ventilated or not. Conclusions There was a high incidence of septic shock (and higher mortality) among the patients admitted to the ICU of Buraidah central hospital, especially among the elderly patients with respiratory infections. PMID:27103899

  11. Group G streptococcal epizootic in a closed cat colony.

    PubMed Central

    Tillman, P C; Dodson, N D; Indiveri, M

    1982-01-01

    An epizootic of beta-hemolytic Lancefield group G streptococcal infections occurred in a specific-pathogen-free colony of laboratory cats. A total of 19 out of 68 animals in a single building were affected over a 10-day period. Clinical signs included fever, depression, lymphadenopathy, pharyngitis, and submandibular edema. The organism was recovered from the pharynx in two of five clinically normal cats from the affected building. Cultures from 12 animals in the same colony but housed in unaffected buildings were negative. Two doses of long-acting penicillin G 72 h apart stopped the outbreak and resulted in negative cultures for previously affected animals. Three months later, two new cases occurred in the same building. The disease was finally eradicated from the colony by depopulating the affected building. PMID:7161373

  12. Group G streptococcal myositis in a patient with myeloproliferative neoplasm.

    PubMed

    Midha, Monica; Rosenthal, Marnie E

    2016-01-01

    While many cases of streptococcal infection are due to Lancefield groups A and B, there has been a rise in reported cases of infections due to group G streptococcus. We present a case of an individual with a hematologic malignancy who developed myositis secondary to group G streptococcus, with no clearly identifiable source of infection. The patient was managed with antibiotic therapy rather than surgical intervention due to high surgical risk related to severe thrombocytopenia. Targeted antibiotics initiated early in the course of disease may prevent the need for surgical intervention. Early diagnosis and treatment are critical to avoid the high morbidity and mortality of life-threatening infections caused by group G streptococcus. PMID:27500083

  13. Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis.

    PubMed

    Karlsson, I; Wernersson, S; Ambrosen, A; Kindahl, H; Södersten, F; Wang, L; Hagman, R

    2013-11-15

    Sepsis is difficult to diagnose and remains a common mortality cause worldwide in both humans and animals. The uterine infection pyometra causes sepsis in more than half of affected dogs and therefore allows the natural physiological development of sepsis to be studied. To find a sepsis-specific biochemical marker that could be combined with conventional clinical criteria for a more robust and quick diagnosis of sepsis, we measured systemic concentrations of high-mobility group box 1 (HMGB1) in 23 healthy control dogs and in 27 dogs with pyometra, 74% of which had sepsis. We also measured concentrations of the major acute phase protein C-reactive protein (CRP) and an indicator for endotoxaemia, prostaglandin F2α metabolite (PGM) to assess the relative contribution of HMGB1 to the detection of systemic inflammation and endotoxaemia. We found that HMGB1 concentrations, in line with concentrations of CRP and PGM, were significantly increased in dogs with pyometra, and that concentrations of CRP, but not HMGB1, were significantly higher in dogs with sepsis compared to dogs without sepsis. Although serum HMGB1 did not differ between dogs with or without sepsis and was not correlated with either CRP or PGM concentrations, HMGB1 was correlated with the total white blood cell counts, suggesting an independent regulation and involvement in inflammation. PMID:24120445

  14. Erythema Nodosum Associated With Streptococcal Infection in Pregnancy

    PubMed Central

    Richards, W. Edward; Reedy, Mark B.; Huddleston, Kevin P.; Jundt, Jeffrey W.

    1995-01-01

    Background: Erythema nodosum (EN) is a condition characterized by the presence of painful erythematous nodules on the pretibial aspects of the lower extremities. EN is thought to be a local inflammatory, immune-mediated reaction to a number of systemic antigenic stimuli. This condition is noted most often in women between menarche and menopause and is associated with certain drugs, infections, and pregnancy. However, no reports in the literature describe EN as a result of streptococcal infection during pregnancy. Case: A 21-year-old, white woman, G3P0020, presented at 13 weeks gestation with a 2-week history of erythematous, tender lesions on the pretibial aspects of both legs consistent with EN. The patient reported having had a “flu-like” illness at the same time the lesions developed. The “flu” symptoms resolved within 10 days without medical intervention, but the lesions on her legs persisted. An initial antistreptolysin-O (ASO) titer was elevated at 960 Todd units (normal values: preschool and adults <85; school-age and young adults <170). Six days later, she presented to the emergency department with complaints consistent with a urinary-tract infection. She was empirically treated with a 10-day course of amoxicillin, 500 mg t.i.d. Although the patient was treated with amoxicillin for a presumed urinary-tract infection (which was culture-negative), the lesions resolved after her completion of the antibiotics. Twelve weeks later, a repeat ASO was within normal limits. The EN lesions did not recur. Conclusion: Although many etiologic factors are identified as causes of EN, the condition is usually self-limiting, requiring only minimal supportive measures until it resolves. A careful history should be obtained and a physical examination performed to exclude other causes. If a recent streptococcal infection is identified or presumed, a 10- to 14-day course of antibiotics is warranted. PMID:18476042

  15. 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

  16. Invasive group A streptococcal infection in the Northern Territory, Australia: case report and review of the literature.

    PubMed

    Middleton, Bianca; Morris, Peter; Carapetis, Jonathan

    2014-11-01

    The increasing incidence of invasive group A streptococcus has been well documented in the temperate climates of North America, Europe and the United Kingdom. Studies also suggest that there are high rates of invasive group A streptococcus infection within the indigenous population of Northern Australia. This review article presents the case of infant Aboriginal twins with invasive group A streptococcal infection complicated by streptococcal toxic shock syndrome, highlighting both the severity and high transmissibility of invasive group A streptococcal disease. We review the epidemiology of group A streptococcal infection and suggest a potential role for chemoprophylaxis of household contacts to reduce the burden of disease within the indigenous population of Northern Australia.

  17. Diagnostic accuracy and clinical relevance of an inflammatory biomarker panel for sepsis in adult critically ill patients.

    PubMed

    Bauer, Philippe R; Kashyap, Rahul; League, Stacy C; Park, John G; Block, Darci R; Baumann, Nikola A; Algeciras-Schimnich, Alicia; Jenkins, Sarah M; Smith, Carin Y; Gajic, Ognjen; Abraham, Roshini S

    2016-02-01

    The objective of this study was to assess the diagnostic accuracy of C-reactive protein (CRP), procalcitonin (PCT), and cellular immune markers levels in sepsis. This was a prospective observational study in adult intensive care unit (ICU) patients, between 2012 and 2014. The 8-color flow cytometric biomarker panel included CD64, CD163, and HLA-DR. Index test results were compared with sepsis, using receiver operating characteristic curve analyses. Multivariate logistic regression assessed the relationship of sets of markers with the probability of sepsis. Of 219 enrolled patients, 120 had sepsis. C-statistic was the highest for CRP (0.86) followed by neutrophil CD64 expression (0.83), procalcitonin (0.82), and Acute Physiology and Chronic Health Evaluation (APACHE) IV (0.72). After adjustment for APACHE IV, the combination of CRP, PCT, and neutrophil CD64 measure remained a significant predictor of sepsis with an excellent AUC (0.90). In a targeted ICU population at increased risk of sepsis, CRP, PCT, and neutrophil CD64 combined improve the diagnostic accuracy of sepsis.

  18. Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.

    PubMed

    Zhang, Songen; Rahman, Milladur; Zhang, Su; Song, Lei; Herwald, Heiko; Thorlacius, Henrik

    2013-01-01

    Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766) on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage.

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

    PubMed

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

    2015-06-01

    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

  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. Estrogen sulfotransferase ablation sensitizes mice to sepsis

    PubMed Central

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R.; Kucera, Heidi; Gaikwad, Nilesh W.; Xu, Meishu; Lu, Peipei; Yan, Jiong; Fu, Haiyan; Liu, Youhua; Yu, Lushan; Huang, Min; Zeng, Su; Xie, Wen

    2015-01-01

    Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the estrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the cecal ligation and puncture (CLP) and lipopolysacharide (LPS) models of sepsis induce the expression of EST and compromise the activity of estrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised estrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes estrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-κB dependent and EST is a NF-κB target gene. The reciprocal regulation of inflammation and EST may represent a yet to be explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis. PMID:26259151

  2. Pseudomonas sepsis with Noma: an association?

    PubMed

    Vaidyanathan, S; Tullu, M S; Lahiri, K R; Deshmukh, C T

    2005-08-01

    We report here a 2.5-year-old male child with community-acquired Pseudomonal sepsis showing the characteristic lesions of ecthyma gangrenosum. The child had development of gangrenous changes of the nose and face - the 'cancrum oris' or 'Noma'. We highlight the possible association of Pseudomonas sepsis and Noma, with malnutrition playing a central role in causing both the diseases.

  3. Pelvic sepsis after stapled hemorrhoidopexy

    PubMed Central

    van Wensen, Remco JA; van Leuken, Maarten H; Bosscha, Koop

    2008-01-01

    Stapled hemorrhoidopexy is a surgical procedure used worldwide for the treatment of grade III and IV hemorrhoids in all age groups. However, life-threatening complications occur occasionally. The following case report describes the development of pelvic sepsis after stapled hemorrhoidopexy. A literature review of techniques used to manage major septic complications after stapled hemorrhoidopexy was performed. There is no standardized treatment currently available. Stapled hemorrhoidopexy is a safe, effective and time-efficient procedure in the hands of experienced colorectal surgeons. PMID:18855996

  4. 'An unusual response of dental sepsis to antibiotics: parallels with the Jarisch-Herxheimer reaction'.

    PubMed

    Moss, Helen; Collier, Jonathan Marc; Collier, Sophie

    2012-06-14

    Spreading odontogenic infections are a common source of hospital admissions to Oral and Maxillofacial Surgery (OMFS) units. This report describes an unusual reaction to routine treatment for a spreading odontogenic infection in a healthy male with no known allergies, requiring the patient to be managed supportively in the resuscitation room. The patient deteriorated rapidly after the administration of paracetamol, intravenous fluids, steroids and antibiotics, demonstrating delusional behaviour, fever, rigors, tachycardia and hypoxia. Fever associated with sepsis can lead to confusional states, but similar symptoms have been described in the literature as a reaction to antibiotic therapy known as Jarisch-Herxheimer (J-H) reaction. This is potentially the first time a J-H like reaction has been described in the context of dental sepsis. The authors feel that the OMFS team should be aware of possible sequelae of medical therapy in patients with acute dental sepsis and be confident in their management of these complications.

  5. Lactic Acidosis in Sepsis: It's Not All Anaerobic: Implications for Diagnosis and Management.

    PubMed

    Suetrong, Bandarn; Walley, Keith R

    2016-01-01

    Increased blood lactate concentration (hyperlactatemia) and lactic acidosis (hyperlactatemia and serum pH < 7.35) are common in patients with severe sepsis or septic shock and are associated with significant morbidity and mortality. In some patients, most of the lactate that is produced in shock states is due to inadequate oxygen delivery resulting in tissue hypoxia and causing anaerobic glycolysis. However, lactate formation during sepsis is not entirely related to tissue hypoxia or reversible by increasing oxygen delivery. In this review, we initially outline the metabolism of lactate and etiology of lactic acidosis; we then address the pathophysiology of lactic acidosis in sepsis. We discuss the clinical implications of serum lactate measurement in diagnosis, monitoring, and prognostication in acute and intensive care settings. Finally, we explore treatment of lactic acidosis and its impact on clinical outcome.

  6. Myeloid-derived suppressor cells accumulate in the liver site after sepsis to induce immunosuppression.

    PubMed

    Ren, Dongping; Bi, Qi; Li, Li; Gao, Yongqiang; Liang, Yu; Li, Yingju; Liu, Jun; Peng, Li; Xiao, Jianhua

    2012-09-01

    Myeloid-derived suppressor cells (MDSCs) play a major role in modulating immune response, but only a few reports focused on MDSCs in the liver of sepsis states. Here, we investigated the changes in MDSCs in liver of the cecal ligation and puncture (CLP) mice. The results of flow cytometry showed that MDSCs accumulate in the liver site of mice after CLP for 7days (CLP7d model mice) and settled to the livers of both normal and LPS stimulated mice. In vitro experiment showed a strong suppressive effect of MDSCs on the proliferation of CD4+ T lymphocytes of spleen. Furthermore, adoptive transfer of the liver MDSCs from CLP7d miceincreased the survival rate of acute hepatic failure (AHF) model mice in vivo. In conclusion, our data suggest that sepsis-induced liver MDSCs may have exert a key role in maintaining the immune homoeostasis in liver during the sepsis state.

  7. [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.

  8. Prevention of Early-onset Neonatal Group B Streptococcal Disease

    PubMed Central

    Marió, M. J. Soto; Valenzuela, I; Vásquez, A. E; Illanes, S. E

    2013-01-01

    Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an opportunistic pathogen that colonizes the gastrointestinal and genitourinary tracts of up to 50% of healthy adults and newborns; it is responsible for significant morbidity and mortality. Early detection can be used to establish the use of antibiotic prophylaxis to significantly reduce neonatal sepsis. This article reviews methods of detection and prevention of GBS infection in the neonate. PMID:24358406

  9. Sepsis-associated encephalopathy: not just delirium

    PubMed Central

    Zampieri, Fernando Godinho; Park, Marcelo; Machado, Fabio Santana; Azevedo, Luciano Cesar Pontes

    2011-01-01

    Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations. PMID:22012058

  10. 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

  11. Evaluation of IL-6, CRP and hs-CRP as Early Markers of Neonatal Sepsis

    PubMed Central

    Ganesan, Purushothaman; Sattar, Shameem Banu Abdul; Shankar, Shenbaga Lalitha

    2016-01-01

    Introduction Bacterial sepsis is a life threatening crisis with high mortality and morbidity in neonates. Due to non-specific clinical presentation, diagnosis of sepsis is still a challenge. It can be diagnosed by blood culture but it is time consuming. So, a reliable marker is needed for the diagnosis of neonatal sepsis so that early treatment can be initiated. Various cytokines, chemokines, acute phase reactants, cell surface markers and interferons have been evaluated to find out the effective marker for early diagnosis of neonatal sepsis. In this study, levels of IL-6, CRP and hs-CRP have been analysed which would favour the diagnosis of neonatal sepsis. Aim This study aimed to detect the levels of IL-6, CRP and hs-CRP in clinically suspected cases of neonatal sepsis and to evaluate and analyze the above parameters as the early markers of neonatal sepsis in comparison with blood culture. Materials and Methods Eighty neonates were included in this study of which 40 were clinically suspected cases of neonatal sepsis who met the inclusion criteria and the other 40 were normal healthy neonates that were taken as controls. After obtaining written informed consent from either parent of all neonates, venous blood samples were collected. Blood culture was performed by conventional method. Estimation of serum IL-6 was done by ELISA method and serum CRP and hs-CRP were done by immunofluorescence assay. Results The CRP level >13.49 mg/l showed sensitivity and specificity of 80% and 65.70% respectively. The IL-6 >51.29 pg/ml showed sensitivity of 100% and specificity of 62.86% and hs-CRP showed sensitivity of 90% and specificity of 32.86%. Combination of IL-6 and CRP showed sensitivity and specificity of 100% and 75.71% respectively. Conclusion Our study suggests that IL-6 is a highly sensitive marker and CRP is a more specific marker for the diagnosis of neonatal sepsis. hs-CRP is a less reliable marker. So, the combination of IL-6 and CRP are the better predictors of

  12. Predictive Value of IL-8 for Sepsis and Severe Infections After Burn Injury: A Clinical Study.

    PubMed

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2015-03-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring postburn inflammation is of paramount importance but, so far, there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As interleukin 8 (IL-8) is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict postburn sepsis, infections, and mortality. Plasma cytokines, acute-phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days after injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure [MOF], and mortality) were recorded. A cutoff level for IL-8 was determined using receiver operating characteristic analysis. Statistical significance is set at P < 0.05. Receiver operating characteristic analysis identified a cutoff level of 234 pg/mL for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cutoff and stratified into high (H) (n = 133) and low (L) (n = 335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area burned and incidence of MOF (P < 0.001). In the H group, IL-8 levels were able to predict sepsis (P < 0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute-phase responses compared with the L group (P < 0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients.

  13. Renal Proteomic Responses to Severe Sepsis and Surgical Trauma: Dynamic Analysis of Porcine Tissue Biopsies.

    PubMed

    Matejovic, Martin; Tuma, Zdenek; Moravec, Jiri; Valesova, Lenka; Sykora, Roman; Chvojka, Jiri; Benes, Jan; Mares, Jan

    2016-10-01

    Although the burden of septic acute kidney injury continues to increase, the molecular pathogenesis remains largely obscure. The aim of this exploratory study was a discovery-driven analysis of dynamic kidney tissue protein expression changes applied for the first time in a classic large mammal model of sepsis. To achieve this goal, analyses of protein expression alterations were performed in serial samples of kidney cortical biopsies (before, 12 and 22 h of sepsis) in mechanically ventilated pigs challenged with continuous infusion of pseudomonas aeruginosa and compared with sham-operated control data. Global protein expression was analyzed using two-dimensional gel electrophoresis and mass spectrometry-based proteomics. Normodynamic sepsis was associated with 43% reduction in glomerular filtration. The exposure to surgical stress per se altered the renal protein expression profile, while sepsis induced distinct and highly dynamic proteome evolution shifting the balance toward cellular distress phenotype. We identified 20 proteins whose expression changes discriminated effects of sepsis from those induced by surgery. The data implicate endoplasmic reticulum stress, oxidative stress, mitochondrial energy metabolism, immune/inflammatory signaling, and tubular transport as major activated pathways. Thus, by coupling the power of sequential tissue proteomics with whole-animal physiological studies, our study helped to establish a first global overview of critical renal proteomic events occurring during surgical trauma and early sepsis in a porcine model. The study supports the notion that multiple potentially subtle and even transient changes in several proteins which are members of key functional interrelated systems appear to play a role in septic acute kidney injury. PMID:27070328

  14. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

    PubMed

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID:27366743

  15. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

    PubMed Central

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID:27366743

  16. Group A β-hemolytic Streptococcal Infection in Children and the Resultant Neuro-psychiatric Disorder; a Cross Sectional Study; Tehran, Iran

    PubMed Central

    Ebrahimi Taj, Farideh; Noorbakhsh, Samileh; Ghavidel Darestani, Sahar; Shirazi, Elham; Javadinia, Shima

    2015-01-01

    Introduction: Group A Beta-Hemolytic Streptococcus (GABHS) can induce PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). GABHS is the most important and common bacterial cause of acute pharyngitis in Iranian children. We studied the role of GABHS (anti-streptococcal antibodies) in suspected cases of PANDAS in a cross sectional studies. Methods: Across sectional study was done in 2 pediatric psychiatric/and neurologic clinics in Tehran (Rasul Akram and Aliasghar Hospital) during 2008–2010. We studied serum anti-streptococcal antibodies (anti streptolysin O, anti Deoxyribonuclease B, and anti-streptokinase (ABcam-ELISA, USA) in 76 cases with psychiatric manifestation (OCD, ADHD) in compare with 39 healthy controls. These antibodies were studied in 53 cases with movement disorders (Tic/Tourette syndrome) in compare with 76 healthy controls. Sensitivity, specificity and positive predictive value of tests were calculated. Results: In movement disorders ASOT, Anti-DNase and Anti streptokinase was significantly higher than controls (P<0.0001, P=0.000, P<0.00001) ASOT (cut off level> 200 IU/ml) had 75% sensitivity; 84% specificity and 80% PPV; Anti-streptokinase (cut off level > 332 IU/ml) had 34% sensitivity; 85% specificity, and 72% PPV; Anti-DNase (cut off level > 140 IU/ml) had 70% sensitivity; 99% specificity and PPV 90% for differentiating the group. ASOT, Anti-DNase and Anti streptokinase titer was significantly higher than controls (P<0.0001, P=0.000, P<0.0001). ASOT had 90% sensitivity; 82% specificity, PPV 92%; Anti streptokinase: 82% sensitivity; 82% specificity, PPV 95%; Anti DNase: 92% sensitivity; 82% specificity, PPV 92% for differentiation the cases from normal controls. Discussion: These findings support that a post infectious immune mechanism to GABHS may play a role in the pathogenesis of PANDAS in our children. A combination of throat culture, rapid antigen detection test, and serologic testing for GABHS

  17. Invasive Group A streptococcal disease in Ireland, 2004 to 2010.

    PubMed

    Martin, J; Murchan, S; O'Flanagan, D; Fitzpatrick, F

    2011-01-01

    Invasive group A streptococcal infections (iGAS) are a major clinical and public health challenge. iGAS is a notifiable disease in Ireland since 2004. The aim of this paper is to describe the epidemiology of iGAS in Ireland for the first time over the seven-year period from 2004 to 2010. The Irish national electronic infectious disease reporting system was used by laboratories to enter the source of iGAS isolates, and by departments of public health to enter clinical and epidemiological details. We extracted and analysed data from 1 January 2004 to 31 December 2010. Over the study period, 400 iGAS cases were notified. The annual incidence of iGAS doubled, from 0.8 per 100,000 population in 2004 to 1.6 in 2008, and then remained the same in 2009 and 2010. The reported average annual incidence rates were highest among children up to five years of age (2.3/100,000) and adults aged over 60 years (3.2/100,000). The most common risk factors associated with iGAS were skin lesions or wounds. Of the 174 people for whom clinical syndrome information was available, 28 (16%) cases presented with streptococcal toxic shock syndrome and 19 (11%) with necrotising fasciitis. Of the 141 cases for whom seven-day outcomes were recorded, 11 people died with iGAS identified as the main cause of death (seven-day case fatality rate 8%). The notification rate of iGAS in Ireland was lower than that reported in the United Kingdom, Nordic countries and North America but higher than southern and eastern European countries. The reasons for lower notification rates in Ireland compared with other countries may be due to a real difference in incidence, possibly due to prescribing practices, or due to artefacts resulting from the specific Irish case definition and/or low reporting in the early stages of a new surveillance system. iGAS disease remains an uncommon but potentially severe disease in Ireland. Ongoing surveillance is required in order to undertake appropriate control measures and gain a

  18. 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

  19. Five additions to the list of Sepsidae Diptera for Vietnam: Perochaeta cuirassa sp. n., Perochaeta lobo sp. n., Sepsis spura sp. n., Sepsis sepsi Ozerov, 2003 and Sepsis monostigma Thompson, 1869

    PubMed Central

    Ang, Yuchen; Meier, Rudolf

    2010-01-01

    Abstract A recent collecting trip to Vietnam yielded three new species and two new records of Sepsidae (Diptera) for the country. Here we describe two new species in the species-poor genus Perochaeta (Perochaeta cuirassa sp. n. andPerochaeta lobo sp. n.) and one to the largest sepsid genus Sepsis (Sepsis spura sp. n.) which is also found in Sumatra and Sulawesi. Two additional Sepsis species are new records for Vietnam (Sepsis sepsi Ozerov, 2003; Sepsis monostigma Thompson, 1869). We conclude with a discussion of the distribution of Perochaeta and the three Sepsis species. PMID:21594042

  20. The Surviving Sepsis Campaign: past, present and future.

    PubMed

    Schorr, Christa A; Dellinger, R Phillip

    2014-04-01

    The Surviving Sepsis Campaign (SSC) was created in 2002 and consists of severe sepsis management guidelines and a sepsis performance improvement program. The second revision of the guidelines, published in 2013, are sponsored by 30 international scientific organizations and contain changes in recommendations for fluids and vasopressor administration. The new 3- and 6-hour sepsis 'bundles' (sets of care elements) include a software program that can be downloaded free from the Surviving Sepsis Campaign website (www.survivingsepsis.org). The traditional intensive care unit and emergency department champion-driven sepsis performance improvement program continues internationally with the kick off of a new grant-funded hospital floor sepsis performance improvement initiative.

  1. Sepsis

    MedlinePlus

    ... fluids are given through a vein. Other medical treatments include: Medicines that increase blood pressure Dialysis if there is kidney failure A breathing machine ( mechanical ventilation ) if there is lung failure

  2. Sepsis

    MedlinePlus

    ... 100.4°F [38°C] and above rectal temperature) in newborns and young infants labored or unusual breathing change in skin color (paler than usual or mildly bluish) or a rash listlessness or lethargy change in the sound of the baby's cry or excessive crying change ...

  3. Hyporesponsiveness of peripheral blood lymphocytes to streptococcal superantigens in patients with guttate psoriasis: evidence for systemic stimulation of T cells with superantigens released from focally infecting Streptococcus pyogenes.

    PubMed

    Tokura, Y; Seo, N; Ohshima, A; Wakita, H; Yokote, R; Furukawa, F; Takigawa, M

    1999-01-01

    Throat infection with Streptococcus pyogenes is the most important trigger for acute guttate psoriasis. We examined the in vitro responses of peripheral blood mononuclear cells (PBMC) to streptococcal superantigens, SPEA and SPEC, and staphylococcal superantigens, SEB and TSST-1, in patients with guttate psoriasis, in patients with chronic plaque psoriasis, and in healthy subjects. PBMC from patients with guttate psoriasis responded poorly to SPEA and SPEC at concentrations of 0.1 and 1 ng/ml as compared with those from patients with plaque psoriasis, but showed high responses to SEB and TSST-1. The hyporesponsiveness recovered after improvement of the skin eruption. There was no significant difference between guttate and chronic types of psoriasis in the percentage of circulating T-cell receptor BV2 or BV8-bearing T cells, responsive to streptococcal superantigens, indicating that T-cell clonal anergy was a mechanism underlying the hyporesponsiveness. Our results suggest that superantigens released from focally infecting S. pyogenes induce a transient activation of relevant T cells, leading to the development of skin eruption and, subsequently, temporary T-cell anergy to these toxins.

  4. Diagnostic Value of Presepsin for Sepsis

    PubMed Central

    Zhang, Jing; Hu, Zhi-De; Song, Jia; Shao, Jiang

    2015-01-01

    Abstract Several individual studies have reported the diagnostic accuracy of presepsin (sCD14-ST) for sepsis, but the results are inconsistent. The present systematic review and meta-analysis pooled data to better ascertain the value of circulatory presepsin as a biomarker for sepsis. Studies published in English before November 7, 2014 and assessing the diagnostic accuracy of presepsin for sepsis were retrieved from medical databases. The quality of eligible studies was assessed using a revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2). The overall diagnostic accuracy of presepsin for sepsis was pooled according to a bivariate model. Publication bias was assessed using Deek funnel plot asymmetry test. Eleven studies satisfied the inclusion criteria. The overall diagnostic sensitivity of presepsin for sepsis was 0.83 (95% CI: 0.77–0.88), and specificity was 0.78 (95% CI: 0.72–0.83). The area under the summary receiver operating characteristic curve was 0.88 (95% CI: 0.84–0.90). The pretest probability of sepsis was 0.56 among all subjects. When presepsin was introduced as the diagnostic test for sepsis, the posttest probabilities were 0.81 for a positive result and 0.19 for a negative. The major design deficits of the included studies were lack of prespecified thresholds and patient selection bias. The publication bias was negative. Presepsin is an effective adjunct biomarker for the diagnosis of sepsis, but is insufficient to detect or rule out sepsis when used alone. PMID:26632748

  5. Dysglycemia and Glucose Control During Sepsis.

    PubMed

    Plummer, Mark P; Deane, Adam M

    2016-06-01

    Sepsis predisposes to disordered metabolism and dysglycemia; the latter is a broad term that includes hyperglycemia, hypoglycemia, and glycemic variability. Dysglycemia is a marker of illness severity. Large randomized controlled trials have provided considerable insight into the optimal blood glucose targets for critically ill patients with sepsis. However, it may be that the pathophysiologic consequences of dysglycemia are dynamic throughout the course of a septic insult and also altered by premorbid glycemia. This review highlights the relevance of hyperglycemia, hypoglycemia, and glycemic variability in patients with sepsis with an emphasis on a rational approach to management. PMID:27229647

  6. 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

  7. Morganella morganii sepsis with massive hemolysis.

    PubMed

    Kim, Jong Hoon; Cho, Chong Rae; Um, Tae Hyun; Rhu, Ji Yoon; Kim, Eu Suk; Jeong, Jae Won; Lee, Hye Ran

    2007-12-01

    Morganella morganii is a facultative gram-negative and anaerobic rod. It may be a cause of devastating infections in neonates and immunocompromised hosts. Some bacterial infections such as Clostridium and Vibrio are associated with hemolysis. However, massive hemolysis caused by M. morganii sepsis has not yet been reported. We observed a 59-yr-old man who had chemotherapy-induced neutropenia and was found to have massive hemolysis and metabolic acidosis due to sepsis. He died 6 hr after admission in spite of aggressive treatment. Two sets of blood cultures revealed the growth of M. morganii. We report here that M. morganii sepsis can cause fatal massive hemolysis leading to death.

  8. Sepsis Resuscitation: Fluid Choice and Dose.

    PubMed

    Semler, Matthew W; Rice, Todd W

    2016-06-01

    Sepsis is a common and life-threatening inflammatory response to severe infection treated with antibiotics and fluid resuscitation. Despite the central role of intravenous fluid in sepsis management, fundamental questions regarding which fluid and in what amount remain unanswered. Recent advances in understanding the physiologic response to fluid administration, and large clinical studies examining resuscitation strategies, fluid balance after resuscitation, colloid versus crystalloid solutions, and high- versus low-chloride crystalloids, inform the current approach to sepsis fluid management and suggest areas for future research.

  9. 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

  10. PCR-Based Identification of Oral Streptococcal Species

    PubMed Central

    Zhu, Min; Dawson, Deborah V.; Cao, Huojun; Levy, Steven M.

    2016-01-01

    The microbial etiology of dental caries is still debated. Among the hypothesized contributors are the “low pH streptococci,” a designation given to unusually acid proficient strains among the primary plaque colonizers S. oralis, S. mitis, S. gordonii, and S. anginosus. However, accurate assignment of species is difficult among the oral streptococci. Our objective was to develop a streamlined method for identifying strains of S. oralis and S. mitis from plaque samples so that they could be analyzed in a separate study devoted to low pH streptococci and caries. Two independent PCR amplifications of a locus highly conserved among streptococci were used for presumptive species identification. Multilocus sequence analysis (MLSA) was used to measure accuracy. Sensitivity was 100% for selecting S. oralis and S. mitis among the clones sampled. Specificity was good except for the most closely related species that could not be reliably distinguished even by MLSA. The results with S. oralis and S. mitis were used to identify new primer sets that expanded the utility of the approach to other oral streptococcal species. These novel primer sets offer a convenient means of presumptive identification that will have utility in many studies where large scale, in-depth genomic analyses are not practical. PMID:27703479

  11. Pressure Sensitivity of Streptococcal Growth in Relation to Catabolism

    PubMed Central

    Marquis, Robert E.; Brown, William P.; Fenn, Wallace O.

    1971-01-01

    The sensitivity of Streptococcus faecalis growth to hydrostatic pressures ranging up to 550 atm was found to depend on the source of adenosine triphosphate for growth. Barotolerance of cultures growing in a complex medium with ribose as major catabolite appeared to be determined primarily by the pressure sensitivity of ribose-degrading enzymes. Apparent activation volumes for growth were nearly identical to those for lactate production from ribose, and yield coefficients per mole of ribose degraded were relatively independent of pressure. In contrast, cultures with glucose as main catabolite were less sensitive to pressure; glycolysis was less severely restricted under high pressure than was growth, and yield coefficients declined with pressure, especially above 400 atm. Thus, two distinct types of barotolerance could be defined—one dominated by catabolic reactions and one dominated by noncatabolic reactions. The results of experiments with a series of other catabolites further supported the view that catabolic reactions can determine streptococcal barotolerance. We also found that growing, glucose-degrading cultures increased in volume under pressure in the same manner that they do at 1 atm. Thus, it appeared that the bacterium has no alternative means of carrying out glycolysis under pressure without dilatation. Also, the observation that cultures grown under pressure did not contain abnormally large or morphologically deformed cells suggested that pressure did not inhibit cell division more than cell growth. PMID:4925191

  12. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview.

    PubMed

    Esposito, S; Bianchini, S; Baggi, E; Fattizzo, M; Rigante, D

    2014-12-01

    The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive-compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing-remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial. PMID:24953744

  13. Cordyceps sinensis mycelium protects mice from group A streptococcal infection.

    PubMed

    Kuo, Chih-Feng; Chen, Cheng-Chih; Luo, Yueh-Hsia; Huang, Robert Y; Chuang, Woei-Jer; Sheu, Chia-Chin; Lin, Yee-Shin

    2005-08-01

    Group A streptococcus (GAS) infection can cause severe invasive diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Cordyceps sinensis, a Chinese herbal medicine, is an immunomodulator. In this study the air-pouch bacterial inoculation model was used to investigate the protective efficacy of C. sinensis mycelium extract against GAS infection. Force-feeding mice with C. sinensis mycelium extract for 3 consecutive days before GAS infection increased the survival rate and reduced local skin-tissue injury compared with mice fed PBS. Bacterial numbers in the air pouch exudates from C. sinensis-treated mice were lower than those from PBS-treated mice. Blood and organs in PBS-treated mice showed bacterial dissemination, but those in C. sinensis-treated mice did not. Three days of pretreatment with C. sinensis extract followed by C. sinensis treatment every other day after GAS infection resulted in 100% survival. The post-GAS-infection levels of aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen in the sera of C. sinensis-treated mice were lower than those of PBS-treated mice. Taken together, these results show that C. sinensis mycelium extract protects by decreasing bacterial growth and dissemination, thereby increasing mouse survival rate. IL-12 and IFN-gamma expression and macrophage phagocytic activity also increased after C. sinensis treatment. PMID:16014434

  14. 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

  15. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview.

    PubMed

    Esposito, S; Bianchini, S; Baggi, E; Fattizzo, M; Rigante, D

    2014-12-01

    The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive-compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing-remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial.

  16. 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

  17. 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

  18. Degradation of 14C-labeled streptococcal cell walls by egg white lysozyme and lysosomal enzymes.

    PubMed Central

    Gallis, H A; Miller, S E; Wheat, R W

    1976-01-01

    The resistance of native and trypsin-treated [14C] glucose-labeled cell walls to degradation by lysozyme and human lysosomal enzymes was confirmed. In contrast, chemically N-acetylated cell walls undergo significant degradation by these enzymes in the pH range of 4.5 to 5.5 without prior removal of the group-specific carbohydrate. N-acetylation after removal of the group A carbohydrate by formamide extraction renders the cell walls considerably more susceptible to these enzymes than by formamaide extraction alone. It appears, therefore, that unless N-acetylation can occur in vivo, streptococcal cell walls are minimally degraded, if at all, by human peripheral blood leukocytes or lysozyme. Examination of leukocyte extracts from normal subjects and patients with post-streptococcal syndromes revealed no qualitative differences in ability to dissolve streptococcal cell walls. Images PMID:773836

  19. Association between plaque-type psoriasis and perianal streptococcal cellulitis and review of the literature.

    PubMed

    Rasi, Abbas; Pour-Heidari, Nargess

    2009-11-01

    Perianal streptococcal dermatitis is an uncommon superficial cutaneous infection of the perianal area almost exclusively described in children. Perianal streptococcal dermatitis is caused by group A beta-hemolytic streptococci and occurs mainly in children between six months and ten years of age. Prior therapy with topical antifungal agents, topical corticosteroids, and oral preparations for pinworms either fails to improve or worsens patient's symptoms. Early antibiotic therapy causes a dramatic and rapid improvement of symptoms. Treatment protocol consists of amoxicillin 40 mg/kg/day, divided into three doses, and/or topical application of mupirocin 2% ointment three times per day for ten days. We describe a four-year-old boy with perianal streptococcal dermatitis who was brought to our clinic with plaque type psoriasis.

  20. Association between plaque-type psoriasis and perianal streptococcal cellulitis and review of the literature.

    PubMed

    Rasi, Abbas; Pour-Heidari, Nargess

    2009-11-01

    Perianal streptococcal dermatitis is an uncommon superficial cutaneous infection of the perianal area almost exclusively described in children. Perianal streptococcal dermatitis is caused by group A beta-hemolytic streptococci and occurs mainly in children between six months and ten years of age. Prior therapy with topical antifungal agents, topical corticosteroids, and oral preparations for pinworms either fails to improve or worsens patient's symptoms. Early antibiotic therapy causes a dramatic and rapid improvement of symptoms. Treatment protocol consists of amoxicillin 40 mg/kg/day, divided into three doses, and/or topical application of mupirocin 2% ointment three times per day for ten days. We describe a four-year-old boy with perianal streptococcal dermatitis who was brought to our clinic with plaque type psoriasis. PMID:19877754

  1. 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 < 0.05). Serum IL-6 levels in elderly 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 < 0.01). Ex vivo stimulation decreased CD25 expression, IL-2 production, and proliferation to a greater extent in CD4+ T cells from elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased

  2. Risk factors for nosocomial nontraumatic coma: sepsis and respiratory failure

    PubMed Central

    Zhou, Ye-Ting; Wang, Shao-Dan; Wang, Guang-Sheng; Chen, Xiao-Dong; Tong, Dao-Ming

    2016-01-01

    Background Coma’s are a major cause of clinical deterioration or death. Identification of risks that predispose to coma are important in managing patients; however, the risk factors for nosocomial nontraumatic coma (NNC) are not well known. Our aim was to investigate the risk factors in patients with NNC. Methods A retrospective case–control design was used to compare patients with NNC and a control group of patients without coma in a population-based cohort of 263 participants from the neurological intensive care unit in Shuyang County People’s Hospital of Northern China. Coma was diagnosed by a Glasgow Coma Scale score ≤8. Adjusted odds ratios for patients with NNC were derived from multivariate logistic regression analyses. Results A total of 96 subjects had NNC. The prevalence of NNC was 36.5% among the subjects. Among these, 82% had acute cerebrovascular etiology. Most of the NNC usually occurred at day 3 after admission to the neurological intensive care unit. Patients with NNC had higher hospital mortality rates (67.7% vs 3%, P<0.0001) and were more likely to have a central herniation (47.9% vs 0%, P<0.001) or uncal herniation (11.5% vs 0%, P<0.001) than those without NNC. Multiple logistic regression showed that systemic inflammatory response syndrome-positive sepsis (odds ratio =4, 95% confidence interval =1.875−8.567, P<0.001) and acute respiratory failure (odds ratio =3.275, 95% confidence interval =1.014−10.573, P<0.05) were the factors independently associated with a higher risk of NNC. Conclusion Systemic inflammatory response syndrome-positive sepsis and acute respiratory failure are independently associated with an increased risk of NNC. This information may be important for patients with NNC.

  3. [Acute rheumatic fever: problems and outlooks].

    PubMed

    Belov, B S

    2003-01-01

    The issue related with acute rheumatic fever still remains to be topical at the present stage, which is accentuated by a high prevalence of rheumatic heart diseases. The results of multiple studies point out at the presence of "rheumatogenetic" A-streptococcal strains possessing certain biological properties. Although there were no changes in the disease semiotics, the intensity degree of clinical signs went down, due to which an early diagnosis of the disease became more complicated. The issues related with the nosological classification of post-streptococcal reactive arthritis and with PANDAS syndrome need to be solved. There is also an urgent necessity in creating high-technological domestic benzathine-penicillins intended for secondary prevention of the disease.

  4. Post-Streptococcal Auto-Antibodies Inhibit Protein Disulfide Isomerase and Are Associated with Insulin Resistance

    PubMed Central

    Aran, Adi; Weiner, Karin; Lin, Ling; Finn, Laurel Ann; Greco, Mary Ann; Peppard, Paul; Young, Terry; Ofran, Yanay; Mignot, Emmanuel

    2010-01-01

    Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (ASLO) or anti-DNAse B (ADB)]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI), an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61) and PDI (P328-338). The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001). Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001), and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039) and insulin resistance (Homeostatic Model Assessment (HOMA) 4.1 vs. 3.1, n = 1215, p = 0.004), in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances. PMID:20886095

  5. Sepsis in Pregnancy: Identification and Management.

    PubMed

    Albright, Catherine M; Mehta, Niharika D; Rouse, Dwight J; Hughes, Brenna L

    2016-01-01

    Sepsis accounts for up to 28% of all maternal deaths. Prompt, appropriate treatment improves maternal and fetal morbidity and mortality. To date, there are no validated tools for identification of sepsis in pregnant women, and tools used in the general population tend to overestimate mortality. Once identified, management of pregnancy-associated sepsis is goal-directed, but because of the lack of studies of sepsis management in pregnancy, it must be assumed that modifications need to be made on the basis of the physiologic changes of pregnancy. Key to management is early fluid resuscitation and early initiation of appropriate antimicrobial therapy directed toward the likely source of infection or, if the source is unknown, empiric broad-spectrum therapy. Efforts directed at identifying the source of infection and appropriate source control measures are critical. Development of an illness severity scoring system and treatment algorithms validated in pregnant women needs to be a research priority.

  6. Group A streptococcal infections in Sweden: a comparative study of invasive and noninvasive infections and analysis of dominant T28 emm28 isolates.

    PubMed

    Eriksson, Björn K G; Norgren, Mari; McGregor, Karen; Spratt, Brian G; Normark, Birgitta Henriques

    2003-11-01

    Surveillance of group A streptococcus (GAS) infections in Sweden during 1996-1997 indicated that T28 isolates were dominant, whereas T1M1 infections were uncommon. Circulating T28 isolates were nearly all emm28, MLST52, and these clones had also been prevalent 10 years earlier. Isolates from invasive and noninvasive infections were of similar types and prevalences. The average national incidence of invasive episodes was 2.9/100,000 population but varied between 0 and 8.3/100,000 population in different counties. It increased markedly with age, reaching 22.9 episodes/100,000 among people aged > or =90 years. The incidence of puerperal sepsis was higher than expected (22.4/100,000 of those at risk), with 1 death. Overall mortality was 16% and was associated with preexisting chronic disease (P=.002). Streptococcal toxic shock syndrome (STSS) developed in approximately 15% of patients with invasive episodes, with a mortality rate of 45%. The use of nonsteroidal anti-inflammatory drugs was not found to be associated with the development of STSS.

  7. Neonatal infectious diseases: evaluation of neonatal sepsis.

    PubMed

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    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. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis.

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

    DOEpatents

    Brady, Linda Jeannine; Seifert, Kyle N.; Adderson, Elisabeth E.; Bohnsack, John F.

    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.

  9. 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

  10. Raftlin: a new biomarker in human sepsis.

    PubMed

    Lee, Wonhwa; Yoo, Hayoung; Ku, Sae-Kwang; Kim, Shin-Woo; Bae, Jong-Sup

    2014-06-01

    Raftlin is a major protein in lipid raft. The aim of this study was to evaluate blood levels of raftlin in septic patients. A prospective study of 82 patients with sepsis was conducted. Human umbilical vein endothelial cells (HUVECs) or mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to mice) or subjected to cecal ligation and puncture (CLP) surgery. Data showed that LPS induced upregulation of the synthesis and secretion of raftlin in LPS-treated HUVECs, and LPS-injected and CLP-mice. In patients admitted to the intensive care unit with sepsis, circulating levels of raftlin were significantly elevated, compared with control donors. Raftlin levels were higher in patients with septic shock, 891.6 (789.7-1,087.8, n = 30) than in patients with severe sepsis, 681.6 (480.1-819.6, n = 22) or sepsis, 496.1 (418.1-738.9, n = 30), compared with healthy volunteers 364.9 (312.1-392.4, n = 21). These results suggest that in septic patients, raftlin blood level is related to the severity of sepsis and the outcome of the patient and may represent a novel marker of endothelial cell dysfunction, and that raftlin can be used as a biomarker for determining the severity of sepsis.

  11. [Are statins a therapeutic alternative in sepsis?].

    PubMed

    Carrillo-Esper, Raúl; Rivera-Buendía, Santos; Carrillo-Córdova, Jorge Raúl; Carrillo-Córdova, Luis Daniel

    2007-01-01

    Sepsis continues to be a major cause of morbidity and mortality. Evidence is emerging from observational studies and basic science research that statins might be associated with reduced mortality in sepsis. Statins have diverse immunomodulatory and antiinflammatory properties independent of their lipid-lowering ability. The protective association between statins and sepsis persisted in high-risk subgroups including patients with diabetes mellitus, those with malignancy, and those receiving steroids. This review discusses the basis of these observations and the current place of statin therapy in patients with sepsis. This is a rapidly growing field of fascinating experimental biology. It suggests an urgent need to investigate the pharmacology of these drugs and reappraise their therapeutic indications in critically ill patients. If this finding is supported by prospective controlled trials, statins may play an important role in sepsis related mortality. By the other hand statins are significantly cheaper than other therapies that have been shown to improve outcome in sepsis, and the demonstration of mortality benefit would have enormous cost-benefit implication.

  12. The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update

    PubMed Central

    Annane, Djillali

    2016-01-01

    Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life-threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic–pituitary–adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol. Disruption of the hypothalamic–pituitary–adrenal axis may translate in patients with sepsis into cardiovascular and other organ dysfunction, and eventually an increase in the risk of death. Exogenous administration of corticosteroids at moderate dose, i.e., <400 mg of hydrocortisone or equivalent for >96 h, may help reversing sepsis-associated shock and organ dysfunction. Corticosteroids may also shorten the duration of stay in the ICU. Except for increased blood glucose and sodium levels, treatment with corticosteroids was rather well tolerated in the context of clinical trials. The benefit of treatment on survival remains controversial. Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 μg of ACTH test versus those with normal response. PMID:27379022

  13. Staphylococcus aureus Sepsis Induces Early Renal Mitochondrial DNA Repair and Mitochondrial Biogenesis in Mice

    PubMed Central

    Bartz, Raquel R.; Fu, Ping; Suliman, Hagir B.; Crowley, Stephen D.; MacGarvey, Nancy Chou; Welty-Wolf, Karen; Piantadosi, Claude A.

    2014-01-01

    Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection. PMID:24988481

  14. Response of lung γδ T cells to experimental sepsis in mice

    PubMed Central

    Hirsh, Mark; Dyugovskaya, Larissa; Kaplan, Viktoria; Krausz, Michael M

    2004-01-01

    γδ T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung γδ T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of γδ T cells progressively increased in lungs during sepsis, and reached a seven-fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P = 0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P < 0·05 versus sham), low interferon-γ (IFN-γ; 8·5 ± 2·5%; P < 0·05 versus control) and interleukin-10 (IL-10) expression, and high tumour necrosis factor-α expression (19·5 ± 1·7%; P < 0·05 versus control). The restoration of cytotoxicity, and increase in IFN-γ and IL-10 expression was observed at day 7 of CLP-induced sepsis. In summary, our results demonstrate significant progressive accumulation of γδ T cells in lungs during CLP-induced ALI. The temporary functional suppression of lung γδ T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage. PMID:15096194

  15. 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 μM) 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

  16. Inhibition of streptococcal pyrogenic exotoxin B using allicin from garlic.

    PubMed

    Arzanlou, Mohsen

    2016-04-01

    Streptococcal pyrogenic exotoxin B (SpeB) is an important virulence factor of group A streptococci (GAS) and inactivation of SpeB results in the significantly decreased virulence of the bacterium. The protein is secreted as an inactive zymogen of 40 KDa (SpeBz) and undergoes proteolytic truncation to result in a 28 KDa mature active protease (SpeBm). In this study the effect of allicin on the proteolytic activity of SpeBm was evaluated using azocasein assay. Allicin neutralized the SpeBm proteolytic activity in a concentration dependent manner (IC50 = 15.71 ± 0.45 μg/ml). The loss of activity was completely reversed by subsequent treatment with a reducing agent, dithiothreitol (DTT; 10 mM final concentration), suggesting that allicin likely inhibits the SpeBm by forming a disulfide linkage with an active thiol group in its active site. This mechanism of action was further confirmed with the fact that DTT did not reverse the SpeBm activity in the presence of E-64, a cysteine protease-specific inhibitor, which works specially by forming a thioether linkage with free sulfhydryl groups in enzymes active site. The MIC of allicin against GAS was found to be 32 μg/ml. Exposure of GAS culture to allicin (25 μg/ml) inhibited maturation of SpeBz to the SpeBm. In conclusion, the results of this study suggest that allicin inhibits the maturation of SpeBz and proteolytic activity of SpeBm and could be a potential therapeutic agent for the treatment of GAS infections. PMID:26911644

  17. Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.

    PubMed

    Wang, Hui-juan; Wang, Bao-zeng; Zhang, Peng-jun; Deng, Jie; Zhao, Zhi-rui; Zhang, Xin; Xiao, Kun; Feng, Dan; Jia, Yan-hong; Liu, You-ning; Xie, Li-xin

    2014-06-01

    The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785-0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

  18. 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.

  19. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    PubMed Central

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    responses or survival during the acute phase of a polymicrobial sepsis challenge. These data indicate that patients consuming caffeine will not be at risk for increased sepsis mortality. PMID:25944789

  20. [Takotsubo cardiomyopathy in the context of Staphylococcus aureus sepsis].

    PubMed

    Núñez, D; Bermejo, R; Rodríguez-Velasco, A

    2014-03-01

    Takotsubo cardiomyopathy consists of a transient dysfunction of the left ventricle. It is characterised by an impaired left ventricular segmentary contractility, without significant coronary lesions in the coronary angiography. It usually occurs after an episode of physical or emotional stress. We present the case of a 70 year-old woman, who, in the postoperative period of an ankle osteosynthesis, developed a Takotsubo cardiomyopathy in the context of a sepsis caused by Staphylococcus aureus. She presented with acute lung oedema and a clinical picture of low cardiac output. The echocardiogram showed left ventricular medioapical akinesia. Coronary angiography was normal. She was treated with supportive measures with good progress. At 33 days from onset she was able to be discharged from hospital to home with normal systolic function on echocardiography.

  1. Acute Obstructive Suppurative Pancreatic Ductitis

    PubMed Central

    Palakodeti, Sandeep; Munroe, Craig

    2016-01-01

    Acute obstructive suppurative pancreatic ductitis (AOSPD) is a rare clinical entity defined as suppuration from the pancreatic duct without concomitant pancreatic cyst, abscess, or necrosis. We describe a case of AOSPD in a woman with a past medical history of type 2 diabetes and chronic pancreatitis who presented with abdominal sepsis, which resolved only after therapeutic endoscopic retrograde cholangiopancreatography. Our case highlights the importance of considering AOSPD as a cause of abdominal sepsis particularly in patients with chronic pancreatitis or any recent pancreatic duct instrumentation and demonstrates that treatment requires prompt drainage and decompression of the pancreatic duct.

  2. Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

    PubMed Central

    2013-01-01

    Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

  3. Application of Whole-Genome Sequencing to an Unusual Outbreak of Invasive Group A Streptococcal Disease

    PubMed Central

    Galloway-Peña, Jessica; Clement, Meredith E.; Sharma Kuinkel, Batu K.; Ruffin, Felicia; Flores, Anthony R.; Levinson, Howard; Shelburne, Samuel A.; Moore, Zack; Fowler, Vance G.

    2016-01-01

    Whole-genome analysis was applied to investigate atypical point-source transmission of 2 invasive group A streptococcal (GAS) infections. Isolates were serotype M4, ST39, and genetically indistinguishable. Comparison with MGAS10750 revealed nonsynonymous polymorphisms in ropB and increased speB transcription. This study demonstrates the usefulness of whole-genome analyses for GAS outbreaks. PMID:27006966

  4. 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…

  5. Elevated biomarkers of endothelial dysfunction/activation at ICU admission are associated with sepsis development.

    PubMed

    Vassiliou, Alice G; Mastora, Zafeiria; Orfanos, Stylianos E; Jahaj, Edison; Maniatis, Nikolaos A; Koutsoukou, Antonia; Armaganidis, Apostolos; Kotanidou, Anastasia

    2014-10-01

    Widespread endothelial activation and dysfunction often precede clinical sepsis. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Such factors include endothelial adhesion molecules like E- and P-selectin, and the intercellular adhesion molecule-1, vascular endothelial cadherin, growth factors such as Angiopoietin-1 and -2 and vascular endothelial growth factor, as well as von Willebrand factor antigen. We sought to investigate whether circulating biomarkers of endothelial activation/dysfunction measured at ICU admission are associated with subsequent sepsis development. Eighty-nine critically-ill patients admitted to a general ICU who met no sepsis criteria were studied. Plasma or serum levels of the above-mentioned endothelium-derived molecules were measured during the first 24h post ICU; acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, age, sex, diagnostic category, and circulating procalcitonin (PCT) and C-reactive protein (CRP) levels were additionally measured or recorded. Forty-five patients subsequently became septic and 44 did not. Soluble (s) E- and P-selectin levels, circulating PCT, SOFA score and diagnostic category were significantly different between the two groups. Multiple logistic regression analysis associated elevated sE- and sP-selectin levels and SOFA with an increased risk of developing sepsis, while multiple Cox regression analysis identified sE- and sP-selectin levels as the only parameters related to sepsis appearance with time [RR=1.026, 95%CI=1.008-1.045, p=0.005; RR=1.005 (by 10 units), 95%CI=1.000-1.010, p=0.034, respectively]. When trauma patients were independently analyzed, multiple Cox regression analysis revealed sE-selectin to be the only molecule associated with sepsis development with time (RR=1.041, 95%CI: 1.019-1.065; p<0

  6. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis

    PubMed Central

    Schmidt, Eric P; Yang, Yimu; Janssen, William J; Gandjeva, Aneta; Perez, Mario J; Barthel, Lea; Zemans, Rachel L; Bowman, Joel C; Koyanagi, Dan E; Yunt, Zulma X; Smith, Lynelle P; Cheng, Sara S; Overdier, Katherine H; Thompson, Kathy R; Geraci, Mark W; Douglas, Ivor S; Pearse, David B; Tuder, Rubin M

    2013-01-01

    Sepsis, a systemic inflammatory response to infection, commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity. We postulated that sepsis-associated ALI is initiated by degradation of the pulmonary endothelial glycocalyx, leading to neutrophil adherence and inflammation. Using intravital microscopy, we found that endotoxemia in mice rapidly induced pulmonary microvascular glycocalyx degradation via tumor necrosis factor-α (TNF-α)-dependent mechanisms. Glycocalyx degradation involved the specific loss of heparan sulfate and coincided with activation of endothelial heparanase, a TNF-α–responsive, heparan sulfate–specific glucuronidase. Glycocalyx degradation increased the availability of endothelial surface adhesion molecules to circulating microspheres and contributed to neutrophil adhesion. Heparanase inhibition prevented endotoxemia-associated glycocalyx loss and neutrophil adhesion and, accordingly, attenuated sepsis-induced ALI and mortality in mice. These findings are potentially relevant to human disease, as sepsis-associated respiratory failure in humans was associated with higher plasma heparan sulfate degradation activity; moreover, heparanase content was higher in human lung biopsies showing diffuse alveolar damage than in normal human lung tissue. PMID:22820644

  7. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis.

    PubMed

    Schmidt, Eric P; Yang, Yimu; Janssen, William J; Gandjeva, Aneta; Perez, Mario J; Barthel, Lea; Zemans, Rachel L; Bowman, Joel C; Koyanagi, Dan E; Yunt, Zulma X; Smith, Lynelle P; Cheng, Sara S; Overdier, Katherine H; Thompson, Kathy R; Geraci, Mark W; Douglas, Ivor S; Pearse, David B; Tuder, Rubin M

    2012-08-01

    Sepsis, a systemic inflammatory response to infection, commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity. We postulated that sepsis-associated ALI is initiated by degradation of the pulmonary endothelial glycocalyx, leading to neutrophil adherence and inflammation. Using intravital microscopy, we found that endotoxemia in mice rapidly induced pulmonary microvascular glycocalyx degradation via tumor necrosis factor-α (TNF-α)-dependent mechanisms. Glycocalyx degradation involved the specific loss of heparan sulfate and coincided with activation of endothelial heparanase, a TNF-α-responsive, heparan sulfate-specific glucuronidase. Glycocalyx degradation increased the availability of endothelial surface adhesion molecules to circulating microspheres and contributed to neutrophil adhesion. Heparanase inhibition prevented endotoxemia-associated glycocalyx loss and neutrophil adhesion and, accordingly, attenuated sepsis-induced ALI and mortality in mice. These findings are potentially relevant to human disease, as sepsis-associated respiratory failure in humans was associated with higher plasma heparan sulfate degradation activity; moreover, heparanase content was higher in human lung biopsies showing diffuse alveolar damage than in normal human lung tissue.

  8. The role of immune and metabolic biomarkers for improved management of sepsis patients.

    PubMed

    Schuetz, Philipp; Mueller, Beat

    2014-09-01

    Sepsis, the body`s overwhelming response to systemic infections, is responsible for significant morbidity, mortality, and financial burden. Pathogens and their antigens stimulate pro- and anti-inflammatory mediators and immune markers which characterize the host defense and orchestrate leukocyte recruitment to the acute site of infection. Different immune and metabolic biomarkers have been studied in relation to sepsis for their diagnostic and/or prognostic aid. Recent studies have provided abundant evidence that specific immune and metabolic biomarkers improve a physician`s ability to guide early sepsis recognition, severity assessment and therapeutic decisions in individual patients. This may allow for a transition from bundled sepsis care (protocols combining several medical practices) to more individualized management. First, lactate has now been widely used for risk stratification and guidance of fluid resuscitation. Second, procalcitonin correlates with risks of bacterial infections and helps guide therapeutic decisions about initiation and withdrawal of anti-microbial therapy. Third, prognostic markers such as pro-adrenomedullin improve early mortality prediction and thereby site-of-care decisions in respiratory infections. For these markers interventional trials have documented their value when integrated in clinical protocols.

  9. Relationship between Age and Peripheral White Blood Cell Count in Patients with Sepsis

    PubMed Central

    Aminzadeh, Zohreh; Parsa, Elham

    2011-01-01

    Objectives: Total white blood cells (WBCs) decrease slightly in the elderly. In response to an acute infection, the number of WBCs increases and in sepsis, the increase is very dramatic. There are some reports about the effects of increased number of WBCs as a predisposing factor of bacteremia. An association between neutrophilia and eucopenia and increased mortality rate in the elderly has also been observed. We compared peripheral WBC counts in young and elderly patients with sepsis. Methods: A case-control study was carried out on 130 admitted patients who were divided into two groups based on age, ≥ 65 years (case group) and < 65 years (control group). All patients were hospitalized with the diagnosis of sepsis in two teaching hospitals in Tehran, Iran, 2001-2006. Results: Mean WBC counts at admission time were 17061.5 ± 14240.2 /μl in the case group and 13567.7 ± 9888.0 /ml in the control group. There were statistically significant associations between age and history of infection and history of hospitalization during the last month in the case group and also between age and source of infection (P < 0.05). Conclusions: The history of infection and the history of hospitalization during the last month with sepsis are important risk factors in elders. PMID:22174963

  10. A blueprint for a sepsis protocol.

    PubMed

    Shapiro, Nathan I; Howell, Michael; Talmor, Daniel

    2005-04-01

    Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is

  11. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    PubMed

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  12. 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.

  13. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    PubMed Central

    Çankayalı, İlkin; Boyacılar, Özden; Demirağ, Kubilay; Uyar, Mehmet; Moral, Ali Reşat

    2016-01-01

    Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required. PMID:27308070

  14. Year in review 2008: Critical Care - sepsis

    PubMed Central

    2009-01-01

    The present report highlights the most important papers appearing in Critical Care and other major journals about severe sepsis, the systemic inflammatory response and multiorgan dysfunction over the past year. A number of these clinical and laboratory studies will have a considerable impact on the sepsis research agenda for years to come. The steroid controversy, the debate over tight glycemic control, the colloid versus crystalloid issue, the value of selective decontamination of the digestive tract, the enlarging role of biomarkers, the value of genomics and rapid diagnostic techniques have all been prominently featured in recent publications. Basic research into novel predictive assays, genetic polymorphisms, and new molecular methods to risk-stratify and to determine treatment options for sepsis have occupied much of the Critical Care publications relating to sepsis pathophysiology in 2008. We will attempt to briefly summarize what we consider to be the most significant contributions to the sepsis literature over the last year, and their likely ramifications in the future, for critical care clinicians, clinical investigators and basic researchers alike. PMID:19886974

  15. Lipopolysaccharide triggers invasive streptococcal disease in mice through a tumour necrosis factor-alpha-dependent mechanism.

    PubMed

    Diao, Hongyan; Kohanawa, Masashi; Yimin; Nakajima, Hirofumi; Sato, Yuichiro; Minagawa, Tomonori; Nakane, Akio

    2002-03-01

    Streptococcus pyogenes sometimes induces invasive streptococcal infection, including streptococcal toxic shock syndrome (STSS). Muscular necrosis is one of the peculiar symptoms of invasive streptococcal infection and STSS. We inoculated S. pyogenes into the muscles of mice. To do so, 5 x 10(8) bacteria in 0.2 ml phosphate-buffered saline were injected into the right hind thigh. None of the mice injected with the bacteria showed muscular necrosis and none died. Tumour necrosis factor-alpha (TNF-alpha) and infiltration of leucocytes were detected in the muscles of infected sites, although the condition of the infected mice did not deteriorate after anti-TNF-alpha monoclonal antibody treatment. The infected mice treated intraperitoneally with Escherichia coli lipopolysaccharide (LPS) showed augmentation of bacterial growth, muscular necrosis and death. TNF-alpha was detected in the sera of the infected mice treated with LPS, but not in the muscles of the infected sites. Infiltration of leucocytes into the infected muscle was not observed in the infected mice treated with LPS. Anti-TNF-alpha monoclonal antibody treatment decreased mortality in the infected mice treated with LPS. Moreover, the infected mice treated with recombinant TNF-alpha showed augmentation of muscular necrosis and death. These results suggest that systemic production of TNF-alpha induced by stimulation with LPS inhibits infiltration of leucocytes into the infected site and exacerbates muscular infection, and that TNF-alpha produced in streptococcal infection is not a defence factor for the host. Invasive streptococcal infection and STSS appear to be induced by both S. pyogenes and the host's immune system.

  16. Endotoxins and other sepsis triggers.

    PubMed

    Opal, Steven M

    2010-01-01

    Endotoxin, or more accurately termed bacterial lipopolysaccharide (LPS), is recognized as the most potent microbial mediator implicated in the pathogenesis of sepsis and septic shock. Yet despite its discovery well over a century ago, the fundamental role of circulating endotoxin in the blood of most patients with septic shock remains enigmatic and a subject of considerable controversy. LPS is the most prominent 'alarm molecule' sensed by the host's early warning system of innate immunity presaging the threat of invasion of the internal milieu by Gram-negative bacterial pathogens. In small doses within a localized tissue space, LPS signaling is advantageous to the host in orchestrating an appropriate antimicrobial defense and bacterial clearance mechanisms. Conversely, the sudden release of large quantities of LPS into the bloodstream is clearly deleterious to the host, initiating the release of a dysregulated and potentially lethal array of inflammatory mediators and procoagulant factors in the systemic circulation. The massive host response to this single bacterial pattern recognition molecule is sufficient to generate diffuse endothelial injury, tissue hypoperfusion, disseminated intravascular coagulation and refractory shock. Numerous attempts to block endotoxin activity in clinical trials with septic patients have met with inconsistent and largely negative results. Yet the groundbreaking discoveries within the past decade into the precise molecular basis for LPS-mediated cellular activation and tissue injury has rekindled optimism that a new generation of therapies that specifically disrupt LPS signaling might succeed. Other microbial mediators found in Gram-positive bacterial and viral and fungal pathogens are now appreciated to activate many of the same host defense networks induced by LPS. This information is providing novel interventions in the continuing effots to improve the care of septic patients.

  17. Direct Testing of Blood Cultures for Detection of Streptococcal Antigens

    PubMed Central

    Wetkowski, Maryellen A.; Peterson, Ellena M.; De La Maza, Luis M.

    1982-01-01

    A direct, rapid, and simple method for the detection of streptococcal antigens of Lancefield groups A, B, C, D, and G from blood cultures was developed by using a coagglutination test. Fifty-five clinical specimens and 117 simulated blood cultures containing gram-positive cocci were tested. Out of 6,261 clinical blood cultures screened, 55 cultures from 53 patients were positive, with organisms resembling streptococci, by Gram stain. Of these cultures, 78% (43 of 55) were pure cultures of streptococci, and 22% (12 of 55) were mixed with at least one other organism. Of the 43 pure cultures only, correct reactions were obtained (grouping correctly or giving no cross-reactions, or both) with 86% (37 of 43) of the isolates, 12% (5 of 43) exhibited cross-reactions, and 2% (1 of 43) gave false-negative reactions. All of the cross-reacting isolates were Streptococcus pneumoniae, which reacted with the group C reagent, and the false-negative reaction occurred with a Streptococcus bovis isolate. However, by using a direct modified bile solubility test, the correct identification of the S. pneumoniae isolates was obtained. Therefore, by using the modified bile solubility test in conjunction with the direct grouping method, 98% (42 of 43) of the isolates in pure culture could be identified accurately and rapidly after the detection of a positive Gram stain. Correct grouping reactions were obtained with 83% (10 of 12) of the mixed blood cultures, and false-negative results occurred with 17% (2 of 12) of them. Both cultures contained an enterococcus and a gram-negative rod. Of the 117 simulated blood cultures, there was only one incorrect grouping reaction; this occurred with an S. bovis isolate that cross-reacted with the group C reagent. The direct grouping reaction was positive when blood cultures contained a minimum of 1 × 108 to 8 × 108 colony-forming units per ml. In general, this procedure provided information on the identification of the organism 24 h earlier than by

  18. Neonatal sepsis caused by Shewanella algae: A case report.

    PubMed

    Charles, Marie Victor Pravin; Srirangaraj, Sreenivasan; Kali, Arunava

    2015-01-01

    Sepsis remains a leading cause of mortality among neonates, especially in developing countries. Most cases of neonatal sepsis are attributed to Escherichia coli and other members of the Enterobacteriaceae family. Shewanella algae (S. algae) is a gram-negative saprophytic bacillus, commonly associated with the marine environment, which has been isolated from humans. Early onset neonatal sepsis caused by S. algae is uncommon. We report a case of S. algae blood stream infection in a newborn with early onset neonatal sepsis.

  19. Mitochondrial dysfunction and resuscitation in sepsis.

    PubMed

    Ruggieri, Albert J; Levy, Richard J; Deutschman, Clifford S

    2010-07-01

    Sepsis is among the most common causes of death in patients in intensive care units in North America and Europe. In the United States, it accounts for upwards of 250,000 deaths each year. Investigations into the pathobiology of sepsis have most recently focused on common cellular and subcellular processes. One possibility would be a defect in the production of energy, which translates to an abnormality in the production of adenosine triphosphate and therefore in the function of mitochondria. This article presents a clear role for mitochondrial dysfunction in the pathogenesis and pathophysiology of sepsis. What is less clear is the teleology underlying this response. Prolonged mitochondrial dysfunction and impaired biogenesis clearly are detrimental. However, early inhibition of mitochondrial function may be adaptive. PMID:20643307

  20. Host innate immune responses to sepsis

    PubMed Central

    Wiersinga, Willem Joost; Leopold, Stije J; Cranendonk, Duncan R; van der Poll, Tom

    2014-01-01

    The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis. PMID:23774844

  1. Role of immunoglobulins in neonatal sepsis

    PubMed Central

    Capasso, L; Borrelli, AC; Cerullo, J; Pisanti, R; Figliuolo, C; Izzo, F; Paccone, M; Ferrara, T; Lama, S; Raimondi, F

    2015-01-01

    Neonates, especially VLBW, are at high risk for sepsis related morbidity and mortality for immaturity of their immune system and invasive NICU practices. The paucity of immunoglobulins in preterm neonates consequently to the immaturity of immune system contributes to their high risk for systemic infection. The use of intravenous IgM enriched immunoglobulins, with higher antimicrobial activity than standard IgG, has been demonstrated in a retrospective study to reduce short term mortality in VLBW infant with proven sepsis. Larger, randomized prospective trials given the enormous burden of morbidity and mortality imposed by neonatal sepsis should urgently be addressed not only to validate this results but also to tailor the optimal scheme of treatment. PMID:25674546

  2. Anticoagulant modulation of inflammation in severe sepsis.

    PubMed

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

    2015-05-01

    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

  3. Disseminated intravascular coagulation in meningococcal sepsis. Case 7.

    PubMed

    Zeerleder, S; Zürcher Zenklusen, R; Hack, C E; Wuillemin, W A

    2003-08-01

    We report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis. The article discusses new therapeutic concepts in the treatment of disseminated intravascular coagulation in meningococcal sepsis, too.

  4. An Evidence Based Approach to Sepsis: Educational Program

    ERIC Educational Resources Information Center

    Perez, Dolores

    2015-01-01

    Evidence-based guidelines for recognizing and treating sepsis have been available for decades, yet healthcare providers do not adhere to the recommendations. Sepsis can progress rapidly if not recognized early. Literature reports reveal that sepsis is the leading cause of death in non-cardiac intensive care units (ICUs), and it is one of the most…

  5. Ghrelin inhibits sympathetic nervous activity in sepsis.

    PubMed

    Wu, Rongqian; Zhou, Mian; Das, Padmalaya; Dong, Weifeng; Ji, Youxin; Yang, Derek; Miksa, Michael; Zhang, Fangming; Ravikumar, Thanjavur S; Wang, Ping

    2007-12-01

    Our previous studies have shown that norepinephrine (NE) upregulates proinflammatory cytokines by activating alpha(2)-adrenoceptor. Therefore, modulation of the sympathetic nervous system represents a novel treatment for sepsis. We have also shown that a novel stomach-derived peptide, ghrelin, is downregulated in sepsis and that its intravenous administration decreases proinflammatory cytokines and mitigates organ injury. However, it remains unknown whether ghrelin inhibits sympathetic activity through central ghrelin receptors [i.e., growth hormone secretagogue receptor 1a (GHSR-la)] in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). Ghrelin was administered through intravenous or intracerebroventricular injection 30 min before CLP. Our results showed that intravenous administration of ghrelin significantly reduced the elevated NE and TNF-alpha levels at 2 h after CLP. NE administration partially blocked the inhibitory effect of ghrelin on TNF-alpha in sepsis. GHSR-la inhibition by the administration of a GHSR-la antagonist, [d-Arg(1),d-Phe(5), d-Trp(7,9),Leu(11)]substance P, significantly increased both NE and TNF-alpha levels even in normal animals. Markedly elevated circulating levels of NE 2 h after CLP were also significantly decreased by intracerebroventricular administration of ghrelin. Ghrelin's inhibitory effect on NE release was completely blocked by intracerebroventricular injection of the GHSR-1a antagonist or a neuropeptide Y (NPY)/Y(1) receptor antagonist. However, ghrelin's downregulatory effect on TNF-alpha release was only partially diminished by these agents. Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. Ghrelin's inhibitory effect on TNF-alpha production in sepsis is partially because of its modulation of the overstimulated sympathetic nerve activation.

  6. The Use of Fluids in Sepsis.

    PubMed

    Avila, Audrey A; Kinberg, Eliezer C; Sherwin, Nomi K; Taylor, Robinson D

    2016-03-10

    Sepsis is a systemic inflammatory response to severe infection causing significant morbidity and mortality that costs the health care system $20.3 billion annually within the United States. It is well established that fluid resuscitation is a central component of sepsis management; however, to date there is no consensus as to the ideal composition of fluid used for resuscitation. In this review, we discuss the progression of clinical research comparing various fluids, as well as the historical background behind fluid selection for volume resuscitation. We conclude that the use of balanced fluids, such as Ringer's Lactate, seems very promising but further research is needed to confirm their role.

  7. Sepsis and septic shock: a review.

    PubMed

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

    2015-01-01

    Sepsis and septic shock are a continuum of disease resulting from a complex host response to infection. They are major health issues in the United States, causing significant financial burden to the health care system in addition to multisystem morbidity and high rates of mortality. In recent decades, landmark trials in sepsis management have demonstrated improved mortality. Although the value of protocol-driven care is currently under question, it is clear that early recognition, prompt resuscitation, and timely use of antibiotics are of utmost importance.

  8. The Use of Fluids in Sepsis

    PubMed Central

    Avila, Audrey A; Sherwin, Nomi K; Taylor, Robinson D

    2016-01-01

    Sepsis is a systemic inflammatory response to severe infection causing significant morbidity and mortality that costs the health care system $20.3 billion annually within the United States. It is well established that fluid resuscitation is a central component of sepsis management; however, to date there is no consensus as to the ideal composition of fluid used for resuscitation. In this review, we discuss the progression of clinical research comparing various fluids, as well as the historical background behind fluid selection for volume resuscitation. We conclude that the use of balanced fluids, such as Ringer’s Lactate, seems very promising but further research is needed to confirm their role. PMID:27081589

  9. Incidence and mortality of sepsis, severe sepsis, and septic shock in intensive care unit patients with candidemia.

    PubMed

    Ng, Kevin; Schorr, Christa; Reboli, Annette C; Zanotti, Sergio; Tsigrelis, Constantine

    2015-08-01

    In this incidence study, of 16 074 patients admitted to the intensive care unit (ICU) from 1/1/2003 to 7/31/2011, 161 cases of candidemia were identified. The incidence of sepsis (27%), severe sepsis (31%), and septic shock (40%) was remarkably high in these cases of candidemia, as was the all-cause in-hospital mortality for sepsis (30%), severe sepsis (44%), and septic shock (65%).

  10. Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays.

    PubMed

    Bloos, Frank

    2015-01-01

    Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can

  11. [Usefulness of sCD14-ST in the diagnosis of sepsis in patient with renal failure].

    PubMed

    Galeano, Dario; Zanoli, Luca; Fatuzzo, Pasquale; Granata, Antonio

    2016-01-01

    Since many years, researchers have focused their studies to find out early sepsis biomarkers for the purpose of gaining time in the application of early goal-directed therapy protocol. Procalcitonin (PCT) is a reliable biomarker for sepsis, although it has a low specificity and prognostic value. Other recently proposed sepsis biomarkers such as interleukins, C-reactive protein (CRP), myeloid cells expressing triggering receptor-1 (TREM-1) and soluble urokinase-type plasminogen activator receptor (suPAR) still have a controversial and uncertain clinical value. In 2004 a new biomarker, soluble CD14 SubType (sCD14-ST, Presepsin), with a good performance in the diagnosis and prognostic evaluation of sepsis has been proposed. First studies highlighted that Presepsin is highly sensitive and specific at the same time. However, further studies on the clinical value of Presepsin are needed, particularly in order to explain the relationship between Presepsin and kidney failure. Indeed, Presepsin is a 13 KDa molecule theoretically totally filtered by glomerulus and reabsorbed and metabolized by proximal convoluted tubules. Therefore, the Presepsin plasmatic level could be highly influenced by an acute kidney injury in the course of sepsis or by a pre-existing chronic kidney disease. In this article we reviewed the latest evidences about the diagnostic and prognostic performances of Presepsin as a sepsis biomarker. We evaluated the usefulness of Presepsin in the context of acute and chronic kidney dysfunction. The great number of articles have been collected and the thorough revision of data from the nephrologists perspective let us consider this work exhaustive and scientifically reliable, although concise: a good starting point for the physician who wants to make use of Presepsin. PMID:27067215

  12. GADD34 suppresses lipopolysaccharide-induced sepsis and tissue injury through the regulation of macrophage activation

    PubMed Central

    Ito, S; Tanaka, Y; Oshino, R; Okado, S; Hori, M; Isobe, K-I

    2016-01-01

    Growth arrest and DNA damage inducible protein 34 (GADD34) is induced by various cellular stresses, such as DNA damage, endoplasmic reticulum stress, and amino-acid deprivation. Although the major roles of GADD34 are regulating ER stress responses and apoptosis, a recent study suggested that GADD34 is linked to innate immune responses. In this report, we investigated the roles of GADD34 in inflammatory responses against bacterial infection. To explore the effects of GADD34 on systemic inflammation in vivo, we employed a lipopolysaccharide (LPS)-induced murine sepsis model and assessed the lethality, serum cytokine levels, and tissue injury in the presence or absence of GADD34. We found that GADD34 deficiency increased the lethality and serum cytokine levels in LPS-induced sepsis. Moreover, GADD34 deficiency enhanced tissue destruction, cell death, and pro-inflammatory cytokine expression in LPS-induced acute liver injury. Pro-inflammatory cytokine production after LPS stimulation is regulated by the Toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway. In vitro experiments revealed that GADD34 suppressed pro-inflammatory cytokine production by macrophages through dephosphorylation of IKKβ. In conclusion, GADD34 attenuates LPS-induced sepsis and acute tissue injury through suppressing macrophage activation. Targeting this anti-inflammatory role of GADD34 may be a promising area for the development of therapeutic agents to regulate inflammatory disorders. PMID:27171261

  13. The influence of genetic polymorphisms in TLR4 and TIRAP, and their expression levels in peripheral blood, on susceptibility to sepsis

    PubMed Central

    ZHANG, JIANPING; YANG, JINGPING; XU, XIYUAN; LIANG, LIANGSHEN; SUN, HAIXIA; LIU, GUOHUA; ZHANG, LIHONG; SU, YUN

    2016-01-01

    The present study aimed to investigate whether genetic polymorphisms in the Toll-like receptor (TLR)-4 and Toll/interleukin-1 receptor (TIR)-associated protein (TIRAP) genes, and/or their expression levels, influence the susceptibility of a patient to sepsis. A total of 106 patients with sepsis were divided into two groups on the basis of their acute physiology and chronic health evaluation (APACHE) II scores: i) Sepsis group A (APACHE II <20) and ii) Sepsis group B (APACHE II >20). In addition, 100 healthy volunteers were enrolled into the control group. Polymerase chain reaction-restriction fragment length polymorphism assay was used to detect the following genetic polymorphisms: The Ser180Leu allele of the TIRAP gene and the Asp299Gly and Thr399I1e alleles of the TLR4 gene. Furthermore, the protein expression levels of TLR4 and TIRAP were analyzed using an enzyme-linked immunosorbent assay. Genetic polymorphisms were not detected for the TLR4 and TIRAP genes; however, the protein expression levels of TLR4 and TIRAP differed significantly between the control, sepsis A and sepsis B groups (P<0.01). An APACHE II score of 20 was used as a baseline in order to differentiate sepsis severity. Pearson analysis demonstrated that TLR4 and TIRAP protein expression levels were positively correlated with sepsis severity (r=0.931 and 0.972; P<0.05), and TLR4 protein expression levels were positively correlated with those of TIRAP (r=0.936; P<0.05). The results of the present study suggested that the protein expression levels of, but not genetic polymorphisms in, TLR4 and TIRAP were associated with the severity of sepsis. PMID:26889229

  14. Can we use C-reactive protein levels to predict severe infection or sepsis in severely burned patients?

    PubMed

    Jeschke, Marc G; Finnerty, Celeste C; Kulp, Gabriela A; Kraft, Robert; Herndon, David N

    2013-01-01

    This is a large cohort analysis in severely burned pediatric children to determine whether C-reactive protein (CRP) can be used as a predictor for severe infection or sepsis. Nine-hundred eighteen pediatric burn patients were enrolled in this study. CRP values were measured throughout acute hospitalization and for up to 6 months postburn. Demographic data, incidence of infection, surgical interventions and other relevant clinical information was compiled from medical records. We performed an extensive literature search to identify models that other groups have developed to determine the effects of CRP levels postburn to assess the value of these parameters as predictors of sepsis or severe infection. Statistical analysis was performed using ANOVA and regression analysis where appropriate. Three-hundred fifteen female and 603 male pediatric patients were enrolled in this study. Average total body surface area (TBSA) burn was 45±23%, with full thickness burn over 32±27% TBSA, and patients were 7±6 years old. CRP values significantly correlated with burn size, survival and gender. Significantly higher levels of CRP were found in large burns, in non-survivors, and in females, p<0.05. Using various described models to determine whether CRP levels change before and after an event can predict sepsis or severe infection, we found that CRP cannot predict severe infection or sepsis. Although CRP is a marker of the inflammatory response postburn, CRP fails to predict infection or sepsis in severely burn patients.

  15. Can we use C-reactive protein levels to predict severe infection or sepsis in severely burned patients?

    PubMed Central

    Jeschke, Marc G; Finnerty, Celeste C; Kulp, Gabriela A; Kraft, Robert; Herndon, David N

    2013-01-01

    This is a large cohort analysis in severely burned pediatric children to determine whether C-reactive protein (CRP) can be used as a predictor for severe infection or sepsis. Nine-hundred eighteen pediatric burn patients were enrolled in this study. CRP values were measured throughout acute hospitalization and for up to 6 months postburn. Demographic data, incidence of infection, surgical interventions and other relevant clinical information was compiled from medical records. We performed an extensive literature search to identify models that other groups have developed to determine the effects of CRP levels postburn to assess the value of these parameters as predictors of sepsis or severe infection. Statistical analysis was performed using ANOVA and regression analysis where appropriate. Three-hundred fifteen female and 603 male pediatric patients were enrolled in this study. Average total body surface area (TBSA) burn was 45±23%, with full thickness burn over 32±27% TBSA, and patients were 7±6 years old. CRP values significantly correlated with burn size, survival and gender. Significantly higher levels of CRP were found in large burns, in non-survivors, and in females, p<0.05. Using various described models to determine whether CRP levels change before and after an event can predict sepsis or severe infection, we found that CRP cannot predict severe infection or sepsis. Although CRP is a marker of the inflammatory response postburn, CRP fails to predict infection or sepsis in severely burn patients. PMID:23875119

  16. [International guidelines of the Surviving Sepsis Campaign : update 2012].

    PubMed

    Briegel, J; Möhnle, P

    2013-04-01

    An update of the international guidelines for therapy of sepsis was published in February 2012 by the Surviving Sepsis Campaign (SSC). The update includes a further development of the guidelines from 2004 and 2008. The guidelines are divided into three sections, sepsis-specific therapeutic measures, recommendations on general intensive care measures for sepsis and finally special features of sepsis in pediatric intensive care medicine are presented in detail. This article discusses the most important amendments in the first two sections and delving deeper into the guidelines.

  17. Therapeutic Targets in Sepsis: Past, Present, and Future.

    PubMed

    Seeley, Eric J; Bernard, Gordon R

    2016-06-01

    Antibiotics and fluids have been standard treatment for sepsis since World War II. Many molecular mediators of septic shock have since been identified. In models of sepsis, blocking these mediators improved organ injury and decreased mortality. Clinical trials, however, have failed. The absence of new therapies has been vexing to clinicians, clinical researchers, basic scientists, and the pharmaceutical industry. This article examines the evolution of sepsis therapy and theorizes about why so many well-reasoned therapies have not worked in human trials. We review new molecular targets for sepsis and examine trial designs that might lead to successful treatments for sepsis. PMID:27229636

  18. Elucidating the role of genomics in neonatal sepsis.

    PubMed

    Srinivasan, Lakshmi; Kirpalani, Haresh; Cotten, Charles Michael

    2015-12-01

    Sepsis is a major cause of neonatal morbidity and mortality, especially in vulnerable preterm populations. Immature immune defenses, and environmental and maternal factors contribute to this risk, with as many as a third of very preterm infants experiencing sepsis during their stay in the neonatal intensive care unit (NICU). Epidemiologic and twin studies have suggested that there is a genetic contribution to sepsis predilection. Several investigators have conducted candidate gene association studies on variants of specific interest and potential functional significance in neonatal sepsis. In this review, we describe details of studies that have evaluated genetic susceptibility in neonatal sepsis, and summarize findings from a review of candidate gene association studies.

  19. 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

  20. The Ratio of Arginine to Dimethylarginines is Reduced and Predicts Outcomes in Patients with Severe Sepsis

    PubMed Central

    Gough, Michael S.; Morgan, Mary Anne M.; Mack, Cynthia M.; Darling, Denise C.; Frasier, Lauren M.; Doolin, Kathleen P.; Apostolakos, Michael J.; Stewart, Judith C.; Graves, Brian T.; Arning, Erland; Bottiglieri, Teodoro; Mooney, Robert A.; Frampton, Mark W.; Pietropaoli, Anthony P.

    2011-01-01

    Objective Arginine deficiency may contribute to microvascular dysfunction, but previous studies suggest that arginine supplementation may be harmful in sepsis. Systemic arginine availability can be estimated by measuring the ratio of arginine to its endogenous inhibitors, asymmetric and symmetric dimethylarginine. We hypothesized that the arginine to dimethylarginine (Arg/DMA) ratio is reduced in patients with severe sepsis and associated with severity of illness and outcomes. Design Case-control and prospective cohort study Setting Medical and surgical intensive care units of an academic medical center Patients and Subjects 109 severe sepsis and 50 control subjects Measurements and Main Results Plasma and urine were obtained in control subjects and within 48 hours of diagnosis in severe sepsis patients. The Arg/DMA ratio was higher in control subjects vs. sepsis patients ((median = 95 [inter-quartile range = 85 – 114]) vs. 34 [24 – 48], p < 0.001), and in hospital survivors vs. non-survivors ((39 [26 – 52]) vs. 27 [19 – 32], p = 0.004). The Arg/DMA ratio was correlated with Acute Physiology and Chronic Health Evaluation II score (Spearman’s correlation coefficient [rho] = − 0.40, p < 0.001) and organ-failure free days (rho = 0.30, p = 0.001). A declining Arg/DMA ratio was independently associated with hospital mortality (odds ratio =1.63 per quartile, 95% confidence interval [CI] = 1.00 – 2.65, p = 0.048) and risk of death over 6 months (hazard ratio = 1.41 per quartile, 95% CI = 1.01 – 1.98, p = 0.043). The Arg/DMA ratio was correlated with the urinary nitrate to creatinine ratio (rho = 0.46, p < 0.001). Conclusions The Arg/DMA ratio is associated with severe sepsis, severity of illness, and clinical outcomes. The Arg/DMA ratio may be a useful biomarker, and interventions designed to augment systemic arginine availability in severe sepsis may still be worthy of investigation. PMID:21378552

  1. Pharmacokinetic and pharmacodynamic considerations when treating patients with sepsis and septic shock.

    PubMed

    De Paepe, Peter; Belpaire, Frans M; Buylaert, Walter A

    2002-01-01

    Sepsis and septic shock are accompanied by profound changes in the organism that may alter both the pharmacokinetics and the pharmacodynamics of drugs. This review elaborates on the mechanisms by which sepsis-induced pathophysiological changes may influence pharmacological processes. Drug absorption following intramuscular, subcutaneous, transdermal and oral administration may be reduced due to a decreased perfusion of muscles, skin and splanchnic organs. Compromised tissue perfusion may also affect drug distribution, resulting in a decrease of distribution volume. On the other hand, the increase in capillary permeability and interstitial oedema during sepsis and septic shock may enhance drug distribution. Changes in plasma protein binding, body water, tissue mass and pH may also affect drug distribution. For basic drugs that are bound to the acute phase reactant alpha(1)-acid glycoprotein, the increase in plasma concentration of this protein will result in a decreased distribution volume. The opposite may be observed for drugs that are extensively bound to albumin, as the latter protein decreases during septic conditions. For many drugs, the liver is the main organ for metabolism. The determinants of hepatic clearance of drugs are liver blood flow, drug binding in plasma and the activity of the metabolic enzymes; each of these may be influenced by sepsis and septic shock. For high extraction drugs, clearance is mainly flow-dependent, and sepsis-induced liver hypoperfusion may result in a decreased clearance. For low extraction drugs, clearance is determined by the degree of plasma binding and the activity of the metabolic enzymes. Oxidative metabolism via the cytochrome P450 enzyme system is an important clearance mechanism for many drugs, and has been shown to be markedly affected in septic conditions, resulting in decreased drug clearance. The kidneys are an important excretion pathway for many drugs. Renal failure, which often accompanies sepsis and septic

  2. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients.

    PubMed

    Claushuis, Theodora A M; van Vught, Lonneke A; Scicluna, Brendon P; Wiewel, Maryse A; Klein Klouwenberg, Peter M C; Hoogendijk, Arie J; Ong, David S Y; Cremer, Olaf L; Horn, Janneke; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Zwinderman, Aeilko H; Bonten, Marc J; Schultz, Marcus J; van der Poll, Tom

    2016-06-16

    Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 10(9)/L, intermediate-low 50 × 10(9) to 99 × 10(9)/L, low 100 × 10(9) to 149 × 10(9)/L, or normal 150 × 10(9) to 399 × 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 10(9)/L and 50 × 10(9) to 99 × 10(9)/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 10(9)/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 10(9)/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal

  3. Pathogenesis of Multiple Organ Failure in Sepsis.

    PubMed

    Rossaint, Jan; Zarbock, Alexander

    2015-01-01

    Sepsis is a severe critical illness syndrome that arises from infectious insults. While the host immune system is generally beneficial, an overshooting and unregulated immune response can cause serious organ tissue injury. During sepsis, systemic hypotension, disturbed perfusion of the microcirculation, and direct tissue-toxicity caused by inflammatory immune reaction can occur and contribute to organ failure. The failure of two or more vital organ systems is termed multi-organ dysfunction syndrome (MODS) and resembles a very critical condition associated with high morbidity and mortality. Importantly, no specific treatment strategy exists to efficiently prevent the development of MODS during sepsis. In this review, we aim to identify the relevant molecular immunological pathways involved in the pathogenesis of MODS during sepsis. We believe that a detailed understanding of this mechanism is necessary for the development of new treatment approaches for septic patients. In particular, knowledge of the endogenous regulators keeping the balance between necessary immune system activation to combat infections and prevention of host tissue damage would greatly improve the chances for the development of effective interventions.

  4. Current treatment of sepsis and endotoxaemia.

    PubMed

    Periti, P

    2000-09-01

    This article reviews the new criteria for selecting the proper antimicrobial agent and dosage regimen for standard treatment of severe sepsis, with the intention of preventing septic shock. After introducing new concepts on the pathogenesis of sepsis and septic shock, the authors analyse the parameters of beta-lactam antibacterial activity, the antibiotic-induced release of bacterial endotoxin and the interrelationships between pharmacokinetics and pharmacodynamics of antibiotics in the search for an optimum dosage regimen of antimicrobial mono- or polytherapy for severely ill septic patients admitted to the intensive care unit. The mortality rate resulting from severe bacterial sepsis, particularly that associated with shock, still approaches 50% in spite of appropriate antimicrobial therapy and optimum supportive care. Bacterial endotoxins that are part of the cell wall are one of the cofactors in the pathogenesis of sepsis and septic shock and are often induced by antimicrobial chemotherapy, even if administered rationally. Not all antimicrobial agents are equally capable of inducing septic shock; this is dependent on their mechanism of action rather than on the causative pathogen species. The quantity of endotoxin released depends on the drug dose and whether filaments or spheroplast formation predominate. Some antibiotics, such as carbapenems, ceftriaxone, cefepime, glycopeptides, aminoglycosides and quinolones, do not have the propensity to provoke septic shock because their rapid bacterial activity induces mainly spheroplast or fragile spheroplast-like bacterial forms.

  5. [Pharmaconutrition with parenteral selenium in sepsis].

    PubMed

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome.

  6. [Pharmaconutrition with parenteral selenium in sepsis].

    PubMed

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. PMID:24021703

  7. Role of biomarkers in sepsis care.

    PubMed

    Samraj, Ravi S; Zingarelli, Basilia; Wong, Hector R

    2013-11-01

    Sepsis is one of the leading causes of mortality and morbidity, even with the current availability of extended-spectrum antibiotics and advanced medical care. Biomarkers offer a tool in facilitating early diagnosis, in identifying patient populations at high risk of complications, and in monitoring progression of the disease, which are critical assessments for appropriate therapy and improvement in patient outcomes. Several biomarkers are already available for clinical use in sepsis; however, their effectiveness in many instances is limited by the lack of specificity and sensitivity to characterize the presence of an infection and the complexity of the inflammatory and immune processes and to stratify patients into homogenous groups for specific treatments. Current advances in molecular techniques have provided new tools facilitating the discovery of novel biomarkers, which can vary from metabolites and chemical products present in body fluids to genes and proteins in circulating blood cells. The purpose of this review was to examine the current status of sepsis biomarkers, with special emphasis on emerging markers, which are undergoing validation and may transition into clinical practice for their informative value in diagnosis, prognosis, or response to therapy. We will also discuss the new concept of combination biomarkers and biomarker risk models, their existing challenges, and their potential use in the daily management of patients with sepsis.

  8. Clinical analysis of cases of neonatal Streptococcus agalactiae sepsis.

    PubMed

    Zeng, S J; Tang, X S; Zhao, W L; Qiu, H X; Wang, H; Feng, Z C

    2016-01-01

    With the advent of antibiotic resistance, pathogenic bacteria have become a major threat in cases of neonatal sepsis; however, guidelines for treatment have not yet been standardized. In this study, 15 cases of neonatal Streptococcus agalactiae sepsis from our hospital were retrospectively analyzed. Of these, nine cases showed early-onset and six cases showed late-onset sepsis. Pathogens were characterized by genotyping and antibiotic sensitivity tests on blood cultures. Results demonstrated that in cases with early-onset sepsis, clinical manifestations affected mainly the respiratory tract, while late-onset sepsis was accompanied by intracranial infection. Therefore, we suggest including a cerebrospinal fluid examination when diagnosing neonatal sepsis. Bacterial genotyping indicated the bacteria were mainly type Ib, Ia, and III S. agalactiae. We recommend treatment with penicillin or ampicillin, since bacteria were resistant to clindamycin and tetracycline. In conclusion, our results provide valuable information for the clinical treatment of S. agalactiae sepsis in neonatal infants.

  9. 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

  10. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    PubMed Central

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  11. Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis.

    PubMed

    Stolk, Roeland F; van der Poll, Tom; Angus, Derek C; van der Hoeven, Johannes G; Pickkers, Peter; Kox, Matthijs

    2016-09-01

    Septic shock is a major cause of death worldwide and a considerable healthcare burden in the twenty-first century. Attention has shifted from damaging effects of the proinflammatory response to the detrimental role of antiinflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to reevaluate the current management of septic shock and to assess whether we are inadvertently compromising or altering the host immune response. In this perspective, we discuss the potential detrimental role of norepinephrine, the cornerstone treatment for septic shock, in sepsis-induced immunoparalysis. We provide a short overview of the current understanding of the immunologic pathophysiology of sepsis, followed by a detailed description of the immunomodulatory effects of norepinephrine and alternative vasopressors. We conclude that although the development of novel therapies aimed at reversing immunoparalysis is underway, the use of norepinephrine may aggravate the development, extent, and duration of sepsis-induced immunoparalysis. Current in vitro and animal data indicate that norepinephrine treatment exerts immunosuppressive and bacterial growth-promoting effects and may increase susceptibility toward infections. However, evidence in humans is circumstantial, as immunologic effects of norepinephrine have not been investigated properly in experimental or clinical studies. Alternatives such as vasopressin/selepressin, angiotensin II, and phenylephrine could have a fundamental advantage over norepinephrine with respect to their immunologic properties. However, also for these agents, in vivo immunologic data in humans are largely lacking. As such, human studies on the immunomodulatory properties of norepinephrine and viable alternatives are highly warranted. PMID:27398737

  12. Hospitalization Type and Subsequent Severe Sepsis

    PubMed Central

    Dickson, Robert P.; Rogers, Mary A. M.; Langa, Kenneth M.; Iwashyna, Theodore J.

    2015-01-01

    Rationale: Hospitalization is associated with microbiome perturbation (dysbiosis), and this perturbation is more severe in patients treated with antimicrobials. Objectives: To evaluate whether hospitalizations known to be associated with periods of microbiome perturbation are associated with increased risk of severe sepsis after hospital discharge. Methods: We studied participants in the U.S. Health and Retirement Study with linked Medicare claims (1998–2010). We measured whether three hospitalization types associated with increasing severity of probable dysbiosis (non–infection-related hospitalization, infection-related hospitalization, and hospitalization with Clostridium difficile infection [CDI]) were associated with increasing risk for severe sepsis in the 90 days after hospital discharge. We used two study designs: the first was a longitudinal design with between-person comparisons and the second was a self-controlled case series design using within-person comparison. Measurements and Main Results: We identified 43,095 hospitalizations among 10,996 Health and Retirement Study–Medicare participants. In the 90 days following non–infection-related hospitalization, infection-related hospitalization, and hospitalization with CDI, adjusted probabilities of subsequent admission for severe sepsis were 4.1% (95% confidence interval [CI], 3.8–4.4%), 7.1% (95% CI, 6.6–7.6%), and 10.7% (95% CI, 7.7–13.8%), respectively. The incidence rate ratio (IRR) of severe sepsis was 3.3-fold greater during the 90 days after hospitalizations than during other observation periods. The IRR was 30% greater after an infection-related hospitalization versus a non–infection-related hospitalization. The IRR was 70% greater after a hospitalization with CDI than an infection-related hospitalization without CDI. Conclusions: There is a strong dose–response relationship between events known to result in dysbiosis and subsequent severe sepsis hospitalization that is not present

  13. Towards Prevention of Acute Syndromes

    PubMed Central

    Ahmed, A.; Thongprayoon, C.; Pickering, B.W.; Akhoundi, A.; Wilson, G.; Pieczkiewicz, D.; Herasevich, V.

    2014-01-01

    Summary Background Identifying patients at risk for acute respiratory distress syndrome (ARDS) before their admission to intensive care is crucial to prevention and treatment. The objective of this study is to determine the performance of an automated algorithm for identifying selected ARDS predisposing conditions at the time of hospital admission. Methods This secondary analysis of a prospective cohort study included 3,005 patients admitted to hospital between January 1 and December 31, 2010. The automated algorithm for five ARDS predisposing conditions (sepsis, pneumonia, aspiration, acute pancreatitis, and shock) was developed through a series of queries applied to institutional electronic medical record databases. The automated algorithm was derived and refined in a derivation cohort of 1,562 patients and subsequently validated in an independent cohort of 1,443 patients. The sensitivity, specificity, and positive and negative predictive values of an automated algorithm to identify ARDS risk factors were compared with another two independent data extraction strategies, including manual data extraction and ICD-9 code search. The reference standard was defined as the agreement between the ICD-9 code, automated and manual data extraction. Results Compared to the reference standard, the automated algorithm had higher sensitivity than manual data extraction for identifying a case of sepsis (95% vs. 56%), aspiration (63% vs. 42%), acute pancreatitis (100% vs. 70%), pneumonia (93% vs. 62%) and shock (77% vs. 41%) with similar specificity except for sepsis and pneumonia (90% vs. 98% for sepsis and 95% vs. 99% for pneumonia). The PPV for identifying these five acute conditions using the automated algorithm ranged from 65% for pneumonia to 91 % for acute pancreatitis, whereas the NPV for the automated algorithm ranged from 99% to 100%. Conclusion A rule-based electronic data extraction can reliably and accurately identify patients at risk of ARDS at the time of hospital

  14. Streptococcal Toxic Shock Syndrome: Life Saving Role of Peritoneal Lavage and Drainage

    PubMed Central

    Yokoyama, Minako; Oyama, Fumie; Ito, Asami; Yokota, Megumi; Matsukura, Daisuke; Tsutsumi, Shinji; Kasai, Tomonori; Nitobe, Yohshiro; Morikawa, Akiko; Ozaki, Takashi; Yokoyama, Yoshihito

    2016-01-01

    PURPOSE We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient’s life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. CASE PRESENTATION A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. CONCLUSIONS The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina. PMID:27579001

  15. Detection of streptococcal class I M protein in psoriasis by confocal immunofluorescent microscopy.

    PubMed

    Talanin, N Y; Shelley, W B; Raeder, R; Shelley, E D; Boyle, M D

    1997-05-01

    Epidemiological evidence implicates Streptococcus pyogenes (group A) infection as a common triggering stimulus for psoriasis. Unequivocal demonstration of streptococcal antigens in psoriatic skin has been difficult due to cross-reactive antigens in both normal human tissue and group A streptococci, which complicate immunohistological analysis. In this study cryostat sections of involved psoriatic skin were stained with monoclonal antibody 111-15504 to group A streptococci. The epitope recognized by this antibody was found to be specific for group A streptococci and is associated with class I M protein. Streptococcal antigens were found in the dermal papillae and epidermis of psoriatic skin lesions of 20 out 38 patients. These findings indicate that specific S. pyogenes antigen, associated with class I M protein, is often present in psoriatic lesions. Such an antigen, originating from focal infection elsewhere could be responsible for T-lymphocyte inflammatory responses triggering the development of psoriatic lesions.

  16. 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-α. 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.

  17. Molecular characterization and phylogenetic distribution of the streptococcal superantigen gene (ssa) from Streptococcus pyogenes.

    PubMed Central

    Reda, K B; Kapur, V; Mollick, J A; Lamphear, J G; Musser, J M; Rich, R R

    1994-01-01

    A striking increase in the frequency and severity of invasive infections caused by Streptococcus pyogenes has occurred in recent years. Among these diseases is streptococcal toxic-shock-like syndrome (TSLS), a condition characterized by fulminant soft-tissue destruction and multiorgan failure. Streptococcal superantigen (SSA), a superantigen isolated from a TSLS-inducing, serotype M3 S. pyogenes strain, has recently been identified. We here describe the cloning, sequencing, and phylogenetic distribution of the SSA structural gene. The 783-bp open reading frame encodes a predicted 260-amino-acid protein that is similar in size to several other bacterial superantigens. The deduced sequence of the mature protein is 60.2% identical to that of staphylococcal enterotoxin B but only 49% identical to that of streptococcal pyrogenic exotoxin A. Southern blot and PCR analysis of 138 group A streptococcal strains representing 65 M protein serotypes and 15 nontypeable isolates identified ssa in 68 strains from 10 distinct clonal lineages. All ssa-positive clones expressed SSA. Of the two clones associated with TSLS, the ET 2-M3 lineage, but not the ET 1-M1 lineage, carried the SSA gene. Further analysis of the ET 2-M3 lineage found evidence for temporal variation in ssa association. Contemporary ET 2-M3 disease isolates had ssa, but two older isolates of this clone recovered in 1910 and 1920 lacked the gene. The clonal and temporal distribution patterns of ssa suggest a relatively recent acquisition of this superantigen-encoding gene by the ET 2-M3 lineage, perhaps by horizontal transfer and recombination. Images PMID:8168951

  18. Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

    PubMed

    Pavone, P; Rapisarda, V; Serra, A; Nicita, F; Spalice, A; Parano, E; Rizzo, R; Maiolino, L; Di Mauro, P; Vitaliti, G; Coco, A; Falsaperla, A; Trifiletti, R R; Cocuzza, S

    2014-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS. PMID:25280028

  19. Use of tuf Sequences for Genus-Specific PCR Detection and Phylogenetic Analysis of 28 Streptococcal Species

    PubMed Central

    Picard, François J.; Ke, Danbing; Boudreau, Dominique K.; Boissinot, Maurice; Huletsky, Ann; Richard, Dave; Ouellette, Marc; Roy, Paul H.; Bergeron, Michel G.

    2004-01-01

    A 761-bp portion of the tuf gene (encoding the elongation factor Tu) from 28 clinically relevant streptococcal species was obtained by sequencing amplicons generated using broad-range PCR primers. These tuf sequences were used to select Streptococcus-specific PCR primers and to perform phylogenetic analysis. The specificity of the PCR assay was verified using 102 different bacterial species, including the 28 streptococcal species. Genomic DNA purified from all streptococcal species was efficiently detected, whereas there was no amplification with DNA from 72 of the 74 nonstreptococcal bacterial species tested. There was cross-amplification with DNAs from Enterococcus durans and Lactococcus lactis. However, the 15 to 31% nucleotide sequence divergence in the 761-bp tuf portion of these two species compared to any streptococcal tuf sequence provides ample sequence divergence to allow the development of internal probes specific to streptococci. The Streptococcus-specific assay was highly sensitive for all 28 streptococcal species tested (i.e., detection limit of 1 to 10 genome copies per PCR). The tuf sequence data was also used to perform extensive phylogenetic analysis, which was generally in agreement with phylogeny determined on the basis of 16S rRNA gene data. However, the tuf gene provided a better discrimination at the streptococcal species level that should be particularly useful for the identification of very closely related species. In conclusion, tuf appears more suitable than the 16S ribosomal RNA gene for the development of diagnostic assays for the detection and identification of streptococcal species because of its higher level of species-specific genetic divergence. PMID:15297518

  20. Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

    PubMed Central

    Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

    2016-01-01

    Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may

  1. Improving the management of sepsis in a district general hospital by implementing the 'Sepsis Six' recommendations.

    PubMed

    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. PMID:26734403

  2. Severe sepsis and septic shock: defining the clinical problem.

    PubMed

    Opal, Steven M

    2003-01-01

    It is generally acknowledged that severe sepsis/septic shock is a major problem in clinical medicine, yet the extent of the problem and its basic immunology remain poorly defined. The generation of accurate statistics about sepsis is confounded by the imprecise and highly variable terminology used to describe sepsis by clinicians around the world. The problem of sepsis is further complicated by the remarkably diverse spectrum of illness encompassed under the term 'sepsis'. Sepsis may range in severity from mild systemic inflammation without significant clinical consequences to multisystem failure in septic shock with an exceedingly high mortality rate. Sepsis connotes a clinical syndrome that may occur in any age group, in markedly different patient populations, and in response to a multitude of microbial pathogens from multiple different anatomical sites within the human body. A concerted effort has been made to standardize definitions of sepsis by the use of international committees and consensus opinions from panels of experts in sepsis research. While consensus definitions of sepsis have proven to be of value, the lack of uniformity in interpretation of these definitions continues to be problematic by clinicians and basic researchers alike. Recently, a new conceptual framework for understanding sepsis has been developed, called the PIRO concept (predisposition, infection, response and organ dysfunction). This has been conceptually modeled from the TNM classification (tumor size, nodal spread, metastases) which has been successfully used in defining treatment and prognostic indicators in clinical oncology. Further refinements in the definitions and predisposing factors of severe sepsis should improve the understanding and management of severe sepsis and septic shock in the near future.

  3. Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.

    PubMed

    Nguyen, H Bryant; Jaehne, Anja Kathrin; Jayaprakash, Namita; Semler, Matthew W; Hegab, Sara; Yataco, Angel Coz; Tatem, Geneva; Salem, Dhafer; Moore, Steven; Boka, Kamran; Gill, Jasreen Kaur; Gardner-Gray, Jayna; Pflaum, Jacqueline; Domecq, Juan Pablo; Hurst, Gina; Belsky, Justin B; Fowkes, Raymond; Elkin, Ronald B; Simpson, Steven Q; Falk, Jay L; Singer, Daniel J; Rivers, Emanuel P

    2016-01-01

    Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions. PMID:27364620

  4. Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.

    PubMed

    Nguyen, H Bryant; Jaehne, Anja Kathrin; Jayaprakash, Namita; Semler, Matthew W; Hegab, Sara; Yataco, Angel Coz; Tatem, Geneva; Salem, Dhafer; Moore, Steven; Boka, Kamran; Gill, Jasreen Kaur; Gardner-Gray, Jayna; Pflaum, Jacqueline; Domecq, Juan Pablo; Hurst, Gina; Belsky, Justin B; Fowkes, Raymond; Elkin, Ronald B; Simpson, Steven Q; Falk, Jay L; Singer, Daniel J; Rivers, Emanuel P

    2016-07-01

    Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.

  5. Is psoriasis induced by streptococcal superantigens and maintained by M-protein-specific T cells that cross-react with keratin?

    PubMed

    Valdimarsson, H; Sigmundsdóttir, H; Jónsdóttir, I

    1997-01-01

    The evidence that T lymphocytes play a key role in the pathogenesis of psoriasis is now compelling. Eruption of psoriatic skin lesions coincides with epidermal infiltration and activation of T cells, and spontaneous or treatment-induced resolution of the lesions is preceded by the reduction or disappearance of epidermal T cells. An upregulation has also been demonstrated for various molecules associated with T-cell mediated inflammation, and treatments selectively directed against T cells have proved very effective. Infections with group A beta-haemolytic streptococci have been associated with onset of acute psoriasis and exacerbation of chronic psoriasis. Such infections are also frequently accompanied by erythematous skin rashes. Also, recent reports indicate that streptococcal superantigens can induce expression of cutaneous lymphocyte antigens (CLA), believed to play a major role in enabling T cells to migrate to the skin. Furthermore, T-cell lines isolated from psoriatic lesions may show strong reactivity to streptococcal antigens. We have postulated that psoriasis is an autoimmune disease mediated by T cells reacting to epitopes that are common to streptococcal M-proteins and keratins. To investigate this possibility, circulating T cells from 12 patients with active psoriasis, paired controls, and six patients with atopic dermatitis were challenged in vitro with five synthetic 20aa (amino acid) M-peptides: production of IFN-gamma and IL-4 was analysed by ELISPOT and RT-PCR techniques. Four of these peptides shared five to six aa sequences with several type I keratins and one did not. In 10 of the 12 psoriasis patients, measurable IFN-gamma production could be induced by one or more of the four peptides that share sequences with keratins. A borderline response was observed in only four of the 18 controls: the dermatitis patients were all negative. The only peptide that shared 6aa with keratins was the one that induced a response in the psoriatic patients most

  6. Group G Beta-Hemolytic Streptococcal Bacteremia Characterized by 16S Ribosomal RNA Gene Sequencing

    PubMed Central

    Woo, Patrick C. Y.; Fung, Ami M. Y.; Lau, Susanna K. P.; Wong, Samson S. Y.; Yuen, Kwok-Yung

    2001-01-01

    Little is known about the relative importance of the four species of Lancefield group G beta-hemolytic streptococci in causing bacteremia and the factors that determine the outcome for patients with group G beta-hemolytic streptococcal bacteremia. From 1997 to 2000, 75 group G beta-hemolytic streptococcal strains were isolated from the blood cultures of 66 patients. Sequencing of the 16S rRNA genes of the group G beta-hemolytic streptococci showed that all 75 isolates were Streptococcus dysgalactiae subspecies equisimilis. The API system (20 STREP) and Vitek system (GPI) successfully identified 65 (98.5%) and 62 (93.9%) isolates, respectively, as S. dysgalactiae subspecies equisimilis with >95% confidence, whereas the ATB Expression system (ID32 STREP) only successfully identified 49 isolates (74.2%) as S. dysgalactiae subspecies equisimilis with >95% confidence. The median age of the patients was 76 years (range, 33 to 99 years). Fifty-six patients (85%) were over 60 years old. All patients had underlying diseases. No source of the bacteremia was identified (primary bacteremia) in 34 patients (52%), whereas 17 (26%) had cellulitis and 8 (12%) had bed sore or wound infections. Fifty-eight patients (88%) had community-acquired group G streptococcal bacteremia. Sixty-two patients (94%) had group G Streptococcus recovered in one blood culture, whereas 4 patients (6%) had it recovered in multiple blood cultures. Fifty-nine patients (89%) had group G Streptococcus as the only bacterium recovered in their blood cultures, whereas in 7 patients other bacteria were recovered concomitantly with the group G Streptococcus in the blood cultures (Staphylococcus aureus in 3, Clostridium perfringens in 2, Citrobacter freundii in 1, and Bacteroides fragilis in 1). Overall, 10 patients (15%) died. Male sex, diagnosis other than cellulitis, hospital-acquired bacteremia, and multiple positive blood cultures were associated with mortality {P < 0.005 (relative risk [RR] = 7.6), P < 0

  7. Appropriateness of diagnosis of streptococcal pharyngitis among Thai community pharmacists according to the Centor criteria.

    PubMed

    Saengcharoen, Woranuch; Jaisawang, Pornchanok; Udomcharoensab, Palita; Buathong, Kittika; Lerkiatbundit, Sanguan

    2016-10-01

    Background Inappropriate use of antibiotic treatment for pharyngitis by community pharmacists is prevalent in developing countries. Little is known about how the pharmacists identify patients with bacterial pharyngitis. Objective To ascertain the appropriateness of diagnosis of streptococcal pharyngitis among Thai community pharmacists according to the Centor criteria and to identify factors related to antibiotic dispensing. Setting 1040 Thai community pharmacists. Method A cross-sectional survey of community pharmacists was conducted in November 2012 to March 2013. The self-administered questionnaires were mailed to 57 % of community pharmacists in the south of Thailand (n = 1040). The survey included questions on diagnosis of streptococcal pharyngitis, knowledge on pharyngitis, and attitudes and control beliefs regarding antibiotic dispensing. Main outcome measure The appropriateness of diagnosis of streptococcal pharyngitis according to the original and modified Centor criteria and determinants of antibiotic dispensing including demographic characteristics of pharmacists, knowledge on pharyngitis, and attitudes and control beliefs on antibiotic dispensing. Results Approximately 68 % completed the questionnaires (n = 703). Compared to the pharmacists who reported not dispensing antibiotics in the hypothetical case with common cold, those reported dispensing antibiotics were more likely to consider the following conditions-presence of cough, mild sore throat and patients with age >60 years as cues for diagnosis of streptococcal pharyngitis (p < 0.05). The use of fewer scores of the clinical prediction rules for diagnosis was observed in antibiotic dispensers, compared to who did not do so (p < 0.005). Antibiotic dispensing was positively associated with period of dispensing experience (>5 years) [odds ratio (OR) 1.52; 95 % confidence interval (CI) 1.03-2.23], belief that antibiotics could shorten duration of pharyngitis (OR 1.48; 95 % CI 1

  8. 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 T

  9. 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

  10. Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury.

    PubMed

    Patil, Naeem K; Parajuli, Nirmala; MacMillan-Crow, Lee Ann; Mayeux, Philip R

    2014-04-01

    Acute kidney injury (AKI) is a complication of sepsis and leads to a high mortality rate. Human and animal studies suggest that mitochondrial dysfunction plays an important role in sepsis-induced multi-organ failure; however, the specific mitochondrial targets damaged during sepsis remain elusive. We used a clinically relevant cecal ligation and puncture (CLP) murine model of sepsis and assessed renal mitochondrial function using high-resolution respirometry, renal microcirculation using intravital microscopy, and renal function. CLP caused a time-dependent decrease in mitochondrial complex I and II/III respiration and reduced ATP. By 4 h after CLP, activity of manganese superoxide dismutase (MnSOD) was decreased by 50% and inhibition was sustained through 36 h. These events were associated with increased mitochondrial superoxide generation. We then evaluated whether the mitochondria-targeted antioxidant Mito-TEMPO could reverse renal mitochondrial dysfunction and attenuate sepsis-induced AKI. Mito-TEMPO (10 mg/kg) given at 6 h post-CLP decreased mitochondrial superoxide levels, protected complex I and II/III respiration, and restored MnSOD activity by 18 h. Mito-TEMPO also improved renal microcirculation and glomerular filtration rate. Importantly, even delayed therapy with a single dose of Mito-TEMPO significantly increased 96-h survival rate from 40% in untreated septic mice to 80%. Thus, sepsis causes sustained inactivation of three mitochondrial targets that can lead to increased mitochondrial superoxide. Importantly, even delayed therapy with Mito-TEMPO alleviated kidney injury, suggesting that it may be a promising approach to treat septic AKI.

  11. Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury.

    PubMed

    Patil, Naeem K; Parajuli, Nirmala; MacMillan-Crow, Lee Ann; Mayeux, Philip R

    2014-04-01

    Acute kidney injury (AKI) is a complication of sepsis and leads to a high mortality rate. Human and animal studies suggest that mitochondrial dysfunction plays an important role in sepsis-induced multi-organ failure; however, the specific mitochondrial targets damaged during sepsis remain elusive. We used a clinically relevant cecal ligation and puncture (CLP) murine model of sepsis and assessed renal mitochondrial function using high-resolution respirometry, renal microcirculation using intravital microscopy, and renal function. CLP caused a time-dependent decrease in mitochondrial complex I and II/III respiration and reduced ATP. By 4 h after CLP, activity of manganese superoxide dismutase (MnSOD) was decreased by 50% and inhibition was sustained through 36 h. These events were associated with increased mitochondrial superoxide generation. We then evaluated whether the mitochondria-targeted antioxidant Mito-TEMPO could reverse renal mitochondrial dysfunction and attenuate sepsis-induced AKI. Mito-TEMPO (10 mg/kg) given at 6 h post-CLP decreased mitochondrial superoxide levels, protected complex I and II/III respiration, and restored MnSOD activity by 18 h. Mito-TEMPO also improved renal microcirculation and glomerular filtration rate. Importantly, even delayed therapy with a single dose of Mito-TEMPO significantly increased 96-h survival rate from 40% in untreated septic mice to 80%. Thus, sepsis causes sustained inactivation of three mitochondrial targets that can lead to increased mitochondrial superoxide. Importantly, even delayed therapy with Mito-TEMPO alleviated kidney injury, suggesting that it may be a promising approach to treat septic AKI. PMID:24500690

  12. Sepsis in the severely immunocompromised patient.

    PubMed

    Kalil, Andre C; Opal, Steven M

    2015-06-01

    The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients.

  13. Sepsis in the severely immunocompromised patient.

    PubMed

    Kalil, Andre C; Opal, Steven M

    2015-06-01

    The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients. PMID:25939918

  14. Carbon monoxide in the treatment of sepsis.

    PubMed

    Nakahira, Kiichi; Choi, Augustine M K

    2015-12-15

    Carbon monoxide (CO), a low-molecular-weight gas, is endogenously produced in the body as a product of heme degradation catalyzed by heme oxygenase (HO) enzymes. As the beneficial roles of HO system have been elucidated in vitro and in vivo, CO itself has also been reported as a potent cytoprotective molecule. Whereas CO represents a toxic inhalation hazard at high concentration, low-dose exogenous CO treatment (~250-500 parts per million) demonstrates protective functions including but not limited to the anti-inflammatory and antiapoptotic effects in preclinical models of human diseases. Of note, CO exposure confers protection in animal models of sepsis by inhibiting inflammatory responses and also enhancing bacterial phagocytosis in leukocytes. These unique functions of CO including both dampening inflammation and promoting host defense mechanism are mediated by multiple pathways such as autophagy induction or biosynthesis of specialized proresolving lipid mediators. We suggest that CO gas may represent a novel therapy for patients with sepsis.

  15. Sepsis management: An evidence-based approach.

    PubMed

    Baig, Muhammad Akbar; Shahzad, Hira; Jamil, Bushra; Hussain, Erfan

    2016-03-01

    The Surviving Sepsis Campaign (SSC) guidelines have outlined an early goal directed therapy (EGDT) which demonstrates a standardized approach to ensure prompt and effective management of sepsis. Having said that, there are barriers associated with the application of evidence-based practice, which often lead to an overall poorer adherence to guidelines. Considering the global burden of disease, data from low- to middle-income countries is scarce. Asia is the largest continent but most Asian countries do not have a well-developed healthcare system and compliance rates to resuscitation and management bundles are as low as 7.6% and 3.5%, respectively. Intensive care units are not adequately equipped and financial concerns limit implementation of expensive treatment strategies. Healthcare policy-makers should be notified in order to alleviate financial restrictions and ensure delivery of standard care to septic patients.

  16. Prediction of Sepsis in the Intensive Care Unit With Minimal Electronic Health Record Data: A Machine Learning Approach

    PubMed Central

    Desautels, Thomas; Calvert, Jacob; Jay, Melissa; Kerem, Yaniv; Shieh, Lisa; Shimabukuro, David; Chettipally, Uli; Feldman, Mitchell D; Barton, Chris; Wales, David J; Das, Ritankar

    2016-01-01

    Background Sepsis is one of the leading causes of mortality in hospitalized patients. Despite this fact, a reliable means of predicting sepsis onset remains elusive. Early and accurate sepsis onset predictions could allow more aggressive and targeted therapy while maintaining antimicrobial stewardship. Existing detection methods suffer from low performance and often require time-consuming laboratory test results. Objective To study and validate a sepsis prediction method, InSight, for the new Sepsis-3 definitions in retrospective data, make predictions using a minimal set of variables from within the electronic health record data, compare the performance of this approach with existing scoring systems, and investigate the effects of data sparsity on InSight performance. Methods We apply InSight, a machine learning classification system that uses multivariable combinations of easily obtained patient data (vitals, peripheral capillary oxygen saturation, Glasgow Coma Score, and age), to predict sepsis using the retrospective Multiparameter Intelligent Monitoring in Intensive Care (MIMIC)-III dataset, restricted to intensive care unit (ICU) patients aged 15 years or more. Following the Sepsis-3 definitions of the sepsis syndrome, we compare the classification performance of InSight versus quick sequential organ failure assessment (qSOFA), modified early warning score (MEWS), systemic inflammatory response syndrome (SIRS), simplified acute physiology score (SAPS) II, and sequential organ failure assessment (SOFA) to determine whether or not patients will become septic at a fixed period of time before onset. We also test the robustness of the InSight system to random deletion of individual input observations. Results In a test dataset with 11.3% sepsis prevalence, InSight produced superior classification performance compared with the alternative scores as measured by area under the receiver operating characteristic curves (AUROC) and area under precision-recall curves

  17. Haemophilus influenzae sepsis resulting from pneumonia.

    PubMed

    Marinella, M A

    1997-01-01

    Haemophilus influenzae is a pleomorphic gram-negative bacterium that causes a myriad of infections in both adults and children. The organism frequently causes respiratory infections in patients with obstructive lung disease but may on occasion cause invasive infections including pneumonia with bacteremia. We report the case of a patient with underlying lung disease and metastatic malignancy in whom sepsis related to pneumonia caused by H. influenzae developed.

  18. ISG12 is a critical modulator of innate immune responses in murine models of sepsis.

    PubMed

    Uhrin, P; Perkmann, T; Binder, B; Schabbauer, G

    2013-09-01

    Sepsis is still a major burden for our society with high incidence of morbidity and mortality each year. Molecular mechanisms underlying the systemic inflammatory response syndrome (SIRS) associated with sepsis are still ill defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. Recently the role of nuclear receptors (NRs) became a major topic of interest in transcriptional regulation of inflammatory processes. Nuclear receptors, such as the peroxisome proliferators-activated receptors (PPARs), have been demonstrated to exert anti-inflammatory properties by interfering with the NFκB pathway. We identified the nuclear envelope protein, interferon stimulated gene 12 (ISG12), which directly interacts with NRs. ISG12 is a co-factor stimulating nuclear export of NRs, thereby reducing the anti-inflammatory potential of NRs such as NR4A1. To examine the role of ISG12 in acute inflammatory processes we used recently generated ISG12 deficient mice. We can clearly demonstrate that lack of ISG12 prolongs survival in experimental sepsis and endotoxemia. Furthermore we can show that several acute inflammatory parameters, such as systemic IL6 cytokine levels, are downregulated in septic ISG12-/- animals. Consistently, similar results were obtained in in vitro experiments in peritoneal macrophages derived from ISG12 deficient mice. In contrast, mice deficient for the nuclear receptor NR4A1 exhibited an exacerbated innate immune response, and showed a significantly higher mortality after lethal endotoxemic challenge. This dramatic phenotype could be restored in ISG12/NR4A1 double deficient mice. We conclude from our data in vitro and in vivo that ISG12 is a novel modulator of innate immune responses regulating anti-inflammatory nuclear receptors such as NR4A1.

  19. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

    2016-03-01

    Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future. PMID:26863125

  20. Reduction in maternal mortality due to sepsis.

    PubMed

    Chhabra, S; Kaipa, A; Kakani, A

    2005-02-01

    The present study was undertaken at a rural medical institute in India to analyse the trends in maternal mortality due to sepsis and the factors associated with change, if any. During the study period of 20 years, a total of 37,155 women delivered, 192 deaths occurred and forty deaths (20.83%) were due to sepsis and it's sequlae. It was revealed that there is a definite decrease in the proportion of deaths due to sepsis, to 10% in the last five years from 35% in earlier years. The change seems to be due to the advocacy of clean deliveries and reduction in case fatality because of alterations in medication and earlier surgical intervention. However the percentage contribution of septic abortion has remained the same. Septic abortion continues to exist inspite of all the current laws and discussion about the availability of a liberal law, which permits abortion almost on request. Most of the women who had died due to septic abortion were married (65%). Deaths due to septic abortion, are persisting even in married women and it is a matter of concern for health providers, policy makers and governments. PMID:15814392

  1. Sepsis and Meningitis due to Listeria Monocytogenes

    PubMed Central

    Aygen, Bilgehan; Esel, Duygu; Kayabas, Uner; Alp, Emine; Sumerkan, Bulent; Doganay, Mehmet

    2007-01-01

    Purpose This study focused on the effect of immuno-compromising conditions on the clinical presentation of severe listerial infection. Patients and Methods Nine human listeriosis cases seen from 1991-2002 were reviewed. All adult patients, from whose blood, peritoneal fluid or cerebrospinal fluid (CSF) the L. monocytogenes was isolated, were included in this retrospective study. Results Listeriosis presented as primary sepsis with positive blood cultures in 5 cases and meningitis with positive CSF cultures in 4 cases. All of these patients had at least one underlying disease, most commonly, hematologic malignancy, diabetes mellitus, amyloidosis and hepatic cirrhosis; 55.6% had received immunosuppressive or corticosteroid therapy within a week before the onset of listeriosis. The patients were adults with a mean age of 60 years. Fever, night sweats, chills and lethargy were the most common symptoms; high temperature (> 38℃), tachycardia, meningeal signs and poor conditions in general were the most common findings on admission. The mortality rate was 33.3% and was strictly associated with the severity of the underlying disease. Mortality differences were significant between sepsis (20%) and meningitis (50%) patients. Conclusion Listeriosis as an uncommon infection in our region and that immuno-suppressive therapy is an important pre-disposing factor of listeriosis. Sepsis and meningitis were more common in this group of patients and had the highest case-fatality rate for food-borne illnesses. PMID:17594151

  2. Coagulation in patients with severe sepsis.

    PubMed

    Levi, Marcel; Poll, Tom van der

    2015-02-01

    In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro)vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways. PMID:25590524

  3. A model for the interplay of inflammatory mediators in sepsis--a study in 48 patients.

    PubMed

    Hack, C E; Nuijens, J H; Strack van Schijndel, R J; Abbink, J J; Eerenberg, A J; Thijs, L G

    1990-01-01

    Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis. Some of these inflammatory parameters appeared to be associated with a poor prognosis. Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit. No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found. Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels. Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein. Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein. Based on these findings we propose a model for the interplay of these inflammatory mediators in the pathogenesis of sepsis. This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.

  4. 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

  5. Use of laparoscopy in the diagnosis and treatment of patients with surgical abdominal sepsis.

    PubMed

    Geis, W P; Kim, H C

    1995-02-01

    Patients often present to the surgeon with abdominal pain, tenderness, and fever. Many exhibit progressive sepsis due to abdominal pathology. Delay in diagnosis and treatment often occurs due to the use of multiple, time-consuming, expensive diagnostic studies. We delineate the use of diagnostic laparoscopy in subsets of patients in whom confusion exists as to the cause of abdominal sepsis--i.e., females in child-bearing years, elderly patients, obese patients, immunosuppressed patients, and patients with suppression of physical findings. The methodical assessment of the entire abdominal cavity is performed utilizing manipulation of the patient's position (Trendelenburg, supine, reverse Trendelenburg, left side up, right side up) and meticulous inspection of the entire small bowel. Diagnoses included acute appendicitis, gangrenous appendicitis, perforated appendicitis with peritonitis or abscess, gangrenous cholecystitis, ischemic bowel disease, perforating carcinoma of the colon, perforating diverticulitis with abscess or peritonitis, tubo-ovarian abscess, closed-loop small-bowel obstruction, megacolon, and perforation of the colon. Laparoscopic treatment of 96% of the patients was performed successfully and a laparoscopic-assisted approach was used in the remainder. There was one mortality (cardiac) and no major morbidity. The development of a Formal Diagnostic Exploratory Laparoscopic (FDEL) approach has aided in the assessment of each of the diagnoses of sepsis in the abdominal cavity. The diagnostic and therapeutic approach laparoscopically avoids extensive preoperative studies, avoids delay in operative intervention, and appears to minimize morbidity and shorten the postoperative recovery interval.

  6. The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

    PubMed

    Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

    2014-07-01

    Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

  7. Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

    PubMed Central

    Sassoon, Catherine S.; Zhu, Ercheng; Fang, Liwei; Subramanian, Veedamali S.; Said, Hamid M.

    2016-01-01

    Objective Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 (THTR-1) and thiamin transporter-2 (THTR-2)), and mitochondrial thiamin pyrophosphate transporter (MTPPT). Design Randomized, controlled study Setting Research laboratory at a Veterans Affairs Medical Center Subjects Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate and severe sepsis with equal number of animals in each group. Measurements and Main Results Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25 %, 50 % and 75 % of cecal length, defined as severe, moderate and mild sepsis, respectively. Control animals underwent laparotomy only. After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of THTR-1, THTR-2, and MTPPT proteins and mRNA were measured. Proinflammatory cytokines (IL-1β and IL-6), and adenosine triphosphate (ATP) were also measured. Sepsis inhibited [3H]thiamin uptake and the inhibition was a function of sepsis severity. Both cell membranes thiamin transporters and MTPPT expression levels were suppressed; also levels of ATP in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham operated controls. Conclusions For the first time we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and MTPPT, leading to ATP depletion. PMID:27065466

  8. Redox regulation of mitophagy in the lung during murine S. aureus sepsis

    PubMed Central

    Chang, Alan L.; Ulrich, Allison; Suliman, Hagir B.; Piantadosi, Claude A.

    2014-01-01

    removes damaged mitochondria and accompanies tissue repair and cell survival. Furthermore, mitophagy in the alveolar region appears to depend on activation of Nrf2. Thus, efforts to promote mitophagy may be a useful therapeutic adjunct for acute lung injury in sepsis. PMID:25450328

  9. 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

  10. Factor v Leiden mutation in severe infection and sepsis.

    PubMed

    Levi, Marcel; Schouten, Marcel; van't Veer, Cees; van der Poll, Tom

    2011-11-01

    In severe infection and sepsis, activation of coagulation frequently occurs, which contributes to the development of multiple organ dysfunction. Factor V Leiden is a relatively common mutation resulting in a mild prohemostatic state and consequently with an increased tendency to develop thrombosis. Hypothetically, patients with factor V Leiden may suffer from more severe coagulopathy in cases of severe infection or sepsis. Aggravation of the procoagulant state in sepsis may subsequently result in more severe organ dysfunction and an increased risk of death. In this article we review the experimental and clinical evidence regarding the relationship between the presence of a factor V Leiden mutation and the incidence and outcome of sepsis.

  11. 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

  12. Autoantibody germ-line gene segment encodes V{sub H} and V{sub L} regions of a human anti-streptococcal monoclonal antibody recognizing streptococcal M protein and human cardiac myosin epitopes

    SciTech Connect

    Quinn, A.; Cunningham, M.W.; Adderson, E.E.

    1995-04-15

    Cross-reactivity of anti-streptococcal Abs with human cardiac myosin may result in sequelae following group A streptococcal infections. Molecular mimicry between group A streptococcal M protein and cardiac myosin may be the basis for the immunologic cross-reactivity. In this study, a cross-reactive human anti-streptococcal/antimyosin mAb (10.2.3) was characterized, and the myosin epitopes were recognized by the Ab identified. mAb 10.2.3 reacted with four peptides from the light meromyosin (LMM) tail fragment of human cardiac myosin, including LMM-10 (1411-1428), LMM-23 (1580-1597), LMM-27 (1632-1649), and LMM-30 (1671-1687). Only LMM-30 inhibited binding of mAb 10.2.3 to streptococcal M protein and human cardiac myosin. Human mAb 10.2.3 labeled cytoskeletal structures within rat heart cells in indirect immunofluorescence, and reacted with group A streptococci expressing various M protein serotypes, PepM5, and recombinant M protein. The nucleotide sequence of gene segments encoding the Ig heavy and light chain V region of mAb 10.2.3 was determined. The light chain V segment was encoded by a VK1 gene segment that was 98.5% identical with germ-line gene humig{sub K}Vi5. The V segment of the heavy chain was encoded by a V{sub H}3a gene segment that differed from the V{sub H}26 germ-line gene by a single base change. V{sub H}26 is expressed preferentially in early development and encodes autoantibodies with anti-DNA and rheumatoid factor specificities. Anti-streptococcal mAb 10.2.3 is an autoantibody encoded by V{sub H} and V{sub L} genes, with little or no somatic mutation. 63 refs., 11 figs.

  13. Efficacy of traditional Chinese medicine on sepsis: a systematic review and Meta-Analysis

    PubMed Central

    Liang, Xiao; Zhou, Miao; Ge, Xin-Yu; Li, Cheng-Bao; Fang, Shang-Ping; Tang, Ling; Shao, Dong-Hua; Xu, Guo

    2015-01-01

    Background: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. Methods: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. Results: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU-stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = -0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-α [SMD = -0.61; 95% CI: -0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. Conclusion: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion. PMID:26884914

  14. 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

  15. 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

  16. Skin CD4+ T cells produce interferon-gamma in vitro in response to streptococcal antigens in chronic plaque psoriasis.

    PubMed

    Brown, D W; Baker, B S; Ovigne, J M; Hardman, C; Powles, A V; Fry, L

    2000-03-01

    Recently, we have demonstrated that group A streptococcal antigen reactive T cells are present in the skin lesions of chronic plaque psoriasis. To determine the cytokine profile (interferon-gamma, interleukin-4 and interleukin-10) of these T cells in response to streptococcal antigens, T cell lines were cultured from untreated lesional skin of 13 patients with chronic plaque psoriasis and 12 patients with other inflammatory skin diseases. T cell lines were incubated with or without a sonicated heat-killed mixture of group A streptococcal isolates for 18 h in the presence of a transport inhibitor, stained for surface CD4 or CD8 and intracellular cytokine expression, and analyzed by flow cytometry. Psoriatic T cell lines were grown from 10 of 13 patients and were predominately CD4+ (64%-85%) with 10%-32% CD8+ T cells. Variable numbers of CD4+ T cells produced interferon-gamma (0.8%-35%, median 13.9) in eight of 10 T cell lines (p < 0.02). In contrast, CD4+ T cells in five of 12 T cell lines obtained from disease controls did not produce or produced minimal interferon-gamma in response to group A streptococcal isolates; this was significantly different from the psoriatic T cell lines (p < 0.05). Small numbers of interleukin-10 positive (0.8%-1.3%) and interleukin-4 positive (2.1%-2.5%) CD4+ T cells induced by group A streptococcal isolates were also present in two out of five and three out of five psoriatic T cell lines, respectively. This was significantly less in each case than the numbers of CD4+/interferon-gamma+ T cells (p < 0.05). Cytokine-positive CD8+ T cells were rarely observed. These findings demonstrate that a subpopulation of CD4+ T cells in chronic plaque psoriasis skin lesions produces interferon-gamma in response to streptococcal antigens and may be relevant to the pathogenesis of psoriasis.

  17. MFHAS1 Is Associated with Sepsis and Stimulates TLR2/NF-κB 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-κB signaling pathway, and MFHAS1 induced the phosphorylation of JNK and p38 after TLR2 stimulation. PMID:26599367

  18. Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult.

    PubMed

    Hale, Andrew J; LaSalvia, Mary; Kirby, James E; Kimball, Allison; Baden, Rachel

    2016-01-01

    Asplenic patients are at increased risk for sepsis and fulminant infection. Sepsis in these patients is typically secondary to encapsulated bacteria, with Streptococcus pneumoniae being the most frequent pathogen. Rare complications of severe sepsis include purpura fulminans and bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). We present the case of a 36-year-old woman, healthy except for splenectomy years prior for idiopathic thrombocytopenic purpura treatment, who presented with fever. Upon presentation to our hospital, three hours after symptoms onset, she had purpura fulminans and shock. Despite timely antimicrobials and maximal resuscitative efforts, her disease progressed and she expired 12 hours after symptoms onset. Autopsy revealed bilateral adrenal hemorrhage; acute adrenal crisis likely contributed to her refractory shock. Prior to her presentation, she had not received guideline-based post-splenectomy care. Sepsis in asplenic patients can be fulminant and rapidly fatal. Streptococcus pneumoniae remains the most frequent cause, despite decreasing rates in recent years related to widespread pneumococcal vaccination. Guideline-based vaccinations and "pill-in-pocket" therapy can be life-saving for asplenic patients. Purpura fulminans represents an extreme manifestation of disseminated intravascular coagulation, is more common in asplenic patients, and portends a poor prognosis. Waterhouse-Friderichsen syndrome can be seen concurrently with purpura fulminans and further portends a poor prognosis; pre-mortem diagnosis requires a high index of suspicion. PMID:27583208

  19. Case of streptococcal toxic shock syndrome caused by rapidly progressive group A hemolytic streptococcal infection during postoperative chemotherapy for cervical cancer.

    PubMed

    Nogami, Yuya; Tsuji, Kousuke; Banno, Kouji; Umene, Kiyoko; Katakura, Satomi; Kisu, Iori; Tominaga, Eiichiro; Aoki, Daisuke

    2014-01-01

    Streptococcal toxic shock syndrome (STSS) is a severe infectious disease caused by group A hemolytic streptococcus (Streptococcus pyogenes). This condition is a serious disease that involves rapidly progressive septic shock. We experienced a case of STSS caused by primary peritonitis during treatment with paclitaxel and cisplatin (TP therapy) as postoperative chemotherapy for cervical cancer. STSS mostly develops after extremity pain, but initial influenza-like symptoms of fever, chill, myalgia and gastrointestinal symptoms may also occur. TP therapy is used to treat many cancers, including gynecological cancer, but may cause adverse reactions of neuropathy and nephrotoxicity and sometimes fever, arthralgia, myalgia, abdominal pain and general malaise. The case reported here indicates that development of STSS can be delayed after chemotherapy and that primary STSS symptoms may be overlooked because they may be viewed as adverse reactions to chemotherapy. To our knowledge, this is the first report of a case of STSS during chemotherapy. PMID:23937219

  20. Sepsis-Induced Takotsubo Cardiomyopathy Leading to Torsades de Pointes

    PubMed Central

    Kamran, Haroon; El-Sherif, Nabil

    2016-01-01

    Background. Takotsubo cardiomyopathy (TCM) is sudden and reversible myocardial dysfunction often attributable to physical or emotional triggers. Case Report. We describe a 51-year-old man presented to emergency department with sepsis from urinary tract infection (UTI). He was placed on cefepime for UTI and non-ST-elevation myocardial infarction protocol given elevated troponins with chest pain. Subsequently, patient was pulseless with torsades de pointes (TdP) and then converted to sinus rhythm with cardioversion. An echocardiogram revealed low ejection fraction with hypokinesis of the apical wall. Over 48 hours, the patient was extubated and stable on 3 L/min nasal cannula. He underwent a cardiac catheterization to evaluate coronary artery disease (CAD) and was found to have mild nonobstructive CAD with no further findings. Conclusion. TCM is a rare disorder presenting with symptoms similar to acute coronary syndrome. Though traditionally elicited by physical and emotional triggers leading to transient left ventricular dysfunction, our case suggests that it may also be triggered by a urinary tract infection and lead to severe QT prolongation and a malignant ventricular arrhythmia in TdP. PMID:27525128

  1. A CLEAR CASE OF MRSA SEPSIS, OF AN UNEXPECTED ORIGIN.

    PubMed

    DeWitt, A; Patel, C; Kuapati, R; Reddy, K

    2015-01-01

    A 56-year-old man with a history of uncontrolled type 2 diabetes mellitus, benign prostatic hypertrophy and history of recent knee and elbow abscess presented to the emergency department with nausea, vomiting, and fevers. Two days prior, he presented to the ER and was diagnosed with acute presumed prostatitis and urinary retention. He was discharged on ciprofloxacin and an indwelling Foley catheter with urology follow-up. After being unable to tolerate oral medications, he presented again to the emergency department, at which time, he was febrile and tachycardic. Physical exam was benign except for a boggy and tender prostate and bilateral CVA tenderness. Labs demonstrated leukocytosis, elevated HbA1C, and pyuria on urinalysis. Urine cultures collected at the patient's earlier emergency department visit demonstrated no growth. Computed tomography indicated an enlarged prostate with patchy areas of low density. He was admitted with sepsis secondary to prostatitis. Blood cultures on day one showed gram-positive cocci , methicillin resistant staph aureus (MRSA isolate) and persistent bacteremia for three days despite therapy with vancomycin. After adequate dosing of vancomycin, sterilization of the blood was achieved, yet urine culture demonstrated growth of MRSA. Transthoracic rchocardiogram (TTE) showed no signs of endocarditis with good visualization of valves. He was successfully treated with 14 days of vancomycin. PMID:27159482

  2. Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette's Syndrome in Preclinical Studies

    PubMed Central

    Spinello, Chiara; Laviola, Giovanni; Macrì, Simone

    2016-01-01

    Accumulating evidence suggests that Tourette's Syndrome (TS) – a multifactorial pediatric disorder characterized by the recurrent exhibition of motor tics and/or vocal utterances – can partly depend on immune dysregulation provoked by early repeated streptococcal infections. The natural and adaptive antibody-mediated reaction to streptococcus has been proposed to potentially turn into a pathological autoimmune response in vulnerable individuals. Specifically, in conditions of increased permeability of the blood brain barrier (BBB), streptococcus-induced antibodies have been proposed to: (i) reach neuronal targets located in brain areas responsible for motion control; and (ii) contribute to the exhibition of symptoms. This theoretical framework is supported by indirect evidence indicating that a subset of TS patients exhibit elevated streptococcal antibody titers upon tic relapses. A systematic evaluation of this hypothesis entails preclinical studies providing a proof of concept of the aforementioned pathological sequelae. These studies shall rest upon individuals characterized by a vulnerable immune system, repeatedly exposed to streptococcus, and carefully screened for phenotypes isomorphic to the pathological signs of TS observed in patients. Preclinical animal models may thus constitute an informative, useful tool upon which conducting targeted, hypothesis-driven experiments. In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS. By the same token, we discuss the limitations of these studies: limited evidence of behavioral phenotypes

  3. Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette's Syndrome in Preclinical Studies.

    PubMed

    Spinello, Chiara; Laviola, Giovanni; Macrì, Simone

    2016-01-01

    Accumulating evidence suggests that Tourette's Syndrome (TS) - a multifactorial pediatric disorder characterized by the recurrent exhibition of motor tics and/or vocal utterances - can partly depend on immune dysregulation provoked by early repeated streptococcal infections. The natural and adaptive antibody-mediated reaction to streptococcus has been proposed to potentially turn into a pathological autoimmune response in vulnerable individuals. Specifically, in conditions of increased permeability of the blood brain barrier (BBB), streptococcus-induced antibodies have been proposed to: (i) reach neuronal targets located in brain areas responsible for motion control; and (ii) contribute to the exhibition of symptoms. This theoretical framework is supported by indirect evidence indicating that a subset of TS patients exhibit elevated streptococcal antibody titers upon tic relapses. A systematic evaluation of this hypothesis entails preclinical studies providing a proof of concept of the aforementioned pathological sequelae. These studies shall rest upon individuals characterized by a vulnerable immune system, repeatedly exposed to streptococcus, and carefully screened for phenotypes isomorphic to the pathological signs of TS observed in patients. Preclinical animal models may thus constitute an informative, useful tool upon which conducting targeted, hypothesis-driven experiments. In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS. By the same token, we discuss the limitations of these studies: limited evidence of behavioral phenotypes

  4. Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette's Syndrome in Preclinical Studies.

    PubMed

    Spinello, Chiara; Laviola, Giovanni; Macrì, Simone

    2016-01-01

    Accumulating evidence suggests that Tourette's Syndrome (TS) - a multifactorial pediatric disorder characterized by the recurrent exhibition of motor tics and/or vocal utterances - can partly depend on immune dysregulation provoked by early repeated streptococcal infections. The natural and adaptive antibody-mediated reaction to streptococcus has been proposed to potentially turn into a pathological autoimmune response in vulnerable individuals. Specifically, in conditions of increased permeability of the blood brain barrier (BBB), streptococcus-induced antibodies have been proposed to: (i) reach neuronal targets located in brain areas responsible for motion control; and (ii) contribute to the exhibition of symptoms. This theoretical framework is supported by indirect evidence indicating that a subset of TS patients exhibit elevated streptococcal antibody titers upon tic relapses. A systematic evaluation of this hypothesis entails preclinical studies providing a proof of concept of the aforementioned pathological sequelae. These studies shall rest upon individuals characterized by a vulnerable immune system, repeatedly exposed to streptococcus, and carefully screened for phenotypes isomorphic to the pathological signs of TS observed in patients. Preclinical animal models may thus constitute an informative, useful tool upon which conducting targeted, hypothesis-driven experiments. In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS. By the same token, we discuss the limitations of these studies: limited evidence of behavioral phenotypes

  5. The streptococcal hemoprotein receptor: a moonlighting protein or a virulence factor?

    PubMed

    Eichenbaum, Zehava

    2012-11-15

    The β-hemolytic group A streptococcus (GAS) is a major pathogen that readily uses hemoglobin to satisfy its requirements for iron. The streptococcal hemoprotein receptor in GAS plays a central role in heme utilization and binds fibronectin and laminin in vitro. Shr inactivation attenuates the virulent M1T1 GAS strain in two murine infection models and reduces bacterial growth in blood and binding to laminin. Shr impact on the globally disseminated M1T1 strain underscores the importance of heme uptake in GAS pathogenesis and raises the possibility of targeting heme-uptake proteins in the development of new methods to combat GAS infections.

  6. Penicillin-susceptible group B streptococcal clinical isolates with reduced cephalosporin susceptibility.

    PubMed

    Nagano, Noriyuki; Nagano, Yukiko; Toyama, Masami; Kimura, Kouji; Shibayama, Keigo; Arakawa, Yoshichika

    2014-09-01

    We characterized penicillin-susceptible group B streptococcal (PSGBS) clinical isolates exhibiting no growth inhibition zone around a ceftibuten disk (CTB(r) PSGBS). The CTB(r) PSGBS isolates, for which augmented MICs of cefaclor and ceftizoxime were found, shared a T394A substitution in penicillin-binding protein 2X (PBP 2X) and a T567I substitution in PBP 2B, together with an additional G429S substitution in PBP 2X or a T145A substitution in PBP 1A, although the T145A substitution in the transglycosidase domain of PBP 1A would have no effect on the level of resistance to ceftibuten.

  7. Update on the management of acute pharyngitis in children.

    PubMed

    Regoli, Marta; Chiappini, Elena; Bonsignori, Francesca; Galli, Luisa; de Martino, Maurizio

    2011-01-01

    Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000. Even the use of the Centor score, in order to evaluate the risk of streptococcal infection, is under debate and the interpretation of the test results may vary considerably. Penicillin is considered all over the world as first line treatment, but oral amoxicillin is also accepted and, due to its better palatability, can be a suitable option. Macrolides should be reserved to the rare cases of proved allergy to β-lactams. Cephalosporins can be used in patients allergic to penicillin (with the exception of type I hypersensibility) and have been also proposed to treat the relapses. PMID:21281502

  8. Update on the management of acute pharyngitis in children

    PubMed Central

    2011-01-01

    Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000. Even the use of the Centor score, in order to evaluate the risk of streptococcal infection, is under debate and the interpretation of the test results may vary considerably. Penicillin is considered all over the world as first line treatment, but oral amoxicillin is also accepted and, due to its better palatability, can be a suitable option. Macrolides should be reserved to the rare cases of proved allergy to β-lactams. Cephalosporins can be used in patients allergic to penicillin (with the exception of type I hypersensibility) and have been also proposed to treat the relapses. PMID:21281502

  9. New perspectives on immunomodulatory therapy for bacteraemia and sepsis.

    PubMed

    Opal, Steven M

    2010-12-01

    Systemic immune dysregulation is generally acknowledged to be the fundamental molecular mechanism that underlies the pathophysiology of severe sepsis and septic shock. In the presence of a systemic infection, microbial pathogens and their soluble mediators induce generalised immune activation and coagulation activation, leading to severe sepsis and septic shock. For decades, immune-based therapies have been devised with the specific intent of inhibiting the pro-inflammatory events that are thought to precipitate the septic process. Despite a clear therapeutic rationale based upon the available experimental evidence, anti-inflammatory therapies targeting the innate or acquired immune response have largely been unsuccessful in clinical trials of sepsis. Compelling evidence now exists that a prolonged state of sepsis-induced immune suppression follows the initial period of stabilisation and resuscitation in many critically ill patients. Sepsis-related immune suppression is evidenced by histological findings of markedly enhanced lymphocytic and monocytic apoptosis, poor response to neoantigens and recall antigens, and increased incidence of infections by opportunistic pathogens. Candidiasis, cytomegalovirus activation and secondary infections by relatively avirulent bacterial pathogens such as Stenotrophomonas and Acinetobacter spp. are commonplace in septic patients during prolonged Intensive Care Unit stays. Immunological tools to detect sepsis-induced immunosuppression are now available, and novel immunoadjuvants are in development to re-establish immune competence in sepsis patients. The intelligent use of immunomodulatory agents in sepsis will necessitate a personalised medicine approach to treat each patient at the appropriate time and with the optimal therapy.

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

    PubMed

    Nasa, Prashant; Juneja, Deven; Singh, Omender

    2012-02-01

    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

  11. Cardiac Function and Dysfunction in Sepsis.

    PubMed

    Fenton, Kimberly E; Parker, Margaret M

    2016-06-01

    Cardiac function and dysfunction are important in the clinical outcomes of sepsis and septic shock. Cardiac dysfunction is not a single entity, but is a broad spectrum of syndromes that result in biventricular cardiac dysfunction manifested by both systolic and diastolic dysfunction and is influenced by cardiac loading conditions (ie, preload and afterload). Elucidating the underlying pathophysiology has proved to be complex. This article emphasizes the underlying pathophysiology of cardiac dysfunction and explores recent evidence related to diagnosis, including the utility of biomarkers, the role of echocardiography, and management goals and treatment. PMID:27229645

  12. Continuous evaluation of changes in the serum proteome from early to late stages of sepsis caused by Klebsiella pneumoniae.

    PubMed

    Raju M, Swathi; V, Jahnavi; Kamaraju, Ratnakar S; Sritharan, Venkataraman; Rajkumar, Karthik; Natarajan, Sumathi; Kumar, Anil D; Burgula, Sandeepta

    2016-06-01

    Serum protein profiles of patients with bacterial sepsis from the day of diagnosis until recovery/mortality were compared from early to late stages in response to severe sepsis using two dimensional electrophoresis. The proteins exhibiting changes during the course of sepsis (20‑28 day mortality) were selected and identified by matrix‑assisted laser desorption ionization‑time of flight‑tandem mass spectrometry. Among the proteins identified, haptoglobin (Hp), transthyretin (TTR), orosomucoid 1/α1 acid glycoprotein (ORM1), α1 antitrypsin (A1AT), serum amyloid A (SAA) and S100A9 exhibited differential expression patterns between survivors (S; n=6) and non‑survivors (NS; n=6), particularly during the early stages of sepsis. Expression factors (EFs), taken as the ratio between the NS and S during early stages, showed ratios of Hp, 0.39 (P≤0.012); TTR, 3.96 (P≤0.03); ORM1, 0.69 (P≤0.79); A1AT, 0.92 (P≤0.87) and SAA, 0.69 (P≤0.01). S100A9, an acute phase protein, exhibited an EF ratio of 1.68 (P≤0.004) during the end stages of sepsis. A delayed rise in levels was observed in Hp, A1AT, ORM1, S100A9 and SAA, whereas TTR levels increased during the early stages of sepsis in NS. Analysis of inflammatory responses in the early stages of sepsis revealed increased mRNA expression in leukocytes of interleukin (IL)‑6 (EF, 2.50), IL‑10 (EF, 1.70) and prepronociceptin (EF, 1.6), which is a precursor for nociceptin in NS compared with S, and higher Toll‑like receptor‑4 (EF, 0.30) levels in S compared with NS. Therefore, a weaker acute phase response in the early stages of sepsis in NS, combined with an inefficient inflammatory response, may contribute to sepsis mortality. PMID:27082932

  13. Science review: The brain in sepsis – culprit and victim

    PubMed Central

    Sharshar, Tarek; Hopkinson, Nicholas S; Orlikowski, David; Annane, Djillali

    2005-01-01

    On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free from blood-brain-barrier, interface between brain and bloodstream, in autonomic nuclei including the vagus nerve, and finally through the damaged endothelium. Recent observations have confirmed that sepsis is associated with excessive brain inflammation and neuronal apoptosis which clinical relevance remains to be explored. In parallel, damage within autonomic nervous and neuroendocrine systems may contribute to sepsis induced organ dysfunction. PMID:15693982

  14. How Can the Microbiologist Help in Diagnosing Neonatal Sepsis?

    PubMed Central

    Paolucci, Michela; Landini, Maria Paola; Sambri, Vittorio

    2012-01-01

    Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS) or later (late-onset neonatal sepsis—LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis. PMID:22319539

  15. 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

  16. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

    PubMed

    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection. PMID:27468649

  17. Sepsis-induced alterations in sleep of rats.

    PubMed

    Baracchi, Francesca; Ingiosi, Ashley M; Raymond, Richard M; Opp, Mark R

    2011-11-01

    Sepsis is a systemic immune response to infection that may result in multiple organ failure and death. Polymicrobial infections remain a serious clinical problem, and in the hospital, sepsis is the number-one noncardiac killer. Although the central nervous system may be one of the first systems affected, relatively little effort has been made to determine the impact of sepsis on the brain. In this study, we used the cecal ligation and puncture (CLP) model to determine the extent to which sepsis alters sleep, the EEG, and brain temperature (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye movement sleep (NREMS) during the dark period, but not during the light period. Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h following CLP surgery, after which REMS increases during dark periods for at least three nights. The EEG is dramatically altered shortly after sepsis induction, as evidenced by reductions in slow-frequency components. Furthermore, sleep is fragmented, indicating that the quality of sleep is diminished. Effects on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the duration of our recording period. Immunohistochemical assays focused on brain stem mechanisms responsible for alterations in REMS, as little information is available concerning infection-induced suppression of this sleep stage. Our immunohistochemical data suggest that REMS suppression after sepsis onset may be mediated, in part, by the brain stem GABAergic system. This study demonstrates for the first time that sleep and EEG patterns are altered during CLP-induced sepsis. These data suggest that the EEG may serve as a biomarker for sepsis onset. These data also contribute to our knowledge of potential mechanisms, whereby infections alter sleep and other central nervous system functions.

  18. Cytokines and acute pancreatitis.

    PubMed

    Brady, M; Christmas, S; Sutton, R; Neoptolemos, J; Slavin, J

    1999-07-01

    Cytokines have been shown to play a pivotal role in multiple organ dysfunction, a major cause of death in severe acute pancreatitis. Moreover, the two-hit hypothesis of the cytokine-induced systemic inflammatory response syndrome explains the variable individual response to severe acute pancreatitis and the impact of secondary events such as sepsis or therapeutic intervention. Many experimental anti-cytokine therapies have been administered following induction of experimental pancreatitis, and have proved to be therapeutic. Patients with severe pancreatitis present early because of pain. Clearly then a window for therapeutic intervention is available between onset of symptoms and peak pro-inflammatory cytokine expression. It is this fundamental observation that convinces many in the field that the treatment of AP will be one of the first clinical successes for novel drugs or therapy that seek to modulate the inflammatory response.

  19. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  20. Vasopressin in sepsis and septic shock.

    PubMed

    Kampmeier, T G; Rehberg, S; Westphal, M; Lange, M

    2010-10-01

    Arginine vasopressin (AVP) and its synthetic, long-acting analog terlipressin (TP) are potent alternative vasoconstrictors in the treatment of septic patients with catecholamine-refractive vasodilatatory shock. The results from one large randomized clinical trial suggest that AVP plus norepinephrine (NE) infusion is as safe and effective as treatment with NE alone in patients with septic shock. Because the desired effects of vasopressin analogs are basically related to their vasopressinergic effects via the V1a receptor, more selective V1 agonists, such as TP, may be more potent in reversing sepsis-related arterial hypotension. In this regard, recent evidence from small-scale studies suggests that continuous low-dose infusion rather than intermittent bolus injection of TP is associated with fewer side effects, such as depression of cardiac output and rebound arterial hypotension. However, because clinical data on the administration of TP in patients with sepsis are limited, it should not currently be used beyond the scope of controlled trials. The optimal time point for the initiation of therapy with vasopressin analogs has yet to be determined. While AVP and TP are commonly used as last-resort therapies in severe septic shock, some evidence supports the initiation of treatment in a less severe state of the disease.

  1. Intestinal radiation syndrome: sepsis and endotoxin

    SciTech Connect

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-03-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.

  2. 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

  3. WISP1-αvβ3 integrin signaling positively regulates TLR-triggered inflammation response in sepsis induced lung injury

    PubMed Central

    Chen, Zhixia; Ding, Xibing; Jin, Shuqing; Pitt, Bruce; Zhang, Liming; Billiar, Timothy; Li, Quan

    2016-01-01

    We recently noted that the matricellular protein WISP1 contributes to sepsis induced acute lung injury (ALI) via integrin β6. In the current study, we pursued further aspects of WISP1 modulation of TLR signaling in lungs of mice after sepsis and TLR4 mediated release of TNF-α in macrophages. After confirming that TLR4 and CD14 are critical in transducing sepsis mediated ALI, we now demonstrate that intrapulmonary αvβ3 is increased by polymicrobrial sepsis in a TLR4, CD14 dependent fashion. Comparison of cultured macrophages revealed that WISP1 increased release of TNF-α from RAW264.7 cells with baseline expression of αvβ3, but primary cultures of peritoneal macrophages (PMø) required activation of TLR4 to induce de novo synthesis of αvβ3 enabling WISP1 to stimulate release of TNF-α. The specific requirement for β3 integrin was apparent when the effect of WISP1 was lost in PMø isolated from β3−/− mice. WISP1 enhanced TLR4 mediated ERK signaling and U0126 (an ERK inhibitor) blocked LPS induced β3 integrin expression and WISP1 enhanced TNF-α release. Collectively these data suggest that WISP1-αvβ3 integrin signaling is involved in TLR4 pathways in macrophages and may be an important contributor to TLR4/CD14 mediated inflammation in sepsis induced lung injury. PMID:27349568

  4. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve.

    PubMed

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  5. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve.

    PubMed

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways.

  6. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

    PubMed Central

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T.; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  7. High burden of invasive beta-haemolytic streptococcal infections in Fiji.

    PubMed

    Steer, A C; Jenney, A J W; Oppedisano, F; Batzloff, M R; Hartas, J; Passmore, J; Russell, F M; Kado, J H H; Carapetis, J R

    2008-05-01

    We undertook a 5-year retrospective study of group A streptococcal (GAS) bacteraemia in Fiji, supplemented by a 9-month detailed retrospective study of beta-haemolytic streptococcal (BHS) infections. The all-age incidence of GAS bacteraemia over 5 years was 11.6/100,000. Indigenous Fijians were 4.7 times more likely to present with invasive BHS disease than people of other ethnicities, and 6.4 times more likely than Indo-Fijians. The case-fatality rate for invasive BHS infections was 28%. emm-typing was performed on 23 isolates: 17 different emm-types were found, and the emm-type profile was different from that found in industrialized nations. These data support the contentions that elevated rates of invasive BHS and GAS infections are widespread in developing countries, and that the profile of invasive organisms in these settings reflects a wide diversity of emm-types and a paucity of types typically found in industrialized countries.

  8. Streptococcal Pharyngitis in a Two-Month-Old Infant: A Case Report

    PubMed Central

    Sharif, Mohammad Reza; Aalinezhad, Marzieh; Sajadian, Seyyed Mohammad Sajad; Haji Rezaei, Mostafa

    2016-01-01

    Introduction Group A β-hemolytic Streptococcus is the most common cause of bacterial pharyngitis among 5 - 15-year-old children, but it is uncommon in children less than three years old and rarely happens in infants less than one year old. Case Presentation The patient was a 62-day-old female infant who presented with fever and poor feeding since two days before admission. At the time of admission, the patient was febrile and ill. Upon examination, a rectal temperature of 38.5°C, multiple right-sided submandibular lymphadenopathies, pharyngeal erythema, and tonsillar exudates were detected. Twenty-four hours after the throat swab was collected and cultured, Streptococcus pyogenes grew on a sheep blood agar medium. The patient’s mother, who also experienced similar symptoms, had a positive throat swab culture for S. pyogenes. Conclusions Although Streptococcal pharyngitis is rare in children less than three years old and the necessity of treatment is not well clarified, in case of streptococcal infection in parents and the occurrence of similar signs and symptoms in their child, considering S. pharyngitis as a possible differential diagnosis seems rational. PMID:27540457

  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

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

    2014-09-01

    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