Sample records for acute streptococcal sepsis

  1. Compliance with the Centers for Disease Control and Prevention antenatal culture protocol for preventing group B streptococcal neonatal sepsis

    Microsoft Academic Search

    Elaine Cheon-Lee; Marvin S. Amstey

    1998-01-01

    OBJECTIVE: Our purpose was to measure the compliance with the Centers for Disease Control and Prevention antenatal culture protocol for preventing group B streptococcal sepsis after extensive education of physicians and staff.STUDY DESIGN: After 2 months of educational activities to familiarize attending physicians, nurses, and laboratory staff with the guidelines, a retrospective chart review of all vaginal deliveries over a

  2. Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues

    PubMed Central

    Hansen, Nellie I.; Sánchez, Pablo J.; Faix, Roger G.; Poindexter, Brenda B.; Van Meurs, Krisa P.; Bizzarro, Matthew J.; Goldberg, Ronald N.; Frantz, Ivan D.; Hale, Ellen C.; Shankaran, Seetha; Kennedy, Kathleen; Carlo, Waldemar A.; Watterberg, Kristi L.; Bell, Edward F.; Walsh, Michele C.; Schibler, Kurt; Laptook, Abbot R.; Shane, Andi L.; Schrag, Stephanie J.; Das, Abhik; Higgins, Rosemary D.

    2011-01-01

    BACKGROUND: Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen. OBJECTIVE: To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers. METHODS: Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ?72 hours plus treatment with antibiotic therapy for ?5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence. RESULTS: Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%). CONCLUSION: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge. PMID:21518717

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

    PubMed

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

    2015-04-01

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

  4. Neonatal sepsis

    PubMed Central

    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 ? 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. PMID:24185532

  5. Mortality from early neonatal group B streptococcal sepsis: influence of obstetric factors.

    PubMed

    Gill, P; Sobeck, J; Jarjoura, D; Hillier, S; Benedetti, T

    1997-01-01

    Our objective was to determine if the neonatal mortality from early group B streptococcal (GBS) septicemia was associated with obstetric factors other than birthweight. Medical records from our institution for all neonates with positive blood cultures for GBS in the first 7 days of life between January 1981 and December 1992 were reviewed (n = 61). All the neonates had received broad-spectrum intravenous antibiotics within 3 h of birth, and all had cerebrospinal fluid (CSF) cultures obtained. In a multivariate model we found a significant association between neonatal mortality and birthweight (P = .01). The other significant associations were with positive CSF cultures (P = .01) and intrapartum invasive fetal scalp electrode monitoring (P = .03). After controlling for these and other variables in the model, the odds of death for the infants with scalp electrode monitoring was 8 times greater (95% CI = 1.1,56), compared to those who had the GBS septicemia but no intrapartum fetal scalp electrode monitoring. In conclusion, the association we found between neonatal fatality from early GBS septicemia and invasive fetal scalp electrode monitoring is plausible and needs further study. PMID:9029383

  6. Post-streptococcal reactive arthritis in children: a distinct entity from acute rheumatic fever

    PubMed Central

    2011-01-01

    There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question. PMID:22013970

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

    PubMed Central

    Hoton, Delphine; Castanares-Zapatero, Diego

    2015-01-01

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

  8. 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-1? and IL-18, and coadministration of endothelial progenitor cells and stromal cell-derived factor-1? 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

  9. Post-streptococcal acute glomerulonephritis complicated by gouty arthritis: a case report.

    PubMed

    Kuniyoshi, Yasutaka; Kamura, Azusa; Yasuda, Sumie; Tashiro, Makoto

    2015-01-01

    Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients. PMID:26080801

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

    PubMed

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

    2014-08-01

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

  11. M protein deficient streptococcal cell walls can induce acute and chronic arthritis rats.

    PubMed

    DeJoy, S Q; Ferguson-Chanowitz, K M; Sapp, T M; Oronsky, A L; Lapierre, L A; Zabriskie, J B; Kerwar, S S

    1990-02-01

    Cell walls from M+ and M- protein variants of group A streptococci were examined for their arthritogenicity in female Lewis rats. Intraperitoneal administration of both of these sonicated cell wall preparations caused a severe acute and chronic arthritis in recipient rats. Histological evaluation of the hind paw of these rats indicated synovial lining hyperplasia, cell infiltration in the subsynovial space, pannus formation, and erosions of bone and cartilage. Joint pathology was similar in the hind paws of rats immunized with cell walls prepared from either the M+ or the M- protein variants. Cell-mediated immunity was also similar when lymph nodes were exposed to cell walls derived from these two preparations. A recombinant M6 protein from streptococci did not elicit a proliferative response from lymph nodes prepared from arthritic rats. These observations indicate that the M protein that has previously been implicated in auto-immunity does not have a critical role in the pathogenesis of streptococcal cell wall arthritis in rats. PMID:2297798

  12. Biomarkers, diagnosis and management of sepsis-induced acute kidney injury: a narrative review.

    PubMed

    Zhang, Zhongheng

    2015-01-01

    Sepsis is a leading cause of acute kidney injury in clinical practice. The diagnosis of sepsis-induced acute kidney injury requires the diagnosis of sepsis and subsequent occurrence of acute kidney injury. The current definition for acute kidney injury is based on Scr and urine output, which is limited by the delayed identification of such patients. Numerous novel biomarkers have been found to be up-regulated in kidney injury, among which cystatin C and neutrophil gelatinase-associated lipocalin are the most studied. In the management of sepsis-induced acute kidney injury, early goal directed therapy may be potentially useful, but requires further validation in large clinical trials. It is well known that fluid overload is harmful in septic patients with established acute kidney injury and should be avoided. Renal replacement therapy is the mainstay treatment for the severe form of sepsis-induced acute kidney injury. However, there is still no consensus on the definition of timing and dosing in clinical practice, and the optimal timing and dosing are still unknown. PMID:25861592

  13. Endothelial progenitor cells (EPC) in sepsis with acute renal dysfunction (ARD)

    Microsoft Academic Search

    Susann A Patschan; Daniel Patschan; Johanna Temme; Peter Korsten; Johannes T Wessels; Michael Koziolek; Elvira Henze; Gerhard A Müller

    2011-01-01

    Introduction  Sepsis is characterized by systemic microvascular dysfunction. Endothelial progenitor cells (EPCs) are critically involved\\u000a in maintaining vascular homeostasis under both physiological and pathological conditions. The aim of the present study was\\u000a to analyze the endothelial progenitor cell system in patients suffering from sepsis with acute renal dysfunction.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Patients with newly diagnosed sepsis were recruited from the ICU in a nonrandomized

  14. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis

    PubMed Central

    Peng, Zhi-Yong; Wang, Hong-Zhi; Carter, Melinda J.; Dileo, Morgan V.; Bishop, Jeffery V.; Zhou, Fei-Hu; Wen, Xiao-Yan; Rimmelé, Thomas; Singbartl, Kai; Federspiel, William J.; Clermont, Gilles; Kellum, John A.

    2011-01-01

    The effect of extracorporeal blood purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal blood purification that did not result in acute changes in a panel of common cytokines associated with inflammation (TNF-?, IL-1?, IL-6, and IL-10). Pre- and immediate post-treatment levels of these cytokines were unchanged compared to the sham therapy of extracorporeal circulation without blood purifying sorbent. The overall survival to 7 days, however, was significantly better in animals that received extracorporeal blood purification compared to those with a sham procedure. This panel of common plasma cytokines along with alanine aminotransferase and creatinine was significantly lower 72 h following extracorporeal blood purification compared to sham-treated rats. Thus, the effects of this procedure on organ function and survival do not appear to be due solely to immediate changes in the usual measured circulating cytokines. These results may have important implications for the design and conduct of future trials in sepsis including defining alternative targets for extracorporeal blood purification and other therapies. PMID:21918497

  15. Mechanisms of acute inflammatory lung injury induced by abdominal sepsis

    Microsoft Academic Search

    Brigitte Neumann; Niko Zantl; Andreas Veihelmann; Klaus Emmanuilidis; Klaus Pfeffer; Claus-Dieter Heidecke; Bernhard Holzmann

    1999-01-01

    Sequestration of neutrophils and release of histotoxic mediators are considered important for the development of pathologic alterations of the lung defined as adult respiratory distress syndrome. Mechanisms of inflammatory lung injury caused by abdominal sepsis were investigated using the colon ascendens stent peritonitis (CASP) model that closely mimics the human disease. In the CASP model, a continuous leakage of intraluminal

  16. 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

  17. Role of peroxynitrite in sepsis-induced acute kidney injury in an experimental model of sepsis in rats.

    PubMed

    Seija, Mariana; Baccino, Cecilia; Nin, Nicolás; Sánchez-Rodríguez, Carolina; Granados, Rosario; Ferruelo, Antonio; Martínez-Caro, Leticia; Ruíz-Cabello, Jesús; de Paula, Marta; Noboa, Oscar; Esteban, Andrés; Lorente, José Angel

    2012-10-01

    The mechanisms involved in sepsis-induced acute kidney injury (AKI) are unknown. We investigated the role of nitrosative stress in sepsis-induced AKI by studying the effects of manganese (III) tetrakis-(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), a peroxynitrite decomposition catalyst, and aminoguanidine (AG), a selective nitric oxide synthase 2 (NOS2) inhibitor and peroxynitrite scavenger, on kidney function of rats subjected to cecal ligation and puncture (CLP). Sprague-Dawley rats (weighing 350 [SD, 50] g) were treated with MnTMPyP (6 mg/kg i.p.) or AG (50 mg/kg i.p.) at t = 12 and 24 h after CLP or sham procedure. At t = 36 h, mean arterial pressure and aortic blood flow were measured, and blood and urine samples were obtained for biochemical determinations, including creatinine clearance, fractional excretion of sodium, and neutrophil gelatinase-associated lipocalin concentration in the urine. Kidney tissue samples were obtained for (i) light microscopy, (ii) immunofluorescence and Western blot for 3-nitrotyrosine and NOS2, (iii) gene expression (quantitative real-time polymerase chain reaction) studies (NOS1, NOS2, NOS3, and superoxide dismutase 1), and (iv) matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Mean arterial pressure was unchanged and aortic blood flow decreased 25% in CLP animals. The sepsis-induced (i) decreased urine output and creatinine clearance and increased fractional excretion of sodium and urinary neutrophil gelatinase-associated lipocalin concentration, (ii) increased protein nitration and NOS2 protein, and (iii) NOS1 and NOS2 upregulation were all significantly attenuated by treatment with MnTMPyP or AG. Nitrated proteins in renal tissue from CLP animals (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were glutamate dehydrogenase, methylmalonate-semialdehyde dehydrogenase, and aldehyde dehydrogenase, mitochondrial proteins involved in energy metabolism or antioxidant defense. Nitro-oxidative stress is involved in sepsis-induced AKI, and protein nitration seems to be one mechanism involved. PMID:22777123

  18. Acute Lung Injury and Fibrosis in a Baboon Model of Escherichia coli Sepsis

    PubMed Central

    Keshari, Ravi S.; Silasi-Mansat, Robert; Zhu, Hua; Popescu, Narcis I.; Peer, Glenn; Chaaban, Hala; Lambris, John D.; Polf, Holly; Lupu, Cristina; Kinasewitz, Gary

    2014-01-01

    Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6–27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-? and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsis-induced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies. PMID:24066737

  19. The Fatty Acid Composition of Maternal Diet Affects Lung Prostaglandin E2 Levels and Survival from Group B Streptococcal Sepsis in Neonatal

    Microsoft Academic Search

    Rat Pups; Jorge I. Rayon; Jane D. Carver; Lance E. Wyble; Doris Wiener; Sonja S. Dickey; Valerie J. Benford; Li T. Chen; Daniel V. Lim

    Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators. The effects of maternal dietary fatty acid composition upon lung prosta- glandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups. Beginning o nd2o fgestation and throughout lactation, pregnant dams were

  20. Early-Age-Related Changes in Proteostasis Augment Immunopathogenesis of Sepsis and Acute Lung Injury

    Microsoft Academic Search

    Manish Bodas; Taehong Min; Neeraj Vij; Amit Gaggar

    2010-01-01

    BackgroundThe decline of proteasomal activity is known to be associated with the age-related disorders but the early events involved in this process are not apparent. To address this, we investigated the early-age-related (pediatric vs. adult) mechanisms that augment immunopathogenesis of sepsis and acute lung injury.Methodology\\/Principal FindingsThe 3-weeks (pediatric) and 6-months (adult) old C57BL\\/6 mice were selected as the study groups.

  1. Haplotype analysis of ApoAI gene and sepsis-associated acute lung injury

    PubMed Central

    2014-01-01

    Background Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high density lipoprotein (HDL) which exerts innate protective effects in systemic inflammation. However, its role in the acute lung injury (ALI) has not been well studied. In the present study we investigated the association between polymorphisms of ApoA1 gene and ALI in a Chinese population. Methods Three polymorphisms of the ApoA1 gene (rs11216153, rs2070665, and rs632153) were genotyped by TaqMan method in 290 patients with sepsis-associated ALI, 285 patients sepsis alone and 330 age- and sex-matched healthy controls. Results We found rs11216153 polymorphism of ApoA1 was associated with ALI, the GG genotype and G allele was common in the ALI patients (76.9%, 88.1%, respectively) than both in the control subjects (55.8%, 75.8%, respectively) and in the sepsis alone patients (58.2%, 78.4%, respectively). Haplotype consisting of these three SNPs strengthened the association with ALI susceptibility. The frequency of haplotype GTG in the ALI samples was significantly higher than that in the healthy control group (OR?=?2.261, 95% CI: 1.735?~?2.946, P <0.001) and the sepsis alone group (OR?=?1.789, 95% CI: 1.373?~?2.331.P?sepsis alone group (OR?=?0.491, 95% CI: 0.356?~?0.676, P <0.001). Conclusions These results indicated that genetic variants in the ApoA1 gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population. PMID:24885977

  2. PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A ?-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat

    PubMed Central

    Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

    2013-01-01

    Objective To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Design Diagnostic cohort. Setting UK general practices. Participants Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Main outcome Predictors of the presence of Lancefield A/C/G streptococci. Results The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3?days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24?h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3?days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ?1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ?1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Conclusions Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci. PMID:24163209

  3. Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury.

    PubMed

    Peters, Esther; van Elsas, Andrea; Heemskerk, Suzanne; Jonk, Luigi; van der Hoeven, Johannes; Arend, Jacques; Masereeuw, Rosalinde; Pickkers, Peter

    2013-01-01

    Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI). Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions. Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function. The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage. The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation. Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism. Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP. In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI. PMID:23131595

  4. Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects

    PubMed Central

    Yasuda, Hideo; Yuen, Peter S.T.; Hu, Xuzhen; Zhou, Hua; Star, Robert A.

    2008-01-01

    Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are HMG-CoA reductase inhibitors that also have pleiotropic actions. They have been reported to increase survival of septic or infectious patients. But the effect of simvastatin, a widely used statin, on sepsis-induced AKI is unknown. The effects of simvastatin and TNF-alpha neutralizing antibody were studied in a clinically relevant model of sepsis-induced AKI using cecal ligation and puncture (CLP) in elderly mice. Simvastatin siginificantly improved CLP-induced mortality and AKI. Simvastatin attenuated CLP-induced tubular damage and reversed CLP-induced reduction of intrarenal microvascular perfusion and renal tubular hypoxia at 24 hours. Simvastatin also restored towards normal CLP-induced renal vascular protein leak and serum TNF-alpha. Neither delayed simvastatin therapy nor TNF-alpha neutralizing antibody improved CLP-induced AKI. Simvastatin improved sepsis-induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect. PMID:16557230

  5. Endogenous Interleukin11 (IL11) Expression Is Increased and Prophylactic Use of Exogenous IL11 Enhances Platelet Recovery and Improves Survival During Thrombocytopenia Associated With Experimental Group B Streptococcal Sepsis in Neonatal Rats

    Microsoft Academic Search

    Mei Chang; Angela Williams; Lori Ishizawa; Annika Knoppel; Carmella van de Ven; Mitchell S. Cairo

    Future preventive and\\/or concurrent therapy of neonatal sepsis may require the use of adjuvant immunohematopoietic therapy. In the present study, using reverse transcription-polymerase chain reaction, we demonstrated a significant increase in IL-11 mRNA extracted from the femurs of group B streptococcus (GBS)-infected rats during acute thrombocytopenia (platelet count: 65.8 ± 19.3 K\\/mm , n=5) compared to that 3 of uninfected

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

    PubMed

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

    2015-06-01

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

  7. Multisystem disease in post-streptococcal arthritis.

    PubMed Central

    Livneh, A; Sharma, K; Sewell, K L; Keiser, H D

    1991-01-01

    The case presented is of a patient with migratory polyarthritis and serological evidence of a recent streptococcal infection, consistent with the diagnosis of acute rheumatic fever, who in addition had multisystem disease manifestations. This case supports the concept that the sequelae of streptococcal infection can encompass a broader clinical spectrum than is suggested by the Jones criteria for the diagnosis of acute rheumatic fever. PMID:2042990

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

    PubMed Central

    Kasap, Belde; Çarman, Kür?at Bora; Yi?, Uluç

    2014-01-01

    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 99th 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.

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

    PubMed Central

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

    2015-01-01

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

  10. Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse model

    PubMed Central

    Bhatty, Minny; Jan, Basit L; Tan, Wei; Pruett, Stephen B; Nanduri, Bindu

    2011-01-01

    Sepsis is a major cause of death worldwide. The associated risks and mortality are known to significantly increase on exposure to alcohol (chronic or acute). The underlying mechanisms of the association of acute ethanol ingestion and poor prognosis of sepsis are largely unknown. The study described here was designed to determine in detail the role of ethanol and TLR4 in the pathogenesis of the sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine production were evaluated using wild type and TLR4 hypo-responsive mice treated with ethanol and then challenged with a non pathogenic strain of Escherichia. coli (E. coli). Ethanol treated mice exhibited a decreased clearance of bacteria and produced lesser amounts of most pro-inflammatory cytokines in both strains of mice at two hours after challenge. Neither ethanol treatment nor a hypo-responsive TLR4 had significant effects on the cell numbers in the peritoneal cavity and spleen 2 hours post infection. The suppressive effect of acute ethanol exposure on cytokine and chemokine production was more pronounced in the wild type mice, but the untreated hyporesponsive mice produced less of most cytokines than untreated wild type mice. The major conclusion of this study is that acute ethanol exposure suppresses pro-inflammatory cytokine production and that a hypo-responsive TLR4 (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels but the cytokines and other mediators induced through other receptors are sufficient to ultimately clear the infection but not enough to induce lethal septic shock. In addition, results reported here demonstrate previously unknown effects of acute ethanol exposure on LIF (leukemia inhibitory factor) and eotaxin and provide the first evidence that IL-9 is induced through TLR4 in vivo. PMID:21872420

  11. [Acute renal failure and sepsis : Just an organ dysfunction due to septic multiorgan failure?].

    PubMed

    Schmidt, C; Steinke, T; Moritz, S; Graf, B M; Bucher, M

    2010-08-01

    Acute renal failure (ARF) is clinically defined as an abrupt, but in principle reversible deterioration of glomerular and tubular function. Regarding pathophysiology, ARF is caused by ischemic renal conditions and toxic mediators. Sepsis is the most common cause of ARF in the intensive care unit and ARF is an independent risk factor for lethality of septic patients. Interventions to protect the kidneys against ARF include preliminary optimization of renal perfusion by volume load with cristalloid solutions and the administration of vasopressors. Daily maximum permissible dosages for colloids should not be exceeded and hyperoncotic colloid solutions should be generally avoided. Dopamine in "renal dosage" is nowadays obsolete. Loop diuretics produce diuresis and can be beneficial to extrarenal organs by improving fluid homeostasis, however diuretics do not improve kidney function and outcome. Therefore, diuretics are not indicated for patients with imminent or existing ARF. Septic patients with ARF can be treated by intermittent and continuous forms of renal replacement therapy, whereas continuous convective and intermittent diffusive methods are equivalent when utilizing an ultrafiltration rate > or =20 ml/h*kg body weight or a therapeutic interval > or =3 times/week. PMID:20694713

  12. 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

    2015-01-01

    The aim of this study was to investigate the influence of ulinastatin (UTI) on high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-?, 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-? 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-? and IL-6 levels in serum and BALF. PMID:25966207

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Effect of siRNA against NF-?B on sepsis-induced acute lung injury in a mouse model

    PubMed Central

    JIN, LI-YAN; LI, CONG-FENG; ZHU, GUANG-FA; WU, CHUN-TING; WANG, JUN; YAN, SHU-FENG

    2014-01-01

    The aim of the present study was to explore the protective effect of small interfering RNA (siRNA) against nuclear factor ?B (NF-?B) p65 on sepsis-induced acute lung injury (ALI) in mice. In total, 70 male Kunming mice were randomly divided into a healthy control group, a sepsis group, a specific interfering group and a scrambled control group (Sc), and the latter three groups were divided into post-operational 6 and 12 h subgroups, each of which consisted of 10 mice. The mice were administered with NF-?B siRNA, scrambled siRNA and normal saline via tail vein injection. Following 1 h, a mouse model of septic ALI was produced by cecal ligation and puncture (CLP) in the two siRNA groups and the sepsis control group. At 6 and 12 h post-operation, the experimental mice were sacrificed and the lung tissue samples were collected. Histopathological changes, wet/dry ratio of lung weight, NF-?B protein and NF-?B p65 mRNA levels, matrix metalloproteinase-9 (MMP-9) mRNA and protein activity were detected. Compared with the sepsis group and the Sc at the corresponding time, the expression levels of NF-?B p65 mRNA, the lung injury of experimental mice, the wet/dry ratio and the levels of MMP-9 mRNA and protein activity decreased, and significant differences were observed at 6 h post-operation (P<0.05). RNA interference against NF-?B p65 was able to decrease the expression of NF-?B and further inhibit the early phasic excessive inflammatory reaction in sepsis, which may alleviate ALI. PMID:24913772

  16. Significance of Measuring S100A12 and sRAGE in the Serum of Sepsis Patients with Postoperative Acute Lung Injury

    Microsoft Academic Search

    Tomohiro Kikkawa; Nobuhiro Sato; Masahiro Kojika; Gaku Takahashi; Kiichi Aoki; Koichi Hoshikawa; Shinji Akitomi; Tatsuyori Shozushima; Kenji Suzuki; Go Wakabayashi; Shigeatsu Endo

    2010-01-01

    Background: There is a report that S100A12 is useful as an early marker of acute lung injury (ALI). The purpose of this study was to determine whether S100A12 or sRAGE is useful as a marker during the development of ALI in postoperative sepsis patients. Methods: The subjects were patients who underwent emergency surgery because of sepsis secondary to perforation of

  17. Targeting Abl kinases to regulate vascular leak during sepsis and acute respiratory distress syndrome.

    PubMed

    Rizzo, Alicia N; Aman, Jurjan; van Nieuw Amerongen, Geerten P; Dudek, Steven M

    2015-05-01

    The vascular endothelium separates circulating fluid and inflammatory cells from the surrounding tissues. Vascular leak occurs in response to wide-spread inflammatory processes, such as sepsis and acute respiratory distress syndrome, because of the formation of gaps between endothelial cells. Although these disorders are leading causes of mortality in the intensive care unit, no medical therapies exist to restore endothelial cell barrier function. Recent evidence highlights a key role for the Abl family of nonreceptor tyrosine kinases in regulating vascular barrier integrity. These kinases have well-described roles in cancer progression and neuronal morphogenesis, but their functions in the vasculature have remained enigmatic until recently. The Abl family kinases, c-Abl (Abl1) and Abl related gene (Arg, Abl2), phosphorylate several cytoskeletal effectors that mediate vascular permeability, including nonmuscle myosin light chain kinase, cortactin, vinculin, and ?-catenin. They also regulate cell-cell and cell-matrix junction dynamics, and the formation of actin-based cellular protrusions in multiple cell types. In addition, both c-Abl and Arg are activated by hyperoxia and contribute to oxidant-induced endothelial cell injury. These numerous roles of Abl kinases in endothelial cells and the current clinical usage of imatinib and other Abl kinase inhibitors have spurred recent interest in repurposing these drugs for the treatment of vascular barrier dysfunction. This review will describe the structure and function of Abl kinases with an emphasis on their roles in mediating vascular barrier integrity. We will also provide a critical evaluation of the potential for exploiting Abl kinase inhibition as a novel therapy for inflammatory vascular leak syndromes. PMID:25814671

  18. Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

    PubMed Central

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

    2013-01-01

    ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

  19. Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury

    PubMed Central

    2010-01-01

    Background Toll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI. Methods A case-control collection from Han Chinese of 298 healthy subjects, 278 sepsis-associated ALI and 288 sepsis alone patients were included. Three tag single nucleotide polymorphisms (SNPs) of the TIRAP gene and two additional SNPs that have previously showed association with susceptibility to other inflammatory diseases were genotyped by direct sequencing. The differences of allele, genotype and haplotype frequencies were evaluated between three groups. Results The minor allele frequencies of both rs595209 and rs8177375 were significantly increased in ALI patients compared with both healthy subjects (odds ratio (OR) = 1.47, 95% confidence interval (CI):1.15-1.88, P = 0.0027 and OR = 1.97, 95% CI: (1.38-2.80), P = 0.0001, respectively) and sepsis alone patients (OR = 1.44, 95% CI: 1.12-1.85, P = 0.0041 and OR = 1.82, 95% CI: 1.28-2.57, P = 0.00079, respectively). Haplotype consisting of these two associated SNPs strengthened the association with ALI susceptibility. The frequency of haplotype AG (rs595209A, rs8177375G) in the ALI samples was significantly higher than that in the healthy control group (OR = 2.13, 95% CI: 1.46-3.09, P = 0.00006) and the sepsis alone group (OR = 2.24, 95% CI: 1.52-3.29, P = 0.00003). Carriers of the haplotype CA (rs595209C, rs8177375A) had a lower risk for ALI compared with healthy control group (OR = 0.69, 95% CI: 0.54-0.88, P = 0.0003) and sepsis alone group (OR = 0.71, 95% CI: 0.55-0.91, P = 0.0006). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. Conclusions These results indicated that genetic variants in the TIRAP gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population. However, the association needs to be replicated in independent studies. PMID:21118491

  20. 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

    2015-01-01

    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. PMID:26169055

  1. Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion.

    PubMed

    Bornstein, S R; Licinio, J; Tauchnitz, R; Engelmann, L; Negrão, A B; Gold, P; Chrousos, G P

    1998-01-01

    Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. All of these patients fulfilled the standard diagnostic criteria for sepsis. Plasma leptin levels were measured in all patients and controls at 09:00. In addition, in a subgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were measured every 4 hours for 24 hours. Mean plasma leptin levels were three-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than controls (3.8 +/- 1.0 ng/ml, p < 0.05). Similarly, ACTH levels were lower (7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p < .001), while plasma cortisol levels were increased (947.6 +/- 144 nmol/l) in patients compared to controls (361.1 +/- 29, p < 0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients with sepsis (1238.0 +/- 543.1 pg/ml) versus controls (6.4 +/- 1.7, p < 0.001). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast, septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis. PMID:9435456

  2. Ghrelin attenuates sepsis-associated acute lung injury oxidative stress in rats.

    PubMed

    Zeng, Mian; He, Wanmei; Li, Lijun; Li, Bin; Luo, Liang; Huang, Xubin; Guan, Kaipan; Chen, Weiling

    2015-04-01

    This study investigated the effect of ghrelin on oxidative stress in septic rat lung tissue. Male Sprague-Dawley rats were divided into sham-operation, sepsis, and ghrelin groups. Sepsis was induced by cecal ligation and puncture. Ghrelin was administered intraperitoneally at 3 and 15 h post-operation. Bronchoalveolar lavage was performed to collect alveolar macrophages (AMs). Inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression in alveolar macrophages and iNOS protein levels were measured by reverse transcription PCR (RT-PCR) and Western blot. Pulmonary pathology was analyzed and nitrotyrosine expression was examined by immunohistochemistry. Plasma superoxide dismutase (SOD) and lung wet/dry weight were measured. In the sepsis group, iNOS mRNA expression in AMs was 1.33 ± 0.05, 1.44 ± 0.08, and 1.57 ± 0.11 at 6, 12, and 20 h post-surgery, respectively, and were higher compared with the sham-operation group (p<0.05). No increase was observed at longer time points. iNOS mRNA expression in the sepsis group was lower compared with the ghrelin group (2.27?± 0.37) (p<0.05) at 20 h post-surgery. iNOS protein levels in the ghrelin group (0.87 ± 0.03, p<0.05) were lower than in the sepsis group at 20 h. Ghrelin group pathological scores were lower than in the sepsis group (p<0.05). Plasma SOD was slightly non-significantly decreased in the ghrelin group. No difference was observed in lung wet/dry weight ratios between sepsis and ghrelin groups. iNOS mRNA expression in AMs was elevated between 6 and 20 h after cecal ligation and puncture (CLP), but did not progress. Ghrelin attenuated pulmonary iNOS protein expression and tended to increase plasma SOD activity. Ghrelin suppressed pulmonary nitrosative stress in septic rats, but did not improve lung wet/dry weight ratios. PMID:25037094

  3. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2013-02-01

    Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset 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 LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis. PMID:23297182

  4. 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-? activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse. PMID:23903370

  5. Pharmacological targets in the renal peritubular microenvironment: implications for therapy for sepsis-induced acute kidney injury

    PubMed Central

    Mayeux, Philip R.; MacMillan-Crow, Lee Ann

    2012-01-01

    One of the most frequent and serious complications to develop in septic patients is acute kidney injury (AKI), a disorder characterized by a rapid failure of the kidneys to adequately filter the blood, regulate ion and water balance, and generate urine. AKI greatly worsens the already poor prognosis of sepsis and increases cost of care. To date, therapies have been mostly supportive; consequently there has been little change in the mortality rates over the last decade. This is due, at least in part, to the delay in establishing clinical evidence of an infection and the associated presence of the systemic inflammatory response syndrome and thus, a delay in initiating therapy. A second reason is a lack of understanding regarding the mechanisms leading to renal injury, which has hindered the development of more targeted therapies. In this review, we summarize recent studies, which have examined the development of renal injury during sepsis and propose how changes in the peritubular capillary microenvironment lead to and then perpetuate microcirculatory failure and tubular epithelial cell injury. We also discuss a number of potential therapeutic targets in the renal peritubular microenvironment, which may prevent or lessen injury and/or promote recovery. PMID:22274552

  6. Neonatal sepsis

    MedlinePLUS

    American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Policy Statement: Recommendations for the Prevention of Perinatal Group B Streptococcal (GBS) Disease. ...

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Early Identification of Sepsis

    Microsoft Academic Search

    Mateus Demarchi Gonsalves; Yasser Sakr

    2010-01-01

    Early diagnosis is crucial to reduce morbidity and mortality from sepsis. Clinical suspicion is the first step to diagnosis,\\u000a and necessitates meticulous history taking and complete clinical examination. Special attention should be paid to identifying\\u000a foci of infection. Biomarkers of host response—including acute phase proteins, procalcitonin, and various cytokines—may be\\u000a useful in the diagnosis and management of patients with sepsis.

  11. Purification methods: a way to treat severe acute inflammation related to sepsis?

    PubMed Central

    2013-01-01

    After numerous negative randomized trials testing drugs for severe sepsis and/or septic shock, the blood purification approach remains one possibility. Many techniques have been proposed, having in common the goal to eliminate blood and/or plasma factors, supposed to play a negative role in outcomes. Among these, high dose of hemofiltration, high volume hemofiltration, high permeability hemofiltration and specific or non-specific hemoperfusion or hemoadsorption have been proposed. Until now, a poor level of proof has been published, questioning the pertinence of such a strategy. To have a chance to succeed, immune monitoring has to be performed to select suitable patients regarding their immune status, the intensity of inflammation and their cellular function. Because of the potential interaction with mediators and cell capture, Rimmelé and colleagues published the results obtained with an in vitro set up, testing different adsorption cartridges in comparison to hemofiltration. They nicely confirmed the complex impact on mediator levels and cell capture and phenotype. This is certainly a more systematic approach to better understand the action of such adsorbing cartridges, which has to be developed. PMID:23805829

  12. Clinical evaluation of a fluorescent antibody test for the serological diagnosis of streptococcal endocarditis.

    PubMed Central

    Shanson, D C; Kirk, N; Humphrey, R

    1985-01-01

    Serum fluorescent streptococcal antibody tests were carried out on 71 patients with clinically suspected infective endocarditis, and a final diagnosis of endocarditis was obtained in 46 patients. A serological diagnosis of streptococcal endocarditis was obtained in 10 patients who had persistently negative blood cultures, as fluorescent streptococcal antibody titres equal to or greater than 400 were detected against at least one of four strains of streptococci used as heterologous antigens. There were no false positive fluorescent antibody results with heterologous antigens during tests on 29 patients who had either non-streptococcal endocarditis, a final diagnosis other than endocarditis, or streptococcal sepsis not associated with endocarditis. A negative result with the heterologous antibody test could not, however, exclude a diagnosis of streptococcal endocarditis as six of 11 patients with endocarditis due to Streptococcus viridans or Str bovis confirmed on blood culture had serum fluorescent antibody titres less than 400 against all the heterologous streptococcal antigens tested. Homologous fluorescent streptococcal antibody titres equal to or greater than 400, using the patient's own blood culture isolate as the antigen, were found in the serum samples of 14 of 15 patients with endocarditis caused by viridans streptococci, three patients with enterococcal endocarditis, two patients with endocarditis caused by Str pneumoniae, and one patient with Str bovis endocarditis. In contrast, all five patients who had clinically insignificant streptococcal bacteraemias had serum fluorescent homologous antibody titres of only 100 or less. These results showed that the homologous serum fluorescent streptococcal antibody test could help to decide the clinical importance of a streptococcus which is initially isolated from only one or two of a number of inoculated blood culture bottles. PMID:3881479

  13. Renal Vascular Resistance in Sepsis

    Microsoft Academic Search

    Christoph Langenberg; Rinaldo Bellomo; Clive N. May; Moritoki Egi; Li Wan; Stanislao Morgera

    2006-01-01

    Aims: To assess changes in renal vascular resistance (RVR) in human and experimental sepsis and to identify determinants of RVR. Methods: We performed a systematic interrogation of two electronic reference libraries using specific search terms. Subjects were animals and patients involved in experimental and human studies of sepsis and septic acute renal failure, in which the RVR was assessed. We

  14. Streptococcal Toxic Shock syndrome.

    PubMed

    Krishna, Vidya; Sankaranarayan, Shuba; Sivaraman, Rajakumar Padur; Prabaharan, Krithika

    2014-09-01

    Streptococcal Toxic Shock syndrome (STSS) is a serious complication caused by exotoxins of Group A Streptococcus (GAS). It presents with fulminant shock and rash, is rapidly progressive with Multi-Organ Dysfunction Syndrome (MODS) and requires aggressive therapy with fluids, antibiotics and source control. PMID:24297338

  15. 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-?) 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-? 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 LPS stimulation (P?=?0.009 and P?=?0.005). Moreover, the concentrations of TNF-? and IL-6 in cell culture supernatants were also significantly higher in the subjects with rs4755453GG genotype than in subjects with CG and CC genotype. None of the 14 tagSNPs showed associations with risk of death and severity among ALI cases. Conclusions Our findings indicated that common genetic variants in TRAF6 were significantly associated with susceptibility to sepsis-induced ALI in Chinese Han population. This was the first genetic evidence supporting a role for TRAF6 in ALI. PMID:22901274

  16. 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-?B activity and inhibition of TNF-?, 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. PMID:24075864

  17. The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

    PubMed Central

    Olguner, Çimen Gülben; Ergür, Bekir U?ur; Altekin, Emel; Ta?dö?en, Ayd?n; Duru, Seden; Girgin, Pelin; Gündüz, Kerim; Cilaker M?c?l?, Serap; Güzelda?, Seda; Akku?, Muhammed

    2013-01-01

    In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis. PMID:23476127

  18. Acute-phase protein alpha-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism.

    PubMed

    Mestriner, F L A C; Spiller, F; Laure, H J; Souto, F O; Tavares-Murta, B M; Rosa, J C; Basile-Filho, A; Ferreira, S H; Greene, L J; Cunha, F Q

    2007-12-01

    The reduction of circulating neutrophil migration to infection sites is associated with a poor outcome of severe sepsis. alpha-1-Acid glycoprotein (AGP) was isolated from the sera of severely septic patients by HPLC and acrylamide gel electrophoresis and identified by mass spectrometry. Both the isolated protein and commercial AGP inhibited carrageenin-induced neutrophil migration into the rat peritoneal cavity when administered i.v. at a dose of 4.0 microg per rat (95 pmol per rat). Analysis by intravital microscopy demonstrated that both proteins inhibited the rolling and adhesion of leukocytes in the mesenteric microcirculation. The inhibitory activity was blocked by 50 mg/kg aminoguanidine, s.c., and was not demonstrable in inducible nitric oxide synthase (iNOS) knockout mice. Incubation of AGP with neutrophils from healthy subjects induced the production of NO and inhibited the neutrophil chemotaxis by an iNOS/NO/cyclic guanosine 3,5-monophosphate-dependent pathway. In addition, AGP induced the l-selectin shedding by neutrophils. The administration of AGP to rats with mild cecal ligation puncture sepsis inhibited neutrophil migration and reduced 7-day survival from approximately 80% to 20%. These data demonstrate that AGP, an acute-phase protein, inhibits neutrophil migration by an NO-dependent process and suggest that AGP also participates in human sepsis. PMID:18048324

  19. Requisite Role of the Cholinergic ?7 Nicotinic Acetylcholine Receptor Pathway in Suppressing Gram-Negative Sepsis-Induced Acute Lung Inflammatory Injury

    PubMed Central

    Su, Xiao; Matthay, Michael A.; Malik, Asrar B.

    2010-01-01

    Although activation of the ?7 nicotinic acetylcholine receptor (?7 nAChR) modulates the response to sepsis, the role of this pathway in the development of sepsis-induced acute lung injury (ALI) is not known. In this study, we addressed the contribution of ?7 nAChR in mediating endotoxin- and live Escherichia coli–induced ALI in mice. Because we found that ?7 nAChR+ alveolar macrophages and neutrophils were present in bronchoalveolar lavage and injured lungs of mice, we tested whether acetylcholine released by lung vagal innervation stimulated these effector cells and thereby down-regulated proinflammatory chemokine/cytokine generation. Administration of ?7 nAChR agonists reduced bronchoalveolar lavage MIP-2 production and transalveolar neutrophil migration and reduced mortality in E. coli pneumonia mice, whereas vagal denervation increased MIP-2 production and airway neutrophil accumulation and increased mortality. In addition, ?7 nAChR?/? mice developed severe lung injury and had higher mortality compared with ?7 nAChR+/+ mice. The immunomodulatory cholinergic ?7 nAChR pathway of alveolar macrophages and neutrophils blocked LPS- and E. coli–induced ALI by reducing chemokine production and transalveolar neutrophil migration, suggesting that activation of ?7 nAChR may be a promising strategy for treatment of sepsis-induced ALI. PMID:19949071

  20. Stroke patterns in neonatal group B streptococcal meningitis.

    PubMed

    Hernández, Marta I; Sandoval, Carmen C; Tapia, Jose L; Mesa, Tomas; Escobar, Raul; Huete, Isidro; Wei, Xing-Chang; Kirton, Adam

    2011-04-01

    Neonatal group B streptococcus meningitis causes neurologic morbidity and mortality. Cerebrovascular involvement is a common, poorly studied, and potentially modifiable pathologic process. We hypothesized that imaging patterns of focal brain infarction are recognizable in neonatal group B streptococcal meningitis. A consecutive case series included term neonates with the following: (1) bacterial meningitis, (2) acute group B streptococcal infection (positive cerebrospinal fluid/blood culture), (3) brain magnetic resonance imaging within 14 days, and (4) acute intraparenchymal focal infarctions (restricted diffusion). Lesions within known arterial territories were classified as arterial ischemic stroke. Clinical presentations, investigations, and neurologic outcomes were recorded. Eight newborns (50% female) with focal infarction were identified. Five presented early (<1 week), and all manifested clinical shock and elevated acute-phase reactants. Less than 50% had prenatal group B streptococcal screening, while 2 of 3 screened were negative. Two distinct patterns of focal infarction were identified: (1) deep perforator arterial stroke to basal ganglia, thalamus, and periventricular white matter (7/8, 88%), and (2) superficial injury with patchy, focal infarctions of the cortical surface (6/8, 75%). Outcomes (mean 23.8 months) were poor, with severe disability or death in 6/8 (75%). Recognizable stroke patterns contribute to severe neurologic outcomes and represent a potentially modifiable pathophysiologic process in neonatal group B streptococcal meningitis. PMID:21397170

  1. Mechanical Ventilation and Acute Lung Injury in Emergency Department Patients with Severe Sepsis and Septic Shock: an Observational Study

    PubMed Central

    Fuller, Brian M.; Mohr, Nicholas M.; Dettmer, Matthew; Kennedy, Sarah; Cullison, Kevin; Bavolek, Rebecca; Rathert, Nicholas; McCammon, Craig

    2013-01-01

    Objectives To characterize the use of mechanical ventilation in the emergency department (ED), with respect to ventilator settings, monitoring, and titration; and to determine the incidence of progression to acute lung injury (ALI) after admission, examining the influence of factors present in the ED on ALI progression. Methods This was a retrospective, observational cohort study of mechanically ventilated patients with severe sepsis and septic shock (June 2005 to May 2010), presenting to an academic ED with an annual census of >95,000 patients. All patients in the study (n = 251) were analyzed for characterization of mechanical ventilation use in the ED. The primary outcome variable of interest was the incidence of ALI progression after ICU admission from the ED and risk factors present in the ED associated with this outcome. Secondary analyses included ALI present in the ED and clinical outcomes comparing all patients progressing to ALI versus no ALI. To assess predictors of progression to ALI, statistically significant variables in univariable analyses at a p ? 0.10 level were candidates for inclusion in a bidirectional, stepwise, multivariable logistic regression analysis. Results Lung-protective ventilation was used in 68 patients (27.1%), and did not differ based on ALI status. Delivered tidal volume was highly variable, with a median tidal volume delivered of 8.8 mL/kg ideal body weight (IBW) (IQR 7.8 to 10.0), and a range of 5.2 to 14.6 mL/kg IBW. Sixty-nine patients (27.5%) in the entire cohort progressed to ALI after admission to the hospital, with a mean onset of 2.1 days (SD ± 1 day). Multivariable logistic regression analysis demonstrated that a higher body mass index, higher Sequential Organ Failure Assessment score, and ED vasopressor use were associated with progression to ALI. There was no association between ED ventilator settings and progression to ALI. Compared to patients who did not progress to ALI, patients progressing to ALI after admission from the ED had an increase in mechanical ventilator duration, vasopressor dependence, and hospital length of stay. Conclusions Lung-protective ventilation is uncommon in the ED, regardless of ALI status. Given the frequency of ALI in the ED, the progression shortly after ICU admission, and the clinical consequences of this syndrome, the effect of ED-based interventions aimed at reducing the sequelae of ALI should be investigated further. PMID:23859579

  2. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

    PubMed Central

    2012-01-01

    Introduction To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed. Methods Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety. Results There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial. Conclusions The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI. Trial Registration www.clinicaltrials.gov: NCTNCT00511186 PMID:22269279

  3. 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 ?-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control's 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group's 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform movements and elevated antibodies against D2R; 2) the originally reported group with choreiform movements and elevated anti-D2R antibodies, similar to SC. Increased antibody mediated CaMKII activation was found in both groups and requires further study as a potential biomarker. PMID:25793715

  4. [Surgical sepsis].

    PubMed

    Sganga, Gabriele

    2015-06-11

    Sepsis represents a clinical syndrome following an infection and it is characterized by classical signs of systemic inflammatory response syndrome (SIRS): fever or ipothermia, tachycardia, tachipnea, leucocytosis or leucopenia. There may also be symptoms related to a specific infection such as a cough in pneumonia or burning with urination in a kidney infection, and abdominal pain in an intraabdominal sepsis. Common locations for the primary infection include lungs, brain, urinary tract, skin and soft tissues, and mainly abdominal organs. Patients who develop sepsis have an increased risk of complications and death and face higher healthcare costs and longer treatment. The infection is caused most commonly by bacteria, but can also be by fungi, viruses, or parasites. Severe sepsis is sepsis causing poor organ function or insufficient blood flow; septic shock is the situation with ipotension and/or need for high dosage of inotropes or vasopressors and multiple organ failure syndrome is when multiple organ dysfunction or failure is present. Outcomes depend on the severity of disease with the risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80%. Prevention, early diagnosis, and treatment, both medical (antibiotics) and surgical (source control), together with the prompt intensive care and organ support are crucial to increase survival rate. PMID:25754409

  5. Invasive Group B Streptococcal

    E-print Network

    Paris-Sud XI, Université de

    illness among newborns. Invasive infections in neonates can result in pneumonia, sepsis, or meningitis neonatal invasive infections were determined over an 18-month period in France. Sixty- four percent proportion of EOD and most cases of LOD (3­8). Different studies have suggested that most neonatal invasive

  6. 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

  7. Antepartum use of antibiotics and early-onset neonatal sepsis: The next 4 years

    Microsoft Academic Search

    Craig V. Towers; Gerald G. Briggs

    2002-01-01

    Objective: The purpose of this study was to analyze the incidence of early-onset neonatal sepsis and the presence of antibiotic resistance of the isolated bacteria and its relationship to antibiotic chemoprophylaxis that occurred during the 4 years that followed the publication of the most recent group B streptococcal guidelines. Study Design: A prospective cohort study was performed between January 1,

  8. 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

  9. Group A beta-hemolytic streptococcal infections.

    PubMed

    Pichichero, M E

    1998-09-01

    GABHS is the most common bacterial cause of tonsillopharyngitis, but this organism also produces acute otitis media; pneumonia; skin and soft-tissue infections; cardiovascular, musculoskeletal, and lymphatic infections; bacteremia; and meningitis. Most children and adolescents who develop a sore throat do not have GABHS as the cause; their infection is viral in etiology. Other bacterial pathogens produce sore throat infrequently (e.g., Chlamydia pneumoniae and Mycoplasma pneumoniae), and when they do, other concomitant clinical illness is present. Classic streptococcal tonsillopharyngitis has an acute onset; produces concurrent headache, stomach ache, and dysphagia; and upon examination is characterized by intense tonsillopharyngeal erythema, yellow exudate, and tender/enlarged anterior cervical glands. Unfortunately only about 20% to 30% of patients present with classic disease. Physicians overdiagnose streptococcal tonsillopharyngitis by a wide margin, which almost always leads to unnecessary treatment with antibiotics. Accordingly, use of throat cultures and/or rapid GABHS detection tests in the office is strongly advocated. Their use has been shown to be cost-effective and to reduce antibiotic overprescribing substantially. Penicillin currently is recommended by the American Academy of Pediatrics and American Heart Association as first-line therapy for GABHS infections; erythromycin is recommended for those allergic to penicillin. Virtually all patients improve clinically with penicillin and other antibiotics. However, penicillin treatment failures do occur, especially in tonsillopharyngitis in which 5% to 35% of patients do not experience bacteriologic eradication. Penicillin treatment failures are more common among patients who have been treated recently with the drug. Cephalosporins or azithromycin are preferred following penicillin treatment failures in selected patients as first-line therapy, based on a history of penicillin failures or lack of compliance and for impetigo. GABHS remain exquisitely sensitive to penicillin in vitro. There are several explanations for penicillin treatment failures, but the possibility of copathogen co-colonization in vivo has received the most attention. Treatment duration with penicillin should be 10 days to optimize cure in GABHS infections. A 5-day regimen is possible and approved by the United States Food and Drug Administration for cefpodoxime (a cephalosporin) and azithromycin (a macrolide). Prevention of rheumatic fever is the primary objective for antibiotic therapy of GABHS infections, but a reduction in contagion and faster clinical improvement also can be achieved. Development of streptococcal toxic shock syndrome and necrotizing fasciitis ("flesh-eating bacteria") are rising concerns. The portal of entry for these invasive GABHS strains is far more often skin and soft tissue than the tonsillopharynx. PMID:9745311

  10. Group A Streptococcal Infections

    MedlinePLUS

    ... NIAID clinical studies on ClinicalTrials.gov . Related Links? Bacterial Infections Emerging and Re-emerging Infectious Diseases National Library ... Protocols for Surveillance of Acute Diseases Caused by Streptococcus pyogenes : Pharyngitis, Impetigo, and Invasive Diseases (PDF). The following ...

  11. Acute Acalculous Cholecystitis Associated with Systemic Sepsis and Visceral Arterial Hypoperfusion: A Case Series and Review of Pathophysiology

    Microsoft Academic Search

    John A. McChesney; Patrick G. Northup; Stephen J. Bickston

    2003-01-01

    Acute acalculous cholecystitis (AAC) is marked by a very high mortality rate but its relative rarity makes its features obscure to many physicians. This often contributes to a delayed diagnosis. In this study, we review one center's experience, examine the clinical features of the disorder, and describe the progression of pathological events that culminate in AAC. We performed a 10-year

  12. Neonatal sepsis: progress towards improved outcomes.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2014-01-01

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

  13. 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. PMID:25447700

  14. 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

  15. Current treatment of severe sepsis

    Microsoft Academic Search

    Ismail Cinel; R. Phillip Dellinger

    2006-01-01

    The treatment of severe sepsis includes three essential principles: eradication of the inciting infection using source control\\u000a measures and empiric antibiotics, hemodynamic resuscitation of hypoperfusion to avoid acute life-threatening organ dysfunction,\\u000a and sustained support of organ system dysfunction using interventions that minimize organ injury. Therapy can be divided into\\u000a immediate steps taken to stabilize the patient, followed by more definitive

  16. 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

  17. Severe sepsis mortality prediction with relevance vector machines

    Microsoft Academic Search

    Vicent J. Ribas; Jesus Caballero Lopez; Adolf Ruiz-Sanmartin; Juan Carlos Ruiz-Rodriguez; Jordi Rello; Anna Wojdel; Alfredo Vellido

    2011-01-01

    Sepsis is a transversal pathology and one of the main causes of death at the Intensive Care Unit (ICU). It has in fact become the tenth most common cause of death in western societies. Its mortality rates can reach up to 45.7% for septic shock, its most acute manifestation. For these reasons, the prediction of the mortality caused by sepsis

  18. JAMA Patient Page: Sepsis

    MedlinePLUS

    ... in English and Spanish. Huan J. Chang, MD, MPH, Writer Cassio Lynm, MA, Illustrator Richard M. Glass, ... Death rates are high, with 20% for sepsis, 40% for severe sepsis, and more than 60% for ...

  19. Scarlet Fever: A Group A Streptococcal Infection

    MedlinePLUS

    ... this? Submit Button Past Emails CDC Features Scarlet Fever: A Group A Streptococcal Infection Language: English Español ( ... red rash that feels rough, like sandpaper. Scarlet Fever Podcast A pediatrician explains the cause, treatment and ...

  20. Human pathogenic streptococcal proteomics and vaccine development.

    PubMed

    Cole, Jason N; Henningham, Anna; Gillen, Christine M; Ramachandran, Vidiya; Walker, Mark J

    2008-03-01

    Gram-positive streptococci are non-motile, chain-forming bacteria commonly found in the normal oral and bowel flora of warm-blooded animals. Over the past decade, a proteomic approach combining 2-DE and MS has been used to systematically map the cellular, surface-associated and secreted proteins of human pathogenic streptococcal species. The public availability of complete streptococcal genomic sequences and the amalgamation of proteomic, genomic and bioinformatic technologies have recently facilitated the identification of novel streptococcal vaccine candidate antigens and therapeutic agents. The objective of this review is to examine the constituents of the streptococcal cell wall and secreted proteome, the mechanisms of transport of surface and secreted proteins, and describe the current methodologies employed for the identification of novel surface-displayed proteins and potential vaccine antigens. PMID:21136841

  1. 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 Central

    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. PMID:25364230

  2. Sepsis biomarkers: a review

    PubMed Central

    2010-01-01

    Introduction Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. Methods We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. Results The search retrieved 3370 references covering 178 different biomarkers. Conclusions Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome. PMID:20144219

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

    PubMed Central

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

    2015-01-01

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

  4. Early onset neonatal sepsis

    Microsoft Academic Search

    Betty Chacko; Inderpreet Sohi

    2005-01-01

    Objective: To study the maternal risk factors and clinico-bacteriological profile of early onset sepsis (EOS), in a tertiary care neonatal\\u000a unit.Methods: Relevant data of neonates born during the study period were obtained from their case records. A diagnosis of early onset\\u000a sepsis was made if either clinical sepsis developed within 72 hours of life or if positive blood\\/CSF cultures were

  5. 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

  6. Adult Zebrafish model of streptococcal infection

    PubMed Central

    Phelps, Hilary A.; Runft, Donna L.

    2009-01-01

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

  7. Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak.

    PubMed

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

    2014-04-01

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

  8. Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak

    PubMed Central

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

    2014-01-01

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

  9. Properties and Biological Role of Streptococcal Fratricins

    PubMed Central

    Berg, Kari Helene; Biørnstad, Truls Johan; Johnsborg, Ola

    2012-01-01

    Competence for natural genetic transformation is widespread in the genus Streptococcus. The current view is that all streptococcal species possess this property. In addition to the proteins required for DNA uptake and recombination, competent streptococci secrete muralytic enzymes termed fratricins. Since the synthesis and secretion of these cell wall-degrading enzymes are always coupled to competence development in streptococci, fratricins are believed to carry out an important function associated with natural transformation. This minireview summarizes what is known about the properties of fratricins and discusses their possible biological roles in streptococcal transformation. PMID:22407687

  10. [Pathophysiology of sepsis].

    PubMed

    Uhle, Florian; Lichtenstern, Christoph; Brenner, Thorsten; Weigand, Markus A

    2015-02-01

    Our understanding of the causes and pathophysiological basis of sepsis has been subject to constant change over the last decades. In today's understanding, sepsis is primarily a pathology of the immune system, triggered by an underlying infection but perpetuated by the host's response itself. Thereby, sepsis should not be categorized to be either a sole pro- or anti-inflammatory syndrome, but rather as a variable continuum of overlaying immune mechanisms. While a overshooting immune reaction predominates in early sepsis, this reaction is rapidly compensated, often leading to a immune dysfunction, rendering the host susceptible for secondary infections. This review aims to provide the reader with an overview of the broad molecular mechanisms contributing to the clinical picture of sepsis. PMID:25723606

  11. Biomarkers of sepsis

    PubMed Central

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  12. Sepsis in the neonate.

    PubMed

    Gardner, Sandra L

    2009-03-01

    In the neonatal intensive care unit, critical care nurses who are not advanced practice nurses cannot make the medical diagnosis of infection/sepsis in the neonate. Even so, the critical care nurse has a critical role in dealing with sepsis infection. The nurse must (1) have a high index of suspicion about the risk of infection, (2) be able to recognize septic/infected newborns, (3) report related concerns to the physician or advanced practice nurse, and (4) advocate on behalf of the infant to ensure a timely diagnostic workup and empiric antibiotics. This article is a guide for understanding issues related to sepsis in the neonatal intensive care unit. PMID:19237048

  13. Streptococcal necrotizing fasciitis ("flesh-eating strep infection").

    PubMed

    Schwartz, S N; Roman, D L; Grosserode, M H; Rowland, M D

    1995-11-01

    Streptococcal necrotizing fasciitis, popularized in the lay literature as the "flesh-eating infection" has gained great notoriety. Necrotizing fasciitis may be lethal not only due to its severity, but also because of difficulty in diagnosis during its early stages. Absence of immunity against certain streptococcal proteins increases the severity of infection. Necrotizing fasciitis may be distinguished from other streptococcal skin and soft tissue infections by clinical examination, imaging studies, and biopsy. Treatment requires a combined medical-surgical approach. PMID:8544013

  14. Renal tumor causing haematuria and sepsis.

    PubMed

    Szendrôi, Attila; Rusz, András; Székely, Eszter; Riesz, Péter; Kelemen, Zsolt

    2003-01-01

    A 28 year old female patient developed hematuria in the 32th week of her pregnancy. She was given antibiotic treatment, since a urinary tract infection was suspected. After delivery symptoms of acute pyelonephritis, then sepsis developed, and conservative therapy had no effect. Ultrasound examination showed unusual renal destruction, so nephrectomy was performed. Surgical intervention revealed the presence of an advanced tumor of the kidney, while histological examination confirmed a Bellini duct carcinoma of the kidney. PMID:14688832

  15. Targeting neutrophils in sepsis.

    PubMed

    Sônego, Fabiane; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2014-08-01

    Sepsis continues to have a high mortality rate worldwide. The multi-step effects of this syndrome make it difficult to develop a comprehensive understanding of its pathophysiology and to identify a direct treatment. Neutrophils play a major role in controlling infection. Interestingly, the recruitment of these cells to an infection site is markedly reduced in severe sepsis. The systemic activation of Toll-like receptors and high levels of TNF-? and nitric oxide are involved in the reduction of neutrophil recruitment due to down-regulation of CXCR2 in neutrophils. By contrast, CCR2 is expressed in neutrophils after sepsis induction and contributes to their recruitment to organs far from the infection site, which contributes to organ damage. This review provides an overview of the recent advances in the understanding of the role of neutrophils in sepsis, highlighting their potential as a therapeutic target. PMID:24867165

  16. Group B streptococcal phospholipid causes pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Curtis, Jerri; Kim, Geumsoo; Wehr, Nancy B.; Levine, Rodney L.

    2003-04-01

    Group B Streptococcus is the most common cause of bacterial infection in the newborn. Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung. We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention.

  17. Group B streptococcal neonatal parotitis.

    PubMed

    Dias Costa, Filipa; Ramos Andrade, Daniel; Cunha, Filipa Inês; Fernandes, Agostinho

    2015-01-01

    Acute neonatal parotitis (ANP) is a rare condition, characterised by parotid swelling and other local inflammatory signs. The most common pathogen is Staphylococcus aureus, but other organisms can be implicated. We describe the case of a 13-day-old term newborn, previously healthy, with late-onset group B Streptococcus (GBS) bacteraemia with ANP, who presented with irritability, reduced feeding and tender swelling of the right parotid. Laboratory evaluation showed neutrophilia, elevated C reactive protein and procalcitonin, with normal serum amylase concentration. Ultrasound findings were suggestive of acute parotitis. Empiric antibiotic therapy was immediately started and adjusted when culture results became available. The newborn was discharged after 10?days, with clinical improvement within the first 72?h. Although S. aureus is the most common pathogen implicated in ANP, GBS should be included in the differential diagnosis. PMID:26063107

  18. Rapidly progressing subperiosteal orbital abscess: an unexpected complication of a group-A streptococcal pharyngitis in a healthy young patient

    PubMed Central

    2012-01-01

    Introduction Complications associated to group-A streptococcal pharyingitis include non-suppurative complications such as acute rheumatic fever and glomerulonephritis and suppurative complications such as peritonsillar or retropharyngeal abscess, sinusitis, mastoiditis, otitis media, meningitis, brain abscess, or thrombosis of the intracranial venous sinuses. Case presentation We described a case of a 15-year-old patient with a history of acute pharyngodinia early followed by improvise fever and a progressive formation of a diffuse orbital edema, corneal hyperaemia, diplopia and severe decrease of visual acuity. The patient was surgically treated with functional endoscopic sinus surgery (FESS) after the response of a maxillofacial computed tomography scans that showed a pansinusitis complicated by a left orbital cellulites. Numerous colonies of Streptococcus pyogenes were found in the samples of pus and an antibiotic therapy with meropenem was initiated on the basis of the sensitivity test to antibiotics. The patient was finally discharged with diagnosis of left orbital cellulites with periorbital abscess, endophtalmitis and acute pansinusitis as a consequence of streptococcal pharyngitis. Conclusion The case highlights the possible unusual complication of a group-A streptococcal pharyingitis in a immunocompetent child and the needing of a prompt surgical and medical approach toward the maxillofacial complications associated to the infection. PMID:23067784

  19. Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome*

    PubMed Central

    Bromberg, Zohar; Raj, Nichelle; Goloubinoff, Pierre; Deutschman, Clifford S.; Weiss, Yoram G.

    2009-01-01

    Objective Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes. We hypothesized that this improvement may be modulated, in part, by an early AdHSP-induced attenuation of alveolar type II cell proliferation. Design Laboratory investigation. Setting Hadassah-Hebrew University and University of Pennsylvania animal laboratories. Subjects Sprague-Dawley Rats (250 g). Interventions Lung injury was induced in male Sprague-Dawley rats via cecal ligation and double puncture. At the time of cecal ligation and double puncture, we injected phosphate-buffered saline, AdHSP, or AdGFP (an adenoviral vector expressing the marker green fluorescent protein) into the trachea. Rats then received subcutaneous bromodeoxyuridine. In separate experiments, A549 cells were incubated with medium, AdHSP, or AdGFP. Some cells were also stimulated with tumor necrosis factor-?. After 48 hrs, cytosolic and nuclear proteins from rat lungs or cell cultures were isolated. These were subjected to immunoblotting, immunoprecipitation, electrophoretic mobility shift assay, fluorescent immunohistochemistry, and Northern blot analysis. Measurements and Main Results Alveolar type I cells were lost within 48 hrs of inducing acute respiratory distress syndrome. This was accompanied by alveolar type II cell proliferation. Treatment with AdHSP preserved alveolar type I cells and limited alveolar type II cell proliferation. Heat shock protein 70 prevented overexuberant cell division, in part, by inhibiting hyperphosphorylation of the regulatory retinoblastoma protein. This prevented retinoblastoma protein ubiquitination and degradation and, thus, stabilized the interaction of retinoblastoma protein with E2F1, a key cell division transcription factor. Conclusions Heat shock protein 70-induced attenuation of cell proliferation may be a useful strategy for limiting lung injury when treating acute respiratory distress syndrome if consistent in later time points. PMID:17989570

  20. Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis

    PubMed Central

    Pastores, S

    2003-01-01

    Recent studies have highlighted the close link between activation of the coagulation system and the inflammatory response in the pathophysiology of severe sepsis. The protein C anticoagulant pathway plays an integral part in modulating the coagulation and inflammatory responses to infection. In patients with sepsis, endogenous protein C levels are decreased, shifting the balance toward greater systemic inflammation, coagulation, and cell death. On the basis of a single large randomised phase 3 trial, drotrecogin alfa (activated), a recombinant form of human activated protein C, was recently approved for the treatment of adult patients with severe sepsis and a high risk of death. Since its approval, several questions have been raised regarding the appropriate use of this agent. Given the increased risk of serious bleeding and the high cost of treatment, drotrecogin alfa (activated) should be reserved at this time for the most acutely ill patients with severe sepsis who meet the criteria that were used in the phase 3 trial. PMID:12566544

  1. [Postoperative anaerobic sepsis].

    PubMed

    Fichev, G; Poromanski, I; Marina, M

    1997-01-01

    As shown by clinical practice, postoperative anaerobic sepsis is a complication more common than usually thought of or microbiologically verified. The exceptionally difficult microbiological verification, regardless of the fact that original registered transport media are employed, is the underlying cause of obligate non-spore forming microorganisms from hemoculture being demonstrated in four patients only. In all of them Bacteroides fragilis is isolated and identified. Also, in all patients a fully developed clinical picture of sepsis is present along with the characteristic laboratory septic syndrome constellation as well. After pointing out the difficulties in diagnosing "post-operative anaerobic sepsis", and more particularly its verification, emphasis is laid on the clinical and laboratory symptoms presented by the patients, and on the important role played by the SIRS system, contributing greatly to an adequately oriented clinical thinking. PMID:9739848

  2. Coagulation in sepsis.

    PubMed

    Jagneaux, Tonya; Taylor, David E; Kantrow, Stephen P

    2004-10-01

    Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation. PMID:15486534

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

    PubMed Central

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

    2014-01-01

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

  4. Severe sepsis and septic shock

    PubMed Central

    Schorr, Christa A; Zanotti, Sergio; Dellinger, R Phillip

    2014-01-01

    Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program. PMID:24335487

  5. Newer approaches to the diagnosis of early onset neonatal sepsis

    Microsoft Academic Search

    U K Mishra; S E Jacobs; L W Doyle; S M Garland

    2006-01-01

    Accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time with 100% sensitivity, rather than high specificity, which allows accurate diagnosis and appropriate antimicrobial treatment or which allows antibiotics to be safely withheld in non-infected infants, is desirable. Many potential markers (acute phase reactants, cell surface

  6. Neuroinflammation in sepsis: sepsis associated delirium.

    PubMed

    Piva, Simone; McCreadie, Victoria A; Latronico, Nicola

    2015-01-01

    Sepsis-associated delirium (SAD) is a clinical manifestation of the involvement of the central nervous system (CNS) during sepsis. The purpose of this review is to provide a concise overview of SAD including the epidemiology and current diagnostic criteria for SAD. We present in detail the pathophysiology with regards to blood-brain-barrier breakdown, cytokine activation and neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly discussed. SAD is the most common form of delirium acquired in the ICU (Intensive Care Unit), and is described in about 50% of septic patients. Clinical features include altered level of consciousness, reduced attention, change in cognition and perceptual disturbances. Symptoms can reversible, but prolonged deficits can be observed in older patients. Pathophysiology of SAD is poorly understood, but involves microvascular, metabolic and, not least, inflammatory mechanisms leading to CNS dysfunction. These mechanisms can be different in SAD compared to ICU delirium associated with other conditions. SAD is diagnosed clinically using validated tools such as CAM-ICU (Confusion Assessment Method for the Intensive Care Medicine) or ICDSC (The Intensive Care Delirium Screening Checklist), which have good specificity but low sensitivity. Neuroimaging studies and EEG (Electroencephalography) can be useful complement to clinical evaluation to define the severity of the condition. Prompt diagnosis and eradication of septic foci whenever possible is vital. Preventive measures for SAD in the critically ill patient requiring long-term sedation include maintaining light levels of sedation using non-benzodiazepine sedatives (either propofol or dexmedetomidine). Early mobilization of patients in the ICU is also recommended. Antipsychotic drugs (haloperidol and atypical antipsychotics) are widely used to treat SAD, but firm evidence of their efficacy is lacking. PMID:25567339

  7. 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)

  8. Thromboxane Receptor Mediates Renal Vasoconstriction and Contributes to Acute Renal Failure in Endotoxemic Mice

    E-print Network

    Just, Armin

    , North Carolina Abstract. Sepsis is a major cause of acute renal failure (ARF) and death. Thromboxane A2, multiple-organ failure, and death. Acute renal failure (ARF) is a common complication of sepsis, which (TxA2) may mediate decreases of renal blood flow (RBF) and/or GFR associated with LPS- induced sepsis

  9. 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

  10. SIRS, Sepsis, and MODS

    Microsoft Academic Search

    G. Berlot; A. Tomasini; M. Viviani

    Despite their introduction into clinical practice nearly 10 years ago and the criticisms raised, the ACCP-SCCM definitions\\u000a are still widely used throughout the world and seem to be robust, and should remain as described [9]. The main criticism is\\u000a based on their broadness and consequent lack of specificity, even though signs and symptoms of sepsis

  11. Tissue Oxygenation in Sepsis

    Microsoft Academic Search

    David Brealey; Mervyn Singer

    1999-01-01

    The effect of sepsis on tissue oxygenation is complex and often confusing. This is in part due to the paucity of data from patients (excluding whole-body studies), and in part to the huge variation in laboratory models which have utilised different species, organs and cell lines, different insults, study durations and methods, fluid resuscitation regimens, and end-points. An organ-variable redistribution

  12. Early-Onset Neonatal Sepsis in the Era of Group B Streptococcal Prevention

    Microsoft Academic Search

    Robert S. Baltimore; Sharon M. Huie; James I. Meek; Anne Schuchat; Katherine L. O'Brien

    Objective. To determine whether intra- partum antibiotic prophylaxis for neonatal group B strep- tococcal (GBS) disease has resulted in an increased rate of non-GBS or antibiotic-resistant early-onset invasive neonatal disease. Methods. Maternal and infant chart review of all in- fants with bacteria other than GBS isolated from blood or spinal fluid in 1996 through 1999 in 19 hospitals (repre- senting

  13. 59 FR- Prevention of Group B Streptococcal Disease: A Public Health Perspective

    Federal Register 2010, 2011, 2012, 2013, 2014

    1994-12-15

    ...Centers for Disease Control and Prevention...Group B Streptococcal Diseases: A Public Health Perspective...SERVICES Centers for Disease Control and Prevention...Group B Streptococcal Disease: A Public Health Perspective...Childhood and Respiratory Diseases Branch, Division...

  14. Sepsis guidelines: Clinical practice implications.

    PubMed

    Lehman, Karen D; Thiessen, Kellie

    2015-06-11

    The Surviving Sepsis Campaign 2012 Guidelines offer recommendations for the care of severely septic patients. These guidelines are appraised and summarized briefly in this article, and a case example illustrates the integration process. These guidelines are important for multidisciplinary team members working together toward the common goal of reducing sepsis mortality. PMID:25968978

  15. Combinatorial search for the ligands that specifically recognize the streptococcal collagen-like

    E-print Network

    Wojciechowski, Jerzy

    Combinatorial search for the ligands that specifically recognize the streptococcal collagen. We employed this combinatorial approach to identify ligands specific for the streptococcal collagen plaques 1. Introduction The streptococcal collagen-like proteins, Scl1 and Scl2, are cell surface proteins

  16. 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 documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders. PMID:24106651

  17. Central line sepsis.

    PubMed

    Peterson, Kimberly K

    2003-01-01

    Since 1980, the placement of central venous access devices has become routine, and these catheters have been of great benefit in the treatment of patients with cancer. Unfortunately, central venous catheters have not been without complications. Central line sepsis has been reported to be one of the most frequently occurring complications, and although it is extremely costly to treat, more importantly, this condition is potentially life threatening to patients. Developing strategies that would prevent central line catheter infections has been a continual challenge for healthcare providers. Studies have been conducted on the use of catheters with antiseptic coatings, antimicrobial coatings, impregnated antimicrobial cuffs, prophylactic antibiotic therapy, antibiotic locks, use of antithrombolytics, different exit site dressings, and the use of various disinfectants for cleansing catheter exit sites. Healthcare providers, including oncology nurses, need to be knowledgeable concerning potential sources of infection and factors that may lead to central line sepsis (Chaiyakunapruk, Veenstra, Lipsky, & Saint, 2002; Darouiche et al., 1999; Little & Palmer, 1998; Veenstra, Saint, Saha, Lumley, & Sullivan, 1999). They need to advocate for the use of sterile technique during catheter insertion and aseptic technique when routine maintenance is provided and be aware of the standard treatments for and potential outcomes of central line catheter infections. In addition, oncology nurses should be encouraged to support and participate in controlled, randomized studies that may provide scientific-based practices that decrease the number of catheter-related infections in the future. PMID:12696220

  18. Are pre-existing markers of chronic kidney disease associated with short-term mortality following acute community-acquired pneumonia and sepsis? A cohort study among older people with diabetes using electronic health records

    PubMed Central

    McDonald, Helen I.; Nitsch, Dorothea; Millett, Elizabeth R. C.; Sinclair, Alan; Thomas, Sara L.

    2015-01-01

    Background We aimed to examine whether pre-existing impaired estimated glomerular filtration rate (eGFR) and proteinuria were associated with mortality following community-acquired pneumonia or sepsis among people aged ?65 years with diabetes mellitus, without end-stage renal disease. Methods Patients were followed up from onset of first community-acquired pneumonia or sepsis episode in a cohort study using large, linked electronic health databases. Follow-up was for up to 90 days, unlimited by hospital discharge. We used generalized linear models with log link, normal distribution and robust standard errors to calculate risk ratios (RRs) for all-cause 28- and 90-day mortality according to two markers of chronic kidney disease: eGFR and proteinuria. Results All-cause mortality among the 4743 patients with pneumonia was 29.6% after 28 days and 37.4% after 90 days. Among the 1058 patients with sepsis, all-cause 28- and 90-day mortality were 35.6 and 44.2%, respectively. eGFR <30 mL/min/1.73 m2 was a risk marker of higher 28-day mortality for pneumonia (RR 1.27: 95% CI 1.12–1.43) and sepsis (RR 1.32: 95% CI 1.07–1.64), adjusted for age, sex, socio-economic status, smoking status and co-morbidities. Neither moderately impaired eGFR nor proteinuria were associated with short-term mortality following either infection. Conclusions People with pre-existing low eGFR but not on dialysis are at higher risk of death following pneumonia and sepsis. This association was not explained by existing co-morbidities. These patients need to be carefully monitored to prevent modifiable causes of death. PMID:25605811

  19. Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis

    Microsoft Academic Search

    S Arnon; I Litmanovitz; R H Regev; S Bauer; R Shainkin-Kestenbaum; T Dolfin

    2007-01-01

    Objectives:To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit.Study Design:Full-term infants <72 h of age, who had risk factors and\\/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h

  20. 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

  1. Ventilatory strategies in patients with sepsis and respiratory failure

    Microsoft Academic Search

    Dean R. Hess; B. Taylor Thompson

    2005-01-01

    Patients with sepsis may require mechanical ventilation due to the acute respiratory distress syndrome (ARDS). It has become\\u000a increasingly accepted that mechanical ventilation can contribute to lung injury in these patients. The modern concept of ventilator-induced\\u000a lung injury is described in the context of alveolar over-distention (volutrauma), alveolar de-recruitment (atelectrauma),\\u000a and biochemical injury and inflammation to the lung parenchyma (biotrauma).

  2. A Rare Presentation of Sepsis from Staphylococcus caprae

    PubMed Central

    Kini, Ganesh D; Parris, Addison R; Tang, Jane S

    2009-01-01

    As a coagulase negative Staphylococcus species, S. caprae is not considered as a clinically-significant member, unlike S. epidermidis. In this report, we describe a case of sepsis resulting from S. caprae infection. This relatively young woman was in generally good health and contracted S. caprae most probably during her treatment of an acute pulmonary embolism. The purpose of this report is to raise awareness of this otherwise innocuous staphylococcal species in clinical settings. PMID:19543552

  3. Energy metabolism in acute and chronic renal failure?3

    Microsoft Academic Search

    Bruno Schneeweiss; Wolfgang Graninger; Felix Siockenhuber; Wilfred Drum; Peter Ferenci; Sabine Eichinger; Georg Grimm; Anton N Laggner; Kurt Lenz

    Energy metabolism was measured by mdi- rect calorimetry in 86 patients with various forms of renal fail- ure and in 24 control subjects. In patients with acute renal fail- ure with sepsis, oxygen consumption, carbon dioxide produc- tion, and resting energy expenditure were increased ( P < 0.05). In other groups with renal failure (acute renal failure without sepsis, chronic

  4. Increased Resistin Levels in Intra-abdominal Sepsis

    PubMed Central

    Yilmaz, Tonguç U.; Kerem, Mustafa; Demirta?, Canan Y.; Pasao?lu, Özge; Ta?cilar, Öge; ?akrak, Ömer; Dikmen, Kür?at; Karahan, Tarkan

    2014-01-01

    Objectives: Resistin, a hormone secreted from adipocytes and considered to be a likely cause of insulin resistance, has recently been accepted as a proinflammatory cytokine. This study aimed to determine the correlation between resistin levels in patients with intra-abdominal sepsis and mortality. Methods: Of 45 patients with intra-abdominal sepsis, a total of 35 adult patients were included in the study. This study was undertaken from December 2011 to December 2012 and included patients who had no history of diabetes mellitus and who were admitted to the general surgery intensive care units of Gazi University and Bülent Ecevit University School of Medicine, Turkey. Evaluations were performed on 12 patients with sepsis, 10 patients with severe sepsis, 13 patients with septic shock and 15 healthy controls. The patients’ plasma resistin, interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-?), interleukin-1 beta (IL-1?), procalcitonin, lactate and glucose levels and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were studied daily for the first five days after admission. A correlation analysis of serum resistin levels with cytokine levels and APACHE II scores was performed. Results: Serum resistin levels in patients with sepsis were significantly higher than in the healthy controls (P <0.001). A significant correlation was found between serum resistin levels and APACHE II scores, serum IL-6, IL-1?, TNF-?, procalcitonin, lactate and glucose levels. Furthermore, a significant correlation was found between serum resistin levels and all-cause mortality (P = 0.02). Conclusion: The levels of resistin were significantly positively correlated with the severity of disease and were a possible mediator of a prolonged inflammatory state in patients with intra-abdominal sepsis. PMID:25364554

  5. Nonspecific Removal of Sepsis Mediators

    Microsoft Academic Search

    Xosé Luis Pérez-Fernandez; Joan Sabater Riera; Rafael Mañez

    Sepsis is a growing clinical problem in our society, with an estimated annual incidence rate of above 300 cases per 100,000\\u000a people and mortality that exceeds 30% in those individuals suffering the disease (Esteban et al. 2007; Angus et al. 2001).\\u000a Despite apparent recent successes in the treatment (Bernard et al. 2001), sepsis morbidity and mortality remain very high.\\u000a This

  6. Severe sepsis in older adults.

    PubMed

    Umberger, Reba; Callen, Bonnie; Brown, Mary Lynn

    2015-01-01

    Severe sepsis may be underrecognized in older adults. Therefore, the purpose of this article is to review special considerations related to early detection of severe sepsis in older adults. Normal organ changes attributed to aging may delay early detection of sepsis at the time when interventions have the greatest potential to improve patient outcomes. Systems are reviewed for changes. For example, the cardiovascular system may have a limited or absent compensatory response to inflammation after an infectious insult, and the febrile response and recruitment of white blood cells may be blunted because of immunosenescence in aging. Three of the 4 hallmark responses (temperature, heart rate, and white blood cell count) to systemic inflammation may be diminished in older adults as compared with younger adults. It is important to consider that older adults may not always manifest the typical systemic inflammatory response syndrome. Atypical signs such as confusion, decreased appetite, and unsteady gait may occur before sepsis related organ failure. Systemic inflammatory response syndrome criteria and a comparison of organ failure criteria were reviewed. Mortality rates in sepsis and severe sepsis remain high and are often complicated by multiple organ failures. As the numbers of older adults increase, early identification and prompt treatment is crucial in improving patient outcomes. PMID:26039648

  7. Neonatal Sepsis and Inflammatory Mediators

    PubMed Central

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

    2014-01-01

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

  8. Septic Acute Kidney Injury: New Concepts

    Microsoft Academic Search

    Rinaldo Bellomo; Li Wan; Christoph Langenberg; Clive May

    2008-01-01

    Acute kidney injury (AKI) is a serious condition that affects many ICU patients. The most common causes of AKI in ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite of our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced

  9. Management of the neonate at risk for early-onset Group B streptococcal disease (GBS EOD): new paediatric guidelines in Belgium.

    PubMed

    Mahieu, L; Langhendries, J-P; Cossey, V; De Praeter, C; Lepage, P; Melin, P

    2014-10-01

    Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source of neonatal morbidity and mortality especially in preterm neonates. The identification of neonates with early-onset sepsis is usually based on perinatal risk factors. Clinical signs are aspecific and laboratory tests are not sensitive. Therefore, many clinicians will overtreat at-risk infants. Inappropriate treatment with antibiotics increases the risk for late-onset sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and costs. In 2003, the Belgian Health Council published guidelines for the prevention of perinatal GBS infections. This report presents the Belgian paediatric management guidelines, which have been endorsed by the Belgian and Flemish societies of neonatology and paediatrics. The most imported changes in the 2014 guidelines are the following: recommendations for a lumbar puncture; clarification of normal spinal fluid parameters and blood neutrophil indices corrected for gestation age; specific timing for diagnostic testing after birth; no indication for diagnostic testing in asymptomatic newborns unless additional risk factors; a revised algorithm for management of neonates according to maternal and neonatal risk factors; and premature infants described as those below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the best evidence and on expert opinion when inadequate evidence exists. PMID:25056493

  10. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes

    PubMed Central

    Martin, Greg S

    2012-01-01

    Sepsis has been around since the dawn of time, having been described for more than 2000 years, although clinical definitions are recent. The consensus sepsis definitions have permitted worldwide epidemiological studies of sepsis to be conducted. We now recognize the common nature of sepsis and the consistency of its disease – particularly severe sepsis and septic shock. The incidence of sepsis, severe sepsis and septic shock continues to increase, and although Gram-positive bacterial pathogens remain the most common cause of sepsis, fungal organisms are increasing rapidly. We have made progress over the past half-century in identifying and treating patients with sepsis, and decreasing fatality rates reflect this progress. However, owing to the increasing incidence of sepsis, the number of people who die each year continues to increase. The mortality with sepsis, particularly related to treating organ dysfunction, remains a priority to clinicians worldwide and is deserving of greater public health attention. PMID:22734959

  11. Evaluation of fibronectin and C-reactive protein levels in patients with sepsis: a case-control study.

    PubMed

    Mamani, Mojgan; Hashemi, Seyyed Hamid; Hajilooi, Mehrdad; Saedi, Farnaz; Niayesh, Amin; Fallah, Mohammad

    2012-01-01

    Sepsis is a significant health problem with an estimated 750,000 new cases in the USA annually. It is also the third leading cause of death in developed countries, equaling the number of fatalities from acute myocardial infarction. The high sepsis-related mortalities mean there is an urgent need to improve the diagnosis and management of sepsis patients. The aim of this study was the evaluation of fibronectin and C-reactive protein (CRP) plasma levels in patients with sepsis and other infectious diseases without sepsis. In a case-control study, 90 patients with sepsis and 90 patients with other infectious diseases without sepsis were studied. Serum levels of fibronectin and CRP were measured. The data were analyzed by SPSS version 15. The mean levels of fibronectin in the cases and controls were 288.97±89.10 mg/l and 341.24±110.53 mg/l respectively (P=0.001). The mean levels of CRP in the cases and controls were 89.42±54.05 µg/ml and 27.42±25.89 µg/ml respectively (P<0.001). Concerning the source of infection, the mean CRP levels were significantly higher in septic patients with urinary tract infection, pneumonia, and soft tissue infection (P<0.001). Decreased levels of fibronectin and increased levels of CRP may be considered as reliable diagnostic markers for sepsis. Also, CRP could be a better predictive factor for sepsis than fibronectin. PMID:22837119

  12. Anaphylatoxin formation in sepsis.

    PubMed

    Bengtson, A; Heideman, M

    1988-05-01

    Complement activation and anaphylatoxin formation were studied in 27 septic patients. The patients were treated with antibiotics and high-dose corticosteroids. Blood samples were drawn on admission and every week thereafter. Plasma levels of complement components C1INH, C3, C4, and C5 were low before the start of treatment but were above normal one week later in both successfully and unsuccessfully treated patients. In contrast, plasma levels of anaphylatoxins C3a/C3adesArg and C5a/C5adesArg were elevated on admission. After successful treatment, plasma levels of C3a/C3adesArg and C5a/C5adesArg returned to normal within one week. Nine patients had ongoing sepsis one week after the start of treatment and a persistent rise in anaphylatoxin concentration. They developed multisystem organ failure with respiratory, hepatic, and renal insufficiency. In vitro studies of Escherichia coli incubation in fresh serum indicated a dose-related formation of C3a/C3adesArg and C5a/C5adesArg. High concentrations of methylprednisolone inhibited the anaphylatoxin formation in vitro. PMID:3282496

  13. Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis

    PubMed Central

    Sardinha, J.; Kelly, M. E. M.; Zhou, J.; Lehmann, C.

    2014-01-01

    Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics. The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS) in mice and intestinal microcirculation was assessed through intravital microscopy. We found that HU308 (CB2 receptor agonist) reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice. AM630 (CB2 receptor antagonist) maintained the level of adherent leukocytes induced by LPS but further reduced muscular and mucosal villi FCD. URB597 (FAAH inhibitor) and JZL184 (MAGL inhibitor) both reduced the number of adherent leukocytes in submucosal venules but did not restore the mucosal villi FCD. Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis. PMID:24803745

  14. Journal of Theoretical Biology 230 (2004) 145155 The dynamics of acute inflammation

    E-print Network

    2004-01-01

    acute inflammation due to infection is defined clinically as sepsis and can culminate in organ failure that the clinical condition of sepsis can arise from several distinct physiological states, each of which requires a different treatment approach. Published by Elsevier Ltd. Keywords: Systemic inflammation; Sepsis; Ordinary

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

    PubMed Central

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

    2014-01-01

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

  16. 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

  17. Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture

    Microsoft Academic Search

    Omar J. Cassol-Jr; Clarissa M. Comim; Bruno R. Silva; Fernanda V. Hermani; Larissa S. Constantino; Francine Felisberto; Fabricia Petronilho; Jaime Eduardo C. Hallak; Bruno S. De Martinis; Antonio W. Zuardi; José A. S. Crippa; João Quevedo; Felipe Dal-Pizzol

    2010-01-01

    Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent

  18. 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

  19. 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-?, interleukin-1?, 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. PMID:24983672

  20. Intrauterine Group A Streptococcal Infections are Exacerbated by Prostaglandin E2

    PubMed Central

    Mason, Katie L.; Rogers, Lisa M.; Soares, Elyara M.; Bani-Hashemi, Tara; Downward, John Erb; Agnew, Dalen; Peters-Golden, Marc; Weinberg, Jason B.; Crofford, Leslie J.; Aronoff, David M.

    2013-01-01

    Streptococcus pyogenes(Group A Streptococcus; GAS) is a major cause of severe postpartum sepsis, a reemerging cause of maternal morbidity and mortality worldwide. Immunological alterations occur during pregnancy to promote maternofetal tolerance, which may increase the risk for puerperal infection. Prostaglandin E2 (PGE2) is an immunomodulatory lipid that regulates maternofetal tolerance, parturition, and innate immunity. The extent to which PGE2 regulates host immune responses to GAS infections in the context of endometritis is unknown. To address this, both an in vivo mouse intrauterine (i.u.) GAS infection model and an in vitro human macrophage-GAS interaction model were utilized. In C57BL/6 mice, i.u. GAS inoculation resulted in local and systemic inflammatory responses and triggered extensive changes in the expression of eicosanoid pathway genes. The i.u. administration of PGE2 increased the mortality of infected mice, suppressed local IL-6 and IL-17A levels, enhanced neutrophilic inflammation, reduced uterine macrophage populations, and increased bacterial dissemination. A role for endogenous PGE2 in modulating anti-streptococcal host defense was suggested because mice lacking the genes encoding the microsomal PGE2 synthase-1 or the EP2 receptor were protected from death, as were mice treated with the EP4 receptor antagonist GW627368X. PGE2 also regulated GAS-macrophage interactions. In GAS-infected human THP-1 (macrophage-like) cells, PGE2 inhibited the production of MCP-1 and TNF-? while augmenting IL-10 expression. PGE2 also impaired the phagocytic ability of human placental macrophages, THP-1 cells, and mouse peritoneal macrophages in vitro. Exploring the targeted disruption of PGE2 synthesis and signaling to optimize existing antimicrobial therapies against GAS may be warranted. PMID:23913961

  1. Ras regulates alveolar macrophage formation of CXC chemokines and neutrophil activation in streptococcal M1 protein-induced lung injury.

    PubMed

    Zhang, Songen; Hwaiz, Rundk; Rahman, Milladur; Herwald, Heiko; Thorlacius, Henrik

    2014-06-15

    Streptococcal toxic shock syndrome (STSS) is associated with a high mortality rate. The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, we examined the role of Ras signaling in M1 protein-induced lung injury. Male C57BL/6 mice received the Ras inhibitor (farnesylthiosalicylic acid, FTS) 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. Administration of FTS reduced M1 protein-induced neutrophil recruitment, edema formation and tissue damage in the lung. M1 protein challenge increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Ras activity decreased M1 protein-induced expression of Mac-1 on neutrophils and secretion of CXC chemokines in the lung. Moreover, FTS abolished M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. Ras inhibition decreased chemokine-mediated neutrophil migration in vitro. Taken together, our novel findings indicate that Ras signaling is a potent regulator of CXC chemokine formation and neutrophil infiltration in the lung. Thus, inhibition of Ras activity might be a useful way to antagonize streptococcal M1 protein-triggered acute lung injury. PMID:24704370

  2. Sepsis Alters the Megakaryocyte–Platelet Transcriptional Axis Resulting in Granzyme B–mediated Lymphotoxicity

    PubMed Central

    Freishtat, Robert J.; Natale, JoAnne; Benton, Angela S.; Cohen, Joanna; Sharron, Matthew; Wiles, Andrew A.; Ngor, Wai-Man; Mojgani, Bahar; Bradbury, Margaret; Degnan, Andrew; Sachdeva, Reecha; DeBiase, Lindsay M.; Ghimbovschi, Svetlana; Chow, Matthew; Bunag, Clarice; Kristosturyan, Ervand; Hoffman, Eric P.

    2009-01-01

    Rationale: Sepsis-related mortality results in part from immunodeficiency secondary to profound lymphoid apoptosis. The biological mechanisms responsible are not understood. Objectives: Because recent evidence shows that platelets are involved in microvascular inflammation and that they accumulate in lymphoid microvasculature in sepsis, we hypothesized a direct role for platelets in sepsis-related lymphoid apoptosis. Methods: We studied megakaryocytes and platelets from a murine-induced sepsis model, with validation in septic children, which showed induction of the cytotoxic serine protease granzyme B. Measurements and Main Results: Platelets from septic mice induced marked apoptosis of healthy splenocytes ex vivo. Platelets from septic granzyme B null (?/?) mice showed no lymphotoxicity. Conclusions: Our findings establish a conceptual advance in sepsis: Septic megakaryocytes produce platelets with acutely altered mRNA profiles, and these platelets mediate lymphotoxicity via granzyme B. Given the contribution of lymphoid apoptosis to sepsis-related mortality, modulation of platelet granzyme B becomes an important new target for investigation and therapy. PMID:19136373

  3. 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.

  4. 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…

  5. Decreased serum and pharyngeal antibody levels specific to streptococcal lipoteichoic acid in children with recurrent tonsillitis

    Microsoft Academic Search

    Yuji Yokoyama; Yasuaki Harabuchi

    2002-01-01

    Objective:Streptococcus (S.) pyogenes is a common cause of primary as well as recurrent tonsillitis (RT). Lipoteichoic acid (LTA) has been proposed as a possible candidate for vaccine formulation against streptococcal infections, because LTA is a common constituent of streptococci and the antibody to LTA inhibits bacterial attachment to epithelial cells in vitro. Streptolysin-O and streptococcal whole cell body are highly

  6. Enhanced Expression of Cell-Specific Surface Antigens on Endothelial Microparticles in Sepsis-Induced Disseminated Intravascular Coagulation

    PubMed Central

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

    2015-01-01

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

  7. Streptococcal cell wall arthritis. Passive transfer of disease with a T cell line and crossreactivity of streptococcal cell wall antigens with Mycobacterium tuberculosis.

    PubMed

    DeJoy, S Q; Ferguson, K M; Sapp, T M; Zabriskie, J B; Oronsky, A L; Kerwar, S S

    1989-08-01

    Primary lymph node cells derived from streptococcal cell wall arthritic rats or those derived from adjuvant arthritic rats proliferated in response to cell wall antigens derived from either streptococcal cell walls or those from M. tuberculosis. In addition, two T cell lines have been isolated from lymph nodes of rats during the chronic phase of streptococcal cell wall arthritis. These T cell lines transfered clinical disease to naive syngeneic irradiated recipients, and they proliferated in the presence of cell wall antigens derived from streptococci or antigens derived from Mycobacterium but failed to proliferate in the presence of the 65-kD antigen (containing the sequence TFGLQLELT) derived from Mycobacterium. These observations indicate that T cells play a crucial role in the pathogenesis of streptococcal cell wall arthritis and suggest that antigenic crossreactivity exists between cell walls of group A streptococci and antigens derived from Mycobacterium. The 65-kD Mycobacterium protein is not involved in the observed antigenic crossreactivity. PMID:2502600

  8. Streptococcal cell wall arthritis. Passive transfer of disease with a T cell line and crossreactivity of streptococcal cell wall antigens with Mycobacterium tuberculosis

    PubMed Central

    1989-01-01

    Primary lymph node cells derived from streptococcal cell wall arthritic rats or those derived from adjuvant arthritic rats proliferated in response to cell wall antigens derived from either streptococcal cell walls or those from M. tuberculosis. In addition, two T cell lines have been isolated from lymph nodes of rats during the chronic phase of streptococcal cell wall arthritis. These T cell lines transfered clinical disease to naive syngeneic irradiated recipients, and they proliferated in the presence of cell wall antigens derived from streptococci or antigens derived from Mycobacterium but failed to proliferate in the presence of the 65-kD antigen (containing the sequence TFGLQLELT) derived from Mycobacterium. These observations indicate that T cells play a crucial role in the pathogenesis of streptococcal cell wall arthritis and suggest that antigenic crossreactivity exists between cell walls of group A streptococci and antigens derived from Mycobacterium. The 65-kD Mycobacterium protein is not involved in the observed antigenic crossreactivity. PMID:2502600

  9. Early-Onset Neonatal Sepsis

    PubMed Central

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

    2014-01-01

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

  10. Brachial artery reactivity in patients with severe sepsis: an observational study

    PubMed Central

    2012-01-01

    Introduction Ultrasound measurements of brachial artery reactivity in response to stagnant ischemia provide estimates of microvascular function and conduit artery endothelial function. We hypothesized that brachial artery reactivity would independently predict severe sepsis and severe sepsis mortality. Methods This was a combined case-control and prospective cohort study. We measured brachial artery reactivity in 95 severe sepsis patients admitted to the medical and surgical intensive care units of an academic medical center and in 52 control subjects without acute illness. Measurements were compared in severe sepsis patients versus control subjects and in severe sepsis survivors versus nonsurvivors. Multivariable analyses were also conducted. Results Hyperemic velocity (centimeters per cardiac cycle) and flow-mediated dilation (percentage) were significantly lower in severe sepsis patients versus control subjects (hyperemic velocity: severe sepsis = 34 (25 to 48) versus controls = 63 (52 to 81), P < 0.001; flow-mediated dilation: severe sepsis = 2.65 (0.81 to 4.79) versus controls = 4.11 (3.06 to 6.78), P < 0.001; values expressed as median (interquartile range)). Hyperemic velocity, but not flow-mediated dilation, was significantly lower in hospital nonsurvivors versus survivors (hyperemic velocity: nonsurvivors = 25 (16 to 28) versus survivors = 39 (30 to 50), P < 0.001; flow-mediated dilation: nonsurvivors = 1.90 (0.68 to 3.41) versus survivors = 2.96 (0.91 to 4.86), P = 0.12). Lower hyperemic velocity was independently associated with hospital mortality in multivariable analysis (odds ratio = 1.11 (95% confidence interval = 1.04 to 1.19) per 1 cm/cardiac cycle decrease in hyperemic velocity; P = 0.003). Conclusions Brachial artery hyperemic blood velocity is a noninvasive index of microvascular function that independently predicts mortality in severe sepsis. In contrast, brachial artery flow-mediated dilation, reflecting conduit artery endothelial function, was not associated with mortality in our severe sepsis cohort. Brachial artery hyperemic velocity may be a useful measurement to identify patients who could benefit from novel therapies designed to reverse microvascular dysfunction in severe sepsis and to assess the physiologic efficacy of these treatments. PMID:22390813

  11. Myocardial Dysfunction in Sepsis and Septic Shock

    Microsoft Academic Search

    Anand Kumar; Aseem Kumar; Joseph E. Parrillo

    Sepsis and septic shock represent a major cause of mortality and morbidity in the developed world. The most widely accepted\\u000a estimate of incidence of severe sepsis in the United States is 750,000 cases per year, with 215,000 annual deaths (1). Over the past 40 years, the incidence of sepsis has increased at approximately 8.7% per year (2). During the same

  12. Association of salivary immunoglobulin A antibody and initial mutans streptococcal infection.

    PubMed

    Smith, D J; King, W F; Akita, H; Taubman, M A

    1998-10-01

    We explored the relationship between mutans streptococcal infection and the development of salivary IgA antibody during initial colonization. Repetitive swabbing (n = 292) of the teeth of 33 children revealed that 45% became infected with mutans streptococci between 13 and 36 months of age. In contrast, mutans streptococci could not be detected in 18 children whose last sample was taken at 39-81 months of age (median age = 62 months). During the period of mutans streptococcal infectivity, immunoglobulin A (IgA) antibody to several mutans streptococcal antigens appeared in most children, whether or not infection had been demonstrated. Robust responses to mutans streptococcal components occurred during or shortly after, but not before the period of mutans streptococcal infectivity. No consistent differences were observed among the summarized patterns of response of infected and uninfected groups of children, although the IgA Western blot patterns of individual subjects were often quite distinct. For example, sets of siblings, who would be presumed to be challenged with similar maternal mutans streptococcal clonotypes, were shown to develop qualitatively different salivary IgA responses to mutans streptococcal components. These results support a discrete period for mutans streptococcal infection and may suggest that the level of maternal infection is a factor in the success of infection of the child during this period. The data also suggest that exposure to mutans streptococci is a sufficient condition for robust mucosal IgA responses to mutans streptococcal antigens during the period of infectivity and that these responses may be different, even among siblings. PMID:9807119

  13. Invasive Group B Streptococcal Infection in Infants, Malawi

    PubMed Central

    Bennett, Sally L.; French, Neil; Phiri, Amos J.; Graham, Stephen M.

    2007-01-01

    Group B streptococci (GBS) are a recently identified cause of neonatal sepsis in Malawi. In Queen Elizabeth Central Hospital, Blantyre, Malawi, during May 2004–June 2005, GBS were isolated from routine blood and cerebrospinal fluid cultures from 57 infants. The incidence of early (EOD) and late onset (LOD) invasive GBS disease was 0.92 and 0.89 cases per 1,000 live births, respectively. Sepsis (52%) was the most common manifestation of EOD; meningitis (43%) and sepsis (36%) were the principal manifestations of LOD. The case-fatality rate was 33% overall (38% EOD, 29% LOD). Serotypes Ia and III were responsible for 77% of disease. All isolates were susceptible to penicillin, but 21% were resistant to erythromycin. The rate and manifestations of neonatal GBS disease in Malawi are similar to those in industrialized countries, but the case-fatality rate is higher than in industrialized countries. Effective locally relevant prevention strategies are needed. PMID:17479883

  14. 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

  15. Brazilian Sepsis Epidemiological Study (BASES study)

    Microsoft Academic Search

    Eliézer Silva; Marcelo de Almeida Pedro; Ana Cristina Beltrami Sogayar; Tatiana Mohovic; Carla Silva; Mariano Janiszewski; Ruy Guilherme Rodrigues Cal; Érica de Sousa; Thereza Phitoe Abe; Joel de Andrade; Jorge Dias de Matos; Ederlon Rezende; Murillo Assunção; Álvaro Avezum; Patrícia CS Rocha; Gustavo Faissol Janot de Matos; André Moreira Bento; Alice Corrêa; Paulo Cesar Bastos Vieira; Elias Knobel

    2004-01-01

    INTRODUCTION: Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome METHODS: This is a multicenter observational cohort study performed in

  16. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

    PubMed

    Kangelaris, Kirsten Neudoerffer; Prakash, Arun; Liu, Kathleen D; Aouizerat, Bradley; Woodruff, Prescott G; Erle, David J; Rogers, Angela; Seeley, Eric J; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A; Calfee, Carolyn S

    2015-06-01

    The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. PMID:25795726

  17. Chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.

    PubMed

    Gondorf, Fabian; Berbudi, Afiat; Buerfent, Benedikt C; Ajendra, Jesuthas; Bloemker, Dominique; Specht, Sabine; Schmidt, David; Neumann, Anna-Lena; Layland, Laura E; Hoerauf, Achim; Hübner, Marc P

    2015-01-01

    Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also present new therapeutic approaches for acute inflammatory diseases that do not impair bacterial control. PMID:25611587

  18. Chronic Filarial Infection Provides Protection against Bacterial Sepsis by Functionally Reprogramming Macrophages

    PubMed Central

    Gondorf, Fabian; Berbudi, Afiat; Buerfent, Benedikt C.; Ajendra, Jesuthas; Bloemker, Dominique; Specht, Sabine; Schmidt, David; Neumann, Anna-Lena; Layland, Laura E.; Hoerauf, Achim; Hübner, Marc P.

    2015-01-01

    Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also present new therapeutic approaches for acute inflammatory diseases that do not impair bacterial control. PMID:25611587

  19. Effect of BML?111 on the intestinal mucosal barrier in sepsis and its mechanism of action.

    PubMed

    Liu, Huaizheng; Liu, Zuoliang; Zhao, Shangping; Sun, Chuanzheng; Yang, Mingshi

    2015-08-01

    5(S),6(R)?7?trihydroxymethyl heptanoate (BML?111) is an lipoxin A4 receptor agonist, which modulates the immune response and attenuates hemorrhagic shock?induced acute lung injury. However, the role of BML?111 in sepsis and in the intestinal mucosal barrier are not well understood. Therefore, the present study was designed to investigate the effect of BML?111 on the intestinal mucosal barrier in a rat model of sepsis. Furthermore, the molecular mechanism of action of BML?111 was evaluated. The cecal ligation and puncture-induced rat model of sepsis was constructed, and BML?111 was administered at three different doses. The results revealed that BML?111 suppressed the elevation of the pro?inflammatory cytokines tumor necrosis factor?? and interleukin?6, while enhancing the elevation of the anti?inflammatory cytokine transforming growth factor?? in the intestine. In addition, BML?111 significantly upregulated rat defensin?5 mRNA expression levels and downregulated the induction of cell apoptosis as well as caspase?3 activity in the intestine. All these results demonstrated that BML?111 exerted protective effects on the intestinal mucosal barrier in sepsis. Further, it was indicated that alterations in the expression of toll-like receptor (TLR)2 and TLR4 may be one of the molecular mechanisms underlying the protective effect of BML?111. The present study therefore suggested that BML-111 may be a novel therapeutic agent for sepsis. PMID:25955406

  20. An interprofessional process to improve early identification and treatment for sepsis.

    PubMed

    Palleschi, Maria Teresa; Sirianni, Susanna; O'Connor, Nancy; Dunn, Deborah; Hasenau, Susan M

    2014-01-01

    The course of sepsis is rapid. Patient outcomes improve when sepsis is diagnosed and treated quickly. The clinical goals of the evidence-based bundled strategies from the International consortium Surviving Sepsis Campaign (SSC) include optimizing timeliness in the delivery of care and creating a continuum for sepsis management that runs from the emergency department (ED) to the acute and critical care settings. Successful implementation of processes that integrate sepsis bundles can improve patient mortality and hospital costs. Improving interprofessional education and collaboration are necessary to facilitate the effective use of bundled strategies. An intervention that included interprofessional education resulted in a statistically significant difference between the three phases studied. There was a statistically significant improvement between the phases for lactate completion X(2) = 16.908 (p < .01) after education. Frequency of blood cultures being obtained before antibiotic administration was nearing statistical significance (p < .054). There was an improvement in time to antibiotic administration between phase 2 (182.09 mean average minutes, SD = 234.06) and phase 3 (91.62 mean average minutes, SD = 167.99). PMID:23534854

  1. Oral dexamethasone for the treatment of pain in children with acute pharyngitis: A randomized, double-blind, placebo-controlled trial

    Microsoft Academic Search

    Blake Bulloch; Amin Kabani; Milton Tenenbein

    2003-01-01

    Study objective: We compare oral dexamethasone with placebo for the relief of pain in children with acute pharyngitis. Methods: We performed a prospective, randomized, double-blind, placebo-controlled trial of children aged 5 to 16 years who presented to the emergency department with acute pharyngitis. Children rated their pain on a standardized color analog scale and had a rapid streptococcal antigen detection

  2. Assay of antibody to group A streptococcal carbohydrate by enzyme-linked immunosorbent assay.

    PubMed Central

    Barrett, D J; Triggiani, M; Ayoub, E M

    1983-01-01

    An indirect enzyme-linked immunosorbent assay system for determination of antibody levels to the group A streptococcal cell wall carbohydrate antigen is described. Optimal conditions for antigen preparation, purification, and conjugation to poly-L-lysine for adequate adsorption to the solid phase are presented. Antibody titers of unknown sera were determined by comparison to known reference standard pool sera. A highly significant correlation (p less than 0.0001) was found between enzyme-linked immunosorbent assay antibody titers and antigen-binding capacity in a previously described radioimmunoassay. Utilizing an isotype-specific anti-immunoglobulin reagent and immunoabsorbent-purified antibody to group A streptococcal cell wall carbohydrate antigen, we were able to detect nanogram quantities of antibody by the enzyme-linked immunosorbent assay technique. This system will provide for more generalized use of group A streptococcal cell wall carbohydrate antigen antibody determinations for the study of immune responses after streptococcal infections and their complications. PMID:6355151

  3. Sepsis induced immunosuppression: Implications for secondary infections and complications

    PubMed Central

    Sundar, Krishna M.; Sires, Mazen

    2013-01-01

    Sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis. This review explores the basis for sepsis related immune dysfunction and discusses its clinical implications for the treating intensivist. Recent trends indicate that a significant proportion of septic patients succumb to the complications of secondary infections and chronic critical care illness from the initial bout of sepsis. Therefore care-givers in the ICU need to be aware of the impediments posed by sepsis-related immune dysfunction that can impair recovery in patients with sepsis and contribute to sepsis-related mortality. PMID:24082613

  4. Sepsis after autologous fat grafting.

    PubMed

    Talbot, Simon G; Parrett, Brian M; Yaremchuk, Michael J

    2010-10-01

    Autologous fat grafting is an increasingly popular technique, with numerous examples of excellent results. Adherence to key principles, including sterile technique and low-volume injection throughout layers of tissue, appears to be critical to obtaining good results. Reports of adverse outcomes are infrequent, but several case reports document both infectious and aesthetic complications. This case report represents an extreme complication, including abscess formation, life-threatening sepsis, and residual deformity. It serves as yet another reminder that early adoption of surgical procedures by those without a sound understanding of the underlying principles and techniques can have disastrous consequences. Furthermore, physicians operating on any patient must understand the potential for complications and be able to manage these appropriately when they occur. PMID:20885205

  5. Pediatric sepsis: a case study.

    PubMed

    Umbriaco, Francesco; Andreoni, Colleen

    2013-01-01

    Abdominal pain with vomiting is a common pediatric complaint in the emergency department setting that can lead to a more insidious disease state. The article depicts a case study of a 21-month-old male child presenting with these signs and symptoms that ultimately resulted in a diagnosis of septic shock. The importance of physical assessment, rapid response to findings with time-constrained empirical interventions, the relevance of pediatric sepsis to the provider, the consideration of access to health care, and a holistic approach to treatment of the patient and the family are highlighted. The application and explanation of evidence-based guidelines is also depicted in the management of the patient. PMID:24176830

  6. A case of group A streptococcal meningitis in an adult

    PubMed Central

    Pattullo, Andrew LS; Bow, Eric J

    1993-01-01

    Group A streptococci are an important cause of soft tissue infections but have rarely been reported as the cause of pyogenic meningitis since the advent of antibiotics. A case of group A streptococcal meningitis in an adult is presented along with a review of similar cases reported in the literature. This case serves to illustrate the virulent nature of this pathogen in infections of the meninges, the potential for associated complications, and the need for rapid diagnosis and appropriate treatment. The source of infection in this and many other cases in the literature is the upper respiratory tract. The case presented responded well to antibiotics but resulted in permanent auditory-vestibular dysfunction. PMID:22346453

  7. Extraction of streptococcal type 12 M protein by cyanogen bromide.

    PubMed Central

    Vosti, K L; Williams, W K

    1978-01-01

    Conditions for the release of streptococcal type 12 M protein from whole cells by cyanogen bromide are described; they demonstrated that methionine is not essential to the structural arrangements which account for some of its immunological and biological properties. The released M protein was separated from other proteins by column chromatography with hydroxylapatite. The type-specific molecules which reacted with precipitating antibodies were found only in the 0.3 M eluate, formed zones with mobilities less than 12% of that of the dye front on electrophoresis in the standard acrylamide disc gel system, formed at least four bands in sodium dodecyl sulfate-acrylamide disc gels with molecular weights ranging from 12,000 to 23,000, and stimulated the formation of opsonic antibodies in rabbits. Cyanogen bromide provides a highly specific method for the release of M proteins which should prove particularly useful in analyses of structural-functional relationships among different M proteins. Images PMID:357290

  8. A prospective treatment for sepsis.

    PubMed

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

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

  9. Ensemble Models of Neutrophil Trafficking in Severe Sepsis

    PubMed Central

    Song, Sang O. K.; Hogg, Justin; Peng, Zhi-Yong; Parker, Robert; Kellum, John A.; Clermont, Gilles

    2012-01-01

    A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture)-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about of the treated population) that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental studies to advance understanding of the complex biological response to severe infection, a problem of growing magnitude in humans. PMID:22412365

  10. Streptococcal infection and necrotizing fasciitis--implications for rehabilitation: a report of 5 cases and review of the literature.

    PubMed

    Balbierz, Janet M; Ellis, Katherine

    2004-07-01

    Five cases are presented of patients who were diagnosed with necrotizing fasciitis secondary to (1) hip disarticulation (in a paraplegic patient); (2) tooth abscess with extensive neck dissection, complicated by sepsis and hypotension with resultant dysphagia and ischemic encephalopathy; (3) below-knee amputation, anoxia, and severe debility; (4) emergent above-knee amputation; and (5) percutaneous endoscopic gastrostomy placement. The latter patient developed abdominal and chest wall necrotizing fasciitis that required skin grafting. Four patients were treated in an acute rehabilitation setting and returned home, and the fifth was rehabilitated in a subacute facility. This report emphasizes the importance of carefully monitoring rehabilitation patients, especially those with impaired sensation. PMID:15241775

  11. Sepsis-related stress response: known knowns, known unknowns, and unknown unknowns

    Microsoft Academic Search

    Jinmin Peng; Bin Du

    2010-01-01

    ABSTRACT: The hypothalamic-pituitary-adrenal (HPA) axis response in sepsis remains to be elucidated. Apart from corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol, many other neuroendocrine factors participate in the regulation of HPA stress response. The HPA response to acute and chronic illness exerts a biphasic profile. Tissue corticosteroid resistance may also play an important role. All of these add to the complexity

  12. Genetic Polymorphisms and Sepsis in Premature Neonates

    PubMed Central

    Esposito, Susanna; Zampiero, Alberto; Pugni, Lorenza; Tabano, Silvia; Pelucchi, Claudio; Ghirardi, Beatrice; Terranova, Leonardo; Miozzo, Monica; Mosca, Fabio; Principi, Nicola

    2014-01-01

    Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1? gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p?=?0.03, p?=?0.05 and p?=?0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEF?1 gene) were associated with a significantly reduced risk of developing sepsis (p?=?0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p?=?0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p?=?0.05 and p?=?0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p?=?0.04, p?=?0.04 and p?=?0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens. PMID:25000179

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

    PubMed Central

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

    2012-01-01

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

  14. A new role for statins in sepsis

    PubMed Central

    2013-01-01

    Several studies have shown promising results regarding the use of statins as an adjunctive treatment for sepsis. Most of those studies were retrospective or observational in nature. The ASEPSIS trial has reported that the administration of atorvastatin reduced clinical progression of sepsis but did not improve mortality. These findings are promising and further multicenter trials are needed to confirm these outcomes and to establish whether this class of medications will offer utility in this regard. PMID:23324213

  15. Diaphragmatic fatigue during sepsis and septic shock

    Microsoft Academic Search

    Sophie Lanone; Camille Taillé; Jorge Boczkowski; Michel Aubier

    In the United States sepsis annually affects 700,000 people and accounts for about 210,000 deaths. Respiratory failure has\\u000a long been known to be a frequent occurrence of this pathological condition and to represent a major contributor to the high\\u000a associated mortality [1]. This contribution discusses of the effects of sepsis and septic shock on respiratory muscle function\\u000a and focuses on

  16. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

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

  17. Use of intravenous immunoglobulin therapy in the treatment of septic shock, in particular severe invasive group A streptococcal disease.

    PubMed

    Raithatha, Ajay H; Bryden, Daniele C

    2012-01-01

    Group A streptococcus (GAS) is a ?-hemolytic bacterium often found in the throat and skin. The two most severe clinical manifestations of GAS are streptococcal toxic shock syndrome and necrotizing fasciitis. Intravenous immunoglobulin (IVIg) is a gamma globulin made from purified pooled plasma of thousands of donors, consisting mainly of IgG. We report the case of a 40-year-old man admitted after 2 days of vomiting and severe right-sided chest pain. He was hypotensive with a sinus tachycardia, pyrexial, and vasodilated. The only other positive finding was a swollen and erythematous chest wall. Muscle layer biopsies and blood cultures soon grew extensive GAS, and an initial diagnosis of necrotizing fasciitis was made. The clinical syndrome was of severe septic shock secondary to invasive GAS. The patient quickly deteriorated with a worsening metabolic acidosis. Despite maximal intensive care therapy including fluids, vasoactive agents, and also activated protein C, the patient continued to remain profoundly hypotensive. A decision was made to commence IVIg, with the aim of immunomodulation of the inflammatory cascade seen in sepsis. Over the next 24 hours the patient improved, was extubated 3 days later, and subsequently discharged from hospital after 2 weeks. Although the evidence for the use of IVIg in severe invasive GAS disease is limited, we feel that on reviewing the available literature its use in this case was justified. The limited worldwide supply and high costs, together with a limited evidence base, warrant restricting its use to cases in which conventional therapy has failed. The literature for use of intravenous immunoglobulin in invasive GAS infection will be reviewed in this article. PMID:22557832

  18. Use of intravenous immunoglobulin therapy in the treatment of septic shock, in particular severe invasive group A streptococcal disease

    PubMed Central

    Raithatha, Ajay H.; Bryden, Daniele C.

    2012-01-01

    Group A streptococcus (GAS) is a ?-hemolytic bacterium often found in the throat and skin. The two most severe clinical manifestations of GAS are streptococcal toxic shock syndrome and necrotizing fasciitis. Intravenous immunoglobulin (IVIg) is a gamma globulin made from purified pooled plasma of thousands of donors, consisting mainly of IgG. We report the case of a 40-year-old man admitted after 2 days of vomiting and severe right-sided chest pain. He was hypotensive with a sinus tachycardia, pyrexial, and vasodilated. The only other positive finding was a swollen and erythematous chest wall. Muscle layer biopsies and blood cultures soon grew extensive GAS, and an initial diagnosis of necrotizing fasciitis was made. The clinical syndrome was of severe septic shock secondary to invasive GAS. The patient quickly deteriorated with a worsening metabolic acidosis. Despite maximal intensive care therapy including fluids, vasoactive agents, and also activated protein C, the patient continued to remain profoundly hypotensive. A decision was made to commence IVIg, with the aim of immunomodulation of the inflammatory cascade seen in sepsis. Over the next 24 hours the patient improved, was extubated 3 days later, and subsequently discharged from hospital after 2 weeks. Although the evidence for the use of IVIg in severe invasive GAS disease is limited, we feel that on reviewing the available literature its use in this case was justified. The limited worldwide supply and high costs, together with a limited evidence base, warrant restricting its use to cases in which conventional therapy has failed. The literature for use of intravenous immunoglobulin in invasive GAS infection will be reviewed in this article. PMID:22557832

  19. Inflammatory markers in SIRS, sepsis and septic shock.

    PubMed

    Herzum, I; Renz, H

    2008-01-01

    Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria. PMID:18336272

  20. Severe sepsis mortality prediction with relevance vector machines.

    PubMed

    Ribas, Vicent J; López, Jesús Caballero; Ruiz-Sanmartin, Adolf; Ruiz-Rodríguez, Juan Carlos; Rello, Jordi; Wojdel, Anna; Vellido, Alfredo

    2011-01-01

    Sepsis is a transversal pathology and one of the main causes of death at the Intensive Care Unit (ICU). It has in fact become the tenth most common cause of death in western societies. Its mortality rates can reach up to 45.7% for septic shock, its most acute manifestation. For these reasons, the prediction of the mortality caused by sepsis is an open and relevant medical research challenge. This problem requires prediction methods that are robust and accurate, but also readily interpretable. This is paramount if they are to be used in the demanding context of real-time decision making at the ICU. In this brief paper, such a method is presented. It is based on a variant of the well-known support vector machine (SVM) model and provides an automated ranking of relevance of the mortality predictors. The reported results show that it outperforms in terms of accuracy alternative techniques currently in use, while simultaneously assessing the relative impact of individual pathology indicators. PMID:22254260

  1. Hospital Variations in Severe Sepsis Mortality.

    PubMed

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

    2014-05-01

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

  2. Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes

    PubMed Central

    Soares, Elyara M.; Mason, Katie L.; Rogers, Lisa M.; Serezani, Carlos H.; Faccioli, Lucia H.; Aronoff, David M.

    2012-01-01

    Puerperal sepsis is a leading cause of maternal mortality worldwide. Streptococcus pyogenes (Group A Streptococcus; GAS) is a major etiologic agent of severe postpartum sepsis yet little is known regarding the pathogenesis of these infections. Tissue macrophages provide innate defense against GAS and their actions are highly regulated. The intracellular second messenger cAMP can negatively regulate macrophage actions against GAS. Because leukotriene (LT) B4 has been shown to suppress intracellular cAMP in macrophages, we hypothesized that it could enhance innate defenses against GAS. We assessed the capacity of LTB4 to modulate anti-streptococcal actions of human macrophages, including placental and decidual macrophages and used a novel intrauterine infection model of GAS in mice lacking the 5-lipoxygenase (5LO) enzyme to determine the role of endogenous LTs in host defense against this pathogen. Animals lacking 5LO were significantly more vulnerable to intrauterine GAS infection than wild-type mice and showed enhanced dissemination of bacteria out of the uterus and a more robust inflammatory response compared to wild-type mice. Additionally, LTB4 reduced intracellular cAMP levels via the BLT1 receptor and was a potent stimulant of macrophage phagocytosis and NADPH oxidase-dependent intracellular killing of GAS. Importantly, interference was observed between the macrophage immunomodulatory actions of LTB4 and the cAMP-inducing lipid prostaglandin E2, suggesting that interplay between pro- and anti-inflammatory compounds may be important in vivo. This work underscores the potential for pharmacological targeting of lipid mediator signaling cascades in the treatment of invasive GAS infections. PMID:23325886

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

    PubMed Central

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

    2015-01-01

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

  4. Enhanced Proliferation and Activation of Peripheral Blood Mononuclear Cells in Patients with Psoriasis Vulgaris Mediated by Streptococcal Antigen with Bacterial DNA

    Microsoft Academic Search

    Yi-Hua Cai; Zhi-Yong Lu; Ruo-Fei Shi; Feng Xue; Xiao-Ying Chen; Meng Pan; Wei-Ru Yuan; Han Xu; Wei-Ping Li; Jie Zheng

    2009-01-01

    Streptococcal infection is believed to have an intimate relationship with psoriasis, although the pathogenic role of streptococcal DNA is not fully understood. To gain a clearer understanding of these dynamics, we investigated the effect of streptococcal DNA on lymphocyte proliferation and activation as well as cytokine secretion in psoriasis. Peripheral blood mononuclear cells (PBMCs) from psoriatic patients had higher proliferative

  5. Superantigen-like gene(s) in human pathogenic Streptococcus dysgalactiae, subsp. equisimilis: genomic localisation of the gene encoding streptococcal pyrogenic exotoxin G ( speG dys )

    Microsoft Academic Search

    Svea Sachse; Peter Seidel; Dieter Gerlach; Elisabeth Günther; Jürgen Rödel; Eberhard Straube; Karl-Hermann Schmidt

    2002-01-01

    Streptococcus pyogenes (GAS) causes about 90% of streptococcal human infections while group C (GCS) and G (GGS) streptococci can be pathogenic for different mammalians. Especially the human pathogenic GCS and GGS, Streptococcus dysgalactiae, subsp. equisimilis, account for 5–8% of the human streptococcal diseases like wound infections, otitis media, purulent pharyngitis and also streptococcal toxic shock syndrome. A defined superantigen so

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

    PubMed Central

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

    2015-01-01

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

  7. Gene Expression Profiles Characterize Inflammation Stages in the Acute Lung Injury in Mice

    Microsoft Academic Search

    Isabelle Lesur; Julien Textoris; Béatrice Loriod; Cécile Courbon; Stéphane Garcia; Marc Leone; Catherine Nguyen; Carol Feghali-Bostwick

    2010-01-01

    Acute Lung Injury (ALI) carries about 50 percent mortality and is frequently associated with an infection (sepsis). Life-support treatment with mechanical ventilation rescues many patients, although superimposed infection or multiple organ failure can result in death. The outcome of a patient developing sepsis depends on two factors: the infection and the pre-existing inflammation. In this study, we described each stage

  8. Prediction of Patient's Response to an Acute Inflammation Treatment by Mixture of Experts

    E-print Network

    Obradovic, Zoran

    is the leading cause of death in non-coronary intensive care units in the United States. In practice, clin and death. When accompanied by an infection, the uncontrolled inflammation is defined as sepsis, which to an infection. If inadequately diagnosed and treated, acute inflammation culminates in sepsis, which

  9. Paraoxonase 1 Activity and Survival in Sepsis Patients

    PubMed Central

    ?nal, Volkan; Yamanel, Levent; Ta?k?n, Gürhan; Tapan, Serkan; Cömert, Bilgin

    2015-01-01

    Background: Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High density lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous studies suggested a possible role of decreased PON1 activity or HDL levels in sepsis patients. Aims: The present study was designed to test a hypothesis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. Study Design: Observational study. Methods: Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 activity and cytokine assays (TNF-? and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients’ disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28th day for any cause intra-hospital mortality. Data were statistically analyzed for effects of study parameters on patients’ survival. Results: In total, 85 patients with sepsis were included in the study. The mean age was 65.2±17.9 years and 48 were male; at the end of the 28-day follow-up period, 46 survived. TNF-? (86.9±10.5 vs 118.6±16.4) and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were significantly higher in non-survivors, while PON1 activity (140.7±42.3 vs 66.7±46.6) and HDL-cholesterol levels (43.6±8.1 vs 34.5±8.9) were significantly higher in survivors (p<0.001 for all). TNF-? (r=?0.763) and IL-6 levels (r=?0.947) showed strong negative correlations, PON1 activity (r=0.644) and HDL-cholesterol levels (r=0.477) showed positive correlations with patient survival (p<0.001 for all). Survival estimates significantly favored TNF-? (Log Rank 59.5, p<0.001) and IL-6 levels (Log Rank 53.2, p<0.001) according to PON1 activity (Log Rank 5.4, p<0.03) and HDL-cholesterol levels (Log Rank 8.3, p<0.005). Regression analyses for relative contributions of parameters to survival showed that higher IL-6 levels (t: ?16.489, p<0.001) were the most significant negative factor for survival, and TNF-? levels (t: ?4.417, p<0.001), whereas PON1 activity had a positive effect (t:3.210, p<0.003). Conclusion: The present study showed that although low PON1 activity and HDL-cholesterol levels were related to mortality, higher levels were not found to be as predictive as cytokine levels for survival.

  10. C-reactive protein in the differentiation of adenoviral, Epstein-Barr viral and streptococcal tonsillitis in children

    Microsoft Academic Search

    A. Putto; O. Meurman; O. Ruuskanen

    1986-01-01

    Sixty-two children with febrile exudative tonsillitis were studied to explore whether quantitative measurements of serum C-reactive protein (CRP) are useful in differentiating viral from streptococcal tonsillitis. There were 23 cases of adenoviral tonsillitis, 21 of EB viral tonsillitis and 18 of streptococcal tonsillitis. Measurements of CRP, WBC counts and erythrocyte sedimentation rates (ESR) were not useful in distinguishing viral from

  11. 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

  12. [Neonatal group A streptococcal meningitis and portal vein thrombosis: a casual association?].

    PubMed

    Hmami, F; Oulmaati, A; Mahmoud, M; Boubou, M; Tizniti, S; Bouharrou, A

    2014-09-01

    Invasive group A streptococcal infections are potentially serious. The occurrence in the neonatal period and meningeal location are two unusual situations. The complications reported in the literature vary; we add the risk of thromboembolic events. We report the case of a newborn, admitted to our department at 22 days of life for late neonatal group A streptococcal meningitis and diffuse cerebral infarction lesions. Ultrasound and abdominal CT scan objectified the presence of portal vein thrombosis and cavernoma. Echocardiography, electrocardiogram, as well as coagulation and thrombophilia tests were normal. Progression was marked by the installation of cerebral atrophy and ventricular dilation without the appearance of signs of portal hypertension over 18 months. We therefore concluded in neonatal group A streptococcal meningitis complicated by multiple thrombosis that can be explained by the invasive properties and hypercoagulability characterizing group A beta-hemolytic streptococcus. However, the characteristics of the fetal circulation may explain the possibility of paradoxical cerebral embolism from portal thrombosis. PMID:25089040

  13. Nonspecific complement activation by streptococcal structures. I. Re-evaluation of HLA cytotoxicity inhibition.

    PubMed

    Tauber, J W; Falk, J A; Falk, R E; Zabriskie, J B

    1976-06-01

    A number of experiments have suggested that there is an antigenic relationship between the HLA complex and streptococcal bacterial structures. Using inhibition of cytotoxicity of HLA antisera as our assay system, it was demonstrated that the inhibitory effect on HLA cytotoxicity by streptococcal antigens is, in reality, due to activation and consumption of components of the alternate complement pathway. In addition, antisera prepared against streptococcal membrane antigens had no cytotoxic effect on a large panel of human lymphocytes, nor did these antisera exhibit immunofluorescent staining of lymphocytes directly. These experiments are compatible with our concept that the HLA complex may have evolved through selective evolutionary pressure as a means of escaping bacterial mimicry. PMID:818334

  14. 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

  15. Current concept of abdominal sepsis: WSES position paper

    PubMed Central

    2014-01-01

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

  16. Use of antiplatelet agents in sepsis: a glimpse into the future.

    PubMed

    Akinosoglou, Karolina; Alexopoulos, Dimitrios

    2014-02-01

    As mechanisms of sepsis pathophysiology have been elucidated with time, sepsis may be considered nowadays, as an uncontrolled inflammatory and pro-coagulant response to a pathogen. In this cascade of events, platelets play a key role, via interaction with endothelial cells and modulation of both innate and adaptive immune system. In that manner, inhibition of platelet function could represent a useful tool for attenuating inflammatory response and improving outcomes. Data on current antiplatelet agents, including acetylsalicylic acid, P2Y12 inhibitors and GPIIb/IIIa antagonists, in animal models are promising. Clinical data in patients hospitalized for pneumonia, at risk for acute lung injury, and/or critically ill revealed an association between antiplatelet therapy and reduction in both short-term mortality and prevalence of acute lung injury, as well as, the need for intensive care unit admission, without a concomitant increased bleeding risk. In need of innovative approach in the treatment of sepsis, further prospective, interventional, randomized trials are pivotal to establish potential use of antiplatelet agents in this context. PMID:24103487

  17. 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

  18. Monitoring of the course of sepsis in hematooncological patients by extrapituitary prolactin expression in peripheral blood monocytes.

    PubMed

    Cejková, P; Chromá, V; Cerná, M; Marková, M; Marek, J; Lacinová, Z; Haluzík, M

    2012-12-14

    Our study explored the role of extrapituitary prolactin (PRL) and toll-like receptors (TLR)2 and TLR4 in defense reaction of immune system to bacterial infection. Forty-two patients diagnosed with sepsis were recruited and blood samples were withdrawn after patients' admission to hospital, after the end of acute phase of sepsis and after the sepsis has been resolved, respectively. Seventeen patients died of sepsis; thus, only one sample collected just before death could be processed. PRL and TLR2/4 mRNA levels were measured in CD14+ blood monocytes by QPCR and PRL -1149 G/T SNP genotyped. The TLRs mRNA expression was markedly elevated in all patients groups in comparison to healthy controls mRNA levels; the highest upregulation of monocytic TLR2 in sepsis (16.4 times, P<0.0001) was detected in patients who did not survive septic complications. PRL mRNA expression in monocytes from non-survivors tended to be lower (4.5 fold decrease, P=NS) compared to control levels and it was 6.2 times reduced compared to PRL mRNA expression in second blood sample from survivors (P<0.05). The PRL -1149 G/T SNP had no effect on PRL mRNA response during sepsis. Our data suggest that increased prolactin mRNA expression in monocytes is associated with better outcome and improved survival rate in sepsis with no apparent effect of PRL -1149 G/T SNP on monocytic prolactin response. PMID:22881229

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

    DOEpatents

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

    2009-09-15

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

  20. [Streptococcal gangrene and so-called "flesh-eating bacteria disease". A rare and devastating disease].

    PubMed

    Fernández Guerrero, M L; Martínez Quesada, G; Bernácer Borja, M; Sarasa Corral, J L

    1999-02-01

    Streptococcal gangrene, an unusual form of necrotizing fasciitis with fatal outcome, has been recently rediscovered and has gained popularity with the name "disease of flesh eating bacteria". The incidence of this and other severe diseases caused by Streptococcus pneumoniae has been suggested to be increasing. Only three patients with this disease have been studied at our institution in the last 12 years and in a review of a bacteremic infections caused by beta-hemolytic streptococci a significant increase of these infections was not observed. We report here the clinical and pathological characteristics of streptococcal gangrene as well as a review of the more recent literature. PMID:10216400

  1. Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management)

    PubMed Central

    2013-01-01

    Objective To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing. Design Open adaptive pragmatic parallel group randomised controlled trial. Setting Primary care in United Kingdom. Patients Patients aged ?3 with acute sore throat. Intervention An internet programme randomised patients to targeted antibiotic use according to: delayed antibiotics (the comparator group for analyses), clinical score, or antigen test used according to clinical score. During the trial a preliminary streptococcal score (score 1, n=1129) was replaced by a more consistent score (score 2, n=631; features: fever during previous 24 hours; purulence; attends rapidly (within three days after onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN). Outcomes Symptom severity reported by patients on a 7 point Likert scale (mean severity of sore throat/difficulty swallowing for days two to four after the consultation (primary outcome)), duration of symptoms, use of antibiotics. Results For score 1 there were no significant differences between groups. For score 2, symptom severity was documented in 80% (168/207 (81%) in delayed antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in antigen test group). Reported severity of symptoms was lower in the clinical score group (?0.33, 95% confidence interval ?0.64 to ?0.02; P=0.04), equivalent to one in three rating sore throat a slight versus moderate problem, with a similar reduction for the antigen test group (?0.30, ?0.61 to ?0.00; P=0.05). Symptoms rated moderately bad or worse resolved significantly faster in the clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63) but not the antigen test group (1.11, 0.88 to 1.40). In the delayed antibiotics group, 75/164 (46%) used antibiotics. Use of antibiotics in the clinical score group (60/161) was 29% lower (adjusted risk ratio 0.71, 95% confidence interval 0.50 to 0.95; P=0.02) and in the antigen test group (58/164) was 27% lower (0.73, 0.52 to 0.98; P=0.03). There were no significant differences in complications or reconsultations. Conclusion Targeted use of antibiotics for acute sore throat with a clinical score improves reported symptoms and reduces antibiotic use. Antigen tests used according to a clinical score provide similar benefits but with no clear advantages over a clinical score alone. Trial registration ISRCTN32027234 PMID:24114306

  2. 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%). PMID:25811137

  3. A qualitative study of GP, NP and patient views about the use of rapid streptococcal antigen detection tests (RADTs) in primary care: ‘swamped with sore throats?’

    PubMed Central

    Leydon, Gerry M; McDermott, Lisa; Moore, Mike; Williamson, Ian; Hobbs, F D Richard; Lambton, Tessa; Cooper, Rebecca; Henderson, Hugo; Little, Paul

    2013-01-01

    Objective To explore patient and healthcare professionals’ (HCP) views of clinical scores and rapid streptococcal antigen detection tests (RADTs) for acute sore throat. Design Qualitative semistructured interview study. Setting UK primary care. Participants General practitioners (GPs), nurse practitioners (NPs) and patients from general practices across Hampshire, Oxfordshire and the West Midlands who were participating in the Primary Care Streptococcal Management (PRISM) study. Method Semistructured, face-to-face and phone interviews were conducted with GPs, NPs and patients from general practices across Hampshire, Oxfordshire and the West Midlands. Results 51 participants took part in the study. Of these, 42 were HCPs (29 GPs and 13 NPs) and 9 were patients. HCPs could see a positive role for RADTs in terms of reassurance, as an educational tool for patients, and for aiding inexperienced practitioners, but also had major concerns about RADT use in clinical practice. Particular concerns included the validity of the tests (the role of other bacteria, and carrier states), the tension and possible disconnect with clinical assessment and intuition, the issues of time and resource use and the potential for medicalisation of self-limiting illness. In contrast, however, experience of using RADTs over time seemed to make some participants more positive about using the tests. Moreover, patients were much more positive about the place of RADTs in providing reassurance and in limiting their antibiotic use. Conclusions It is unlikely that RADTs will have a (comfortable) place in clinical practice in the near future until health professionals’ concerns are met, and they have direct experience of using them. The routine use of clinical scoring systems for acute upper respiratory illness also face important barriers related to clinicians’ perceptions of their utility in the face of clinician experience and intuition. PMID:23558734

  4. Polymicrobial Sepsis Increases Susceptibility to Chronic Viral Infection and Exacerbates CD8+ T Cell Exhaustion.

    PubMed

    Condotta, Stephanie A; Khan, Shaniya H; Rai, Deepa; Griffith, Thomas S; Badovinac, Vladimir P

    2015-07-01

    Patients who survive sepsis display suppressed immune functions, often manifested as an increased susceptibility to secondary infections. Recently, using a cecal-ligation and puncture (CLP) model of sepsis, we showed that sepsis induces substantial and long-lasting changes in the available naive CD8(+) T cell repertoire affecting the capacity of the host to respond to newly encountered acute infections. However, the extent to which sepsis changes the host susceptibility to chronic infection and affects CD8(+) T cell responses is currently unknown. In this study, we demonstrate that inbred and outbred mice recovering from a septic event are more susceptible to lymphocytic choriomeningitis virus (LCMV) clone-13 infection exhibited by mortality and viral burden. Primary virus-specific CD8(+) T cells in LCMV clone-13-infected septic mice displayed exacerbated CD8(+) T cell exhaustion illustrated by increased inhibitory molecule expression (e.g., programmed cell death 1, lymphocyte-activation gene 3, and 2B4) and diminished Ag-driven cytokine production (e.g., IFN-?, TNF-?) compared with similarly infected sham-treated mice. Importantly, therapeutic inhibitory molecule dual blockade (anti-PD-L1 and anti-lymphocyte-activation gene 3) increased the number of circulating LCMV-specific CD8(+) T cells, and improved CD8(+) T cell function and pathogen control in chronically infected septic mice. Together, these results illustrate that polymicrobial sepsis compromises the overall health of the host leading to increased vulnerability to chronic infection and exacerbated CD8(+) T cell exhaustion. Collectively, our findings suggest that septic survivors may be more susceptible and at greater risk for developing exhaustible CD8(+) T cells upon encountering a subsequent chronic infection. PMID:25980007

  5. Large dose ketamine inhibits lipopolysaccharide-induced acute lung injury in rats

    Microsoft Academic Search

    J. Yang; W. Li; M. Duan; Z. Zhou; N. Lin; Z. Wang; J. Sun; J. Xu

    2005-01-01

    Background: Sepsis is associated with the highest risk of progression to acute lung injury or the acute respiratory distress syndrome. Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. Our study was designed to investigate the effect of ketamine on the endotoxin-induced acute lung injury in vivo.

  6. Late-onset Streptococcus pasteurianus sepsis in a preterm baby in a neonatal intensive care unit

    PubMed Central

    Tarakç?, Nuriye; Da??, Hatice Türk; U?ur, Ay?e Rüveyda; Tuncer, ?nci; Ta?tekin, Ayhan

    2014-01-01

    Apnea, cyanosis, lethargy and prolongation in capillary filling time developed on the postnatal 37th day in a preterm baby who was born at the 30th gestational week with a birth weight of 1 300 g. Acute phase reactants and immature/total neutrophil count ratio were found to be high. The patient who was diagnosed with sepsis was successfully treated with meropenem which was started empirically. In his blood culture Streptococcus pasteurianus grew. S. pasteurianus is in the subgroup of streptococcus bovis which is one of the D group streptococci and its previous name is S. bovis type II/2. In the literature, there are very few cases of neonatal infection related with this bacterium. As far as we know, this is first case of neonatal sepsis caused by S. pasteurianus in Turkey. In addition, we tried to determine the clinical properties of neonatal infections arising from S. pasteurianus by reviewing the literature.

  7. Procalcitonin in severe acute respiratory syndrome (SARS)

    Microsoft Academic Search

    Ai Ping Chua; Kang Hoe Lee

    2004-01-01

    Objective and methods. The role of procalcitonin (PCT) in severe acute respiratory syndrome (SARS) has not been highlighted so far. We described retrospectively eight cases of sepsis from pneumonia of various microbiological aetiologies including two due to SARS, compared their PCT concentrations and provided further descriptors of SARS as a viral pneumonia.Results. Like any viral pneumonia, patients with SARS had

  8. Idiotypic specificity of rabbit antibodies to streptococcal group polysaccharides.

    PubMed

    Braun, D G; Kelus, A S

    1973-11-01

    Anti-idiotypic antisera against six restricted rabbit streptococcal group specific antibodies have been raised in rabbits matched for allotypes. All these antisera reacted specifically with their homologous idiotypes on double-diffusion tests in agarose gel. In addition, they showed a high incidence of cross-specificities with group-specific hyperimmune sera induced in both closely related and unrelated individuals. These precipitating cross-specificities could be explained for two systems by the interference of rheumatoid factor. Two idiotypic antibody systems have been analyzed in detail; these were restricted antibodies produced in a father and in one of his offspring. The methods employed included binding inhibition of radio-labeled homologous Fab fragments and hemagglutination inhibition with homologous idiotypic coat. The data demonstrated that only related rabbits produced, besides non-cross-reacting antibodies, idiotypically similar antibodies raised to the same antigen. About one-third of the cross-reactive idiotypes showed binding inhibition between 31 and 92%. Inhibition of binding above 50% in the paternal idiotypic system was only achieved by one offspring antibody whereas the F(1) progeny idiotypic system was inhibited to this extent by seven antibodies of related rabbits. In contrast, 87.5% and 91.7% of antibodies of unrelated rabbits were less than 20% inhibitory. Within this study two idiotypically identical antibodies have not been found. This implies that A-variant-specific antibodies of related rabbits which produced antipolysaccharide antibodies were structurally different. Cross-reaction, even if greater than 90% by binding inhibition, appears to involve only part and not all of the variable regions. PMID:4200777

  9. A streptococcal effector protein that inhibits Porphyromonas gingivalis biofilm development.

    PubMed

    Christopher, Aaron B; Arndt, Annette; Cugini, Carla; Davey, Mary E

    2010-11-01

    Dental plaque formation is a developmental process involving cooperation and competition within a diverse microbial community, approximately 70?% of which is composed of an array of streptococci during the early stages of supragingival plaque formation. In this study, 79 cell-free culture supernatants from a variety of oral streptococci were screened to identify extracellular compounds that inhibit biofilm formation by the oral anaerobe Porphyromonas gingivalis strain 381. The majority of the streptococcal supernatants (61 isolates) resulted in lysis of P. gingivalis cells, and some (17 isolates) had no effect on cell viability, growth or biofilm formation. One strain, however, produced a supernatant that abolished biofilm formation without affecting growth rate. Analysis of this activity led to the discovery that a 48 kDa protein was responsible for the inhibition. Protein sequence identification and enzyme activity assays identified the effector protein as an arginine deiminase. To identify the mechanism(s) by which this protein inhibits biofilm formation, we began by examining the expression levels of genes encoding fimbrial subunits; surface structures known to be involved in biofilm development. Quantitative RT-PCR analysis revealed that exposure of P. gingivalis cells to this protein for 1 h resulted in the downregulation of genes encoding proteins that are the major subunits of two distinct types of thin, single-stranded fimbriae (fimA and mfa1). Furthermore, this downregulation occurred in the absence of arginine deiminase enzymic activity. Hence, our data indicate that P. gingivalis can sense this extracellular protein, produced by an oral streptococcus (Streptococcus intermedius), and respond by downregulating expression of cell-surface appendages required for attachment and biofilm development. PMID:20705665

  10. Neutrophil migration under normal and sepsis conditions.

    PubMed

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host. PMID:25567338

  11. Plasma Procalcitonin in Sepsis and Organ Failure

    Microsoft Academic Search

    H Yukioka; G Yoshida; S Kurita; N Kato

    Introduction: Because the use of procalcitonin (PCT) as a marker of bacterial infection has been advocated, this study was carr ied out to determine the usefulness of plasma PCT in the early diagnosis and differentiation of patients with non-infectious systemic infl ammatory response syndrome (SIRS) from those with sepsis, and the relationship between plasma PCT level and severity of organ

  12. Rahnella aquatilis Sepsis in an Immunocompetent Adult

    Microsoft Academic Search

    CHULHUN LUDGERUS CHANG; JOSEPH JEONG; JEONG HWAN SHIN

    1999-01-01

    Rahnella aquatilis is a member of the family Enterobacteri- aceae, and its natural habitat is water. The organism is rarely isolated in clinical specimens. The infections ascribed to this organism are bacteremia (6, 10), sepsis (4), respiratory infec- tion (5), urinary tract infection (1), and wound infection (7) in immunocompromised patients and infective endocarditis (8) in patients with congenital heart

  13. Prediction of neonatal sepsis by thromboelastography

    Microsoft Academic Search

    H. W. Grant; G. P. Hadley

    1997-01-01

    The thromboelastogram (TEG) measures functional defects in coagulation, from fibrin formation through platelet aggregation to fibrinolysis. It is comparable with standard laboratory tests of coagulation; however, it provides additional useful qualitative information. This prospective study documents the TEG findings in 103 neonates: 60 were normal and healthy and provided a reference range; 12 surgical babies had established sepsis, 15 had

  14. Clinical review: Blood purification for sepsis

    PubMed Central

    2011-01-01

    Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis. PMID:21371356

  15. [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

  16. Management of acute paraesophageal hernia

    Microsoft Academic Search

    Mohammed Bawahab; Philip Mitchell; Neal Church; Estifanos Debru

    2009-01-01

    Background  Acute paraesophageal hernia is a surgical emergency presenting with sudden chest or abdominal pain, dysphagia, vomiting, retching\\u000a or significant anemia. Severe cases can present with respiratory failure or systemic sepsis. This can be due to gastric volvulus,\\u000a incarceration, strangulation, severe bleeding or perforation. Traditionally this has been treated with an open surgery. The\\u000a purpose of this study is to develop

  17. Serum procalcitonin levels in the postmortem diagnosis of sepsis.

    PubMed

    Bode-Jänisch, S; Schütz, S; Schmidt, A; Tschernig, T; Debertin, A S; Fieguth, A; Hagemeier, L; Teske, J; Suerbaum, S; Klintschar, M; Bange, F C

    2013-03-10

    Procalcitonin is regarded as a valuable marker for sepsis in living persons and even in post-mortem investigations. At the Institute of Legal Medicine, 25 autopsy cases with suspected bacterial infectious diseases or sepsis were examined using the semi-quantitative PCT-Q(®)-test (B.R.A.H.M.S., Germany) in 2010 and 2011. As controls, 75 cadavers were used for which there was no suspicion of a bacterial infectious disease or sepsis. Femoral blood was cultured from the cases and from controls, and samples from the brain, heart, lungs, liver, spleen and kidneys were examined histologically for findings seen in sepsis. Twelve cases in the sepsis/infectious disease group (48%) were classifiable as sepsis following synopsis of PCT levels, autopsy results, and histopathological and microbiological findings. This study shows that the semi-quantitative PCT-Q(®)-test is a useful supplementary marker in routine autopsy investigations, capable of classifying death as due to sepsis. PMID:23434379

  18. Impact of corticosteroids on experimental meningococcal sepsis in mice.

    PubMed

    Levy, Michaël; Antunes, Ana; Fiette, Laurence; Deghmane, Ala-Eddine; Taha, Muhamed-Kheir

    2015-09-01

    Neisseria meningitidis is responsible for septicemia and meningitis with high fatality that is associated with an excessive inflammatory reaction particularly with hyperinvasive isolates of the clonal complex ST-11 (cc11). However, anti-inflammatory adjuvant treatment remains controversial and difficult to assess in patients. We addressed this topic in a well-defined experimental meningococcal infection in transgenic mice expressing the human transferrin. Mice were infected by intra-peritoneal challenge with bioluminescent serogroup C/cc11 strain. After 3h of infection mice were differentially treated every 6h by saline, amoxicillin alone or amoxicillin and dexamethasone (DXM). Infected mice were scored for clinical status, temperature and weight. Biological markers of inflammation were also quantified. Significant clinical improvement was observed in mice treated with amoxicillin and DXM compared to the two other groups. A significant reduction of the inflammatory reaction assessed by CRP and Lipocalin 2 (two acute phase proteins) was also observed with this treatment. DXM significantly increased blood levels of IL-10 at 6h post-infection. DXM/amoxicillin treated mice, compared to the two other groups, also showed lower levels of TNF-? and lower bacterial blood load assessed by serial dilutions of blood and bioluminescence dynamic imaging. Our results suggest that DXM, added to an appropriate antibiotic therapy, has a beneficial effect on experimental sepsis with a hyperinvasive meningococcal strain in transgenic mice expressing human transferrin. This is most likely due to the reduction of inflammatory response by an early induction of IL-10 cytokine. These data may allow better decision-making to use or not corticotherapy during meningococcal sepsis. PMID:26066898

  19. Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions

    Microsoft Academic Search

    H. Dele Davies; Carol E. Adair; Anne Schuchat; Donald E. Low; Reg S. Sauve; Allison McGeer

    Background: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada. Our aim was to determine physician practices with regard to this condition before and after pub- lication of Canadian guidelines and to monitor concurrent trends in the inci- dence of neonatal GBS disease. Methods: We used repeat cross-sectional

  20. ORIGINAL ARTICLE M1T1 group A streptococcal pili promote epithelial

    E-print Network

    Nizet, Victor

    of the globally disseminated M1T1 GAS clone, the leading agent of both GAS pharyngitis and severe invasive, and skin. However, in contrast to findings reported for group B streptococcal and pneumo- coccal pili, we. Crotty Alexander Department of Medicine, Division of Pulmonary and Critical Care, Massachusetts General

  1. Group A streptococcal infections and tic disorders in an Italian pediatric population

    Microsoft Academic Search

    Francesco Cardona; Graziella Orefici

    2001-01-01

    Background: The relationship between childhood tic disorders and group A streptococcal (GAS) infections has been recently investigated by several research groups, but no systematic evaluation of laboratory indicators of GAS infections has been provided. Objective: The aim of our study was to seek clinical and laboratory evidence of GAS infections in a large population of children affected with tic disorders.

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

    Microsoft Academic Search

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

    2009-01-01

    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

  3. 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…

  4. Alterations of T helper lymphocyte subpopulations in sepsis, severe sepsis, and septic shock: a prospective observational study.

    PubMed

    Li, Jia; Li, Ming; Su, Longxiang; Wang, Huijuan; Xiao, Kun; Deng, Jie; Jia, Yanhong; Han, Gencheng; Xie, Lixin

    2015-06-01

    Circulating lymphocyte number was significantly decreased in patients with sepsis. However, it remains unknown which severity phase (sepsis, severe sepsis, and septic shock) does it develop and what happen on each subpopulation. Eight patients with differing severities of sepsis (31 sepses, 33 severe sepses, and 16 septic shocks) were enrolled. Quantitative real-time polymerase chain reaction (RT-PCR) of Th1, Th2, and Th17; regulatory T (Treg) cell-specific transcription factor T-bet; GATA-3; RORgammat (ROR?t); forkhead box P3 (FOXP3); and IL-17 mRNA were performed, and the enzyme-linked immunosorbent assay (ELISA) was used to detect serum interferon (IFN)-?, IL-4, and IL-10. In this study, the Th1, Th2, Treg transcription factors, and related cytokines IFN-?, IL-4, and IL-10 levels of sepsis and severe sepsis patients in peripheral blood were significantly higher than those of the normal controls. Except for IL-17, the T-bet, GATA-3, and IFN-? levels of septic shock patients were lower than those of sepsis patients. We also observed that the proportions of Th17/Treg in the sepsis and septic shock groups were inversed. From the above, the inflammatory response especially the adaptive immune response is still activated in sepsis and severe sepsis, but significant immunosuppression was developed in septic shock. In addition, the proportion of Th17/Treg inversed may be associated with the illness aggravation of patients with sepsis. PMID:25403265

  5. A comparison study between Candida parapsilosis sepsis and Candida albicans sepsis in preterm infants.

    PubMed

    Hua, Shaodong; Huang, Jieting; Wu, Zhixin; Feng, Zhichun

    2012-01-01

    In this study, we aimed to investigate the clinical characteristics of Candida parapsilosis sepsis in preterm infants. In this retrospective analysis of the clinical data of 11 cases of Candida parapsilosis sepsis and 13 cases of C. albicans sepsis, the two groups were compared for research using one-way analysis of variance (one-way ANOVA), chi2 test, and non-conditional logistic regression analysis. Compared to the C. albicans sepsis group, the C. parapsilosis group demonstrated a significantly lower birth weight (1331.8 +/- 252.41 vs. 1721.2 +/- 589.08) and significantly longer hospital stay (69.909 +/- 20.782 vs. 38.385 +/- 19.923) (t'/t = 2.160, -3.787; p = 0.045, 0.01, respectively); the incidences of retinopathy of prematurity (ROP) (72.7% vs. 30.8%), tienam administration (72.7% vs. 23.1%), pneumothorax, and thoracic closed drainage (27.3% vs. 0) were higher (chi2 = 4.196, 5.916, 4.052; p = 0.041, 0.015, 0.044, respectively). Logistic regression analysis indicated only hospital stay and tienam administration in the regression equation (chi2 = 18.008, p = 0.000). Compared with C. albicans sepsis, an average length hospital stay and administration of tienam are the high-risk factors for C. parapsilosis sepsis. With regard to the other predisposing factors of preterm infant fungal sepsis, there were no differences between the two groups. PMID:23427514

  6. Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis

    Microsoft Academic Search

    Maria Pino-Yanes; Almudena Corrales; Milena Casula; Jesús Blanco; Arturo Muriel; Elena Espinosa; Miguel García-Bello; Antoni Torres; Miguel Ferrer; Elizabeth Zavala; Jesús Villar; Carlos Flores

    2010-01-01

    BackgroundToll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with

  7. Evaluation of radionuclide bone-imaging for the early detection of sepsis in a model of equine neonatal osteomyelitis

    E-print Network

    Taylor, James Rutledge

    1986-01-01

    abscesses. It is well documented today, however, that regions of osteomyelitis can appear as areas of decreased uptake, or "cold spots". ' ' Most likely in the early phase of osteomyelitis, 11, 12, 14 acute inflammation of the bone and marrow causes... of the requirements for the degree of MASTER OF SCIENCE December 1986 Major Subject: Veterinary Med1cal Sciences EVALUATION OF RADIONUCLIOE BONE-IMAGING FOR THE EARLY DETECTION OF SEPSIS IN A MODEL OF EQUINE NEONATAL OSTEOMYELITIS A Thesis by JAMES RUTLEOGE...

  8. Psychiatric Disorders in First-Degree Relatives of Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)

    Microsoft Academic Search

    LORRAINE LOUGEE; SUSAN J. PERLMUTTER; ROB NICOLSON; MARJORIE A. GARVEY; SUSAN E. SWEDO

    2000-01-01

    ObjectiveTo determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and\\/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS).

  9. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis

    Microsoft Academic Search

    A C J Windsor; S Kanwar; A G K Li; E Barnes; J A Guthrie; J I Spark; F Welsh; P J Guillou; J V Reynolds

    1998-01-01

    Background—In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis.Aims—To determine whether TEN can attenuate the acute phase response and improve clinical

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

    PubMed Central

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

    2012-01-01

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

  11. Fulminant sepsis caused by Bacillus cereus in patients with hematologic malignancies: analysis of its prognosis and risk factors.

    PubMed

    Inoue, Daichi; Nagai, Yuya; Mori, Minako; Nagano, Seiji; Takiuchi, Yoko; Arima, Hiroshi; Kimura, Takaharu; Shimoji, Sonoko; Togami, Katsuhiro; Tabata, Sumie; Yanagita, Soshi; Matsushita, Akiko; Nagai, Kenichi; Imai, Yukihiro; Takegawa, Hiroshi; Takahashi, Takayuki

    2010-05-01

    Bacillus cereus is a growing concern as a cause of life-threatening infections in patients with hematologic malignancies. However, the risk factors for patients with unfavorable outcomes have not been fully elucidated. At our institution, we observed the growth of B. cereus in blood culture in 68 patients with (23) or without (45) hematologic malignancies treated from September 2002 to November 2009. We defined a case as having sepsis when more than two blood culture sets were positive for B. cereus or only a single set was positive in the absence of other microorganisms in patients who had definite infectious lesions. We determined 12 of 23 patients with hematologic malignancies as having sepsis, as well as 10 of 45 patients without hematologic malignancies (p = 0.012). Of the 12 patients with hematologic malignancies, four patients with acute leukemia died of B. cereus sepsis within a few days. In our cohort, risk factor analysis demonstrated that a neutrophil count of 0/mm(3), central venous (CV) catheter insertion, and the presence of central nervous system (CNS) symptoms were significantly associated with a fatal prognosis (p = 0.010, 0.010, and 0.010, respectively). Analysis of data from our cohort in conjunction with those from 46 previously reported patients with B. cereus sepsis identified similar risk factors, that is, acute leukemia, extremely low neutrophil count, and CNS symptoms (p = 0.044, 0.004, and 0.002, respectively). These results indicate that appropriate prophylaxis and early therapeutic intervention against possible B. cereus sepsis are crucially important in the treatment of hematologic malignancies. PMID:20367571

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

    PubMed Central

    Takeuchi, Muneyuki; Tachibana, Kazuya

    2015-01-01

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

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

    PubMed

    Saraceni, Christine; Schwed-Lustgarten, Daniel

    2013-12-01

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

  14. The effects of moderate-dose steroid therapy in sepsis: A placebo-controlled, randomized study

    PubMed Central

    Yildiz, Orhan; Tanriverdi, Fatih; Simsek, Serap; Aygen, Bilgehan; Kelestimur, Fahrettin

    2011-01-01

    BACKGROUND: Despite the new developments in sepsis treatment, mortality rate is still high. In this study, we aimed to investigate endocrinologic changes and the effects of moderate dosage steroid treatment in patients with sepsis. METHODS: Fifty-five patients were included in the study. Basal hormonal evaluation and adrenocorticotropin hormone (ACTH) stimulation test were performed within 24 h in all patients. Both groups received standard treatment for sepsis. However, one group (steroid group) was also given intravenous prednisolone (20 mg/day). All-cause mortality was assessed during the first 28 days. RESULTS: Analysis of the findings revealed a 59.3% mortality rate in steroid group compared with a 53.6% mortality rate in placebo group (p = 0.787). Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, and peak cortisol and ACTH levels were significant factors related to mortality. The incidence of adrenal insufficiency (AI) was 10.9% and relative adrenal insufficiency (RAI) 36.4%. It was also found that steroid treatment did not have any effects on the mortality of patients with AI and RAI (p = 0.075 and p = 0.999, respectively). CONCLUSIONS: Moderate-dose steroid therapy has no effect on mortality. Higher basal cortisol and peak cortisol levels were found more reliable mortality indicators compared to RAI. In addition, the study revealed that ACTH level was a significant indicator of mortality. PMID:22973341

  15. Role of KATP channels in sepsis.

    PubMed

    Buckley, James F; Singer, Mervyn; Clapp, Lucie H

    2006-11-01

    Sepsis is an infection-induced inflammatory syndrome responsible for approximately 10% of all deaths worldwide. While pathophysiological mechanisms remain to be fully unravelled, new insights and discoveries are yielding significant improvements in outcome, particularly in the high mortality conditions of shock and multi-organ failure. One potential target is the ATP-sensitive potassium (K(ATP)) channel, an ion channel critical to the cardiovascular stress response. Excessive activation of the vascular channel is now recognised as a major cause of hypotension and vascular hyporesponsiveness to catecholamines in septic shock. Some researchers advocate therapeutic blockade of these channels; however, outside the vasculature, channel opening may actually represent a protective mechanism against cellular damage. In this review we critically examine the role of the K(ATP) channel in sepsis. PMID:16963005

  16. Myocardial Depression in Sepsis and Septic Shock

    Microsoft Academic Search

    A. Kumar; J. E. Parrillo

    Myocardial dysfunction is an important component in the hemodynamic collapse induced by sepsis and septic shock. A series\\u000a of inflammatory cascades triggered by the inciting infection generate circulatory myocardial depressant substances, including\\u000a TNF-?, IL-1?, PAF and lysozyme. Current evidence suggests that septic myocardial depression in humans is characterized by\\u000a reversible biventricular dilatation, decreased systolic contractile function, and decreased response to

  17. Role of KATP channels in sepsis

    Microsoft Academic Search

    James F. Buckley; Mervyn Singer; Lucie H. Clapp

    2006-01-01

    Sepsis is an infection-induced inflammatory syndrome responsible for ?10% of all deaths worldwide. While pathophysiological mechanisms remain to be fully unravelled, new insights and discoveries are yielding significant improvements in outcome, particularly in the high mortality conditions of shock and multi-organ failure. One potential target is the ATP-sensitive potassium (KATP) channel, an ion channel critical to the cardiovascular stress response.

  18. Pathogenesis, therapy, and prevention of meningococcal sepsis

    Microsoft Academic Search

    David S. Stephens; Shanta M. Zimmer

    2002-01-01

    Neisseria meningitidis (meningococcus), an exclusive pathogen of humans, is the cause of sepsis (meningococcemia) and meningitis, often in otherwise\\u000a healthy individuals. Several hundred thousand cases of meningococcal disease occur worldwide each year, a number that is frequently\\u000a accentuated by epidemic outbreaks. In recent years, significant advances, fueled by new molecular approaches and genome sequencing\\u000a projects, have improved our understanding of

  19. Emergency department antimicrobial considerations in severe sepsis.

    PubMed

    Green, Robert S; Gorman, Sean K

    2014-11-01

    Severe sepsis and septic shock are common problems in the emergency department patient population and require expert clinical skill by members of the emergency department team to maximize optimal patient outcomes. Although various guidelines have been developed for the management of these patients, issues around antimicrobial-related considerations in critically ill patients require further evidence-based attention. In this review article, important factors related to patient illness, microorganism, timing of antimicrobial administration, and source control are discussed. PMID:25441038

  20. The protein C pathway and sepsis.

    PubMed

    Della Valle, Patrizia; Pavani, Giulia; D'Angelo, Armando

    2012-03-01

    After the discovery of the key components of the protein C (PC) pathway a beneficial effect on survival of the infusion of activated protein C (APC) in animal models of sepsis was demonstrated, leading to the development of recombinant human activated protein C (rh-APC) as a therapeutic agent. It soon became clear that rather than the anticoagulant and profibrinolytic activities of APC, its anti-inflammatory and cytoprotective properties played a major role in the treatment of patients with severe sepsis. Such properties affect the response to inflammation of endothelial cells and leukocytes and are exerted through binding of APC to at least five receptors with intracellular signaling. The main APC protective mechanism involves binding of the Gla-domain to the endothelial protein C receptor (EPCR) and cleavage of protease activated receptor 1 (PAR-1), eliciting suppression of proinflammatory cytokines synthesis and of intracellular proapoptotic pathways and activation of endothelial barrier properties. However, thrombin cleaves PAR-1 with much higher catalytic efficiency, followed by pro-inflammatory, pro-apoptotic and barrier disruptive intracellular signaling, and it is unclear how APC can exert a protective activity through the cleavage of PAR-1 when thrombin is also present in the same environment. Interestingly, in endothelial cell cultures, PAR-1 cleavage by thrombin results in anti-inflammatory and barrier protective signaling provided occupation of EPCR by the PC gla-domain, raising the possibility that the beneficial effects of rh-APC might be recapitulated in vivo by administration of h-PC zymogen to patients with severe sepsis. Recent reports of h-PC infusion in animal models of sepsis support this hypothesis. PMID:22154246

  1. Implications of the new international sepsis guidelines for nursing care.

    PubMed

    Kleinpell, Ruth; Aitken, Leanne; Schorr, Christa A

    2013-05-01

    Sepsis is a serious worldwide health care condition that is associated with high mortality rates, despite improvements in the ability to manage infection. New guidelines for the management of sepsis were recently released that advocate for implementation of care based on evidence-based practice for both adult and pediatric patients. Critical care nurses are directly involved in the assessment of patients at risk for developing sepsis and in the treatment of patients with sepsis and can, therefore, affect outcomes for critically ill patients. Nurses' knowledge of the recommendations in the new guidelines can help to ensure that patients with sepsis receive therapies that are based on the latest scientific evidence. This article presents an overview of new evidence-based recommendations for the treatment of adult patients with sepsis, highlighting the role of critical care nurses. PMID:23635930

  2. Mesenchymal stem cells as a therapeutic tool to treat sepsis

    PubMed Central

    Lombardo, Eleuterio; van der Poll, Tom; DelaRosa, Olga; Dalemans, Wilfried

    2015-01-01

    Sepsis is a clinical syndrome caused by a deregulated host response to an infection. Sepsis is the most frequent cause of death in hospitalized patients. Although knowledge of the pathogenesis of sepsis has increased substantially during the last decades, attempts to design effective and specific therapies targeting components of the derailed host response have failed. Therefore, there is a dramatic need for new and mechanistically alternative therapies to treat this syndrome. Based on their immunomodulatory properties, adult mesenchymal stem or stromal cells (MSCs) can be a novel therapeutic tool to treat sepsis. Indeed, MSCs reduce mortality in experimental models of sepsis by modulating the deregulated inflammatory response against bacteria through the regulation of multiple inflammatory networks, the reprogramming of macrophages and neutrophils towards a more anti-inflammatory phenotype and the release of anti-microbial peptides. This report will review the current knowledge on the effects of MSC treatment in preclinical experimental small animal models of sepsis. PMID:25815121

  3. Mesenchymal stem cells as a therapeutic tool to treat sepsis.

    PubMed

    Lombardo, Eleuterio; van der Poll, Tom; DelaRosa, Olga; Dalemans, Wilfried

    2015-03-26

    Sepsis is a clinical syndrome caused by a deregulated host response to an infection. Sepsis is the most frequent cause of death in hospitalized patients. Although knowledge of the pathogenesis of sepsis has increased substantially during the last decades, attempts to design effective and specific therapies targeting components of the derailed host response have failed. Therefore, there is a dramatic need for new and mechanistically alternative therapies to treat this syndrome. Based on their immunomodulatory properties, adult mesenchymal stem or stromal cells (MSCs) can be a novel therapeutic tool to treat sepsis. Indeed, MSCs reduce mortality in experimental models of sepsis by modulating the deregulated inflammatory response against bacteria through the regulation of multiple inflammatory networks, the reprogramming of macrophages and neutrophils towards a more anti-inflammatory phenotype and the release of anti-microbial peptides. This report will review the current knowledge on the effects of MSC treatment in preclinical experimental small animal models of sepsis. PMID:25815121

  4. Gene expression profiling in sepsis: timing, tissue, and translational considerations.

    PubMed

    Maslove, David M; Wong, Hector R

    2014-04-01

    Sepsis is a complex inflammatory response to infection. Microarray-based gene expression studies of sepsis have illuminated the complex pathogen recognition and inflammatory signaling pathways that characterize sepsis. More recently, gene expression profiling has been used to identify diagnostic and prognostic gene signatures, as well as novel therapeutic targets. Studies in pediatric cohorts suggest that transcriptionally distinct subclasses might account for some of the heterogeneity seen in sepsis. Time series analyses have pointed to rapid and dynamic shifts in transcription patterns associated with various phases of sepsis. These findings highlight current challenges in sepsis knowledge translation, including the need to adapt complex and time-consuming whole-genome methods for use in the intensive care unit environment, where rapid diagnosis and treatment are essential. PMID:24548661

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

    Microsoft Academic Search

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

    2009-01-01

    Background and ObjectivesRhabdomyolysis is often associated with sepsis and gram positive bacterial pathogens are reported to be the most frequent cause of sepsis induced rhabdomyolysis. We report the pattern of infecting bacterial pathogens and associated causal factors in a South-Indian cohort.Design, Setting, Participants & MeasurementsRetrospective cohort study of adult patients with community acquired bacterial sepsis complicated by rhabdomyolysis from March

  6. Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

    Microsoft Academic Search

    Anthony Flynn; Bhalaghuru Chokkalingam Mani; Paul J. Mather

    2010-01-01

    Cardiac dysfunction is a well-recognized complication of severe sepsis and septic shock. Cardiac dysfunction in sepsis is\\u000a characterized by ventricular dilatation, reduction in ejection fraction and reduced contractility. Initially, cardiac dysfunction\\u000a was considered to occur only during the “hypodynamic” phase of shock. But we now know that it occurs very early in sepsis\\u000a even during the “hyperdynamic” phase of septic

  7. 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. PMID:25466727

  8. [Group B streptococcal infections in adults, excluding genital infections].

    PubMed

    Peirotti, M G; Gonzalez, S E; Littvik, A M; Vacaflor, L; Kassar, M A; Moreno, S; Bottiglieri, M T

    2002-01-01

    Group B streptococcus (GBS) or Streptococcus agalactiae is recognized as a mayor cause of neonatal meningitis, sepsis and infections during pregnancy. However, in recent years there have been several reports concerning GBS infections in non pregnant adult population, specially in immunocompromised hosts and in patients with severe underlying diseases such as diabetes mellitus and cancer. We report a series of 45 cases which occurred in nonpregnant adult population during a period of two years. The average age was 50.8 years and most patients (38/44) had one or more risk factors: diabetes mellitus was the most significant underlying disease. The most frequent infection localization was skin and soft tissues followed by urinary tract infection. Several isolated cases of pneumonia, bacteremia, endocarditis, endometritis and peritonitis were observed. GBS infections should no longer be exclusively considered as perinatal and peripartum events. New clinical presentations are arising in non pregnant adult population with special incidence in immunocompromised hosts. We are obliged to keep this in mind and remember that SGB may be a possible etiologic agent for infections, particularly in skin and soft tissues of diabetic patients. PMID:12600008

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

    PubMed Central

    2011-01-01

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

  10. The Outcome of Polymicrobial Sepsis is Independent of T and B Cells

    PubMed Central

    Bosmann, Markus; Russkamp, Norman F.; Patel, Vinay R.; Zetoune, Firas S.; Sarma, J. Vidya; Ward, Peter A.

    2011-01-01

    The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene-1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1?/? mice were atrophic and completely devoid of CD3+ T cells and CD19+ B cells. Wildtype mice and Rag-1?/? mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wildtype and Rag-1?/? mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in BUN and LDH levels. Survival curves of wildtype and Rag-1?/? mice after CLP were superimposable, with 35% survival in the wildtype group and 27% survival in the Rag-1?/? group, respectively (not significant, P=0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wildtype and Rag-1?/? mice 8 h after CLP or sham surgery. Compared to sham surgery mice, the highest mediator levels were observed for G-CSF, KC, IL-6, MCP-1 and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1?/? mice compared to wildtype mice. In conclusion, the absence of T and B cells in the CLP model employed does not appear to affect the acute outcome of severe sepsis. PMID:21701414

  11. The outcome of polymicrobial sepsis is independent of T and B cells.

    PubMed

    Bosmann, Markus; Russkamp, Norman F; Patel, Vinay R; Zetoune, Firas S; Sarma, J Vidya; Ward, Peter A

    2011-10-01

    The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1 mice were atrophic and completely devoid of CD3 T cells and CD19 B cells. Wild-type mice and Rag-1 mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wild-type and Rag-1 mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in blood urea nitrogen and lactate dehydrogenase levels. Survival curves of wild-type and Rag-1 mice after CLP were superimposable, with 35% survival in the wild-type group and 27% survival in the Rag-1 group, respectively (not significant, P = 0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wild-type and Rag-1 mice 8 h after CLP or sham surgery. Compared with sham surgery mice, the highest mediator levels were observed for granulocyte colony-stimulating factor, keratinocyte chemoattractant, IL-6, monocyte chemotactic protein 1, and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1 mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis. PMID:21701414

  12. Late-onset Leclercia adecarboxylata sepsis in a premature neonate.

    PubMed

    Nelson, M U; Maksimova, Y; Schulz, V; Bizzarro, M J; Gallagher, P G

    2013-09-01

    The epidemiology, etiology and outcome of neonatal sepsis are changing over time. While monitoring longitudinal trends in neonatal sepsis in our institution, we encountered a case of late-onset neonatal sepsis due to Leclercia adecarboxylata. A Gram-negative rod previously not encountered in the clinical setting, L. adecarboxylata has recently emerged as a human pathogen, primarily in immunosuppressed patients. This report describes the clinical and laboratory features of this case of late-onset L. adecarboxylata sepsis, and reviews significant features of infection associated with this emerging pathogen. PMID:23986093

  13. Haemophilus influenzae: a forgotten cause of neonatal sepsis?

    PubMed

    Dobbelaere, A; Jeannin, P; Bovyn, T; Ide, L

    2015-06-01

    Due to the introduction of the conjugate vaccine against serotype b, neonatal sepsis caused by Haemophilus influenzae became very rare. There is little data in Belgium concerning the prevalence of H. influenzae early onset neonatal sepsis and articles about neonatal sepsis and H. influenzae published in the last decade are scarce. We report two invasive infections with a non-typeable H. influenzae. These cases show that neonatal sepsis caused by non-typeable H. influenzae may be underestimated and we believe that there is need for a better registration of this kind of infection. PMID:25443773

  14. Gingivitis and Toothbrushes: Potential Roles in Viridans Streptococcal Bacteraemia

    Microsoft Academic Search

    H. F. Kennedy; D. Morrison; D. Tomlinson; B. E. S. Gibson; J. Bagg; C. G. Gemmell

    2003-01-01

    We report a case of Streptococcus oralis bacteraemia in a paediatric neutropenic patient with acute myeloid leukaemia whose predominant form of oral compromise was severe gingivitis, rather than mucositis. By phenotypic and genotypic analyses, the strain of S. oralis from blood culture was indistinguishable from an isolate from his mouth, suggesting that gingivitis may have provided a portal of entry

  15. Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1).

    PubMed

    Baker, Matthew D; Gendlina, Inessa; Collins, Carleen M; Acharya, K Ravi

    2004-09-01

    Streptococcal pyrogenic exotoxin A (SpeA1) is a bacterial superantigen associated with scarlet fever and streptococcal toxic shock syndrome (STSS). SpeA1 is found in both monomeric and dimeric forms, and previous work suggested that the dimer results from an intermolecular disulfide bond between the cysteines at positions 90 of each monomer. Here, we present the crystal structure of the dimeric form of SpeA1. The toxin crystallizes in the orthorhombic space group P212121, with two dimers in the crystallographic asymmetric unit. The final structure has a crystallographic R-factor of 21.52% for 7248 protein atoms, 136 water molecules, and 4 zinc atoms (one zinc atom per molecule). The implications of SpeA1 dimer on MHC class II and T-cell receptor recognition are discussed. PMID:15295110

  16. The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme

    PubMed Central

    Persson, Helena; Vindebro, Reine

    2013-01-01

    The human bacterial pathogen Streptococcus pyogenes has developed a broad variety of virulence mechanisms to evade the actions of the host immune defense. One of the best-characterized factors is the streptococcal cysteine protease SpeB, an important multifunctional protease that contributes to group A streptococcal pathogenesis in vivo. Among many suggested activities, SpeB has been described to degrade various human plasma proteins, including immunoglobulins (Igs). In this study, we show that SpeB has no Ig-cleaving activity under physiological conditions and that only Igs in a reduced state, i.e., semimonomeric molecules, are cleaved and degraded by SpeB. Since reducing conditions outside eukaryotic cells have to be considered nonphysiological and IgG in a reduced state lacks biological effector functions, we conclude that SpeB does not contribute to S. pyogenes virulence through the proteolytic degradation of Igs. PMID:23569114

  17. Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?

    Microsoft Academic Search

    Helgi Valdimarsson; Barbara S. Baker; Ingileif Jónsdóttir; Ann Powles; Lionel Fry

    1995-01-01

    Psoriasis is a T-cell-mediated disease that can be triggered by infection with group A ?-haemolytic streptococci. It is proposed that psoriatic skin lesions are initiated by exotoxin-activated T cells, and persist because of specific T cells that react both with streptococcal M protein and a skin determinant, possibly a variant of keratin. As discussed here by Helgi Valdimarsson and colleagues,

  18. Bacterial Vaginosis and Group B Streptococcal Colonization and Preterm Delivery in a Low-Risk Population

    Microsoft Academic Search

    George Daskalakis; Angeliki Papapanagiotou; Spyros Mesogitis; Nikolaos Papantoniou; Konstantinos Mavromatis; Aris Antsaklis

    2006-01-01

    Objective: To evaluate the relationship between bacterial vaginosis (BV) and group B streptococcal (GBS) colonization in the 2nd trimester of pregnancy and preterm delivery. Methods: 1,197 pregnant women between 22 and 25 weeks’ gestation had a high vaginal swab for assessment of BV and GBS. Exclusion criteria were: previous preterm delivery, or mid-trimester abortion or termination of pregnancy, multiple gestation,

  19. Serum opacity factor promotes group A streptococcal epithelial cell invasion and virulence

    Microsoft Academic Search

    Anjuli M. Timmer; Sascha A. Kristian; Vivekanand Datta; Arthur Jeng; Christine M. Gillen; Mark J. Walker; Bernard Beall; Victor Nizet

    2006-01-01

    Summary Serum opacity factor (SOF) is a bifunctional cell surface protein expressed by 40-50% of group A streptococcal (GAS) strains comprised of a C-terminal domain that binds fibronectin and an N-terminal domain that mediates opacification of mammalian sera. The sof gene was recently discov- ered to be cotranscribed in a two-gene operon with a gene encoding another fibronectin-binding protein, sfbX.

  20. Evaluation of a rapid method for the detection of streptococcal group A antigen directly from throat swabs.

    PubMed Central

    Venezia, R A; Ryan, A; Alward, S; Kostun, W A

    1985-01-01

    Throat swabs from 196 pediatric patients were processed by a direct extraction-latex agglutination method (Group A Strep Direct Antigen Identification Test [DAI]) that detects group A streptococci in the specimen. The method requires a 45-min enzymatic extraction period at 37 degrees C and a 4-min reaction period with antibody-linked latex particles. The results were compared with those of the culture and fluorescent antibody methods and the clinical presentation of the patient for pharyngitis. Ninety-three percent of the specimens resulted in agreement by all tests, and 28% were culture positive for group A streptococci. Compared with the culture method, the DAI had a sensitivity and a specificity of 83% and 99%, respectively. The positive predictive values were 98% versus the culture method and 93% versus the fluorescent antibody method, whereas the negative predictive values were 94% versus both other methods. Of the 14 discrepant results when both clinical presentation of an acute pharyngitis and the test results were compared, the culture method provided the best correlation. An additional 64 specimens were processed by the DAI and another direct extraction-latex agglutination method (Culturette Ten-Minute Group A Strep ID Test), and the results were compared with those of the culture method. This group had a 40.6% culture isolation rate for group A streptococci. The sensitivity and specificity of the DAI and Strep ID methods versus the culture method were 81 and 100%, and 77 and 97%, respectively. These results indicate that the DAI is accurate for diagnosing group A streptococcal pharyngitis directly from throat swabs. However, negative results in the presence of a symptomatic patient must be confirmed by standard culture techniques. PMID:3884656

  1. Enteral feeding increases sepsis in infants with short bowel syndrome

    Microsoft Academic Search

    Thomas R Weber

    1995-01-01

    Sepsis secondary to bacterial translocation is common in infants with short bowel syndrome (SBS). Although early feeding is advocated to enhance adaptation in SBS, the effects of feeding on sepsis in SBS patients have not been examined. Twenty-one infants and children (aged 2 months to 3 years) with SBS (<80 cm small bowel length) from a variety of causes (15

  2. Ignác Semmelweis and the Etiology of Fetal and Neonatal Sepsis

    Microsoft Academic Search

    Tonse N K Raju

    1999-01-01

    It is well known that Ignác Semmelweis discovered the etiology and prophylaxis of puerperal sepsis. However, few historians have focused on his understanding of the pathophysiology of fetal and neonatal sepsis. Based on several key observations, Semmelweis realized that puerperal fever (also known as “childbed fever”) could be transmitted to the fetus, especially when the first stage of labor was

  3. Cefotaxime for treatment of neonatal sepsis and meningitis

    Microsoft Academic Search

    Carla M. Odio

    1995-01-01

    Neonatal sepsis is a clinical syndrome characterized by systemic signs and symptoms, and bacteremia during the first month of life. The incidence is relatively low (one to eight cases\\/1000 live births), yet the risk of mortality is approximately 25%. Meningitis in the neonate is usually a sequela of bacteremia; however, it is discussed with neonetal sepsis, because they commonly share

  4. Effects of lornoxicam on the physiology of severe sepsis

    Microsoft Academic Search

    Dilek Memi?; Beyhan Karamanl?o?lu; Alparslan Turan; Onur Koyuncu; Zafer Pamukçu

    2004-01-01

    INTRODUCTION: The purpose of the present study was to evaluate the effects of intravenous lornoxicam on haemodynamic and biochemical parameters, serum cytokine levels and patient outcomes in severe sepsis. METHODS: A total of 40 patients with severe sepsis were included, and were randomly assigned (20 per group) to receive either lornoxicam (8 mg administered intravenously every 12 hours for six

  5. Clinically-oriented therapies in sepsis: a review

    Microsoft Academic Search

    Marc-Jacques Dubois; Jean-Louis Vincent

    2000-01-01

    Our insight of the sepsis response has evolved to encompass not only the pro-inflammatory but also an anti-inflammatory reaction following infection. Clinical trials have been designed to target either bacterial products, endotoxin in particular, or mediators involved in the sepsis response, but until recently the majority of them have given unfavorable results. In this article, we provide a scope of

  6. Early Cutaneous Alterations in Experimental Sepsis by Pseudomonas aeruginosa

    Microsoft Academic Search

    Haritini Petropoulou; Evangelos J. Giamarellos-Bourboulis; Nicolaos Kavatzas; Alexandros Stratigos; Maria Mouktaroudi; Theodoros Adamis; Fotini Baziaka; Andreas D. Katsambas; Nicolaos G. Stavrianeas

    2004-01-01

    Background: To evaluate whether histopathologic findings of skin in sepsis by Pseudomonas aeruginosa correlate with the clinical course. Methods: Histological alterations after bacterial challenge by one susceptible (A) and two multidrug-resistant isolates (B and C) of P. aeruginosa were studied in 18 rabbits. Sepsis was induced by the intravenous infusion of 1 × 108 CFU by a catheter in the

  7. What is the role of renin inhibition during rat septic conditions: preventive effect of aliskiren on sepsis-induced lung injury.

    PubMed

    Akpinar, Erol; Halici, Zekai; Cadirci, Elif; Bayir, Yasin; Karakus, Emre; Calik, Muhammet; Topcu, Atilla; Polat, Beyzagul

    2014-10-01

    Sepsis and sepsis-related acute lung injuries (ALIs) are one of the main causes of death among hospitalized patients. Renin-angiotensin-aldosterone system (RAAS) has been reported to have role in sepsis. However, there is no study on aliskiren, a renin inhibitor, on sepsis-induced ALI. We aimed to investigate the potential protective effects of aliskiren in a model of cecal ligation and puncture (CLP)-induced lung injury. The rats were separated into five groups: sham, CLP, CLP?+?aliskiren 50 mg/kg (per orem (p.o.)), CLP?+?aliskiren 100 mg/kg (p.o.), and sham?+?aliskiren 100 mg/kg (p.o.). CLP model was applied via ligation of cecum and two punctures. After experiment, biochemical, molecular, and pathologic examinations were performed on lung and serum samples of rats. In our study, sepsis decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in lung tissues of rats while aliskiren increased the SOD and GSH and decreased MDA. Also, sepsis caused a significant increase in pro-inflammatory cytokine levels (TNF-?, IL-1?, and IL-6) while aliskiren administration decreased these cytokines. Also, aliskiren administration at high dose protected lungs in pathologic evaluation. As a result of RAAS inhibition, aliskiren caused a decrease in serum angiotensin II level and increase in serum renin level. In light of these observations, we can suggest that the therapeutic administration of aliskiren prevented oxidative stress changes and cytokine changes and also protected lung tissues during CLP-induced sepsis by changing status of RAAS. PMID:25005757

  8. Broncho-pleuropericardial fistula complicating staphylococcal sepsis

    PubMed Central

    Arab, Abeer A.; Kattan, Maan A.; Alyafi, Walid A.; Alhashemi, Jamal A.

    2011-01-01

    This is a rare case of broncho-pleuropericardial fistula in a 12-year-old female who presented with fever, painful joint swelling, and pleural and pericardial effusion secondary to disseminated methicillin-sensitive Staphylococcus aureus infection. The pleural and pericardial effusion were drained, however, air leak was observed from both tubes and was synchronous with mechanical inspiration. A broncho-pleuropericardial fistula was suspected and confirmed with computed tomography. This case report demonstrated that disseminated S. aureus bacteremia could result in broncho-pleuropericardial fistula. The ability of disseminated staphylococcal infection to produce pnemopericardium should be added to the list of other complications associated with disseminated staphylococcal sepsis. PMID:22144936

  9. Protective Effect of Carbon Monoxide Donor Compounds in Endotoxin-Induced Acute Renal Failure

    Microsoft Academic Search

    Shunji Shiohira; Takumi Yoshida; Satsuki Shirota; Ken Tsuchiya; Kosaku Nitta

    2007-01-01

    Background: Sepsis is a common cause of acute renal failure (ARF) in clinical practice. However, the precise mechanism of endotoxin-induced ARF is not fully understood. There have been several reports that inhalation of carbon monoxide (CO) gas could be protective against acute rejection in intestine, lung, and kidney transplantation. Thus, we investigated the direct effect of CO in an experimental

  10. Acute nephrotoxic and obstructive injury primes the kidney to endotoxin-driven cytokine\\/chemokine production

    Microsoft Academic Search

    R A Zager; A C M Johnson; S Y Hanson; S Lund

    2006-01-01

    Gram-negative sepsis is a frequent complication in patients with acute renal failure. This study tested whether acute tubular injury, for example, induced by cisplatin (CP) or urinary tract obstruction, enhances renal cytokine responses to endotoxin (lipopolysaccharide (LPS)), potentially contributing to tissue damage. CD-1 mice were subjected to CP or vehicle injection. After 24 or 72 h, LPS or its vehicle

  11. 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

  12. Therapeutic potential of HMGB1-targeting agents in sepsis

    PubMed Central

    Wang, Haichao; Zhu, Shu; Zhou, Rongrong; Li, Wei; Sama, Andrew E.

    2008-01-01

    Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens but also initiate an inflammatory response upon recognition of pathogen-associated molecular patterns (PAMPs). The prevailing theories of sepsis as a dysregulated inflammatory response, as manifested by excessive release of inflammatory mediators such as tumour necrosis factor and high-mobility group box 1 protein (HMGB1), are supported by extensive studies employing animal models of sepsis. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss the therapeutic potential of several HMGB1-targeting agents (including neutralising antibodies and steroid-like tanshinones) in experimental sepsis. PMID:18980707

  13. Gamma globulin, Evan's blue, aprotinin A PLA 2 inhibitor, tetracycline and antioxidants protect epithelial cells against damage induced by synergism among streptococcal hemolysins, oxidants and proteinases: relation to the prevention of post-streptococcal sequelae and septic shock 1 Supported by an endowment fund contributed by the late Dr. S.M. Robbins of Cleveland, Ohio, USA. 1

    Microsoft Academic Search

    Isaac Ginsburg; Milu Sadovnic

    1998-01-01

    An in vitro model was employed to study the potential role of streptococcal extra-cellular products, rich in streptolysin O, in cellular injury as related to streptococcal infections and post-streptococcal sequelae. Extra-cellular products (EXPA) rich in streptolysin O were isolated from type 4, group A hemolytic streptococci grown in a chemostat, in a synthetic medium. EXPA induced moderate cytopathogenic changes in

  14. Obstetrician preferences for prenatal strategies to reduce early-onset group B streptococcal infection in neonates: A population-based survey

    Microsoft Academic Search

    Anna Petrova; John C. Smulian; Cande V. Ananth

    2002-01-01

    Objective: In light of a recent proposal to legislate group B streptococcal prevention strategies in New Jersey, this study examined obstetrician preferences and practices toward group B streptococcal prevention strategies in neonates. Study Design: This was a mail survey of American College of Obstetricians and Gynecologists Fellows in New Jersey. Physician characteristics, existing guideline preferences, and reported actual group B

  15. Abrogation of streptococcal pyrogenic exotoxin B-mediated suppression of phagocytosis in U937 cells by Cordyceps sinensis mycelium via production of cytokines

    Microsoft Academic Search

    Chih-Feng Kuo; Cheng-Chih Chen; Chiou-Feng Lin; Ming-Shiou Jan; Robert Y. Huang; Yueh-Hsia Luo; Woei-Jer Chuang; Chia-Chin Sheu; Yee-Shin Lin

    2007-01-01

    Streptococcal pyrogenic exotoxin B (SPE B) is a virulent factor in group A streptococcal infection. We previously showed that SPE B reduced phagocytosis in human monocytic U937 cells. Here we show that the mycelium extract of Cordyceps sinensis (CS), a Chinese immunomodulatory herbal medicine, increased phagocytosis in U937 cells. Neither heat nor trypsin pretreatment prevented CS extract from causing this

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

    PubMed

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

    2015-08-01

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

  17. Toward the Early Diagnosis of Neonatal Sepsis and Sepsis-Like Illness Using Novel Heart Rate Analysis

    Microsoft Academic Search

    M. Pamela Griffin; J. Randall Moorman

    2001-01-01

    Background and Objective. Abrupt clini- cal deterioration because of sepsis is a major cause of morbidity and mortality in neonates, and earlier diagno- sis should improve therapy of this potentially cata- strophic illness. In practice, clinical signs and laboratory data have not been perceived as sensitive or specific for early stages of sepsis. Because heart rate characteristics (HRC) are abnormal

  18. Antibiotic dosing in critically ill patients with acute kidney injury

    Microsoft Academic Search

    Rachel F. Eyler; Bruce A. Mueller

    2011-01-01

    A common cause of acute kidney injury (AKI) is sepsis, which makes appropriate dosing of antibiotics in these patients essential. Drug dosing in critically ill patients with AKI, however, can be complicated. Critical illness and AKI can both substantially alter pharmacokinetic parameters as compared with healthy individuals or patients with end-stage renal disease. Furthermore, drug pharmacokinetic parameters are highly variable

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  1. Sepsis-induced immunoparalysis: mechanisms, markers, and treatment options.

    PubMed

    Hamers, L; Kox, M; Pickkers, P

    2015-04-01

    Sepsis remains the leading cause of death in the ICU. Considering the key role of the immune system in sepsis, immunomodulation represents an attractive target for adjunctive therapy. Until recently, clinical trials focused on suppression of the immune system, but this approach failed to improve sepsis outcome. Recent advances in the understanding of sepsis have led to the view that not the initial hyperinflammatory state, but rather a profoundly suppressed state of the immune system, called sepsis-induced immunoparalysis, accounts for the majority of sepsis-related deaths. Immunoparalysis results in ineffective clearance of septic foci, and renders the septic patient more vulnerable to secondary infections, as well as reactivation of latent infections. Several mechanisms behind immunoparalysis have been recognised. Furthermore, due to recognition of the importance of immunoparalysis, immunostimulatory treatment is emerging as a possible adjunctive treatment for sepsis. As such, identification of patients suffering from immunoparalysis using biomarkers is of utmost importance to guide immunostimulatory treatment. In this review, an short overview of the concept of immunoparalysis is presented, while the main focus is on potential biological markers of immunoparalysis and promising immunostimulatory therapeutic agents. The challenging heterogeneity of septic patients in respect to immunomodulatory advances will be discussed, and recommendations for future research are provided. PMID:24878876

  2. Sustained expression of lipocalin-2 during polymicrobial sepsis.

    PubMed

    Vazquez, Daniel E; Niño, Diego F; De Maio, Antonio; Cauvi, David M

    2015-07-01

    Sepsis is a major healthcare problem and a leading cause of death worldwide. There is no dependable diagnosis, and treatment for this condition remains mainly supportive. The etiology of sepsis is related to an overwhelming inflammatory response. In this regard, the antimicrobial protein lipocalin-2 (Lcn2) has been associated with several inflammatory conditions, but its contribution to polymicrobial sepsis is unclear. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP), and Lcn2 mRNA levels and protein expression were measured in liver and lung tissues. We observed that Lcn2 expression was robustly induced in liver and lung of C57BL/6?J (B6) mice, and remained elevated during the stage of innate immune dysfunction observed in sepsis. This response was different in A/J mice, suggesting a contribution of the genetic background, probably due to differences in IL-10 expression between these two mouse strains. Indeed, IL-10 was found to regulate Lcn2 expression in both primary and J774A.1 macrophages. Thus, Lcn2 expression is highly regulated during CLP-induced sepsis, suggesting that this antimicrobial protein could have a role as a potential biomarker for the diagnosis of sepsis. PMID:25227123

  3. Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis

    PubMed Central

    Kellum, John A.; Kong, Lan; Fink, Mitchell P.; Weissfeld, Lisa A.; Yealy, Donald M.; Pinsky, Michael R.; Fine, Jonathan; Krichevsky, Alexander; Delude, Russell L.; Angus, Derek C.

    2015-01-01

    Background Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of pro-inflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8–39.0) (P<.001). Conclusions The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest when both proinflammatory and anti-inflammatory cytokine levels are high. PMID:17698689

  4. Pediatric Severe Sepsis in US Children’s Hospitals

    PubMed Central

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

    2014-01-01

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

  5. NOVEL HMGB1-INHIBITING THERAPEUTIC AGENTS FOR EXPERIMENTAL SEPSIS

    PubMed Central

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

    2010-01-01

    Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens, but also initiate an inflammatory response by producing early (e.g., TNF and IFN-gamma) and late (e.g., HMGB1) proinflammatory cytokines. Here we briefly review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss therapeutic potential of several HMGB1-inhibiting agents (including neutralizing antibodies and steroid-like tanshinones) in experimental sepsis. PMID:19333143

  6. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media

    PubMed Central

    Di Pierro, Francesco; Donato, Guido; Fomia, Federico; Adami, Teresa; Careddu, Domenico; Cassandro, Claudia; Albera, Roberto

    2012-01-01

    Background The oral probiotic Streptococcus salivarius K12 has been shown clearly to antagonize the growth of Streptococcus pyogenes, the most important bacterial cause of pharyngeal infections in humans, by releasing two bacteriocins named salivaricin A2 and salivaricin B. Unpublished observations indicate that it can also antagonize the growth of other bacteria involved in acute otitis media. Because of its ability to colonize the oral cavity and its safety profile, we have tested its efficacy in reducing the incidence of streptococcal pharyngitis and/or tonsillitis and episodes of acute otitis media. Methods We enrolled 82 children, including 65 with and 17 without a recent diagnosis of recurrent oral streptococcal pathology. Of those with recurrent pathology, 45 were treated daily for 90 days with an oral slow-release tablet containing five billion colony-forming units of S. salivarius K12 (Bactoblis®), and the remaining 20 served as an untreated control group. The 17 children without a recent diagnosis of recurrent oral pathology were used as an additional control group. After 90 days of treatment, a 6-month follow-up period without treatment was included to evaluate a possible persistent protective role for the previously administered product. Results The 41 children who completed the 90-day course of Bactoblis showed a reduction in their episodes of streptococcal pharyngeal infection (about 90%) and/or acute otitis media (about 40%), calculated by comparing infection rates in the previous year. The 90-day treatment also reduced the reported incidence of pharyngeal and ear infections by about 65% in the 6-month follow-up period during which the product was not administered. Subjects tolerated the product well, with no side effects or dropouts reported. Conclusion Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal pathology reduced episodes of streptococcal pharyngeal infections and/or tonsillitis as well as episodes of acute otitis media. PMID:23233809

  7. Rahnella aquatilis Sepsis in a Premature Newborn

    PubMed Central

    Kuzdan, Canan; Soysal, Ahmet; Özdemir, Hülya; Co?kun, ?enay; Akman, ?pek; Bilgen, Hülya; Özek, Eren; Bak?r, Mustafa

    2015-01-01

    Rahnella aquatilis is an infrequently isolated Gram-negative rod within the Enterobacteriaceae family. The organism's natural habitat is water. The organism is rarely isolated from clinical specimens and it seldom causes infection in immunocompetent individuals. Here we present a one-month-old boy who was born prematurely at 27th week of gestation by cesarean section with a birth weight of 730?g. He developed sepsis caused by Rahnella aquatilis during the treatment for ventilator associated pneumonia due to Stenotrophomonas maltophilia with ciprofloxacin. He was successfully treated with a combination of amikacin plus meropenem. Although R. aquatilis is one of the saprophyticus organisms, it may cause life-threatening infection in newborn.

  8. Time course of cytokine levels in sepsis.

    PubMed

    Thijs, L G; Hack, C E

    1995-11-01

    In severe sepsis, a network of proinflammatory cytokines (TNF, IL-1 beta, IL-6, IL-8) is activated and blood levels of these cytokines are elevated, albeit inconsistently and with large individual variations. In addition, elevated blood levels of anti-inflammatory cytokines (IL-10), as well as of soluble cytokine receptors (sTNF-RI and II, IL-1ra), have been found. They seem to have a regulatory function in the host response. Levels of TNF and IL-6 are usually highest at the time of admission, whereas the time course of IL-1 beta levels (when detectable) can vary considerably. Limited data on IL-8 levels suggest that they may remain elevated for longer periods. Elevated levels of sTNFR and IL-1ra may also persist for a prolonged period of time. The pathogenetic significance of these observations is still unclear, but persistingly high levels of proinflammatory cytokines may be associated with organ failure and mortality. PMID:8636533

  9. Rahnella aquatilis Sepsis in a Premature Newborn.

    PubMed

    Kuzdan, Canan; Soysal, Ahmet; Özdemir, Hülya; Co?kun, ?enay; Akman, ?pek; Bilgen, Hülya; Özek, Eren; Bak?r, Mustafa

    2015-01-01

    Rahnella aquatilis is an infrequently isolated Gram-negative rod within the Enterobacteriaceae family. The organism's natural habitat is water. The organism is rarely isolated from clinical specimens and it seldom causes infection in immunocompetent individuals. Here we present a one-month-old boy who was born prematurely at 27th week of gestation by cesarean section with a birth weight of 730?g. He developed sepsis caused by Rahnella aquatilis during the treatment for ventilator associated pneumonia due to Stenotrophomonas maltophilia with ciprofloxacin. He was successfully treated with a combination of amikacin plus meropenem. Although R. aquatilis is one of the saprophyticus organisms, it may cause life-threatening infection in newborn. PMID:26090257

  10. Lactobacillus sepsis associated with probiotic therapy.

    PubMed

    Land, Michael H; Rouster-Stevens, Kelly; Woods, Charles R; Cannon, Michael L; Cnota, James; Shetty, Avinash K

    2005-01-01

    Probiotic strains of lactobacilli are increasingly being used in clinical practice because of their many health benefits. Infections associated with probiotic strains of lactobacilli are extremely rare. We describe 2 patients who received probiotic lactobacilli and subsequently developed bacteremia and sepsis attributable to Lactobacillus species. Molecular DNA fingerprinting analysis showed that the Lactobacillus strain isolated from blood samples was indistinguishable from the probiotic strain ingested by the patients. This report indicates, for the first time, that invasive disease can be associated with probiotic lactobacilli. This report should not discourage the appropriate use of Lactobacillus or other probiotic agents but should serve as a reminder that these agents can cause invasive disease in certain populations. PMID:15629999

  11. A latent class approach for sepsis diagnosis supports use of procalcitonin in the emergency room for diagnosis of severe sepsis

    PubMed Central

    2013-01-01

    Background Given the acknowledged problems in sepsis diagnosis, we use a novel way with the application of the latent class analysis (LCA) to determine the operative characteristics of C-reactive protein (CRP), D-dimer (DD) and Procalcitonin (PCT) as diagnostic tests for sepsis in patients admitted to hospital care with a presumptive infection. Methods Cross-sectional study to determine the diagnostic accuracy of three biological markers against the gold standard of clinical definition of sepsis provided by an expert committee, and also against the likelihood of sepsis according to LCA. Patients were recruited in the emergency room within 24 hours of hospitalization and were follow-up daily until discharge. Results Among 765 patients, the expert committee classified 505 patients (66%) with sepsis, 112 (15%) with infection but without sepsis and 148 (19%) without infection. The best cut-offs points for CRP, DD, and PCT were 7.8 mg/dl, 1616 ng/ml and 0.3 ng/ml, respectively; but, neither sensitivity nor specificity reach 70% for any biomarker. The LCA analysis with the same three tests identified a “cluster” of 187 patients with several characteristics suggesting a more severe condition as well as better microbiological confirmation. Assuming this subset of patients as the new prevalence of sepsis, the ROC curve analysis identified new cut-off points for the tests and suggesting a better discriminatory ability for PCT with a value of 2 ng/ml. Conclusions Under a “classical” definition of sepsis three typical biomarkers (CRP, PCT and DD) are not capable enough to differentiate septic from non-septic patients in the ER. However, a higher level of PCT discriminates a selected group of patients with severe sepsis. PMID:24050481

  12. In-111 WBC imaging in musculoskeletal sepsis

    SciTech Connect

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

    1984-01-01

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

  13. Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster.

    PubMed Central

    Earhart, C. A.; Vath, G. M.; Roggiani, M.; Schlievert, P. M.; Ohlendorf, D. H.

    2000-01-01

    The streptococcal pyrogenic toxins A, B, and C (SPEA, SPEB, and SPEC) are responsible for the fever, rash, and other toxicities associated with scarlet fever and streptococcal toxic shock syndrome. This role, together with the ubiquity of diseases caused by Streptococcus pyogenes, have prompted structural analyses of SPEA by several groups. Papageorgiou et al. (1999) have recently reported the structure of SPEA crystallized in the absence of zinc. Zinc has been shown to be important in the ability of some staphylococcal and streptococcal toxins to stimulate proliferation of CD4+ T-cells. Since cadmium is more electron dense than zinc and typically binds interchangeably, we grew crystals in the presence of 10 mM CdCl2. Crystals have been obtained in three space groups, and the structure in the P2(1)2(1)2(1) crystal form has been refined to 1.9 A resolution. The structural analysis revealed an identical tetramer as well as a novel tetrahedral cluster of cadmium in all three crystal forms on a disulfide loop encompassing residues 87-98. No cadmium was bound at the site homologous to the zinc site in staphylococcal enterotoxins C (SECs) despite the high structural homology between SPEA and SECs. Subsequent soaking of crystals grown in the presence of cadmium in 10 mM ZnCl2 showed that zinc binds in this site (indicating it can discriminate between zinc and cadmium ions) using the three ligands (Asp77, His106, and His110) homologous to the SECs plus a fourth ligand (Glu33). PMID:11045630

  14. Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs.

    PubMed

    Chacon-Cabrera, Alba; Rojas, Yeny; Martínez-Caro, Leticia; Vila-Ubach, Monica; Nin, Nicolas; Ferruelo, Antonio; Esteban, Andrés; Lorente, José A; Barreiro, Esther

    2014-12-01

    Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V(T) [V(T) = 9 mL/kg], moderate V(T) [V(T) = 15 mL/kg], and high V(T) [V(T) = 25 mL/kg]) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V(T) rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor ? (TNF-?) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-? remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents. PMID:25168016

  15. Plasminogen is a critical host pathogenicity factor for group A streptococcal infection.

    PubMed

    Sun, Hongmin; Ringdahl, Ulrika; Homeister, Jonathon W; Fay, William P; Engleberg, N Cary; Yang, Angela Y; Rozek, Laura S; Wang, Xixi; Sjöbring, Ulf; Ginsburg, David

    2004-08-27

    Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot-dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens. PMID:15333838

  16. The CURB65 pneumonia severity score outperforms generic sepsis and early warning scores in predicting mortality in community-acquired pneumonia

    Microsoft Academic Search

    Gavin Barlow; Dilip Nathwani; Peter Davey

    2007-01-01

    Background: The performance of CURB65 in predicting mortality in community-acquired pneumonia (CAP) has been tested in two large observational studies. However, it has not been tested against generic sepsis and early warning scores, which are increasingly being advocated for identification of high-risk patients in acute medical wards.Method: A retrospective analysis was performed of data prospectively collected for a CAP quality

  17. The Incidence of Leukemia and Mortality from Sepsis in Patients with Severe Congenital Neutropenia Receiving Long Term G-CSF Therapy

    Microsoft Academic Search

    Philip S. Rosenberg; Blanche P. Alter; Audrey A. Bolyard; Mary Ann Bonilla; Laurence A. Boxer; Bonnie Cham; Carol Fier; Melvin Freedman; George Kannourakis; Sally Kinsey; Beate Schwinzer; Connie Zeidler; Karl Welte; David C. Dale

    2006-01-01

    In patients with severe congenital neutro- penia (SCN), sepsis mortality is reduced by treatment with granulocyte colony- stimulating factor (G-CSF), but my- elodsyplastic syndrome and acute my- eloid leukemia (MDS\\/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman- Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN,

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Biomarkers for Sepsis: A Review with Special Attention to India

    PubMed Central

    Nelson, George E.; Gupta, Amita

    2014-01-01

    Sepsis is a serious infection and still a common cause of morbidity and mortality in resource-limited settings such as India. Even when microbiologic diagnostics are available, bacteremia is only identified in a proportion of patients who present with sepsis and bloodstream infections. Biomarkers have been used in a variety of disease processes and can help aid in diagnosing bacterial infections. There have been numerous biomarkers investigated to aid with diagnosis and prognostication in sepsis with the majority suffering from lack of sensitivity or specificity. Procalcitonin has been heralded as the biomarker that holds the most promise for bloodstream infections. Data are emerging in India, and in this review, we focus on the current data of biomarkers in sepsis with particular attention to how biomarkers could be used to augment diagnosis and treatment in India. PMID:24772418

  20. A generic pathogen capture technology for sepsis diagnosis

    E-print Network

    Cooper, Ryan Mcomber

    2013-01-01

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

  1. Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded beta-helix.

    PubMed

    Smith, Nicola L; Taylor, Edward J; Lindsay, Anna-Marie; Charnock, Simon J; Turkenburg, Johan P; Dodson, Eleanor J; Davies, Gideon J; Black, Gary W

    2005-12-01

    Streptococcus pyogenes (group A Streptococcus) causes severe invasive infections including scarlet fever, pharyngitis (streptococcal sore throat), skin infections, necrotizing fasciitis (flesh-eating disease), septicemia, erysipelas, cellulitis, acute rheumatic fever, and toxic shock. The conversion from nonpathogenic to toxigenic strains of S. pyogenes is frequently mediated by bacteriophage infection. One of the key bacteriophage-encoded virulence factors is a putative "hyaluronidase," HylP1, a phage tail-fiber protein responsible for the digestion of the S. pyogenes hyaluronan capsule during phage infection. Here we demonstrate that HylP1 is a hyaluronate lyase. The 3D structure, at 1.8-angstroms resolution, reveals an unusual triple-stranded beta-helical structure and provides insight into the structural basis for phage tail assembly and the role of phage tail proteins in virulence. Unlike the triple-stranded beta-helix assemblies of the bacteriophage T4 injection machinery and the tailspike endosialidase of the Escherichia coli K1 bacteriophage K1F, HylP1 possesses three copies of the active center on the triple-helical fiber itself without the need for an accessory catalytic domain. The triple-stranded beta-helix is not simply a structural scaffold, as previously envisaged; it is harnessed to provide a 200-angstroms-long substrate-binding groove for the optimal reduction in hyaluronan viscosity to aid phage penetration of the capsule. PMID:16314578

  2. Short-course antimicrobial therapy of streptococcal pharyngitis.

    PubMed

    Block, Stan L

    2003-10-01

    While penicillin administered orally or intramuscularly is the least expensive course of pharyngitis treatment, there are many limitations to its use. These include the need for extended treatment (i.e., 10 days) and poor palatability of its liquid formulation and an alarming increase in the rates of failure with standard doses of either IM or oral penicillin. Increasing rates of beta-lactamase-producing normal flora and eradication of protective alpha-streptococci may also play a role in penicillin treatment failure. Thus practitioners may consider switching to amoxicillin in higher doses (up to 40 to 60 mg/kg/day divided twice daily, maximum dose 1 gram twice daily) as first-line therapy (Figure 1), similar to what we have done for acute otitis media. Five-day short-course treatment with cefdinir or cefpodoxime may be suitable alternatives, especially in patients with penicillin hypersensitivity (not anaphylaxis). Concerns with higher costs of these second-line agents and potential for resistance must be balanced with concerns for patient adherence with penicillin treatment and the recent increasing rate of penicillin failures. In light of recent reports regarding the high rate of failure with azithromycin and increasing macrolide resistance, clinicians should prescribe standard doses of this drug for 5 days with caution. PMID:14601914

  3. Shedding metabo'light' on the search for sepsis biomarkers.

    PubMed

    Dos Santos, Claudia C

    2015-01-01

    The clinical presentation of severe infection with generalized inflammation is similar, if not identical, to systemic inflammation induced by sterile tissue injury. Novel models and unbiased technologies are urgently needed for biomarker identification and disease profiling in sepsis. Here we briefly review the article of Kamisoglu and colleagues in this issue of Critical Care on comparing metabolomics data from different studies to assess whether responses elicited by endotoxin recapitulate, at least in part, those seen in clinical sepsis. PMID:26148483

  4. Soluble interleukin-2 receptor as a predictor of neonatal sepsis

    Microsoft Academic Search

    Michael L. Spear; John L. Stefano; Paul Fawcett; Roy Proujansky

    1995-01-01

    We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results. (J PEDIATR 1995;126:982-5)

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

    PubMed Central

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

    2014-01-01

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

  6. Sepsis Syndrome in Children: Can We Do Better?

    Microsoft Academic Search

    Marieke Emonts; Ronald de Groot

    2004-01-01

    \\u000a Sepsis is a significant healthcare problem both in industrialized and developing countries. In the United States the incidence\\u000a of disease is 56 and 240 per 100,000 per year in children and adults respectively. In adults underlying disease is present\\u000a in 83%. Approximately 50% of the children have underlying diseases. Annual total costs of sepsis in the United States are\\u000a estimated

  7. Wound sepsis after cholecystectomy: effect of incidental appendicectomy.

    PubMed Central

    Pollock, A V; Evans, M

    1977-01-01

    The records of a consecutive series of 224 patients were analysed to discover the effect of incidental appendicectomy on the wound sepsis rate after cholecystectomy. One hundred and five patients had had a cholecystectomy alone and 119 cholecystectomy with incidental appendicectomy. The incidence of wound sepsis in patients not given adequate antibiotic prophylaxis was significantly lower (16-1%) when cholecystectomy alone was carried out than when the appendix was removed as well (41-1%). PMID:831968

  8. Pelvic Sepsis After Extended Hartmann’s?Procedure

    Microsoft Academic Search

    Anders Tøttrup; Lise Frost

    2005-01-01

    PURPOSE  An extended Hartmanns procedure is occasionally useful in rectal resections, because anastomotic, perineal, and functional problems are eliminated. This study was designed to examine the occurrence of pelvic sepsis after this procedure and identify possible risk factors.METHODS  Medical records were available for 163 patients (89 females) undergoing rectal resection with colostomy and closure of the rectal remnant. Information about pelvic sepsis

  9. Spontaneous Neutrophil Migration Patterns during Sepsis after Major Burns

    PubMed Central

    Jones, Caroline N.; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A.; Warren, H. Shaw; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel

    2014-01-01

    Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns. PMID:25489947

  10. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

    PubMed Central

    Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

    2012-01-01

    Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

  11. Identification of predictors of early infection in acute burn patients.

    PubMed

    Schultz, Laura; Walker, Sandra A N; Elligsen, Marion; Walker, Scott E; Simor, Andrew; Mubareka, Samira; Daneman, Nick

    2013-11-01

    Burn patients are at high risk for infections; however, common indicators of infection are unreliable in this population and can lead to unnecessary use of antibiotics. The study objective was to determine if predictors of early infection in adult acute burn patients are identified to provide clinicians with a practical tool to aid in the diagnosis of infection, thereby minimizing unnecessary exposure to antimicrobials. A retrospective chart review of all adult acute burn injury patients admitted over a 1 year period to the burn centre at Sunnybrook Health Sciences Centre was conducted. Early infection was defined as one that occurred within the first 10 days after injury and in accordance with American Burn Association guidelines. Those without infection were compared to patients with infection generally and also to patients with sepsis specifically. The period prevalence of early infection and sepsis in our patients was 50% (56/111) and 16% (18/111), respectively. It was determined that heart rate ?110 bpm, systolic blood pressure ?100 mmHg and intubation were the best predictors of sepsis (p<0.05); and fraction of inhaled oxygen >25% and maximum temperature ?39 °C were the best predictors of infection (p<0.05). This pilot project identified significant predictors of early infection and sepsis in acute burns and will be validated in a prospective study. PMID:23664774

  12. Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury.

    PubMed

    Quoilin, C; Mouithys-Mickalad, A; Lécart, S; Fontaine-Aupart, M-P; Hoebeke, M

    2014-10-01

    To investigate the role of oxidative stress and/or mitochondrial impairment in the occurrence of acute kidney injury (AKI) during sepsis, we developed a sepsis-induced in vitro model using proximal tubular epithelial cells exposed to a bacterial endotoxin (lipopolysaccharide, LPS). This investigation has provided key features on the relationship between oxidative stress and mitochondrial respiratory chain activity defects. LPS treatment resulted in an increase in the expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX-4), suggesting the cytosolic overexpression of nitric oxide and superoxide anion, the primary reactive nitrogen species (RNS) and reactive oxygen species (ROS). This oxidant state seemed to interrupt mitochondrial oxidative phosphorylation by reducing cytochrome c oxidase activity. As a consequence, disruptions in the electron transport and the proton pumping across the mitochondrial inner membrane occurred, leading to a decrease of the mitochondrial membrane potential, a release of apoptotic-inducing factors and a depletion of adenosine triphosphate. Interestingly, after being targeted by RNS and ROS, mitochondria became in turn producer of ROS, thus contributing to increase the mitochondrial dysfunction. The role of oxidants in mitochondrial dysfunction was further confirmed by the use of iNOS inhibitors or antioxidants that preserve cytochrome c oxidase activity and prevent mitochondrial membrane potential dissipation. These results suggest that sepsis-induced AKI should not only be regarded as failure of energy status but also as an integrated response, including transcriptional events, ROS signaling, mitochondrial activity and metabolic orientation such as apoptosis. PMID:25019585

  13. ACUTE LEUKEMIAS ACUTE MYELOGENOUS

    E-print Network

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  15. Use of intravenous immunoglobulin in the treatment of twelve youths with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

    PubMed

    Kovacevic, Miro; Grant, Paul; Swedo, Susan E

    2015-02-01

    This is a case series describing 12 youths treated with intravenous immunoglobulin (IVIG) for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Although it is a clinically based series, the case reports provide new information about the short-term benefits of IVIG therapy, and are the first descriptions of long-term outcome for PANDAS patients. PMID:25658609

  16. Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study

    PubMed Central

    Morgenthaler, Nils G; Struck, Joachim; Christ-Crain, Mirjam; Bergmann, Andreas; Müller, Beat

    2005-01-01

    Introduction Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. Methods Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. Results On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20–2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100–2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in surviving than in nonsurviving sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. Conclusion Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results. PMID:15693965

  17. Structural relationship between the enzymatic and streptococcal binding sites of human salivary alpha-amylase.

    PubMed

    Scannapieco, F A; Bhandary, K; Ramasubbu, N; Levine, M J

    1990-12-31

    Previous studies have demonstrated that human salivary alpha-amylase specifically binds to the oral bacterium Streptococcus gordonii. This interaction is inhibited by substrates such as starch and maltotriose suggesting that bacterial binding may involve the enzymatic site of amylase. Experiments were performed to determine if amylase bound to the bacterial surface possessed enzymatic activity. It was found that over one-half of the bound amylase was enzymatically active. In addition, bacterial-bound amylase hydrolyzed starch to glucose which was then metabolized to lactic acid by the bacteria. In further studies, the role of amylase's histidine residues in streptococcal binding and enzymatic function was assessed after their selective modification with diethyl pyrocarbonate. DEP-modified amylase showed a marked reduction in both enzymatic and streptococcal binding activities. These effects were diminished when DEP modification occurred in the presence of maltotriose. DEP-modified amylase had a significantly altered secondary structure when compared with native enzyme or amylase modified in the presence of maltotriose. Collectively, these results suggest that human salivary alpha-amylase may possess multiple sites for bacterial binding and enzymatic activity which share structural similarities. PMID:2125215

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

    PubMed Central

    Helm, Caitlin E.; Blackwood, R. Alexander

    2015-01-01

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

  19. Identification of Major Streptococcal Species by rrn-Amplified Ribosomal DNA Restriction Analysis

    PubMed Central

    Schlegel, Laurent; Grimont, Francine; Grimont, Patrick A. D.; Bouvet, Anne

    2003-01-01

    Amplified ribosomal DNA restriction analysis (rrn-ARDRA) is based on PCR amplification and restriction of a fragment of rRNA genes including 16S and 23S genes and the intergenic spacer. rrn-ARDRA was evaluated for the identification of species within the genus Streptococcus. A total of 148 type and reference strains of pyogenic, oral, and group D streptococci were examined in order to construct a database for identification of streptococci. The amplified product was a single band approximately 4,500 bp long. This amplicon was digested separately with three (HhaI, MboII, and Sau3A) restriction endonucleases. Respectively, 27, 26, and 28 major patterns were observed after HhaI, MboII, and Sau3A restrictions. Streptococcal strains belonging to different species had different patterns or different combination of patterns. An identification system based upon a combination of the three restriction patterns in a single database was then proposed. rrn-ARDRA was successfully applied to 11 clinical isolates whose identification to the species level was difficult to obtain by phenotypic analysis. Using a database of well-characterized strains, rrn-ARDRA is a powerful method for the identification of streptococcal isolates. PMID:12574263

  20. Induction of immune responses to functional determinants of a cell surface streptococcal antigen.

    PubMed Central

    Todryk, S M; Kelly, C G; Munro, G H; Lehner, T

    1996-01-01

    Antibodies directed against the cell surface adhesin, termed streptococcal antigen I/II of Streptococcus mutans can protect against dental caries. Streptococcal antigen I/II (SA I/II) interacts with salivary glycoproteins and promotes adhesion to the tooth surface. Topical application of monoclonal antibodies which recognize a domain within residues 816-1213 (fragment 3) prevents colonization by S. mutans in primates. In this study the immunogenicity and antigenicity of fragment 3 was investigated in five strains of mice. Fragment 3 induced an immune response following immunization with whole cells of S. mutans in all strains of mice. Immunization with recombinant fragment 3 also induced T-cell proliferative and antibody responses both to fragment 3 and to the SA I/II. Antibody responses to the previously defined adhesion determinants (residues 1005-1044) were weak or undetectable. Immunization of three representative strains of mice with a recombinant polypeptide (residues 975-1044) comprising this adhesion epitope and an adjacent T-cell epitope (residues 975-1004) elicited both T- and B-cell responses to the polypeptide and to native SA I/II. The B-cell epitopes overlapped with the adhesion determinant. These findings provide a means of directing immune responses to functional determinants of SA I/II. Images Figure 1 PMID:8666436

  1. Streptococcal hyaluronic acid: proposed mechanisms of degradation and loss of synthesis during stationary phase.

    PubMed Central

    van de Rijn, I

    1983-01-01

    Streptococcal hyaluronic acid was found to distribute into two discrete sizes. Cellular hyaluronic acid from strain D181 had an average molecular weight of 10 X 10(6), whereas the average molecular weight of extracellular hyaluronic acid from the same strain was 2 X 10(6). Cellular streptococcal hyaluronic acid was purified to homogeneity. Proteases were unable to cleave the purified cellular polymer, indicating that a peptide was not involved in cross-linking five extracellular hyaluronate polymers to form a cell-bound complex. Lipids apparently are not part of the cellular hyaluronic acid because phosphorus and glycerol were not detected by radioisotopic techniques, and denaturing conditions did not change the size of the polymer. Membranes obtained from various strains of group A and C streptococci cleaved the cellular form of the hyaluronate polymer demonstrating the presence of a membrane-bound hyaluronidase-like activity. By contrast, this activity was not found in the extracellular products of the strains studied. Furthermore, membranes derived from streptococci at the stationary phase of growth no longer had the capacity to synthesize hyaluronic acid. The loss of this property appeared to be due to changes in the structure of the membrane. Images PMID:6358186

  2. Induction of a regulatory phenotype in human CD4+ T cells by streptococcal M protein.

    PubMed

    Price, Jeffrey D; Schaumburg, Jessica; Sandin, Charlotta; Atkinson, John P; Lindahl, Gunnar; Kemper, Claudia

    2005-07-15

    Regulatory T cells (Tregs) participate in the control of the immune response. In the human system, an IL-10-secreting, T regulatory type 1 cell (Tr1)-like subset of Tregs can be induced by concurrent cross-linking of the TCR and CD46 on naive CD4(+) T cells. Because many viral and bacterial pathogens, including the major human pathogen Streptococcus pyogenes, bind to CD46, we asked whether this bacterium can directly induce Tr1-like cells through the streptococcal ligand for CD46, the M protein. The M5 and M22 proteins were found to induce T cells to develop into the IL-10-producing Tr1-like phenotype. Moreover, whole M5-expressing bacteria, but not isogenic M-negative bacteria, led to proliferation and IL-10 secretion by T cells. The interaction between the M5 protein and T cells was dependent on CD46 and the conserved C repeat region of M5. Supernatants derived from T cells stimulated with M proteins or M protein-expressing bacteria suppressed bystander T cell proliferation through IL-10 secretion. In addition, activation of CD46 through streptococcal M protein induced the expression of granzyme B, providing a second means for these cells to regulate an immune response. These findings suggest that binding to CD46 and exploiting its signaling pathway may represent a strategy employed by a number of important human pathogens to induce directly an immunosuppressive/regulatory phenotype in T cells. PMID:16002662

  3. The Effect of a Silver Nanoparticle Polysaccharide System on Streptococcal and Saliva-Derived Biofilms

    PubMed Central

    Di Giulio, Mara; Di Bartolomeo, Soraya; Di Campli, Emanuela; Sancilio, Silvia; Marsich, Eleonora; Travan, Andrea; Cataldi, Amelia; Cellini, Luigina

    2013-01-01

    In this work, we studied the antimicrobial properties of a nanocomposite system based on a lactose-substituted chitosan and silver nanoparticles: Chitlac-nAg. Twofold serial dilutions of the colloidal Chitlac-nAg solution were both tested on Streptococcus mitis, Streptococcus mutans, and Streptococcus oralis planktonic phase and biofilm growth mode as well as on saliva samples. The minimum inhibitory and bactericidal concentrations of Chitlac-nAg were evaluated together with its effect on sessile cell viability, as well as both on biofilm formation and on preformed biofilm. In respect to the planktonic bacteria, Chitlac-nAg showed an inhibitory/bactericidal effect against all streptococcal strains at 0.1% (v/v), except for S. mitis ATCC 6249 that was inhibited at one step less. On preformed biofilm, Chitlac-nAg at a value of 0.2%, was able to inhibit the bacterial growth on the supernatant phase as well as on the mature biofilm. For S. mitis ATCC 6249, the biofilm inhibitory concentration of Chitlac-nAg was 0.1%. At sub-inhibitory concentrations, the Streptococcal strains adhesion capability on a polystyrene surface showed a general reduction following a concentration-dependent-way; a similar effect was obtained for the metabolic biofilm activity. From these results, Chitlac-nAg seems to be a promising antibacterial and antibiofilm agent able to hinder plaque formation. PMID:23812080

  4. The effect of a silver nanoparticle polysaccharide system on streptococcal and saliva-derived biofilms.

    PubMed

    Di Giulio, Mara; Di Bartolomeo, Soraya; Di Campli, Emanuela; Sancilio, Silvia; Marsich, Eleonora; Travan, Andrea; Cataldi, Amelia; Cellini, Luigina

    2013-01-01

    In this work, we studied the antimicrobial properties of a nanocomposite system based on a lactose-substituted chitosan and silver nanoparticles: Chitlac-nAg. Twofold serial dilutions of the colloidal Chitlac-nAg solution were both tested on Streptococcus mitis, Streptococcus mutans, and Streptococcus oralis planktonic phase and biofilm growth mode as well as on saliva samples. The minimum inhibitory and bactericidal concentrations of Chitlac-nAg were evaluated together with its effect on sessile cell viability, as well as both on biofilm formation and on preformed biofilm. In respect to the planktonic bacteria, Chitlac-nAg showed an inhibitory/bactericidal effect against all streptococcal strains at 0.1% (v/v), except for S. mitis ATCC 6249 that was inhibited at one step less. On preformed biofilm, Chitlac-nAg at a value of 0.2%, was able to inhibit the bacterial growth on the supernatant phase as well as on the mature biofilm. For S. mitis ATCC 6249, the biofilm inhibitory concentration of Chitlac-nAg was 0.1%. At sub-inhibitory concentrations, the Streptococcal strains adhesion capability on a polystyrene surface showed a general reduction following a concentration-dependent-way; a similar effect was obtained for the metabolic biofilm activity. From these results, Chitlac-nAg seems to be a promising antibacterial and antibiofilm agent able to hinder plaque formation. PMID:23812080

  5. Necrotizing fasciitis and myositis caused by streptococcal flesh-eating bacteria.

    PubMed

    García-Casares, E; Mateo Soria, L; García-Melchor, E; Riera Alonso, E; Olivé Marqués, A; Holgado Pérez, S; Tena Marsà, X; Molinos Abós, S

    2010-12-01

    Three types of group A streptococcal infections are particularly feared: necrotizing fasciitis, myositis, and streptococcal toxic shock syndrome (TSS). We present 3 cases of necrotizing fasciitis due to Streptococcus pyogenes, one in an immunocompromised patient who had received kidney transplant and 2 healthy patients. Mean age of patients was 52 years (range, 42-67 years), and all 3 were male. One spontaneous case in absence of any obvious portal of entry is reported. The clinical course was initially indolent but quickly destructive. All patients required emergency surgical debridement and intravenous antibiotics. In 2 cases, intravenous immunoglobulin therapy was added. Differential diagnoses include septic arthritis, cellulitis, gout, other causes of tenosynovitis, erysipelas, and deep vein thrombosis.Blood and soft-tissue cultures should be obtained to identify the bacteria, and emergency computed tomography or magnetic resonance imaging scan should be performed to confirm the diagnosis and define the extension of the necrosis. Aggressive surgical debridement in the first 24 to 48 hours and antibiotic treatment, including penicillin and clindamycin, are the cornerstones in the management of these infections. Adjuvant intravenous immunoglobulin therapy might be useful in case of TSS. Diagnostic and treatment delays are the main causes of mortality in these infections. PMID:21085016

  6. Sepsis otopathy: experimental sepsis leads to significant hearing impairment due to apoptosis and glutamate excitotoxicity in murine cochlea

    PubMed Central

    Schmutzhard, Joachim; Glueckert, Rudolf; Pritz, Christian; Blumer, Michael J. F.; Bitsche, Mario; Lackner, Peter; Fille, Manfred; Riechelmann, Herbert; Harkamp, Matthias; Sitthisak, Thongrong; Schrott-Fischer, Annelies

    2013-01-01

    SUMMARY Hearing loss is frequent in intensive care patients and can be due to several causes. However, sepsis has not been examined as a possible cause. The aim of this study is to assess the influence of experimental sepsis on hearing thresholds and to evaluate pathological changes in the cochlea. The cecal ligation puncture technique was used to induce sepsis in 18 mice. Results were compared with those from 13 sham-operated and 13 untreated control mice. The hearing thresholds of the animals were evaluated with auditory evoked brainstem responses prior to the induction of sepsis and again at the peak of the disease. Immediately after the second measurement, the mice were sacrificed and the inner ears harvested and prepared for further evaluation. The cochleae were examined with light microscopy, electron microscopy and immunohistochemistry for Bax, cleaved caspase-3 and Bcl-2. The mice with sepsis showed a significant hearing loss but not the control groups. Induction of apoptosis could be shown in the supporting cells of the organ of Corti. Furthermore, excitotoxicity could be shown at the basal pole of the inner hair cells. In this murine model, sepsis leads to significant hearing impairment. The physiological alteration could be linked to apoptosis in the supporting cells of the organ of Corti and to a disturbance of the synapses of the inner hair cells. PMID:23471916

  7. Herlyn-Werner-Wunderlich Syndrome Complicated with Pyocolpos: An Unusual Cause of Postabortal Sepsis

    PubMed Central

    Sharma, Deepti; Janu, MK; Gaikwad, Ramesh; Usha, MG

    2011-01-01

    Obstructive mullerian anomalies give rise to a spectrum of clinical presentations and are uncommon in routine gynecologic practice. The patient usually becomes symptomatic in early reproductive years. Recurrent pelvic pain, dysmenorrhea, enlarging abdominopelvic mass, and abnormal vaginal discharge are the common presenting symptoms. We describe a rare case of a mullerian anomaly getting diagnosed 13 years after attaining menarche during the evaluation of postabortal sepsis. Patient presented 2 weeks following evacuation carried out for missed abortion, with acute abdominal pain, fever and foul smelling discharge per vaginum. The anomaly was identified as uterus didelphys with obstructed left hemivagina and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome) complicated by pyocolpos. She was successfully managed by single-stage transvaginal septum resection under laparoscopic control.

  8. Neonatal sepsis and multiple skin abscess in a newborn with Down's syndrome: A case report.

    PubMed

    Kali, Arunava; Sivaraman, Umadevi; Sreenivasan, Srirangaraj; Stephen, Selvaraj

    2013-01-01

    Neonatal sepsis is a leading cause of neonatal mortality. Congenital heart disease accounts for additional risk of sepsis in neonates. Here we report a case of Down's syndrome with late onset neonatal sepsis associated with multiple superficial skin abscesses simulating staphylococcal infection. The baby was empirically treated with vancomycin. Subsequently, multidrug resistant Klebsiella pneumoniae was detected from both pus and blood culture. Change to appropriate antibiotic resulted in clinical recovery. Although sepsis is one of the major ailments in neonates, atypical presentations of neonatal sepsis in Down's syndrome patients are underreported. Here we highlight the atypical presentation of Klebsiella sepsis and the importance of early antibiogram in such cases. PMID:23483739

  9. A New Cecal Slurry Preparation Protocol with Improved Long-Term Reproducibility for Animal Models of Sepsis

    PubMed Central

    Starr, Marlene E.; Steele, Allison M.; Saito, Mizuki; Hacker, Bill J.; Evers, B. Mark; Saito, Hiroshi

    2014-01-01

    Sepsis, a life-threatening systemic inflammatory response syndrome induced by infection, is widely studied using laboratory animal models. While cecal-ligation and puncture (CLP) is considered the gold standard model for sepsis research, it may not be preferable for experiments comparing animals of different size or under different dietary regimens. By comparing cecum size, shape, and cecal content characteristics in mice under different experimental conditions (aging, diabetes, pancreatitis), we show that cecum variability could be problematic for some CLP experiments. The cecal slurry (CS) injection model, in which the cecal contents of a laboratory animal are injected intraperitoneally to other animals, is an alternative method for inducing polymicrobial sepsis; however, the CS must be freshly prepared under conventional protocols, which is a major disadvantage with respect to reproducibility and convenience. The objective of this study was to develop an improved CS preparation protocol that allows for long-term storage of CS with reproducible results. Using our new CS preparation protocol we found that bacterial viability is maintained for at least 6 months when the CS is prepared in 15% glycerol-PBS and stored at -80°C. To test sepsis-inducing efficacy of stored CS stocks, various amounts of CS were injected to young (4–6 months old), middle-aged (12–14 months old), and aged (24–26 months old) male C57BL/6 mice. Dose- and age-dependent mortality was observed with high reproducibility. Circulating bacteria levels strongly correlated with mortality suggesting an infection-mediated death. Further, injection with heat-inactivated CS resulted in acute hypothermia without mortality, indicating that CS-mediated death is not due to endotoxic shock. This new CS preparation protocol results in CS stocks which are durable for freezing preservation without loss of bacterial viability, allowing experiments to be performed more conveniently and with higher reproducibility than before. PMID:25531402

  10. Update in sepsis and pulmonary infections 2013.

    PubMed

    Wunderink, Richard G; Walley, Keith R

    2014-07-01

    The Journal has been in the vanguard of publications of the respiratory microbiome, including a National Institutes of Health Workshop report, establishing the normal microbiome in patients with various risks, and in the correlation of microbiome changes with disease exacerbations and lung transplant. A new classification scheme for healthcare-associated pneumonia, risks for nosocomial Pseudomonas pneumonia, and associations between community-acquired pneumonia and risks or outcomes have been reported. The increasingly recognized role of viral respiratory tract infections was reflected in publications regarding incidence rates, risk factors, and associations with other respiratory diseases. Significant contributions to understanding and treating sepsis emerged in 2013. The role of tissue damage was highlighted in a series of publications. A much greater understanding of the importance of pathways that directly impact the pathogen at the site of infection and subsequent pathogen clearance has emerged. The Journal published important contributions across the spectrum of ineffective therapy (activated protein C), novel therapeutic ideas (statins and extracorporeal membrane oxygenation), and solidly beneficial approaches (early protocolized care). Biomarker development is maturing to include a wide array of molecular measurements increasingly aimed at aiding improved therapy. PMID:24983219

  11. Damage control in trauma and abdominal sepsis.

    PubMed

    Waibel, Brett H; Rotondo, Michael F

    2010-09-01

    Damage control surgery, initially formalized <20 yrs ago, was developed to overcome the poor outcomes in exsanguinating abdominal trauma with traditional surgical approaches. The core concepts for damage control of hemorrhage and contamination control with abbreviated laparotomy followed by resuscitation before definitive repair, although simple in nature, have led to an alteration in which emergent surgery is handled among a multitude of problems, including abdominal sepsis and battlefield surgery. With the aggressive resuscitation associated with damage control surgery, understanding of abdominal compartment syndrome has expanded. It is probably through avoiding this clinical entity that the greatest improvement in surgical outcomes for various emergent surgical problems has occurred in the past two decades. However, with its success, new problems have emerged, including increases in enterocutaneous fistulas and open abdomens. But as with any crisis, innovative strategies are being developed. New approaches to control of the open abdomen and reconstruction of the abdominal wall are being developed from negative pressure dressing therapies to acellular allograft meshes. With further understanding of new resuscitative strategies, the need for damage control surgery may decline, along with its concomitant complications, at the same time retaining the success that damage control surgery has brought to the critically ill trauma and general surgery patient in the past few years. PMID:20724875

  12. Late-onset neonatal sepsis: recent developments.

    PubMed

    Dong, Ying; Speer, Christian P

    2015-05-01

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

  13. [Surgical treatment of patients for abdominal sepsis].

    PubMed

    2014-08-01

    Results of surgical treatment of 201 patients, suffering abdominal sepsis (AS), which have occurred after operations on abdominal organs, were analyzed. Expediency of application of modern scales for the patients state severity estimation, prognostic sign-posts and dynamic of the pathological process course in every patient was substantiated. Existing systems of prognostication (APACHE II, SOFA, MODS) are applied restrictedly for diagnosis of infection in patients, what demands relaparotomy performance in presence of clinical signs of intraabdominal infection, which persists. For prognostication of the treatment result and determination of indications for relaparotomy conduction in patients, suffering severe AS and infectious-toxic shock (ITSH), the most informative is application of the Manheim's index of peritonitis together with analysis of clinico-laboratory indices for formation of groups of patients in risk, to whom reoperation is indicated. Advantages of relaparotomy "on demand" conduction were proved in comparison with "programmed" relaparotomy during the staged surgical treatment of patients, suffering severe AS and ITSH. Complex surgical treatment with substantiation of indications and choice of adequate method of intervention secures improvement of the treatment results in these severely ill patients. PMID:25507013

  14. [Surgical treatment of patients for abdominal sepsis].

    PubMed

    Kryvoruchko, I A; Usenko, O Iu; Andreieshchev, S A

    2014-08-01

    Results of surgical treatment of 201 patients, suffering abdominal sepsis (AS), which have occurred after operations on abdominal organs, were analyzed. Expediency of application of modern scales for the patients state severity estimation, prognostic sign-posts and dynamic of the pathological process course in every patient was substantiated. Existing systems of prognostication (APACHE II, SOFA, MODS) are applied restrictedly for diagnosis of infection in patients, what demands relaparotomy performance in presence of clinical signs of intraabdominal infection, which persists. For prognostication of the treatment result and determination of indications for relaparotomy conduction in patients, suffering severe AS and infectious-toxic shock (ITSH), the most informative is application of the Manheim's index of peritonitis together with analysis of clinico-laboratory indices for formation of groups of patients in risk, to whom reoperation is indicated. Advantages of relaparotomy "on demand" conduction were proved in comparison with "programmed" relaparotomy during the staged surgical treatment of patients, suffering severe AS and ITSH. Complex surgical treatment with substantiation of indications and choice of adequate method of intervention secures improvement of the treatment results in these severely ill patients. PMID:25417285

  15. Early and Late Onset Sepsis in Late Preterm Infants

    PubMed Central

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

    2009-01-01

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

  16. Group B streptococcal infections in children in a tertiary care hospital in southern Taiwan

    Microsoft Academic Search

    Ching-Shu Wu; Shih-Min Wang; Wen-Chien Ko; Jiunn-Jong Wu; Yao-Jong Yang; Ching-Chuan Liu

    Group B Streptococcus (GBS) is widely recognized as a leading cause of neonatal sepsis and meningitis. Recently, GBS infections in older children have been increasingly noted. This retrospective study investigated the clinical features, distribution of serotypes, and antimicrobial susceptibility of GBS isolates in a tertiary care center in southern Taiwan over a 12-year period. GBS isolates recovered from various infected

  17. Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders

    Microsoft Academic Search

    Syed A. Morshed; Salina Parveen; James F. Leckman; Marcos T. Mercadante; Maria H. Bittencourt Kiss; Euripedes C. Miguel; Ayse Arman; Yanki Yazgan; Takao Fujii; Surojit Paul; Bradley S. Peterson; Heping Zhang; Robert A. King; Lawrence Scahill; Paul J. Lombroso

    2001-01-01

    Background: Some cases of Tourette’s syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection.Methods: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups:

  18. Pregnancy-Associated Severe Sepsis: Contemporary State and Future Challenges.

    PubMed

    Oud, Lavi

    2014-09-01

    Pregnancy is associated with an increased risk of infection related to its associated mechanical and physiological changes. Sepsis remains among the top causes of maternal death worldwide and is associated with substantial maternal morbidity. However, there are sparse data on pregnancy-associated severe sepsis (PASS), related in part to infrequent reports, varying case definitions and methodological approach, small cohort size, and often limited focus on severe sepsis in selected phases of pregnancy outcomes. Available reports vary, but indicate that PASS is a rare but likely increasing complication, and it is more likely to develop with increased maternal age, among minority women, the poor, those lacking health insurance, those with chronic illness or pregnancy-associated complications, and following invasive procedures. Obstetric sites of infection are the most prevalent, but non-obstetric infections often underlie pregnancy-associated severe sepsis, though the source of infection is often not readily apparent during initial care. Women with PASS can have a rapidly fatal course and require heightened clinician vigilance for early diagnosis and timely effective intervention. Nevertheless, available reports raise concerns about prevalent substandard care of these patients, contributing to adverse outcomes. The case fatality of PASS appears lower than that in the general population with severe sepsis, while the long-term outcomes of survivors remain unknown. PMID:25199805

  19. Erythrocyte Ca2+ pump is defective during sepsis.

    PubMed

    Lau, Y T; Hsieh, C C; Liu, M S; Hwang, T L; Chen, M F; Cheng, H S

    1994-11-01

    Saturated Ca2+ extrusion rate through the Ca2+ pump of erythrocytes was determined by the cobalt-exposure method in normal subjects and septic patients. From 48 normal subjects, the value of Vmax of erythrocyte Ca2+ pump was 14.83 +/- 0.49 mmol/L cells/hr; from 29 sepsis patients, it was 9.49 +/- 0.59 mmol/L cels/hr, significantly (P < 0.001) lower than that from the erythrocytes of normal subjects. When the severity of sepsis was evaluated by the septic severity score (SSS), a significant correlation (P < 0.0001) was observed between the Vmax of Ca2+ pump and the patient's SSS, indicating that the inhibition of Ca2+ pump depended on the degree of the pathological development of sepsis. Since the ATP-dependent Ca2+ transport in rat liver plasma membrane is also reduced during the late stage of sepsis [Lau et al., Circ Shock 38:238-244, 1992], impairment of the activity of Ca2+ pump appears to have a general pathophysiological significance in the development of severe sepsis. PMID:7600635

  20. Molecular microbiological methods in the diagnosis of neonatal sepsis

    PubMed Central

    Venkatesh, Mohan; Flores, Angela; Luna, Ruth Ann; Versalovic, James

    2010-01-01

    Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current gold standard for diagnosis of sepsis, namely blood culture, suffers from low sensitivity and a reporting delay of approximately 48–72 h. Rapid detection of sepsis and institution of antimicrobial therapy may improve patient outcomes. Rapid and sensitive tests that can inform clinicians regarding the institution or optimization of antimicrobial therapy are urgently needed. The ideal diagnostic test should have adequate specificity and negative predictive value to reliably exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively searched for neonatal studies that evaluated molecular methods for diagnosis of sepsis. We identified 19 studies that were assessed with respect to assay methodology and diagnostic characteristics. In addition, we also reviewed newer molecular microbiological assays of relevance that have not been fully evaluated in neonates. Molecular methods offer distinct advantages over blood cultures, including increased sensitivity and rapid diagnosis. However, diagnostic accuracy and cost–effectiveness should be established before implementation in clinical practice. PMID:20818947

  1. Impact of a sepsis educational program on nurse competence.

    PubMed

    Delaney, Margaret M; Friedman, M Isabel; Dolansky, Mary A; Fitzpatrick, Joyce J

    2015-04-01

    Sepsis is an emerging life-threatening entity and a worldwide epidemic. Nurses are in key positions to identify patients with sepsis, mobilize the medical team, and implement interventions. A study of self-assessed nurse competence was conducted to determine the influence of a specially designed sepsis education program on nurses' perceived ability to identify early, intervene, and care for patients with sepsis. The program was a multimodal design incorporating online interactive didactic presentations, video vignettes, pre- and postknowledge tests, and high-fidelity medical simulation scenarios. A sample of 82 critical care and emergency department nurses in a 1-year critical care nurse training program was used for this study. Pretest and posttest module knowledge scores and self-assessed competence data were collected and analyzed. No improvement in the overall self-assessed competence scores was found; however, self-perceived frequency of use of competence behaviors improved. Participants felt more competent on three sepsis-targeted statements, and posttest knowledge scores showed significant improvement. PMID:25856453

  2. Interleukin-8 in sepsis: relation to shock and inflammatory mediators.

    PubMed Central

    Hack, C E; Hart, M; van Schijndel, R J; Eerenberg, A J; Nuijens, J H; Thijs, L G; Aarden, L A

    1992-01-01

    Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis. PMID:1612748

  3. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study

    PubMed Central

    James, Stefan K.; Siegbahn, Agneta; Varenhorst, Christoph; Held, Claes; Ycas, Joseph; Husted, Steen E.; Cannon, Christopher P.; Becker, Richard C.; Steg, Ph Gabriel; Åsenblad, Nils; Wallentin, Lars

    2014-01-01

    In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as “on-treatment”. Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling. PMID:24127651

  4. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study.

    PubMed

    Storey, Robert F; James, Stefan K; Siegbahn, Agneta; Varenhorst, Christoph; Held, Claes; Ycas, Joseph; Husted, Steen E; Cannon, Christopher P; Becker, Richard C; Steg, Ph Gabriel; Åsenblad, Nils; Wallentin, Lars

    2014-01-01

    In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p?=?0.019), with fewer deaths following these AEs (33 vs. 71; p?sepsis in the ticagrelor group (7 vs. 23; p?=?0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p?sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling. PMID:24127651

  5. Concurrent poststreptococcal acute glomerulonephritis and Schönlein-Henoch purpura.

    PubMed

    Onisawa, S; Morishima, N; Ichimura, T

    1989-08-01

    A 5-year-old Japanese boy developed concurrent poststreptococcal acute glomerulonephritis (PSAGN) and Schönlein-Henoch purpura (SHP). An elevated titer of ASK on admission confirmed the preceding streptococcal infection. Arthritis of the left knee and petechiae on admission were regarded as features of SHP. The presence of SHP was further confirmed by the pathological finding of leukocytoclastic vasculitis in the skin. PSAGN was strongly suspected due to the findings of microscopic hematuria and hypocomplementemia in the acute phase. The concurrence of SHP and PSAGN suggests similar underlying pathophysiological processes as poststreptococcal sequelae. At the height of the illness, peripheral blood lymphocyte subset analysis showed a marked increase in the suppressor inducer T subset and a reciprocal decrease in the helper T subset. This alteration in T lymphocyte subsets was regarded as indicative of the immunological derangement in this patient. PMID:2514574

  6. Prognosis of acute pancreatitis.

    PubMed

    Imrie, C W

    1995-01-01

    The prognosis of an individual attack of acute pancreatitis is dependent on its severity and whether or not sepsis develops in or around the pancreas. Approximately 20-25% of patients with acute pancreatitis have a severe form of the disease which usually necessitates high dependency or intensive care management in the first week or two of illness. While most of these patients can readily be identified by experienced clinical judgement a proportion of them do not appear unduly ill at first presentation. For this reason a number of objective grading systems have been devised which identified the group of patients with the greatest likelihood of developing major complications and being at risk of death. The most commonly utilised systems in the United Kingdom are the eight factor Glasgow scoring scale and the APACHE II system. The measurement of C-reactive protein is also helpful and it has recently been shown that the combining of the Glasgow scoring system with CRP results in 80% or better sensitivity and specificity for those who develop major clinical complications. The body mass index (BMI) when over 30 kgs/m2 is also a useful marker of an adverse outcome, and CT scanning is another method of grading severity. The newer markers of interleukin 6 and PMN elastase have yet to be proved in a large prospective clinical study but do show considerable promise as being of value in identifying the patient at risk. PMID:7668494

  7. Kinetics of Circulating Damage-Associated Molecular Patterns in Sepsis

    PubMed Central

    Miki, Takahiro; Iba, Toshiaki

    2015-01-01

    Circulating levels of conventional biomarkers and damage-associated molecular patterns were examined in 30 severe sepsis patients (20 survivors and 10 nonsurvivors). Plasma levels of interleukin 6, CRP, and procalcitonin reached their peaks on Day 0 (onset of sepsis) or Day 1 and declined rapidly thereafter despite the persistent severity. In contrast, elevated levels of histone H3, nucleosome, and high-mobility group protein Box 1 remained for longer periods of time. The peak level of histone H3 in the nonsurvivors was higher than that of the survivors (p < 0.05 on Day 7). The cutoff value of the histone H3 on Day 7 for death was 0.08?AU and the area under the receiver operating characteristic curve showed discriminative powers of 0.74. Measurement of circulating levels of the histone H3 provides additional information to that of the conventional indicators of inflammation for determining the severity of sepsis. PMID:26161427

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

    PubMed

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

    2014-06-01

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

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

    Microsoft Academic Search

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

    2009-01-01

    INTRODUCTION: The effect of sepsis on epidermal wound healing has not been previously studied. It was hypothesised that epidermal wound healing is disturbed in severe sepsis. METHODS: Blister wounds were induced in 35 patients with severe sepsis and in 15 healthy controls. The healing of the wounds was followed up by measuring transepidermal water loss and blood flow in the

  10. Alternative Splicing of SMPD1 in Human Sepsis

    PubMed Central

    Kramer, Marcel; Quickert, Stefanie; Sponholz, Christoph; Menzel, Uwe; Huse, Klaus; Platzer, Matthias; Bauer, Michael; Claus, Ralf A.

    2015-01-01

    Acid sphingomyelinase (ASM or sphingomyelin phosphodiesterase, SMPD) activity engages a critical role for regulation of immune response and development of organ failure in critically ill patients. Beside genetic variation in the human gene encoding ASM (SMPD1), alternative splicing of the mRNA is involved in regulation of enzymatic activity. Here we show that the patterns of alternatively spliced SMPD1 transcripts are significantly different in patients with systemic inflammatory response syndrome and severe sepsis/septic shock compared to control subjects allowing discrimination of respective disease entity. The different splicing patterns might contribute to the better understanding of the pathophysiology of human sepsis. PMID:25898364

  11. Neuromuscular deterioration in the early stage of sepsis in rats

    PubMed Central

    Cankayali, Ilkin; Dogan, Yusuf Hakan; Solak, Ilhami; Demirag, Kubilay; Eris, Oguz; Demirgoren, Serdar; Moral, Ali Resat

    2007-01-01

    Introduction Critical illness polyneuropathy (CIP) is a clinical condition frequently seen in patients being treated in critical care units in the final stage of sepsis. The etiopathology of CIP is still unclear, and the onset time of appearance of the electrophysiological findings has not been elucidated. The very little research that has been carried out on this topic is limited to clinical electrophysiological and histopathological studies. In this study, electrophysiological alterations in the early stage of experimentally induced sepsis were investigated in septic rats. Methods We conducted a prospective, randomized, controlled experimental study in an animal basic science laboratory with 30 male Sprague-Dawley rats, weighing 200 to 250 g. All of the rats were randomly assigned to one of two groups. In the sepsis group (n = 20), cecal ligation and puncture (CLP) was performed to induce experimental sepsis. In the sham-operated group (n = 10), laparotomy without CLP was performed. Before and 24 hours after CLP and laparotomy, the right sciatic nerve was stimulated from the sciatic notch and compound muscle action potentials (CMAPs) were recorded from the gastrocnemius muscle. Recordings of latency, amplitude, and duration of the CMAP were evaluated. Results CMAP durations before and 24 hours after surgery were 0.45 ± 0.05 ms and 0.48 ± 0.05 ms, respectively, in the sham-operated group and 0.46 ± 0.05 ms and 0.55 ± 0.01 ms, respectively, in the sepsis group. Latency measurements in the sham-operated group were 0.078 ± 0.010 ms and 0.080 ± 0.015 ms, respectively, whereas measurements were found to be prolonged in the sepsis group: 0.094 ± 0.015 ms and 0.149 ± 0.054 ms before and 24 hours after surgery, respectively (p < 0.05). CMAP amplitudes in the sham-operated group before and 24 hours after surgery were 8.41 ± 0.79 mV and 8.28 ± 1.92 mV, respectively, whereas in the sepsis group the amplitude measurements decreased to 7.60 ± 1.75 mV and 4.87 ± 3.44 mV, respectively (p < 0.05). Conclusion The results of the study indicate that electrophysiological alterations appear in the first 24 hours after experimental sepsis and are characterized by an increase in latency and a decrease in CMAP amplitude. The results also suggest that electrophysiological findings seen in patients with CIP might appear before clinical signs of CIP. PMID:17204135

  12. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis

    Microsoft Academic Search

    Mitchell M. Levy; R. Phillip Dellinger; Sean R. Townsend; Walter T. Linde-Zwirble; John C. Marshall; Julian Bion; Christa Schorr; Antonio Artigas; Graham Ramsay; Richard Beale; Margaret M. Parker; Herwig Gerlach; Konrad Reinhart; Eliezer Silva; Maurene Harvey; Susan Regan; Derek C. Angus

    2010-01-01

    Objective  The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock.\\u000a A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC\\u000a guideline recommendations on process improvement and patient outcomes.\\u000a \\u000a \\u000a \\u000a Design and setting  A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards

  13. Beta-haemolytic group A, C and G streptococcal infections in Western Norway: a 15-year retrospective survey.

    PubMed

    Oppegaard, O; Mylvaganam, H; Kittang, B R

    2015-02-01

    Pyogenic streptococci cause significant morbidity and mortality, and the incidence of invasive group C and G streptococcal disease appears to be increasing. In this retrospective study we describe the epidemiological characteristics of invasive group A, C and G, along with non-invasive group C and G streptococcal infections in Western Norway from 1999 to 2013. A total of 512 invasive streptococcal infections were identified, of these 297 (58%) were group A (GAS), 24 (5%) group C (GCS) and 188 (37%) group G streptococci (GGS). In the non-invasive group, 4935 GCS and GGS-infections were identified. GCS and GGS were treated as one group (GCGS) for statistical purposes. All microbial categories displayed increasing incidence with age, seasonal variation and a male predominance. The incidence of invasive GCGS infections increased significantly from 1.4/100,000 inhabitants in 1999 to 6.3/100,000 in 2013 (p <0.001). Conversely, the annual rates of invasive GAS infection exhibited marked fluctuations, ranging from 2.7/100,000 (2000) to 8.3/100,000 (1999), but no significant temporal trends were observed. The incidence of non-invasive GCGS infections decreased significantly during the study period (p <0.001). The most frequently encountered emm-types among the 209 iGAS-isolates analysed were emm1 (24%), emm3 (14%) and emm28 (14%); whereas stG643 (19%), stG485 (15%) and stG6 (13%) were most prevalent among the 122 iGCGS-isolates available for typing. The increasing burden of invasive ?-haemolytic streptococcal disease in our community calls for sustained attentiveness to the clinical and molecular aspects of GAS, GCS and GGS infections. PMID:25658557

  14. Gluten ataxia and post-streptococcal central nervous system syndromes: Emerging immune-mediated disorders of the central nervous system?

    Microsoft Academic Search

    Adrian Wills; Russell Dale; Gavin Giovannoni

    2005-01-01

    Opinion statement  There is an “emerging concept” that central nervous system dysfunction can be caused by an aberrant immune response triggered\\u000a by exogenous antigens such as the food allergen gluten or streptococcal infection. The hypothesis of a gluten sensitive ataxia\\u000a remains unproven, but is worthy of consideration. The data in support of this hypothesis require critical review before any\\u000a treatment recommendations

  15. Lemierre Syndrome: A Case of Postanginal Sepsis

    PubMed Central

    Seo, Young Tak; Kim, Ji Hoon; Ha, Byung Wook; Choi, Hyo Sun; Kim, Yong Tai; Ham, Young Hwan

    2007-01-01

    Lemierre syndrome is a rare disease that's characterized by internal jugular vein thrombosis and septic emboli. These symptoms typically develop after acute oropharyngeal infection by Fusobacterium necrophorum1). Although this syndrome is less frequently seen in modern times due to the availability of antibiotics, physicians must be aware of the syndrome in order to initiate prompt antibiotics therapy, including coverage of the anerobic organisms. We discuss here the case of an 18-year-old female with Lemierre syndrome and we review the relevant literature on this syndrome. PMID:17939341

  16. Streptococcal Infections

    MedlinePLUS

    ... Strep throat - a sore, red throat, sometimes with white spots on the tonsils Scarlet fever - an illness that follows strep throat. It causes a red rash on the body. Impetigo - a skin infection Toxic shock syndrome Cellulitis and necrotizing fasciitis (flesh-eating disease) Group ...

  17. Acute epiglottitis as the initial presentation of pediatric Systemic Lupus Erythematosus

    PubMed Central

    Charuvanij, Sirirat; Houghton, Kristin M

    2009-01-01

    We report a case of a 5-year old girl, who initially presented with acute epiglottitis, sepsis and multi-organ failure. She was subsequently diagnosed as having Systemic Lupus Erythematosus. To the best of our knowledge, this article describes the first case of Haemophilus influenzae type f epiglottitis as the initial presentation of SLE in childhood. PMID:19878586

  18. The inflammation–coagulation axis as an important intermediate pathway in acute lung injury

    Microsoft Academic Search

    Marcel Levi; Marcus Schultz

    2008-01-01

    Markers of inflammation, coagulation, and fibrinolysis predict an adverse outcome in patients with sepsis. These markers also seem predictive of an adverse outcome in patients with localized infection and inflammation, such as in acute lung injury. Whether this is entirely related to the disease or is also due to ventilation strategies that may be harmful for the lungs, however, is

  19. Functional Genomic Insights into Acute Lung Injury: Role of Ventilators and Mechanical Stress

    Microsoft Academic Search

    Stephanie A. Nonas; James H. Finigan; Li Gao; Joe G. N. Garcia

    2005-01-01

    Acute lung injury (ALI) is a complex and devastating illness, often occurring in the setting of sepsis and trauma. Despite recent ad- vances in the understanding and treatment of ALI, pathogenic mechanisms and genetic modifiers in ALI remain incompletely un- derstood. Furthermore, there has been increasing interest in the identificationofgeneticvariationsthatcontributetoALIsusceptibil- ity and severity in order to gain unique insights into

  20. Imaging Acute Renal Failure with Polyamine Dendrimer-Based MRI Contrast Agents

    Microsoft Academic Search

    James W. Dear; Hisataka Kobayashi; Martin W. Brechbiel; Robert A. Star

    2006-01-01

    Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF.

  1. Opening the microcirculation: can vasodilators be useful in sepsis?

    Microsoft Academic Search

    Mattijn Buwalda; Can Ince

    2002-01-01

    Objective. A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy, which raises the driving pressure of the microcirculation and thereby promotes flow, could recruit such shunted microcirculatory units and improve

  2. Abdominal wall cellulitis and sepsis secondary to percutaneous cecostomy

    Microsoft Academic Search

    Thomas J. Maginot; Philip N. Cascade

    1993-01-01

    We report 1 case of abdominal wall cellulitis and sepsis which developed following percutaneous placement of a Cope catheter\\u000a for cecal decompression in a patient with Ogilvie's syndrome. This case highlights that further laboratory investigation and\\u000a clinical evaluation are needed to determine the safest and most efficacious technique of percutaneous drainage.

  3. Clinical manifestations of disordered microcirculatory perfusion in severe sepsis

    Microsoft Academic Search

    Stephen Trzeciak; Emanuel P Rivers

    2005-01-01

    Microcirculatory dysfunction plays a pivotal role in the development of the clinical manifestations of severe sepsis. Prior to the advent of new imaging technologies, clinicians had been limited in their ability to assess the microcirculation at the bedside. Clinical evidence of microcirculatory perfusion has historically been limited to physical examination findings or surrogates that could be derived from global parameters

  4. Systemic inflammatory response syndrome, sepsis, and antimicrobial therapy

    Microsoft Academic Search

    Martin Furr

    2003-01-01

    Neonatal sepsis is a serious and often fatal disease of the foal. Research has documented that the clinical syndrome which results from bacterial infection of the neonate is the result of a widespread and florid inflammatory response which is termed the systemic inflammatory response syndrome (SIRS). Successful treatment of affected individuals is possible, and an important component of the treatment

  5. Protective effects of heparin on endothelial cells in sepsis

    PubMed Central

    Ma, Jianqi; Bai, Jinghui

    2015-01-01

    Objective: This study aims to observe the protective effects of heparin on endothelial cells in sepsis and explore the involved signal pathway regulated by heparin. Methods Human vascular endothelial cells were treated by TNF? in vitro to simulate the inflammatory environment when sepsis occurred. They were intervened by heparin and the expression levels of soluble thrombomodulin (sTM) and serum activated protein C (APC) were detected by ELISA, the regulatory mechanism of heparin improving vascular endothelial cells injury induced by TNF? was detected by Western Blotting method, the methylation of histone in the gene promoter region of endothelial nitric oxide synthase (eNOS) and monocyte chemotactic protein-1 (MCP-1) were detected using chromatin immunoprecipitation method. Results Heparin could inhibit the secretion of sTM and APC protein and the expression of MCP-1 gene which involved in NF-?B signal pathway. Conclusions Heparin could protect vascular endothelial cells from injury induced by TNF? and sepsis, the mechanisms were related with the effects of heparin on the histone methylation of promoter region and the regulation of heparin on the MAPK and NF-?B signal pathways. These results provide a theoretical basis for the application of heparin in the prevention and treatment of vascular disease related with sepsis.

  6. Bench-to-bedside review: ?-Adrenergic modulation in sepsis

    PubMed Central

    2009-01-01

    Sepsis, despite recent therapeutic progress, still carries unacceptably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, could be an interesting new therapeutic target for septic shock. ?-Adrenergic regulation of the immune function in sepsis is complex and is time dependent. However, ?2 activation as well as ?1 blockade seems to downregulate proinflammatory response by modulating the cytokine production profile. ?1 blockade improves cardiovascular homeostasis in septic animals, by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. ?-Blockers could also be of interest in the systemic catabolic response to sepsis, as they oppose epinephrine which is known to promote hyperglycemia, lipid and protein catabolism. The role of ?-blockers in coagulation is less clear cut. They could have a favorable role in the septic pro-coagulant state, as ?1 blockade may reduce platelet aggregation and normalize the depressed fibrinolytic status induced by adre-nergic stimulation. Therefore, ?1 blockade as well as ?2 activation improves sepsis-induced immune, cardiovascular and coagulation dysfunctions. ?2 blocking, however, seems beneficial in the metabolic field. Enough evidence has been accumulated in the literature to propose ?- adrenergic modulation, ?1 blockade and ?2 activation in particular, as new promising therapeutic targets for septic dyshomeostasis, modulating favorably immune, cardiovascular, metabolic and coagulation systems. PMID:19863760

  7. Fatal sepsis by Bacillus circulans in an immunocompromised patient

    PubMed Central

    Alebouyeh, M; Gooran Orimi, P; Azimi-rad, M; Tajbakhsh, M; Tajeddin, E; Jahani Sherafat, S; Nazemalhosseini mojarad, E; Zali, MR

    2011-01-01

    An immunosuppressed man was admitted to hospital with diarrhea and a history of urinary tract infection. He was subjected to treatment with antibiotics. The patient died of putative severe sepsis. The etiological agent was a carbapenemase producing isolate of Bacillus circulans with resistance to all prescribed antimicrobial agents. PMID:22347600

  8. Syndecan 1 Shedding Contributes to Pseudomonas aeruginosa Sepsis

    Microsoft Academic Search

    Allan Haynes; Frank Ruda; Jeffrey Oliver; Abdul N. Hamood; John A. Griswold; Pyong Woo Park; Kendra P. Rumbaugh

    2005-01-01

    The innate immune system is comprised of many components that function coordinately to prevent bacterial sepsis. However, thermal injury suppresses many of these factors, and the opportunistic pathogen Pseudomonas aeruginosa takes advantage of this condition, making it one of the leading causes of morbidity and mortality in the setting of thermal injury. P. aeruginosa is extremely efficient at colonizing burn

  9. Therapeutic approaches to innate immunity: severe sepsis and septic shock

    Microsoft Academic Search

    Elias Lolis; Richard Bucala

    2003-01-01

    Severe sepsis leading to shock is the principal cause of death in non-cardiac intensive care units. This condition develops because of a dysregulation in host responses, such that the mechanisms initially recruited to fight infection produce life-threatening tissue damage and death. Recent advances in our understanding of innate immunity, and the interaction between the inflammatory and the haemostatic cascades, are

  10. Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock

    Microsoft Academic Search

    Djillali Annane; Virginie Maxime; Fidaa Ibrahim; Jean Claude Alvarez; Emuri Abe; Philippe Boudou

    2006-01-01

    Rationale: Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard. Objective: We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimu- lation test, and the prevalence of sepsis-associated adrenal insufficiency. Methods: This was an inception

  11. Cerebral blood flow is reduced in patients with sepsis syndrome

    SciTech Connect

    Bowton, D.L.; Bertels, N.H.; Prough, D.S.; Stump, D.A.

    1989-05-01

    The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO/sub 2/ in nine patients with sepsis syndrome using the /sup 133/Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, the specific reactivity of the cerebral vasculature to changes in CO/sub 2/ was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study.

  12. Crosstalk between the coagulation and complement systems in sepsis.

    PubMed

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

    2014-05-01

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

  13. Late implant sepsis after fracture surgery in HIV positive patients.

    PubMed

    Graham, Simon Matthew; Bates, Jes; Mkandawire, Nyengo; Harrison, William J

    2015-04-01

    A prospective cohort study was undertaken to assess the incidence of late-implant sepsis after internal fixation in HIV-positive patients. A total of 91 HIV-positive patients (67 males and 24 females) who underwent 103 procedures (111 implants) were followed up for a mean period of 27 months (range 12-66 months). No occurrences of late implant sepsis were found in 100 implants (94 procedures) in 82 patients at 27 months' follow-up (range 12-66 months). Nine patients (9 procedures, 9 implants) developed early infections within 6 weeks and were treated with antibiotics (6 patients), amputation (1 patient) or removal of metal work (2 patients). There was no evidence of subsequent late implant sepsis in any of these patients, at a mean follow-up of 25 months (range 12-52 months). This study demonstrates that it is safe to perform internal fixation in HIV-positive patients, with no observed increase risk of late implant sepsis. There is no indication to remove implants after fracture union, other than for the general clinical indications that may lead to removal of metal work in any patient. PMID:25601086

  14. CNS leptin action modulates immune response and survival in sepsis.

    PubMed

    Tschöp, Johannes; Nogueiras, Ruben; Haas-Lockie, Sarah; Kasten, Kevin R; Castañeda, Tamara R; Huber, Nadine; Guanciale, Kelsey; Perez-Tilve, Diego; Habegger, Kirk; Ottaway, Nickki; Woods, Stephen C; Oldfield, Brian; Clarke, Iain; Chua, Streamson; Farooqi, I Sadaf; O'Rahilly, Stephen; Caldwell, Charles C; Tschöp, Matthias H

    2010-04-28

    Sepsis describes a complex clinical syndrome that results from an infection, setting off a cascade of systemic inflammatory responses that can lead to multiple organ failure and death. Leptin is a 16 kDa adipokine that, among its multiple known effects, is involved in regulating immune function. Here we demonstrate that leptin deficiency in ob/ob mice leads to higher mortality and more severe organ damage in a standard model of sepsis in mice [cecal ligation and puncture (CLP)]. Moreover, systemic leptin replacement improved the immune response to CLP. Based on the molecular mechanisms of leptin regulation of energy metabolism and reproductive function, we hypothesized that leptin acts in the CNS to efficiently coordinate peripheral immune defense in sepsis. We now report that leptin signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenous CNS leptin action is required for an adequate systemic immune response. These findings reveal the existence of a relevant neuroendocrine control of systemic immune defense and suggest a possible therapeutic potential for leptin analogs in infectious disease. PMID:20427662

  15. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis

    Microsoft Academic Search

    Rienk Nieuwland; R. J. Berckmans; S. McGregor; A. N. Boing; F. P. H. Th. M Romijn; Rudi G. J. Westendorp; C. Erik Hack; Augueste Sturk

    2000-01-01

    Patients with meningococcal sepsis gen- erally suffer from disseminated intravas- cular coagulation (DIC). The aim of this study was to address whether these patients have elevated numbers of circu- lating microparticles that contribute to the development of DIC. Plasma samples from 5 survivors, 2 nonsurvivors, and 5 healthy volunteers were analyzed for the presence of microparticles by flow cytom- etry.

  16. Erythropoietin improves skeletal muscle microcirculation and tissue bioenergetics in a mouse sepsis model

    PubMed Central

    Kao, Raymond; Xenocostas, Anargyros; Rui, Tao; Yu, Pei; Huang, Weixiong; Rose, James; Martin, Claudio M

    2007-01-01

    Introduction The relationship between oxygen delivery and consumption in sepsis is impaired, suggesting a microcirculatory perfusion defect. Recombinant human erythropoietin (rHuEPO) regulates erythropoiesis and also exerts complex actions promoting the maintenance of homeostasis of the organism under stress. The objective of this study was to test the hypothesis that rHuEPO could improve skeletal muscle capillary perfusion and tissue oxygenation in sepsis. Methods Septic mice in three experiments received rHu-EPO 400 U/kg subcutaneously 18 hours after cecal ligation and perforation (CLP). The first experiment measured the acute effects of rHuEPO on hemodynamics, blood counts, and arterial lactate level. The next two sets of experiments used intravital microscopy to observe capillary perfusion and nicotinamide adenine dinucleotide (NADH) fluorescence post-CLP after treatment with rHuEPO every 10 minutes for 40 minutes and at 6 hours. Perfused capillary density during a three-minute observation period and NADH fluorescence were measured. Results rHuEPO did not have any effects on blood pressure, lactate level, or blood cell numbers. CLP mice demonstrated a 22% decrease in perfused capillary density compared to the sham group (28.5 versus 36.6 capillaries per millimeter; p < 0.001). Treatment of CLP mice with rHuEPO resulted in an immediate and significant increase in perfused capillaries in the CLP group at all time points compared to baseline from 28.5 to 33.6 capillaries per millimeter at 40 minutes; p < 0.001. A significant increase in baseline NADH, suggesting tissue hypoxia, was noted in the CLP mice compared to the sham group (48.3 versus 43.9 fluorescence units [FU]; p = 0.03) and improved with rHuEPO from 48.3 to 44.4 FU at 40 minutes (p = 0.02). Six hours after treatment with rHuEPO, CLP mice demonstrated a higher mean perfused capillary density (39.4 versus 31.7 capillaries per millimeter; p < 0.001) and a lower mean NADH fluorescence as compared to CLP+normal saline mice (49.4 versus 52.7 FU; p = 0.03). Conclusion rHuEPO produced an immediate increase in capillary perfusion and decrease in NADH fluorescence in skeletal muscle. Thus, it appears that rHuEPO improves tissue bioenergetics, which is sustained for at least six hours in this murine sepsis model. PMID:17509156

  17. Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1?.

    PubMed

    Shalova, Irina N; Lim, Jyue Yuan; Chittezhath, Manesh; Zinkernagel, Annelies S; Beasley, Federico; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Rapisarda, Annamaria; Chen, Jinmiao; Duan, Kaibo; Yang, Henry; Poidinger, Michael; Melillo, Giovanni; Nizet, Victor; Arnalich, Francisco; López-Collazo, Eduardo; Biswas, Subhra K

    2015-03-17

    Sepsis is characterized by a dysregulated inflammatory response to infection. Despite studies in mice, the cellular and molecular basis of human sepsis remains unclear and effective therapies are lacking. Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. However, the response of these cells in human sepsis and their contribution to sepsis pathogenesis is poorly understood. To investigate this, we performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Our results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. Mechanistically, hypoxia inducible factor-1? (HIF1?) mediated this functional re-programming of monocytes, revealing a potential mechanism for their therapeutic targeting to regulate human sepsis. PMID:25746953

  18. Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Geladopoulos, Taxiarchis; Chrisofos, Michael; Koutoukas, Pantelis; Vassiliadis, John; Alexandrou, Ioannis; Tsaganos, Thomas; Sabracos, Labros; Karagianni, Vassiliki; Pelekanou, Emilia; Tzepi, Ira; Kranidioti, Hariklia; Koussoulas, Vassilios; Giamarellou, Helen

    2006-10-01

    Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines. PMID:16980890

  19. Long pentraxin PTX3 deficiency worsens LPS-induced acute lung injury

    Microsoft Academic Search

    Bing Han; Jack J. Haitsma; Yu Zhang; Xiaohui Bai; Matthew Rubacha; Shaf Keshavjee; Haibo Zhang; Mingyao Liu

    2011-01-01

    Objective  Long pentraxin PTX3 is an inflammatory mediator and a component of the humoral arm of innate immunity. PTX3 expression is\\u000a increased in animals with acute lung injury (ALI) and in patients with sepsis or acute respiratory distress syndrome and is\\u000a considered to be a potential biomarker for these diseases. However, the role of PTX3 in the pathogenesis of ALI is

  20. Percutaneous CT-Guided Catheter Drainage of Infected Acute Necrotizing Pancreatitis:Techniques and Results

    Microsoft Academic Search

    Patrick C. Freeny; Ellen Hauptmann; Sandra J. Althaus; L. William Traverso; Mika Sinanan

    1998-01-01

    OBJECTIVE. The objective of this paper was to assess the safety and efficacy of percuta- neous catheter drainage for initial treatment of infected acute necrotizing pancreatitis. MATERIALS AND METHODS. Thirty-four patients with acute necrotizing pancreatitis shown with contrast-enhanced CT were treated for sepsis with percutaneous catheter drain- age. Extent of necrosis was less than 30% in 10 cases. 3(1-50% in

  1. Genomics of Acute Lung Injury and Vascular Barrier Dysfunction

    Microsoft Academic Search

    Roberto F. Machado; Joe G. N. Garcia

    \\u000a Acute lung injury (ALI) is a devastating ­syndrome of diffuse alveolar damage that develops via a variety of local and systemic\\u000a insults such as sepsis, trauma, ­pneumonia, and aspiration. It is interestingly to note that only a subset of individuals\\u000a exposed to potential ALI-inciting insults develop the disorder and the severity of the disease varies from complete resolution\\u000a to death.

  2. Epidemiology, Classification, Etiopathogenesis, and Diagnosis of Acute Pancreatitis

    Microsoft Academic Search

    Gianluca Guercioni; Walter Siquini; Emidio Senati

    \\u000a In 1925, Moynihan described the dramatic nature of acute pancreatitis as the “most terrible of all calamities that occurs\\u000a in connection with the abdominal viscera. The suddenness of its onset, the illimitable agony which accompanies it, and the\\u000a mortality attendant upon it renders it the most formidable of catastrophes” [1]. From mild and self-limiting disease to multiorgan failure and sepsis,

  3. Sinomenine hydrochloride protects against polymicrobial sepsis via autophagy.

    PubMed

    Jiang, Yu; Gao, Min; Wang, Wenmei; Lang, Yuejiao; Tong, Zhongyi; Wang, Kangkai; Zhang, Huali; Chen, Guangwen; Liu, Meidong; Yao, Yongming; Xiao, Xianzhong

    2015-01-01

    Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs). The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN) is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl) is widely used to treat rheumatoid arthritis (RA). However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP) in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA) was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3) puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS)-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM). 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities. PMID:25625512

  4. Beneficial effects of ulinastatin on gut barrier function in sepsis

    PubMed Central

    Jiang, Longyuan; Yang, Lianhong; Zhang, Meng; Fang, Xiangshao; Huang, Zitong; Yang, Zhengfei; Zhou, Tianen

    2013-01-01

    Background & objectives: The gut contains some endogenous and exogenous microorganisms that can become potential pathogens of sepsis under certain circumstances. Therefore, the integrity and normal function of gut barrier is important for preventing the development of sepsis. The present study was designed to assess the effects of ulinastatin, a urinary trypsin inhibitor on gut barrier function and mortality in experimental sepsis. Methods: Male Sprague-Dawley rats were subjected to ceacal ligation and puncture (CLP) or sham procedure. Rats were then treated with ulinastatin 50,000 U/kg/day or saline. The mortality rate was determined. Histology, apoptosis assays, and PCR were performed using ileum specimens at 3, 6, and 12 h following CLP. Serum levels of tumour necrosis factor ? (TNF-?) and interleukin-6 (IL-6) were also measured at 0, 3, 6, and 12 h following CLP. Results: Compared with the saline-treated CLP rats, the ulinastatin CLP rats had significantly increased survival time (P<0.05), lower histopathological scores of intestinal injury (P<0.05), reduced apoptosis detected by terminal deoxynucleotidyl transferase dUTP nick end labelling assay and caspase 3 activity (P<0.01). Moreover, RD-5 mRNA expression was significantly higher in ulinastatin-treated CLP animals than saline controls (P<0.05). These results suggested a preserved integrity and function of the gut barrier. Significantly lower plasma TNF? and IL-6 levels were detected in CLP rats with ulinastatin treatment, which contributed to increased survival time. Interpretation & conclusions: Our results suggest that ulinastatin has a therapeutic potential to prevent gut barrier dysfunction in the early stage of sepsis, thereby improving the outcome of sepsis. Further studies need to be done to understand the mechanism of action of ulinastatin. PMID:24521634

  5. A2B Adenosine Receptor Blockade Enhances Macrophage-Mediated Bacterial Phagocytosis and Improves Polymicrobial Sepsis Survival in Mice

    PubMed Central

    Belikoff, Bryan G.; Hatfield, Stephen; Georgiev, Peter; Ohta, Akio; Lukashev, Dmitriy; Buras, Jon A.; Remick, Daniel G.; Sitkovsky, Michail

    2013-01-01

    Antimicrobial treatment strategies must improve to reduce the high mortality rates in septic patients. In noninfectious models of acute inflammation, activation of A2B adenosine receptors (A2BR) in extracellular adenosine-rich microenvironments causes immunosuppression. We examined A2BR in antibacterial responses in the cecal ligation and puncture (CLP) model of sepsis. Antagonism of A2BR significantly increased survival, enhanced bacterial phagocytosis, and decreased IL-6 and MIP-2 (a CXC chemokine) levels after CLP in outbred (ICR/CD-1) mice. During the CLP-induced septic response in A2BR knockout mice, hemodynamic parameters were improved compared with wild-type mice in addition to better survival and decreased plasma IL-6 levels. A2BR deficiency resulted in a dramatic 4-log reduction in peritoneal bacteria. The mechanism of these improvements was due to enhanced macrophage phagocytic activity without augmenting neutrophil phagocytosis of bacteria. Following ex vivo LPS stimulation, septic macrophages from A2BR knockout mice had increased IL-6 and TNF-? secretion compared with wild-type mice. A therapeutic intervention with A2BR blockade was studied by using a plasma biomarker to direct therapy to those mice predicted to die. Pharmacological blockade of A2BR even 32 h after the onset of sepsis increased survival by 65% in those mice predicted to die. Thus, even the late treatment with an A2BR antagonist significantly improved survival of mice (ICR/CD-1) that were otherwise determined to die according to plasma IL-6 levels. Our findings of enhanced bacterial clearance and host survival suggest that antagonism of A2BRs offers a therapeutic target to improve macrophage function in a late treatment protocol that improves sepsis survival. PMID:21242513

  6. Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains?

    PubMed Central

    Nogueira, R. D.; King, W. F.; Gunda, G.; Culshaw, S.; Taubman, M. A.; Mattos-Graner, R. O.; Smith, D. J.

    2008-01-01

    The interplay between mucosal immune responses to natural exposure to mutans streptococci and the incorporation and accumulation of these cariogenic microorganisms in oral biofilms is unclear. An initial approach to explore this question would be to assess the native secretory immunity emerging as a consequence of Streptococcus mutans infection. To this end, we analyzed salivary immunoglobulin A (IgA) antibody to mutans streptococcal glucosyltransferase (Gtf) and glucan binding protein B (GbpB) and to domains associated with enzyme function and major histocompatibility complex (MHC) class II binding in two experiments. Salivas were collected from approximately 45-day-old Sprague-Dawley rats, which were then infected with S. mutans SJ32. Infection was verified and allowed to continue for 2 to 2.5 months. Salivas were again collected following the infection period. Pre- and postinfection salivas were then analyzed for IgA antibody activity using peptide- or protein-coated microsphere Luminex technology. S. mutans infection induced significant levels of salivary IgA antibody to Gtf (P < 0.002) and GbpB (P < 0.001) in both experiments, although the levels were usually far lower than the levels achieved when mucosal immunization is used. Significantly (P < 0.035 to P < 0.001) elevated levels of postinfection salivary IgA antibody to 6/10 Gtf peptides associated with either enzyme function or MHC binding were detected. The postinfection levels of antibody to two GbpB peptides in the N-terminal region of the six GbpB peptides assayed were also elevated (P < 0.031 and P < 0.001). Interestingly, the patterns of the rodent response to GbpB peptides were similar to the patterns seen in salivas from young children during their initial exposure to S. mutans. Thus, the presence of a detectable postinfection salivary IgA response to mutans streptococcal virulence-associated components, coupled with the correspondence between rat and human mucosal immune responsiveness to naturally presented Gtf and GbpB epitopes, suggests that the rat may be a useful model for defining mucosal responses that could be expected in humans. Under controlled infection conditions, such a model could prove to be helpful for unraveling relationships between the host response and oral biofilm development. PMID:18474645

  7. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

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

  8. MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis-induced lung injury.

    PubMed

    Mannam, Praveen; Shinn, Amanda S; Srivastava, Anup; Neamu, Radu F; Walker, Wendy E; Bohanon, Michael; Merkel, Jane; Kang, Min-Jong; Dela Cruz, Charles S; Ahasic, Amy M; Pisani, Margaret A; Trentalange, Mark; West, A Phillip; Shadel, Gerald S; Elias, Jack A; Lee, Patty J

    2014-04-01

    Sepsis is a systemic inflammatory response to infection and a major cause of death worldwide. Because specific therapies to treat sepsis are limited, and underlying pathogenesis is unclear, current medical care remains purely supportive. Therefore targeted therapies to treat sepsis need to be developed. Although an important mediator of sepsis is thought to be mitochondrial dysfunction, the underlying molecular mechanism is unclear. Modulation of mitochondrial processes may be an effective therapeutic strategy in sepsis. Here, we investigated the role of the kinase MKK3 in regulation of mitochondrial function in sepsis. Using clinically relevant animal models, we examined mitochondrial function in primary mouse lung endothelial cells exposed to LPS. MKK3 deficiency reduces lethality of sepsis in mice and by lowering levels of lung and mitochondrial injury as well as reactive oxygen species. Furthermore, MKK3 deficiency appeared to simultaneously increase mitochondrial biogenesis and mitophagy through the actions of Sirt1, Pink1, and Parkin. This led to a more robust mitochondrial network, which we propose provides protection against sepsis. We also detected higher MKK3 activation in isolated peripheral blood mononuclear cells from septic patients compared with nonseptic controls. Our findings demonstrate a critical role for mitochondria in the pathogenesis of sepsis that involves a previously unrecognized function of MKK3 in mitochondrial quality control. This mitochondrial pathway may help reveal new diagnostic markers and therapeutic targets against sepsis. PMID:24487387

  9. Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis.

    PubMed

    Kim, Sunghee; Mi, Lijun; Zhang, Lurong

    2012-08-01

    Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its tumor necrosis factor-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to systemic inflammatory response syndrome (SIRS), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/mL, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis. PMID:22647538

  10. Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study

    Microsoft Academic Search

    John A. Kellum; Lan Kong; Mitchell P. Fink; Lisa A. Weissfeld; Donald M. Yealy; Michael R. Pinsky; Jonathan Fine; Alexander Krichevsky; Russell L. Delude; Derek C. Angus

    2007-01-01

    Background: Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evi- dence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and de- termine if specific patterns, including the

  11. The perfect storm: older adults and acute kidney injury.

    PubMed

    Hain, Debra; Paixao, Rute

    2015-01-01

    Older adults have a high risk for acute kidney injury (AKI), often necessitating critical care admission. The majority of older adults live with 1 or more chronic conditions requiring multiple medications, and when faced with acute illness increased vulnerability can lead to poor health outcomes. When combined with circumstances that exacerbate chronic conditions, clinicians may witness the perfect storm. Some factors that contribute to AKI risk include the aging kidney, sepsis, polypharmacy, and nephrotoxic medications and contrast media. This paper discusses specific risks and approaches to care for older adults with AKI who are in critical care. PMID:26039649

  12. Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

    PubMed Central

    Almog, Yaniv; Perl, Yael; Novack, Victor; Galante, Ori; Klein, Moti; Pencina, Michael J.; Douvdevani, Amos

    2014-01-01

    Aim The aim of the current study is to assess the mortality prediction accuracy of circulating cell-free DNA (CFD) level at admission measured by a new simplified method. Materials and Methods CFD levels were measured by a direct fluorescence assay in severe sepsis patients on intensive care unit (ICU) admission. In-hospital and/or twenty eight day all-cause mortality was the primary outcome. Results Out of 108 patients with median APACHE II of 20, 32.4% have died in hospital/or at 28-day. CFD levels were higher in decedents: median 3469.0 vs. 1659 ng/ml, p<0.001. In multivariable model APACHE II score and CFD (quartiles) were significantly associated with the mortality: odds ratio of 1.05, p?=?0.049 and 2.57, p<0.001 per quartile respectively. C-statistics for the models was 0.79 for CFD and 0.68 for APACHE II. Integrated discrimination improvement (IDI) analyses showed that CFD and CFD+APACHE II score models had better discriminatory ability than APACHE II score alone. Conclusions CFD level assessed by a new, simple fluorometric-assay is an accurate predictor of acute mortality among ICU patients with severe sepsis. Comparison of CFD to APACHE II score and Procalcitonin (PCT), suggests that CFD has the potential to improve clinical decision making. PMID:24955978

  13. Identification of Streptococcal M-Protein Cardiopathogenic Epitopes in Experimental Autoimmune Valvulitis

    PubMed Central

    Kirvan, Christine A.; Galvin, Jeffrey E.; Hilt, Silvia; Kosanke, Stanley; Cunningham, Madeleine W.

    2014-01-01

    The M protein of rheumatogenic group A streptococci induces carditis and valvulitis in Lewis rats and may play a role in pathogenesis of rheumatic heart disease. To identify epitopes of M5 protein that produce valvulitis, synthetic peptides spanning A, B, and C repeat regions contained within the extracellular domain of the streptococcal M5 protein were investigated. A repeat region peptides NT4, NT5/6, and NT7 induced valvulitis similar to the intact pepsin fragment of M5 protein. T cell lines from rats with valvulitis recognized M5 peptides NT5/6 and NT6. Passive transfer of an NT5/6-specific T cell line into naïve rats produced valvulitis characterized by infiltration of CD4+ cells and upregulation of VCAM-1, while an NT6-specific T cell line did not target the valve. Our new data suggests that M protein-specific T cells may be important mediators of valvulitis in the Lewis rat model of rheumatic carditis. PMID:24346820

  14. Identification of streptococcal m-protein cardiopathogenic epitopes in experimental autoimmune valvulitis.

    PubMed

    Kirvan, Christine A; Galvin, Jeffrey E; Hilt, Silvia; Kosanke, Stanley; Cunningham, Madeleine W

    2014-03-01

    The M protein of rheumatogenic group A streptococci induces carditis and valvulitis in Lewis rats and may play a role in pathogenesis of rheumatic heart disease. To identify the epitopes of M5 protein that produce valvulitis, synthetic peptides spanning A, B, and C repeat regions contained within the extracellular domain of the streptococcal M5 protein were investigated. A repeat region peptides NT4, NT5/6, and NT7 induced valvulitis similar to the intact pepsin fragment of M5 protein. T cell lines from rats with valvulitis recognized M5 peptides NT5/6 and NT6. Passive transfer of an NT5/6-specific T cell line into naïve rats produced valvulitis characterized by infiltration of CD4+ cells and upregulation of VCAM-1, while an NT6-specific T cell line did not target the valve. Our new data suggests that M protein-specific T cells may be important mediators of valvulitis in the Lewis rat model of rheumatic carditis. PMID:24346820

  15. Invasive group A streptococcal infections in the San Francisco Bay area, 1989-99.

    PubMed Central

    Passaro, D. J.; Smitht, D. S.; Hett, E. C.; Reingold, A. L.; Daily, P.; van Beneden, C. A.; Vugia, D. J.

    2002-01-01

    To describe the epidemiology of invasive group A streptococcal (iGAS) infections in the San Francisco Bay Area, population-based active surveillance for laboratory-confirmed iGAS was conducted by the California Emerging Infections Program in three California counties. From January 1989 to December 1999, 1415 cases of iGAS were identified. Mean iGAS incidence was 4.06/100,000 person-years and case fatality ratio was 13%, with no linear trends over time. Incidence was lowest in adolescents, was higher in men than women (4.4 vs. 3.2/100,000 person-years), and was higher in African-Americans (6.7) than in non-Hispanic (4.1) or Hispanic (3.4) Whites, Asians (2.2) or Native Americans (17/100,000 person-years). Injecting drug use was the riskiest underlying condition and was associated with the highest attributable risk. Cases were associated with several underlying conditions, but 23% occurred in previously healthy persons. From 1989-1999, iGAS infections in the San Francisco Bay Area became neither more common nor more deadly. PMID:12558329

  16. Seroprevalence of antibodies to group B streptococcal polysaccharides in Gambian mothers and their newborns.

    PubMed Central

    Suara, R. O.; Adegbola, R. A.; Mulholland, E. K.; Greenwood, B. M.; Baker, C. J.

    1998-01-01

    In developing countries, little is known about the relationship between group B streptococcal (GBS) colonization in pregnant women and serum antibody levels to capsular polysaccharide antigens of these organisms. This study examined the prevalence of antibodies to two polysaccharides of GBS, Ia and III, in 124 Gambian women with known GBS colonization at delivery and their newborns. Mean antibody levels in maternal-cord serum pairs were 4.06 +/- 0.25 micrograms/mL and 2.64 +/- 0.20 micrograms/mL for type Ia GBS, and 1.1 +/- 0.52 microgram/mL and 0.78 +/- 0.43 microgram/mL for type III GBS. Women colonized with type V GBS had significantly higher antibody levels to type III GBS than did noncolonized women, but no difference was found when these groups were compared for antibody levels to type Ia GBS. Women > or = 20 years had significantly higher antibody levels to type III GBS compared with younger women and those colonized by other GBS serotypes. Maternal antibodies to types la and III GBS were transferred across the placenta to newborns. The rarity of GBS disease in Gambia and other developing countries may be due to the prevalence of maternally derived GBS antibodies, the low prevalence of colonization with serotype III strains, or other undefined factors. PMID:9510625

  17. The Superantigen Streptococcal Pyrogenic Exotoxin C (SPE-C) Exhibits a Novel Mode of Action

    PubMed Central

    Li, Pei-Lin; Tiedemann, Rodger E.; Moffat, S. Louise; Fraser, John D.

    1997-01-01

    Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen that stimulates V?2-bearing human T cells, but is inactive in mice. SPE-C binds with high affinity to both human HLA-DR and murine I-E molecules, but not to murine I-A molecules in a zinc-dependent fashion. Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatibility complex (MHC) class II ?-chain binding site common to all other bacterial superantigens. Despite this, SPE-C cross-links MHC class II to induce homotypic aggregation of class II–bearing B cells. Nondenaturing sodium dodecyl sulfate electrophoresis and size exclusion chromatography revealed that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or alkaline pH. These data support a recent crystal structure of SPE-C and reveal yet another mechanism by which bacterial superantigens ligate and cross-link MHC class II. PMID:9236189

  18. Recombination Drives Genetic Diversification of Streptococcus dysgalactiae Subspecies equisimilis in a Region of Streptococcal Endemicity

    PubMed Central

    McMillan, David J.; Kaul, Santosh Y.; Bramhachari, P. V.; Smeesters, Pierre R.; Vu, Therese; Karmarkar, M. G.; Shaila, Melkote S.; Sriprakash, Kadaba S.

    2011-01-01

    Infection of the skin or throat by Streptococcus dysgalactiae subspecies equisimilis (SDSE) may result in a number of human diseases. To understand mechanisms that give rise to new genetic variants in this species, we used multi-locus sequence typing (MLST) to characterise relationships in the SDSE population from India, a country where streptococcal disease is endemic. The study revealed Indian SDSE isolates have sequence types (STs) predominantly different to those reported from other regions of the world. Emm-ST combinations in India are also largely unique. Split decomposition analysis, the presence of emm-types in unrelated clonal complexes, and analysis of phylogenetic trees based on concatenated sequences all reveal an extensive history of recombination within the population. The ratio of recombination to mutation (r/m) events (11?1) and per site r/m ratio (41?1) in this population is twice as high as reported for SDSE from non-endemic regions. Recombination involving the emm-gene is also more frequent than recombination involving housekeeping genes, consistent with diversification of M proteins offering selective advantages to the pathogen. Our data demonstrate that genetic recombination in endemic regions is more frequent than non-endemic regions, and gives rise to novel local SDSE variants, some of which may have increased fitness or pathogenic potential. PMID:21857905

  19. A Glimpse of Streptococcal Toxic Shock Syndrome from Comparative Genomics of S. suis 2 Chinese Isolates

    PubMed Central

    Wang, Jing; Zheng, Feng; Pan, Xiuzhen; Liu, Di; Li, Ming; Song, Yajun; Zhu, Xinxing; Sun, Haibo; Feng, Tao; Guo, Zhaobiao; Ju, Aiping; Ge, Junchao; Dong, Yaqing; Sun, Wen; Jiang, Yongqiang; Wang, Jun; Yan, Jinghua; Yang, Huanming; Wang, Xiaoning; Gao, George F.; Yang, Ruifu; Wang, Jian; Yu, Jun

    2007-01-01

    Background Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. Methods and Findings To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of ?89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. Conclusions To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections. PMID:17375201

  20. Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase.

    PubMed

    Cork, Amanda J; Ericsson, Daniel J; Law, Ruby H P; Casey, Lachlan W; Valkov, Eugene; Bertozzi, Carlo; Stamp, Anna; Jovcevski, Blagojce; Aquilina, J Andrew; Whisstock, James C; Walker, Mark J; Kobe, Bostjan

    2015-01-01

    Group A Streptococcus (GAS) is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen). Streptococcal surface enolase (SEN) is an octameric ?-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen) on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen) binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SENK312A and SENK362A is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen) to its binding sites, leading to more efficient plasmin(ogen) binding and activation. PMID:25807546

  1. Prospective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005–2007

    PubMed Central

    Jenney, Adam; Kado, Joseph; Good, Michael F.; Batzloff, Michael; Waqatakirewa, Lepani; Mullholland, E. Kim; Carapetis, Jonathan R.

    2009-01-01

    We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005–2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6–12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1–92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention. PMID:19193265

  2. Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation*

    PubMed Central

    Sumitomo, Tomoko; Nakata, Masanobu; Higashino, Miharu; Terao, Yutaka; Kawabata, Shigetada

    2013-01-01

    Group A Streptococcus (GAS) is an important human pathogen that possesses an ability to translocate across the epithelial barrier. In this study, culture supernatants of tested GAS strains showed proteolytic activity against human occludin and E-cadherin. Utilizing various types of protease inhibitors and amino acid sequence analysis, we identified SpeB (streptococcal pyrogenic exotoxin B) as the proteolytic factor that cleaves E-cadherin in the region neighboring the calcium-binding sites within the extracellular domain. The cleaving activities of culture supernatants from several GAS isolates were correlated with the amount of active SpeB, whereas culture supernatants from an speB mutant showed no such activities. Of note, the wild type strain efficiently translocated across the epithelial monolayer along with cleavage of occludin and E-cadherin, whereas deletion of the speB gene compromised those activities. Moreover, destabilization of the junctional proteins was apparently relieved in cells infected with the speB mutant, as compared with those infected with the wild type. Taken together, our findings indicate that the proteolytic efficacy of SpeB in junctional degradation allows GAS to invade deeper into tissues. PMID:23532847

  3. Utility of the shock index in patients with sepsis.

    PubMed

    Tseng, Jim; Nugent, Kenneth

    2015-06-01

    The shock index (SI) equals the heart rate/systolic blood pressure and has been used to predict clinical outcomes, especially in trauma and surgery patients. The authors reviewed the literature to determine its utility in the management of patients with sepsis and in the prediction of adverse outcomes in these patients. The medical literature was searched using PubMed, Scopus, Web of Science and Google Scholar databases to identify articles in English on the SI in humans. These studies demonstrated that the SI could help evaluate the adequacy of fluid resuscitation and the potential response to additional fluid. It can predict the presence of lactic acidosis. The SI also helps predict the development of organ failure and mortality. Consequently, this easily available bedside measurement has utility in the identification, management and prediction of prognosis in patients with sepsis. PMID:25782337

  4. Commercial Multiplex Technologies for the Microbiological Diagnosis of Sepsis

    PubMed Central

    Lebovitz, Evan E.; Burbelo, Peter D.

    2013-01-01

    In patients with suspected sepsis, rapid and accurate diagnosis of the causative infectious agent is critical. Although clinicians often use empiric antimicrobial therapy until the blood cultures are available to potentially adjust treatment, this approach is often not optimum for patient care. Recently, several commercial molecular multiplex technologies have shown promise for fast and comprehensive diagnosis of microorganisms and their antimicrobial resistance signatures. While one class of multiplex technologies is directed at improving the speed and diagnostic information obtained from positive blood cultures, the other identifies the causative microorganisms directly from clinical blood samples. The goal of this review is to provide an overview of these molecular technologies and describe their performance capabilities compared to standard blood cultures and in some cases to each other. We discuss the current clinical impact, limitations, and likely futures advances these multiplex technologies may have in guiding the management of patients with sepsis. PMID:23636778

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

    PubMed

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

    2015-01-01

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

  6. Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis?

    Microsoft Academic Search

    Stefanie Meyer; Philipp Schuetz; Melanie Wieland; Charly Nusbaumer; Beat Mueller; Mirjam Christ-Crain

    2011-01-01

    There is ongoing controversy as to whether hormonal changes of the euthyroid sick syndrome are predictors of poor outcome\\u000a in sepsis and critical illness. In this prospective study, the prognostic accuracy of thyroid hormone levels in 103 critically\\u000a ill adult patients on admission and during follow up in a medical intensive care unit (ICU) was assessed and was compared\\u000a to

  7. Bench to bedside: A role for erythropoietin in sepsis

    Microsoft Academic Search

    Andrew P Walden; J Duncan Young; Edward Sharples

    2010-01-01

    ABSTRACT: Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions,

  8. Neonatal Sepsis: Staphylococcus aureus as the predominant pathogen

    Microsoft Academic Search

    G. Karthikeyan; K. Premkumar

    2001-01-01

    96 consecutive inborn neonates with blood culture proven bacterial sepsis during the period January to June 1997 were studied.\\u000a Lethargy with refusal of feeds (28%), fever (28%) and respiratory distress (31.3%) were the major presenting features. Half\\u000a of them (n=48) were of early onset ( 48 hours). Staphylococcus aureus\\u000a (n=59, 61.5%) was the predominant pathogen and 66% of them were

  9. Dog-bite induced sepsis: a report of four cases

    Microsoft Academic Search

    S. Hovenga; J. E. Tulleken; L. V. M. Möller; S. A. Jackson; J. G. Zijlstra

    1997-01-01

    Occasionally, a dog-bite is complicated by a systemic overwhelming infection. We report four consecutive patients who were\\u000a admitted to our intensive care unit because of sepsis syndrome following dog-bites. The history of these patients did not\\u000a reveal any immunocompromising conditions. Capnocytophaga canimorsus (C. canimorsus) was cultured from the blood culture of 2 patients. Our data illustrate that in patients with

  10. Early onset neonatal sepsis: diagnostic dilemmas and practical management.

    PubMed

    Bedford Russell, A R; Kumar, R

    2015-07-01

    Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms. PMID:25425652

  11. Microvesicular Caspase-1 Mediates Lymphocyte Apoptosis in Sepsis

    PubMed Central

    Exline, Matthew C.; Justiniano, Steven; Hollyfield, Jennifer L.; Berhe, Freweine; Besecker, Beth Y.; Das, Srabani; Wewers, Mark D.; Sarkar, Anasuya

    2014-01-01

    Objective Immune dysregulation during sepsis is poorly understood, however, lymphocyte apoptosis has been shown to correlate with poor outcomes in septic patients. The inflammasome, a molecular complex which includes caspase-1, is essential to the innate immune response to infection and also important in sepsis induced apoptosis. Our group has recently demonstrated that endotoxin-stimulated monocytes release microvesicles (MVs) containing caspase-1 that are capable of inducing apoptosis. We sought to determine if MVs containing caspase-1 are being released into the blood during human sepsis and induce apoptosis.. Design Single-center cohort study Measurements 50 critically ill patients were screened within 24 hours of admission to the intensive care unit and classified as either a septic or a critically ill control. Circulatory MVs were isolated and analyzed for the presence of caspase-1 and the ability to induce lymphocyte apoptosis. Patients remaining in the ICU for 48 hours had repeated measurement of caspase-1 activity on ICU day 3. Main Results Septic patients had higher microvesicular caspase-1 activity 0.05 (0.04, 0.07) AFU versus 0.0 AFU (0, 0.02) (p<0.001) on day 1 and this persisted on day 3, 0.12 (0.1, 0.2) versus 0.02 (0, 0.1) (p<0.001). MVs isolated from septic patients on day 1 were able to induce apoptosis in healthy donor lymphocytes compared with critically ill control patients (17.8±9.2% versus 4.3±2.6% apoptotic cells, p<0.001) and depletion of MVs greatly diminished this apoptotic signal. Inhibition of caspase-1 or the disruption of MV integrity abolished the ability to induce apoptosis. Conclusion These findings suggest that microvesicular caspase-1 is important in the host response to sepsis, at least in part, via its ability to induce lymphocyte apoptosis. The ability of microvesicles to induce apoptosis requires active caspase-1 and intact microvesicles. PMID:24643116

  12. [Changes of the intraabdominal pressure in patients with abdominal sepsis].

    PubMed

    Kursov, S V

    2013-01-01

    64 patients with abdominal sepsis were included in the study of the intraabdominal pressure changes before and after the operation. The study demonstrated that the use of the crystalloids alone leads to the development of the capillary leak syndrome in comparison with the therapy regimen using colloids. The aggressive fluid resuscitation, associated with high numbers of central venous pressure, increasing 1177Pa (120 mm H2O), was connected with the increase of the intraabdominal pressure. PMID:23996037

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

    PubMed Central

    Ferrer, Ricard; Artigas, Antonio

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. [Host inflammatory and anti-inflammatory response during sepsis].

    PubMed

    Adib-Conquy, M; Cavaillon, J-M

    2012-10-01

    Sepsis still remains the major complication for patients admitted in intensive care units (ICU), and is responsible for numerous deaths. ICU patients admitted after sepsis, hemorrhagic shock, severe trauma, severe burns or major surgery show a systemic inflammatory response syndrome (SIRS). This syndrome is characterized by an exacerbation of inflammation, with increased levels of pro- (IL-1?, TNF?, IL-6, IL-8) as well as anti-inflammatory (IL-10, IL-1Ra, TGF?) cytokines into their bloodstream. During sepsis, the bacteria release microbial motifs such as peptidoglycan, lipopolysaccharide (LPS) and DNA that initiate the inflammatory response, and are involved in the onset of multiple organ failure. The same microbial motifs can also be found in patients with a SIRS of non-infectious origin, following the translocation of bacteria from their digestive tract. This translocation is certainly contributing to the difficulty of discriminating between septic and SIRS patients using biological markers. Furthermore, the host response is accompanied by an alteration of the ex vivo response of circulating leukocytes, particularly monocytes. This hyporesponsiveness to LPS is associated with a decreased activation of the transcription factor NF-?B (required for the expression of pro-inflammatory cytokines) and an increased expression of negative regulators of the NF-?B pathway. However, the leukocyte hyporesponsiveness is not a global phenomenon, it depends on the type of patient, on the receptor-activator pair, on the timing, and on the cytokine. PMID:22542429

  16. Nanomechanics of the Endothelial Glycocalyx in Experimental Sepsis

    PubMed Central

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

    2013-01-01

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

  17. Efficacy of Xuebijing for coagulopathy in patients with sepsis

    PubMed Central

    Hou, Si-Yuan; Feng, Xing-Huo; Lin, Chang-Liang; Tan, Yong-Feng

    2015-01-01

    Objectives: To provide evidence of the clinical efficacy of Xuebijing (XBJ) on blood coagulation in patients with sepsis. Methods: We conducted this meta-analysis in The People’s Hospital of Liaoning Province, Shenyang, China between December 2013 and May 2014. We searched a number of databases for relevant randomized controlled trials (RCTs) published before December 2013 using the keywords ‘Xuebijing’, ‘coagulation’ and ‘sepsis’. Statistical analysis was performed with Review Manager 5.2 from the Cochrane Collaboration. Results: Fourteen RCTs involving 867 patients were included. Compared with placebo, XBJ injection significantly improved platelets (mean differences [MD] = 42.14, 95% confidence interval [CI]: 22.42 - 61.86, p<0.00001), shortened the activated partial thromboplastin time (MD = -4.81, 95% CI: -7.86 - [-1.76], p=0.002), shortened the prothrombin time (MD = -2.33, 95% CI: -4.15 - [-0.51], p=0.01), and shortened the thrombin time (MD = -2.05, 95% CI: -3.52 - [-0.58], p=0.006). However, no significant difference was found between the XBJ injection and the placebo group for fibrinogen (MD = 0.21, 95% CI: -0.38 - 0.81, p=0.48). Conclusion: Xuebijing injection may improve coagulopathy in patients with sepsis. High-quality and large sample clinical trials are needed for confirmation. PMID:25719579

  18. Decline in Sepsis-associated Neonatal and Infant Deaths in the United States 1979 Through 1994

    Microsoft Academic Search

    Barbara J. Stoll; Robert C. Holman; Anne Schuchat

    ABSTRACT. Background. Infant mortality in,the United States has continued to decline in recent years, but changes in sepsis-associated deaths among infants have not been evaluated previously. Methods. Data from US death records were analyzed for the period 1979 through 1994 to assess trends in sepsis-associated deaths among newborns and older in- fants. Results. Annual neonatal mortality associated with sepsis declined

  19. Antimicrobial Resistance of Escherichia coli Strains Causing Neonatal Sepsis between 1998 and 2008

    Microsoft Academic Search

    Elisabet Guiral; Jordi Bosch; Jordi Vila; Sara M. Soto

    2012-01-01

    Background: Bloodstream infections are a significant cause of neonatal morbidity and death. An increase in the incidence of early neonatal sepsis due to Escherichia coli has been reported. The objective was to evaluate the antimicrobial resistance of E. coli strains causing early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) and their evolution. Methods:E. coli strains from EONS and hospital-acquired

  20. Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in Gram-negative sepsis

    Microsoft Academic Search

    Jimmy F. P. Berbee; Caroline C. van der Hoogt; Robert Kleemann; Emile F. Schippers; Richard L. Kitchens; Jaap T. van Dissel; Irma A. J. M. Bakker-Woudenberg; Louis M. Havekes; Patrick C. N. Rensen

    2006-01-01

    Gram-negative sepsis is a major death cause in intensive care units. Accumulating evidence indicates the protective role of plasma lipoproteins such as high-density lipoprotein (HDL) in sepsis. It has recently been shown that septic HDL is almost depleted from apolipoprotein CI (apoCI), suggesting that apoCI may be a protective factor in sepsis. Sequence analysis revealed that apoCI possesses a highly

  1. ROS-induced ATF3 causes susceptibility to secondary infections during sepsis-associated immunosuppression

    Microsoft Academic Search

    Wolfram Hoetzenecker; Bernd Echtenacher; Emmanuella Guenova; Konrad Hoetzenecker; Florian Woelbing; Jürgen Brück; Anna Teske; Nadejda Valtcheva; Kerstin Fuchs; Manfred Kneilling; Ji-Hyeon Park; Kyu-Han Kim; Kyu-Won Kim; Petra Hoffmann; Claus Krenn; Tsonwin Hai; Kamran Ghoreschi; Tilo Biedermann; Martin Röcken

    2011-01-01

    Sepsis, sepsis-induced hyperinflammation and subsequent sepsis-associated immunosuppression (SAIS) are important causes of death. Here we show in humans that the loss of the major reactive oxygen species (ROS) scavenger, glutathione (GSH), during SAIS directly correlates with an increase in the expression of activating transcription factor 3 (ATF3). In endotoxin-stimulated monocytes, ROS stress strongly superinduced NF-E2–related factor 2 (NRF2)–dependent ATF3. In

  2. Biomarkers for the differentiation of sepsis and SIRS: the need for the standardisation of diagnostic studies

    Microsoft Academic Search

    T. C. HallD; D. K. Bilku; D. Al-Leswas; C. Horst; A. R. Dennison

    Introduction  Sepsis is a leading cause of death in the critically ill patient. It is a heterogeneous disease and it is frequently difficult\\u000a to make an unequivocal and expeditious diagnosis. The current ‘gold standard’ in diagnosing sepsis is the blood culture but\\u000a this is only available after a significant time delay. Mortality rates from sepsis remain high, however, the introduction\\u000a of

  3. Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions.

    PubMed

    Duong, Sean; Condotta, Stephanie A; Rai, Deepa; Martin, Matthew D; Griffith, Thomas S; Badovinac, Vladimir P

    2014-04-15

    Mortality from sepsis frequently results from secondary infections, and the extent to which sepsis affects pathogen-specific memory CD8 T cell responses remains unknown. Using the cecal ligation and puncture model of polymicrobial sepsis, we observed rapid apoptosis of pre-existing memory CD8 T cells after sepsis induction that led to a loss in CD8 T cell-mediated protection. Ag sensitivity (functional avidity) and Ag-driven secondary expansion of memory CD8 T cells were decreased after sepsis, further contributing to the observed loss in CD8 T cell-mediated immunity. Moreover, Ag-independent bystander activation of memory CD8 T cells in response to heterologous infection was also significantly impaired early after sepsis induction. The reduced sensitivity of pre-existing memory CD8 T cells to sense inflammation and respond to heterologous infection by IFN-? production was observed in inbred and outbred hosts and controlled by extrinsic (but not cell-intrinsic) factors, suggesting that sepsis-induced changes in the environment regulate innate functions of memory CD8 T cells. Taken together, the data in this study revealed a previously unappreciated role of sepsis in shaping the quantity and functionality of infection- or vaccine-induced memory CD8 T cells and will help further define the decline in T cell-mediated immunity during the sepsis-induced phase of immunosuppression. PMID:24646738

  4. Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice.

    PubMed

    Chung, Su Wol; Liu, Xiaoli; Macias, Alvaro A; Baron, Rebecca M; Perrella, Mark A

    2008-01-01

    Sepsis is characterized by a systemic response to severe infection. Although the inflammatory phase of sepsis helps eradicate the infection, it can have detrimental consequences if left unchecked. Therapy directed against inflammatory mediators of sepsis has shown little success and has the potential to impair innate antimicrobial defenses. Heme oxygenase-1 (HO-1) and the product of its enzymatic reaction, CO, have beneficial antiinflammatory properties, but little is known about their effects on microbial sepsis. Here, we have demonstrated that during microbial sepsis, HO-1-derived CO plays an important role in the antimicrobial process without inhibiting the inflammatory response. HO-1-deficient mice suffered exaggerated lethality from polymicrobial sepsis. Targeting HO-1 to SMCs and myofibroblasts of blood vessels and bowel ameliorated sepsis-induced death associated with Enterococcus faecalis, but not Escherichia coli, infection. The increase in HO-1 expression did not suppress circulating inflammatory cells or their accumulation at the site of injury but did enhance bacterial clearance by increasing phagocytosis and the endogenous antimicrobial response. Furthermore, injection of a CO-releasing molecule into WT mice increased phagocytosis and rescued HO-1-deficient mice from sepsis-induced lethality. These data advocate HO-1-derived CO as an important mediator of the host defense response to sepsis and suggest CO administration as a possible treatment for the disease. PMID:18060048

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

    PubMed Central

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

    2014-01-01

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

  6. Inadequate Exercise as a Risk Factor for Sepsis Mortality

    PubMed Central

    Williams, Paul T.

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  8. [Diagnosis and management of acute pharyngotonsillitis in the primary care pediatrician's office].

    PubMed

    Vicedomini, D; Lalinga, G; Lugli, N; D'Avino, A

    2014-02-01

    Acute pharyngotonsillitis is one of the most frequent causes of visits in the primary care pediatrician'office. Group A b-hemolytic streptococci (GABHS) or Streptococcus pyogenes causes 15-30% of cases of acute pharyngotonsillitis in pediatric age. Children with pharyngotonsillitis due to GABHS commonly present sore throat, fever more than 38 °C, tonsillar exudate, and tender cervical adenopathy, but the severity of illness ranges from mild throat pain to classic exudative tonsillitis with high fever. The McIsaac criteria is a clinical scoring system to predict the likelihood of streptococcal infection among children. This score is based on 5 clinical criteria: age 3-14 years, fever more than 38°C, tonsillar swelling or exudate, tender and enlarged anterior cervical lymph nodes, and absence of cough, but none of these findings is specific for GABHS pharyngotonsillitis. Culture of a throat swab on a blood agar plate (BAP) remains the gold standard for the diagnosis of acute streptococcal pharyngotonsillitis. Because of the major disadvantage of culturing throat swabs on BAP culture is the delay in obtaining the results (at least 1 day), in the past decades rapid antigen detection test (RAD) were introduced for the rapid identification of GABHS directly from throat swabs. Accurate diagnosis and treatment of GABHS pharyngotonsillitis provides positive benefits, including prevention of complications, such as acute rheumatic fever and peritonsillar abscess and reduce the acute morbidity associated with the illness. Conversely, improper diagnosis may result in negative consequences, including unnecessary antibiotic prescriptions that confer increased health care costs and contibute to the development of bacterial resistance. PMID:24608583

  9. Effects of Antenatal Antibiotics on the Incidence and Bacteriological Profile of Early-Onset Neonatal Sepsis

    Microsoft Academic Search

    V. Laugel; P. Kuhn; J. Beladdale; L. Donato; B. Escande; D. Astruc; J. Messer

    2003-01-01

    Background: Recommendations for the use of antenatal antibiotics have been widely implemented in the past few years, notably to prevent group B streptococcal disease or to prolong pregnancy in the case of preterm premature rupture of the membranes. Objectives: We designed a retrospective study to assess the potential effects of this increasing use of antibiotics on the incidence and bacteriological

  10. Facilitated intranasal induction of mucosal and systemic immunity to mutans streptococcal glucosyltransferase peptide vaccines.

    PubMed

    Smith, D J; King, W F; Barnes, L A; Trantolo, D; Wise, D L; Taubman, M A

    2001-08-01

    Synthetic peptide vaccines which are derived from functional domains of Streptococcus mutans glucosyltransferases (GTF) have been shown to induce protective immunity in Sprague-Dawley rats after subcutaneous injection in the salivary gland region. Since mucosal induction of salivary immunity would be preferable in humans, we explored methods to induce mucosal antibody in the rat to the GTF peptide vaccines HDS and HDS-GLU after intranasal administration. Several methods of facilitation of the immune response were studied: the incorporation of peptides in bioadhesive poly(D,L-lactide-coglycolide) (PLGA) microparticles, the use of monoepitopic (HDS) or diepitopic (HDS-GLU) peptide constructs, or the use of mucosal adjuvants. Salivary immunoglobulin A (IgA) responses were not detected after intranasal administration of diepitopic HDS-GLU peptide constructs in alum or after incorporation into PLGA microparticles. However, significant primary and secondary salivary IgA and serum IgG antibody responses to HDS were induced in all rats when cholera holotoxin (CT) or a detoxified mutant Escherichia coli heat-labile enterotoxin (R192G LT) were intranasally administered with HDS peptide constructs in PLGA. Coadministration of LT with HDS resulted in predominantly IgG2a responses in the serum, while coadministration with CT resulted in significant IgG1 and IgG2a responses to HDS. Serum IgG antibody, which was induced to the HDS peptide construct by coadministration with these adjuvants, also bound intact mutans streptococcal GTF in an enzyme-linked immunosorbent assay and inhibited its enzymatic activity. Thus, immune responses which are potentially protective for dental caries can be induced to peptide-based GTF vaccines after mucosal administration if combined with the CT or LT R192G mucosal adjuvant. PMID:11447149

  11. Functional Analysis of the Quorum-Sensing Streptococcal Invasion Locus (sil)

    PubMed Central

    Belotserkovsky, Ilia; Baruch, Moshe; Peer, Asaf; Dov, Eran; Ravins, Miriam; Mishalian, Inbal; Persky, Merav; Smith, Yoav; Hanski, Emanuel

    2009-01-01

    Group A streptococcus (GAS) causes a wide variety of human diseases, and at the same time, GAS can also circulate without producing symptoms, similar to its close commensal relative, group G streptococcus (GGS). We previously identified, by transposon-tagged mutagenesis, the streptococcal invasion locus (sil). sil is a quorum-sensing regulated locus which is activated by the autoinducer peptide SilCR through the two-component system SilA-SilB. Here we characterize the DNA promoter region necessary for SilA-mediated activation. This site is composed of two direct repeats of 10 bp, separated by a spacer of 11 bp. Fusion of this site to gfp allowed us to systematically introduce single-base substitutions in the repeats region and to assess the relative contribution of various positions to promoter strength. We then developed an algorithm giving different weights to these positions, and performed a chromosome-wide bioinformatics search which was validated by transcriptome analysis. We identified 13 genes, mostly bacteriocin related, that are directly under the control of SilA. Having developed the ability to quantify SilCR signaling via GFP accumulation prompted us to search for GAS and GGS strains that sense and produce SilCR. While the majority of GAS strains lost sil, all GGS strains examined still possess the locus and ?63% are able to respond to exogenously added SilCR. By triggering the autoinduction circle using a minute concentration of synthetic SilCR, we identified GAS and GGS strains that are capable of sensing and naturally producing SilCR, and showed that SilCR can be sensed across these streptococci species. These findings suggest that sil may be involved in colonization and establishment of commensal host-bacterial relationships. PMID:19893632

  12. Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats.

    PubMed

    Lotan, Dafna; Benhar, Itai; Alvarez, Kathy; Mascaro-Blanco, Adita; Brimberg, Lior; Frenkel, Dan; Cunningham, Madeleine W; Joel, Daphna

    2014-05-01

    Group A ?-hemolytic streptococcal (GAS) infection is associated with a spectrum of neuropsychiatric disorders. The leading hypothesis regarding this association proposes that a GAS infection induces the production of auto-antibodies, which cross-react with neuronal determinants in the brain through the process of molecular mimicry. We have recently shown that exposure of rats to GAS antigen leads to the production of anti-neuronal antibodies concomitant with the development of behavioral alterations. The present study tested the causal role of the antibodies by assessing the behavior of naïve rats following passive transfer of purified antibodies from GAS-exposed rats. Immunoglobulin G (IgG) purified from the sera of GAS-exposed rats was infused directly into the striatum of naïve rats over a 21-day period. Their behavior in the induced-grooming, marble burying, food manipulation and beam walking assays was compared to that of naïve rats infused with IgG purified from adjuvant-exposed rats as well as of naïve rats. The pattern of in vivo antibody deposition in rat brain was evaluated using immunofluorescence and colocalization. Infusion of IgG from GAS-exposed rats to naïve rats led to behavioral and motor alterations partially mimicking those seen in GAS-exposed rats. IgG from GAS-exposed rats reacted with D1 and D2 dopamine receptors and 5HT-2A and 5HT-2C serotonin receptors in vitro. In vivo, IgG deposits in the striatum of infused rats colocalized with specific brain proteins such as dopamine receptors, the serotonin transporter and other neuronal proteins. Our results demonstrate the potential pathogenic role of autoantibodies produced following exposure to GAS in the induction of behavioral and motor alterations, and support a causal role for autoantibodies in GAS-related neuropsychiatric disorders. PMID:24561489

  13. Metal-Mediated Modulation of Streptococcal Cysteine Protease Activity and Its Biological Implications

    PubMed Central

    Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Landero Figueroa, Julio A.; Caruso, Joseph A.

    2014-01-01

    Streptococcal cysteine protease (SpeB), the major secreted protease produced by group A streptococcus (GAS), cleaves both host and bacterial proteins and contributes importantly to the pathogenesis of invasive GAS infections. Modulation of SpeB expression and/or its activity during invasive GAS infections has been shown to affect bacterial virulence and infection severity. Expression of SpeB is regulated by the GAS CovR-CovS two-component regulatory system, and we demonstrated that bacteria with mutations in the CovR-CovS two-component regulatory system are selected for during localized GAS infections and that these bacteria lack SpeB expression and exhibit a hypervirulent phenotype. Additionally, in a separate study, we showed that expression of SpeB can also be modulated by human transferrin- and/or lactoferrin-mediated iron chelation. Accordingly, the goal of this study was to investigate the possible roles of iron and other metals in modulating SpeB expression and/or activity in a manner that would potentiate bacterial virulence. Here, we report that the divalent metals zinc and copper inhibit SpeB activity at the posttranslational level. Utilizing online metal-binding site prediction servers, we identified two putative metal-binding sites in SpeB, one of which involves the catalytic-dyad residues 47Cys and 195His. Based on our findings, we propose that zinc and/or copper availability in the bacterial microenvironment can modulate the proteolytic activity of SpeB in a manner that preserves the integrity of several other virulence factors essential for bacterial survival and dissemination within the host and thereby may exacerbate the severity of invasive GAS infections. PMID:24799625

  14. Defining the structural basis of human plasminogen binding by streptococcal surface enolase.

    PubMed

    Cork, Amanda J; Jergic, Slobodan; Hammerschmidt, Sven; Kobe, Bostjan; Pancholi, Vijay; Benesch, Justin L P; Robinson, Carol V; Dixon, Nicholas E; Aquilina, J Andrew; Walker, Mark J

    2009-06-19

    The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of Streptococcus pneumoniae alpha-enolase. Site-directed mutagenesis of surface-located lysine residues (SEN(K252 + 255A), SEN(K304A), SEN(K334A), SEN(K344E), SEN(K435L), and SEN(Delta434-435)) was used to examine their roles in maintaining structural integrity, enzymatic function, and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SEN(K344E), as determined by circular dichroism spectroscopy and MS. However, ion mobility MS revealed distinct differences in the stability of several mutant octamers in comparison with wild type. Enzymatic analysis indicated that SEN(K344E) had lost alpha-enolase activity, which was also reduced in SEN(K334A) and SEN(Delta434-435). Surface plasmon resonance demonstrated that the capacity to bind human plasminogen was abolished in SEN(K252 + 255A), SEN(K435L), and SEN(Delta434-435). The lysine residues at positions 252, 255, 434, and 435 therefore play a concerted role in plasminogen acquisition. This study demonstrates the ability of combining in silico structural modeling with ion mobility-MS validation for undertaking functional studies on complex protein structures. PMID:19363026

  15. PTX3 as a potential biomarker of acute lung injury: supporting evidence from animal experimentation

    Microsoft Academic Search

    Xiaolin He; Bing Han; Xiaohui Bai; Yu Zhang; Marcelo Cypel; Marco Mura; Shaf Keshavjee; Mingyao Liu

    2010-01-01

    Objective  Increased expression of long pentraxin 3 (PTX3) has been found in patients with sepsis or acute respiratory distress syndrome.\\u000a Tissue factor (TF) activation plays an important role in the pathogenesis of acute lung injury. The present study sought to\\u000a determine the relationship between PTX3 expression and TF activation in acute lung injury.\\u000a \\u000a \\u000a \\u000a Methods  Lung injury was induced by intratracheal instillation of

  16. Streptococcus suis-Related Prosthetic Joint Infection and Streptococcal Toxic Shock-Like Syndrome in a Pig Farmer in the United States

    PubMed Central

    Kennedy, Cassie C.; Gottschalk, Marcelo; Cunningham, Scott A.; Patel, Robin; Virk, Abinash

    2014-01-01

    Streptococcus suis is an emerging swine-associated zoonotic agent that can cause meningitis and septicemia in humans. We present, to our knowledge, the first case of S. suis arthroplasty infection and streptococcal toxic shock-like syndrome due to an nonencapsulated serotype 5 strain in North America. PMID:24719433

  17. The Structure and Function of Serum Opacity Factor: A Unique Streptococcal Virulence Determinant That Targets High-Density Lipoproteins

    PubMed Central

    Courtney, Harry S.; Pownall, Henry J.

    2010-01-01

    Serum opacity factor (SOF) is a virulence determinant expressed by a variety of streptococcal and staphylococcal species including both human and animal pathogens. SOF derives its name from its ability to opacify serum where it targets and disrupts the structure of high-density lipoproteins resulting in formation of large lipid vesicles that cause the serum to become cloudy. SOF is a multifunctional protein and in addition to its opacification activity, it binds to a number of host proteins that mediate adhesion of streptococci to host cells, and it plays a role in resistance to phagocytosis in human blood. This article will provide an overview of the structure and function of SOF, its role in the pathogenesis of streptococcal infections, its vaccine potential, its prevalence and distribution in bacteria, and the molecular mechanism whereby SOF opacifies serum and how an understanding of this mechanism may lead to therapies for reducing high-cholesterol concentrations in blood, a major risk factor for cardiovascular disease. PMID:20671930

  18. Acute respiratory disease in University of the Philippines and University of Wisconsin students

    PubMed Central

    Evans, Alfred S.; D'Allessio, Donn A.; Espiritu-Campos, Lourdes; Dick, Elliot C.

    1967-01-01

    In a comparison of acute respiratory disease patterns and incidence in students in a semi-tropical climate at the University of the Philippines with those in students in a temperate climate at the University of Wisconsin, USA, it was found that, while respiratory infections were the commonest cause of infirmary admissions in both institutions, yet, contrary to expectations, their incidence and relative importance were actually greater in the Philippine students than in the Wisconsin students. Peak rates occurred during the rainy season in the Philippines and during the coldest months in Wisconsin. Acute infectious mononucleosis was absent in the Philippines and streptococcal sore throat and primary atypical pneumonia were rare, but the three conditions were common in Wisconsin. The authors suggest that this difference in clinical pattern may be due to immunity in the Philippines students as a result of prior childhood infection. PMID:5299672

  19. Computing network-based features from physiological time series: application to sepsis detection.

    PubMed

    Santaniello, Sabato; Granite, Stephen J; Sarma, Sridevi V; Winslow, Raimond L

    2014-01-01

    Sepsis is a systemic deleterious host response to infection. It is a major healthcare problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identify sepsis by using static scores derived from bed-side measurements individually, i.e., without systematically accounting for potential interactions between these signals and their dynamics. In this study, we apply network-based data analysis to take into account interactions between bed-side physiological time series (PTS) data collected in ICU patients, and we investigate features to distinguish between sepsis and non-sepsis conditions. We treated each PTS source as a node on a graph and we retrieved the graph connectivity matrix over time by tracking the correlation between each pair of sources' signals over consecutive time windows. Then, for each connectivity matrix, we computed the eigenvalue decomposition. We found that, even though raw PTS measurements may have indistinguishable distributions in non-sepsis and early sepsis states, the median /I of the eigenvalues computed from the same data is statistically different (p <; 0.001) in the two states and the evolution of /I may reflect the disease progression. Although preliminary, these findings suggest that network-based features computed from continuous PTS data may be useful for early sepsis detection. PMID:25570825

  20. Value of Caffeic Acid Phenethyl Ester Pretreatment in Experimental Sepsis Model in Rats

    PubMed Central

    Alici, Ozlem; Kavakli, Havva Sahin; Koca, Cemile; Altintas, Neriman Defne; Aydin, Murat; Alici, Suleyman

    2015-01-01

    Background and Aim. The aim of this study was to determine the actions of caffeic acid phenethyl ester (CAPE) on the changes of endothelin-1 (ET-1) level, tumor necrosis factor- (TNF-) alpha, and oxidative stress parameters such as superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in experimental sepsis model in rats. Materials and Methods. Twenty-four rats were randomly divided into three experimental groups: sham (group 1), sepsis (group 2), and sepsis + CAPE (group 3), n = 8 each. CAPE was administered (10?µmol/kg) intraperitoneally to group 3 before sepsis induction. Serum ET-1, serum TNF-alpha, tissue SOD activity, and tissue MDA levels were measured in all groups. Results. Pretreatment with CAPE decreased ET-1, TNF-alpha, and MDA levels in sepsis induced rats. Additionally SOD activities were higher in rats pretreated with CAPE after sepsis induction. Conclusion. Our results demonstrate that CAPE may have a beneficial effect on ET and TNF-alpha levels and oxidative stress parameters induced by sepsis in experimental rat models. Therefore treatment with CAPE can be used to avoid devastating effects of sepsis. PMID:25948886

  1. The Effect of Hospital Volume on Mortality in Patients Admitted with Severe Sepsis

    PubMed Central

    Shahul, Sajid; Hacker, Michele R.; Novack, Victor; Mueller, Ariel; Shaefi, Shahzad; Mahmood, Bilal; Ali, Syed Haider; Talmor, Daniel

    2014-01-01

    Importance The association between hospital volume and inpatient mortality for severe sepsis is unclear. Objective To assess the effect of severe sepsis case volume and inpatient mortality. Design Setting and Participants Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. Exposures The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. Main Outcomes and Measures Inpatient mortality. Results Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (?10 severe sepsis cases per year) was 1.188 (95% CI: 1.074–1.315), while the odds ratio was 1.090 (95% CI: 1.031–1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64–38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51–32.64) for hospitals with the highest volume. Conclusions and Relevance We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients. PMID:25264788

  2. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been desc...

  3. In vivo arginine production and intravascular nitric oxide synthesis in hypotensive sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arginine is important in the response to infections and is a precursor for the synthesis of the vasodilator nitric oxide (NO). Low plasma arginine is correlated with a worse prognosis in patients with sepsis, and increased NO has been implicated in the hypotension of sepsis. Data on in vivo arginine...

  4. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolotis in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC...

  5. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactoferrin, a normal component of human colostrum, milk, tears, and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NE...

  6. Evaluation of central venous catheter sepsis by differential quantitative blood culture

    Microsoft Academic Search

    S. T. Fan; C. H. Teoh-Chan; K. F. Lau

    1989-01-01

    The accuracy of differential quantitative blood culture in the diagnosis of central venous catheter sepsis was evaluated in 24 parenterally-fed patients in whom catheter sepsis was suspected. The pour-plate quantitative culture technique was performed immediately before removal of the catheter on blood drawn through the central venous catheter and a peripheral vein. If bacterial colonies in the catheter blood specimen

  7. Ureteroscopic Management of Sepsis Associated with Ureteral Stone Impaction: Is It Still Contraindicated?

    Microsoft Academic Search

    Jong-Ming Hsu; Marcelo Chen; Wen-Chou Lin; Huang-Kuang Chang; Stone Yang

    2005-01-01

    Introduction: Retrograde decompression is generally not advocated for patients with sepsis owing to ureteral obstruction by stone impaction, and the initial treatment of choice is percutaneous nephrostomy (PCN). We report our experience with the treatment of urosepsis with retrograde ureteroscopy (URS) instead of PCN drainage. Patients and Methods: Fifty-six consecutive patients diagnosed with ureteral stone-related sepsis received URS as primary

  8. Role of Interleukin 12 in Experimental Neonatal Sepsis Caused by Group B Streptococci

    Microsoft Academic Search

    GIUSEPPE MANCUSO; VITALIANO CUSUMANO; FRANCESCO GENOVESE; MARIA GAMBUZZA; CONCETTA BENINATI; GIUSEPPE TETI

    1997-01-01

    Cytokines are suspected to play an important role in systemic infections by group B streptococci (GBS), an important cause of neonatal sepsis. This work was undertaken to determine if interleukin 12 (IL-12) is produced in mouse pups infected with GBS and has a role in this sepsis model. IL-12 elevations were measured by both an enzyme-linked immunosorbent assay and a

  9. CRTH2 Is A Critical Regulator of Neutrophil Migration and Resistance to Polymicrobial Sepsis

    PubMed Central

    Ishii, Makoto; Asano, Koichiro; Namkoong, Ho; Tasaka, Sadatomo; Mizoguchi, Kosuke; Asami, Takahiro; Kamata, Hirofumi; Kimizuka, Yoshifumi; Fujiwara, Hiroshi; Funatsu, Yohei; Kagawa, Shizuko; Miyata, Jun; Ishii, Ken; Nakamura, Masataka; Hirai, Hiroyuki; Nagata, Kinya; Kunkel, Steven L.; Hasegawa, Naoki; Betsuyaku, Tomoko

    2012-01-01

    Although arachidonic acid cascade has been shown to be involved in sepsis, little is known about the role of prostaglandin D2 and its newly found receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), on the septic response. Severe sepsis is associated with the failure of neutrophil migration. To investigate whether CRTH2 influences neutrophil recruitment and the lethality during sepsis, sepsis was induced by cecal ligation and puncture (CLP) surgery in mice. CRTH2 knockout (?/?) mice were highly resistant to CLP-induced sepsis, which was associated with lower bacterial load and lower production of TNF-?, IL-6, and CCL3. IL-10, an anti-inflammatory cytokine, was higher in CRTH2?/? mice, blunting CLP-induced lethality in CRTH2?/? mice. Neutrophil accumulation in the peritoneum was more pronounced after CLP in CRTH2?/? mice, which was associated with higher CXCR2 level in circulating neutrophils. Furthermore, sepsis caused a decrease in the level of acetylation of histone H3, an activation mark, at the CXCR2 promoter in WT neutrophils, suggesting that CXCR2 expression levels are epigenetically regulated. Finally, both pharmacological depletion of neutrophils and inhibition of CXCR2 abrogated the survival benefit in CRTH2?/? mice. These results demonstrate that genetic ablation of CRTH2 improved impaired neutrophil migration and survival during severe sepsis, which was mechanistically associated with epigenetic mediated CXCR2 expression. Thus, CRTH2 is a potential therapeutic target for polymicrobial sepsis. PMID:22544936

  10. Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis

    Microsoft Academic Search

    C Kaymak; E Kadioglu; E Ozcagli; G Osmanoglu; S Izdes; C Agalar; H Basar; S Sardas

    2008-01-01

    Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and

  11. Lack of evidence for qualitative treatment by disease severity interactions in clinical studies of severe sepsis

    Microsoft Academic Search

    William L Macias; David R Nelson; Mark Williams; Rekha Garg; Jonathan Janes; Andreas Sashegyi

    2005-01-01

    INTRODUCTION: The design of clinical trials of interventions aimed at reducing mortality in patients with severe sepsis assumes that the relative treatment effect of the intervention is independent of the patients' risk for death. We reviewed published data from phase III clinical studies of severe sepsis to determine whether a relationship exists between risk for death and the relative benefit

  12. State-of-the-art therapy for severe sepsis and multisystem organ dysfunction

    Microsoft Academic Search

    Samir S Awad

    2003-01-01

    Despite spectacular advances in life-support technology, the management of patients with severe sepsis continues to be a significant health care challenge because of the associated major morbidity, high mortality, and health economic implications. Severe sepsis with associated multisystem organ dysfunction (MOD) is the leading cause of death in the intensive care unit. Recent understanding of the pathophysiology now demonstrates that

  13. Corticosteroids, nonsteroidal anti-inflammatory drugs, and naloxone in the sepsis syndrome

    Microsoft Academic Search

    William M. Long; Charles L. Sprung

    1987-01-01

    Corticosteroids have proven to be effective as adjunctive treatment in sepsis and severe typhoid fever when used early and in high doses. If corticosteroids are given in high doses (30 mg\\/kg), they should be administered in 1–2 doses, and not to exceed 4 total doses within 24 hours. The efficacy of the drug may be diminished in more severe sepsis,

  14. Endotoxin elimination in sepsis: physiology and therapeutic application

    Microsoft Academic Search

    Klaus Buttenschoen; Peter Radermacher; Hendrik Bracht

    2010-01-01

    Purpose  The present review summarizes key papers on the elimination of endotoxin in human.\\u000a \\u000a \\u000a \\u000a Results  Lipopolysaccharides (LPS) are extremely strong stimulators of inflammatory reactions, act at very low concentrations, and\\u000a are involved in the pathogenesis of sepsis and septic shock. Elimination of LPS is vital; therefore, therapeutic detoxification\\u000a of LPS may offer new perspectives. Multiple mechanisms eliminate LPS in human comprising molecules

  15. Is boosting the immune system in sepsis appropriate?

    PubMed Central

    2014-01-01

    A relative immunosuppression is observed in patients after sepsis, trauma, burns, or any severe insults. It is currently proposed that selected patients will benefit from treatment aimed at boosting their immune systems. However, the host immune response needs to be considered in context with pathogen-type, timing, and mainly tissue specificity. Indeed, the immune status of leukocytes is not universally decreased and their activated status in tissues contributes to organ failure. Accordingly, any new immune-stimulatory therapeutic intervention should take into consideration potentially deleterious effects in some situations. PMID:24886820

  16. Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania

    Microsoft Academic Search

    Neema Kayange; Erasmus Kamugisha; Damas L Mwizamholya; Seni Jeremiah; Stephen E Mshana

    2010-01-01

    BACKGROUND: Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC), Tanzania to determine the prevalence of neonatal sepsis, predictors of positive

  17. Acute Pancreatitis and Pregnancy

    MedlinePLUS

    Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation of the pancreas manifested ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  18. Acute rheumatic Fever and rheumatic heart disease among children - american samoa, 2011-2012.

    PubMed

    Beaudoin, Amanda; Edison, Laura; Introcaso, Camille E; Goh, Lucy; Marrone, James; Mejia, Amelita; Beneden, Chris Van

    2015-05-29

    Acute rheumatic fever is a nonsuppurative, immune-mediated consequence of group A streptococcal pharyngitis (strep throat). Recurrent or severe acute rheumatic fever can cause permanent cardiac valve damage and rheumatic heart disease, which increases the risk for cardiac conditions (e.g., infective endocarditis, stroke, and congestive heart failure). Antibiotics can prevent acute rheumatic fever if administered no more than 9 days after symptom onset. Long-term benzathine penicillin G (BPG) injections are effective in preventing recurrent acute rheumatic fever attacks and are recommended to be administered every 3-4 weeks for 10 years or until age 21 years to children who receive a diagnosis of acute rheumatic fever. During August 2013, in response to anecdotal reports of increasing rates of acute rheumatic fever and rheumatic heart disease, CDC collaborated with the American Samoa Department of Health and the Lyndon B. Johnson Tropical Medical Center (the only hospital in American Samoa) to quantify the number of cases of pediatric acute rheumatic fever and rheumatic heart disease in American Samoa and to assess the potential roles of missed pharyngitis diagnosis, lack of timely prophylaxis prescription, and compliance with prescribed BPG prophylaxis. Using data from medical records, acute rheumatic fever incidence was calculated as 1.1 and 1.5 cases per 1,000 children aged ?18 years in 2011 and 2012, respectively; 49% of those with acute rheumatic fever subsequently received a diagnosis of rheumatic heart disease. Noncompliance with recommended prophylaxis with BPG after physician-diagnosed acute rheumatic fever was noted for 22 (34%) of 65 patients. Rheumatic heart disease point prevalence was 3.2 cases per 1,000 children in August 2013. Establishment of a coordinated acute rheumatic fever and rheumatic heart disease control program in American Samoa, likely would improve diagnosis, treatment, and patient compliance with BPG prophylaxis. PMID:26020139

  19. Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

    PubMed Central

    Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

    2012-01-01

    Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

  20. Multiple gene-to-gene interactions in children with sepsis: a combination of five gene variants predicts outcome of life-threatening sepsis

    PubMed Central

    2014-01-01

    Introduction The aim of the study was to identify the dependency structure of genetic variants that can influence the outcome for paediatric patients with sepsis. Methods We evaluated the role of single nucleotide polymorphisms for five genes: bactericidal permeability increasing protein (BPI; rs5743507), lipopolysaccharide-binding protein (LBP; rs2232618), toll-like receptor 4 (TLR4; rs4986790), heat shock protein 70 (HSP 70; rs2227956), and interleukin 6 (IL-6; rs1800795) in 598 children aged 0 to 19 years that were admitted to a paediatric intensive care unit with fever, systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or multiple organ dysfunction syndrome. A control group of 529 healthy individuals was included. Multi-way contingency tables were constructed and statistically evaluated using log-linear models. Typical gene combinations were found for both study groups. Results Detailed analyses of the five studied gene profiles revealed significant differences in sepsis survival. Stratification into high-risk, intermediate-risk, and low-risk groups of paediatric patients can predict the severity of sepsis. Conclusions Analysis of single nucleotide polymorphisms for five genes can be used as a predictor of sepsis outcome in children. PMID:24383711

  1. Sepsis in intensive care unit patients with traumatic brain injury: factors associated with higher mortality

    PubMed Central

    Cardozo, Luis Carlos Maia; da Silva, Redson Ruy

    2014-01-01

    Objective Patients with traumatic brain injury are particularly susceptible to sepsis, which may exacerbate the systemic inflammatory response and lead to organ dysfunction. The influence of clinical variables on the mortality of intensive care unit patients with traumatic brain injury and sepsis was investigated. Methods The present investigation was a retrospective study involving 175 patients with traumatic brain injury who were treated in a period of 1 year at a reference hospital for trauma and who had sepsis, severe sepsis, or septic shock. Demographic and clinical data were obtained, and the SOFA score was calculated at the time sepsis was found and after 72 hours. Results There was a predominance of young men with severe traumatic brain injury, multiple head injuries, sepsis with a pulmonary focus, prolonged hospital stay, and high mortality (37.7%). Circulatory and respiratory failure had a high incidence, but renal and coagulation failure were less frequent, and liver failure was not observed. After logistic regression, the presence of septic shock and respiratory failure 72 hours after the sepsis diagnosis was associated with higher mortality, with an odds ratio of 7.56 (95%CI=2.04-27.31, p=0.0024) and 6.62 (95%CI=1.93-22.78, p=0.0027), respectively. In addition, there was a higher mortality among patients who had no organ failure on D1 but who developed the condition after 72 hours of sepsis and in those patients who already had organ failure at the time sepsis was diagnosed and remained in this condition after 72 hours. Conclusion Septic shock and progressive organ (particularly respiratory) dysfunction increases the mortality of patients with traumatic brain injury and sepsis. PMID:25028949

  2. Gut-Origin sepsis; evolution of a concept

    PubMed Central

    Deitch, Edwin A.

    2012-01-01

    The concept of bacterial translocation and gut-origin sepsis as a cause of systemic infectious complications and the multiple organ dysfunction syndrome (MODS) in surgical and ICU patients has emerged over the last several decades, although the exact clinical relevance of these phenomenon continue to be debated. Thus, the goal of this review will be to trace the evolution of gut-origin sepsis and gut-induced MODS and put these disorders and observations into clinical perspective. Additionally, the mechanisms leading to gut-derived complications will be explored as well as therapeutic options to limit or prevent these complications. From this work, several major conclusions emerge. First, that bacterial translocation occurs clinically and is responsible for increased infectious complications in patients undergoing major abdominal surgery. However, the phenomenon of bacterial translocation is not sufficient to explain the development of MODS in ICU patients. Instead, the development of MODS in these high risk patients is likely due to gut injury and the systemic spread of non-microbial, tissue injurious factors that reach the systemic circulation via the intestinal lymphatics. These observations have resulted in the gut lymph hypothesis of MODS. PMID:22534256

  3. Improved Diagnostic Accuracy of Group A Streptococcal Pharyngitis Using Real-Time Biosurveillance

    PubMed Central

    Fine, Andrew M.; Nizet, Victor; Mandl, Kenneth D.

    2013-01-01

    Background Clinical prediction rules do not incorporate real time incidence data to adjust estimates of disease risk in symptomatic patients. Objective To measure the value of integrating local incidence data into a clinical decision rule for diagnosing group A streptococcal (GAS) pharyngitis in patients age 15 years and older. Design Retrospective analysis of clinical and biosurveillance predictors of GAS pharyngitis. Setting Large U.S.-based retail-health chain. Patients 82,062 patient visits for pharyngitis. Measurements Accuracy of the Centor score, was compared with that of a biosurveillance-responsive score, essentially an adjusted Centor score based on real-time GAS pharyngitis information from the 14 days prior to a patient’s visit – the recent local proportion positive (RLPP). Results Increased RLPP correlated with likelihood of GAS pharyngitis (r2 =0.79, p<0.001). Local incidence data enhanced diagnostic models. For example, when RLPP >0.30, managing patients with Centor scores of 1 as if scores were 2 would identify 62,537 previously missed patients annually while misclassifying 18,446 patients without GAS pharyngitis. Decreasing the score of patients with Centor values of 3 by one point for RLPP <0.20, would spare unnecessary antibiotics for 166,616 patients while missing 18,812 true positives. Limitations Analyses were conducted retrospectively. Real time regional GAS pharyngitis data are generally not yet available to clinicians. Conclusions Incorporating live biosurveillance data into clinical guidelines for GAS pharyngitis and other communicable diseases should be considered to reduce missed cases when the contemporaneous incidence is elevated and spare unnecessary antibiotics when the contemporaneous incidence is low. Delivering epidemiologic data to the point of care will enable the use of real-time pre-test probabilities in medical decision-making. Primary Funding Source The Mentored Public Health Research Scientist Development Award K01 HK000055 from the Centers for Disease Control and Prevention and R01 LM007677 from the National Library of Medicine, National Institutes of Health. PMID:21930851

  4. Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

    PubMed

    Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

    2014-12-01

    The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B titers, as well as a history of more frequent throat infections than controls (p<0.0001). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease or organ- and nonorgan-specific autoimmunity seem not more frequent in children and adolescents with PANDAS than in healthy controls. A potential relationship between autoimmunity and PANDAS should be assessed further in larger studies. Children and adolescents with PANDAS should not be actually screened for thyroid function, celiac disease and/or autoimmune diseases. PMID:25151976

  5. Simvastatin inhibits apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax

    PubMed Central

    Fu, Hui; Wang, Qiao-sheng; Luo, Qiong; Tan, Si; Su, Hua; Tang, Shi-lin; Zhao, Zheng-liang; Huang, Li-ping

    2014-01-01

    BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group (sepsis group) and simvastatin+sepsis serum intervention group (simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and flow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR. RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum; however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group. CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis. PMID:25548604

  6. Anti-CD18 antibody attenuates neutropenia and alveolar capillary-membrane injury during gram-negative sepsis.

    PubMed

    Walsh, C J; Carey, P D; Cook, D J; Bechard, D E; Fowler, A A; Sugerman, H J

    1991-08-01

    Activated polymorphonuclear leukocytes (PMNs) are implicated in the pathogenesis of acute lung injury (ALI) associated with sepsis. Adhesion of activated PMNs to endothelial monolayers is mediated by the CD18 adhesion-receptor complex on the PMN cell surface. Monoclonal antibody 60.3 (MoAb 60.3) blocks CD18-dependent PMN-endothelial adhesion in vitro and in vivo. This study was designed to determine the role of CD18-dependent PMN adhesion in ALI associated with gram-negative sepsis. Anesthetized, ventilated (FiO2 0.5, positive end-expiratory pressure 5 cm H2O) pigs received sterile saline (control, n = 8) or live Pseudomonas aeruginosa, 5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/min (septic, n = 9) for 1 hour. A third group (n = 7) received MoAb 60.3, 2 mg/kg intravenously, 15 minutes before Pseudomonas infusion. Animals were studied for 300 minutes. MoAb 60.3 significantly (p less than 0.05) attenuated the neutropenia seen in sepsis (15 +/- 1 vs 6 +/- 1 x 10(3) PMNs/mm3 at 300 min). Alveolar-capillary membrane injury was assessed by bronchoalveolar-lavage protein content and extravascular lung water determination. MoAb 60.3 significantly (p less than 0.05) reduced BAL protein at 300 minutes (388 +/- 75 vs 1059 +/- 216 micrograms/ml in septic animals) and attenuated the increase in extravascular lung water to 240 minutes (7.1 +/- 2 vs 14.2 +/- 1.2 ml/kg in septic animals). Systemic hypotension, decreased cardiac index, pulmonary hypertension, and relative hypoxemia, all characteristic of this model, were not altered by MoAb 60.3. These data suggest that, in this model of septic ALI, neutropenia is, in part, CD18 dependent and that blocking CD18-dependent PMN adhesion protects the alveolar-capillary membrane independently of altered hemodynamic status. PMID:1677491

  7. The Specific Roles of JAK/STAT Signaling Pathway in Sepsis.

    PubMed

    Cai, Bin; Cai, Jian-Ping; Luo, Yu-Long; Chen, Cheng; Zhang, Sen

    2015-08-01

    The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway is a principal signaling pathway for the signal transduction of many pivotal cytokines involved in sepsis. Binding of cytokines to corresponding receptors can activate associated JAK kinases, which selectively phosphorylate STATs. Activated STATs then translocate to the nucleus and play a critical role in the transcription of target genes. During the past several years, significant progress has been made in the understanding of the roles of JAK/STAT pathway in sepsis. The aims of this review are to describe the present knowledge about JAK/STAT signaling pathway, describe the specific roles of JAK/STAT pathway in sepsis, and put forward the prospect for future studies of JAK/STAT signaling pathway in sepsis. A PubMed database search was performed for studies of JAKs and STATs in sepsis. It has been shown that a variety of cytokines can exert their biological effects via the JAK/STAT signaling pathway. JAK/STAT pathway has been shown related to the release of various cytokines and inflammatory mediators and involved in the regulation of immune response in sepsis. Moreover, JAK/STAT pathway has been shown involved in organ damage and other dysfunctions in sepsis models. PMID:25676437

  8. Sepsis and glucocorticoids upregulate p300 and downregulate HDAC6 expression and activity in skeletal muscle

    PubMed Central

    Alamdari, Nima; Smith, Ira J.; Aversa, Zaira

    2010-01-01

    Muscle wasting during sepsis is in part regulated by glucocorticoids. In recent studies, treatment of cultured muscle cells in vitro with dexamethasone upregulated expression and activity of p300, a histone acetyl transferase (HAT), and reduced expression and activity of the histone deacetylases-3 (HDAC3) and -6, changes that favor hyperacetylation. Here, we tested the hypothesis that sepsis and glucocorticoids regulate p300 and HDAC3 and -6 in skeletal muscle in vivo. Because sepsis-induced metabolic changes are particularly pronounced in white, fast-twitch skeletal muscle, most experiments were performed in extensor digitorum longus muscles. Sepsis in rats upregulated p300 mRNA and protein levels, stimulated HAT activity, and reduced HDAC6 expression and HDAC activity. The sepsis-induced changes in p300 and HDAC expression were prevented by the glucocorticoid receptor antagonist RU38486. Treatment of rats with dexamethasone increased expression of p300 and HAT activity, reduced expression of HDAC3 and -6, and inhibited HDAC activity. Finally, treatment with the HDAC inhibitor trichostatin A resulted in increased muscle proteolysis and expression of the ubiquitin ligase atrogin-1. Taken together, our results suggest for the first time that sepsis-induced muscle wasting may be regulated by glucocorticoid-dependent hyperacetylation caused by increased p300 and reduced HDAC expression and activity. The recent development of pharmacological HDAC activators may provide a novel avenue to prevent and treat muscle wasting in sepsis and other catabolic conditions. PMID:20538901

  9. Time course of nitric oxide synthases, nitrosative stress, and poly(ADP ribosylation) in an ovine sepsis model

    PubMed Central

    2010-01-01

    Introduction Different isoforms of nitric oxide synthases (NOS) and determinants of oxidative/nitrosative stress play important roles in the pathophysiology of pulmonary dysfunction induced by acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors are largely undetermined. Methods Twenty-four chronically instrumented sheep were subjected to inhalation of 48 breaths of cotton smoke and instillation of live Pseudomonas aeruginosa into both lungs and were euthanized at 4, 8, 12, 18, and 24 hours post-injury. Additional sheep received sham injury and were euthanized after 24 hrs (control). All animals were mechanically ventilated and fluid resuscitated. Lung tissue was obtained at the respective time points for the measurement of neuronal, endothelial, and inducible NOS (nNOS, eNOS, iNOS) mRNA and their protein expression, calcium-dependent and -independent NOS activity, 3-nitrotyrosine (3-NT), and poly(ADP-ribose) (PAR) protein expression. Results The injury induced severe pulmonary dysfunction as indicated by a progressive decline in oxygenation index and concomitant increase in pulmonary shunt fraction. These changes were associated with an early and transient increase in eNOS and an early and profound increase in iNOS expression, while expression of nNOS remained unchanged. Both 3-NT, a marker of protein nitration, and PAR, an indicator of DNA damage, increased early but only transiently. Conclusions Identification of the time course of the described pathogenetic factors provides important additional information on the pulmonary response to ALI and sepsis in the ovine model. This information may be crucial for future studies, especially when considering the timing of novel treatment strategies including selective inhibition of NOS isoforms, modulation of peroxynitrite, and PARP. PMID:20602787

  10. Mannose-binding lectin polymorphisms and the risk of sepsis: evidence from a meta-analysis.

    PubMed

    Zhang, A-Q; Yue, C-L; Pan, W; Gao, J-W; Zeng, L; Gu, W; Jiang, J-X

    2014-10-01

    Several studies have evaluated the association between mannose-binding lectin (MBL) polymorphisms and sepsis. However, the results are inconclusive and conflicting. To better understand the roles of MBL polymorphisms in sepsis, we conducted a comprehensive meta-analysis. All relevant studies were searched from PubMed, EMBASE and Web of Knowledge databases, with the last report up to 7 May 2013. Twenty-nine studies addressing four MBL polymorphisms (-550G/C, -221G/C, structure variant A/O, Gly54Asp) were analysed for susceptibility to sepsis and one study for sepsis-related mortality. Overall, significant associations between structure variant A/O and susceptibility to sepsis were observed for AO + OO vs. AA [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·05-1·52, P = 0·01] and O vs. A (OR 1·19, 95% CI 1·02-1·40, P = 0·03). In subgroup analysis based on age group, increased risk was found in the paediatric group in the dominant model (OR 1·72, 95% CI 1·16-2·56, P = 0·007). Moreover, there was a slight association between the +54A/B polymorphism and susceptibility to sepsis in Caucasians (recessive model: OR 10·64, 95% CI 1·24-91·65, P = 0·03). However, no association was observed for -550G/C and -221G/C polymorphisms both overall and in subgroup analysis. For sepsis-related mortality, only one study suggested AO/OO was associated with in-hospital mortality in pneumococcal sepsis patients after controlling for confounding variables. Our meta-analysis indicated that MBL structure variants might be associated with susceptibility to sepsis but further studies with a large sample size should be conducted to confirm these findings. PMID:24398289

  11. Understanding the potential role of statins in pneumonia and sepsis

    PubMed Central

    Yende, Sachin; Milbrandt, Eric B.; Kellum, John A.; Kong, Lan; Delude, Russell L.; Weissfeld, Lisa A.; Angus, Derek C.

    2011-01-01

    Objective To examine the association of statin use with clinical outcomes and circulating biomarkers in community-acquired pneumonia (CAP) and sepsis. Design Multicenter inception cohort study. Setting Emergency departments of 28 US hospitals. Patients 1895 subjects hospitalized with CAP. Interventions None. Measurements and Main Results Our approach consisted of two different comparison cohorts, each reflecting methods used in prior publications in this area. We first compared subjects with prior statin use (prior use cohort), defined as a history of statin use in the week before admission, to those with no prior use. We then compared prior statin users whose statins were continued in-hospital (continued use cohort) to those with either no prior use or no inhospital use. We adjusted for patient characteristics, including demographics, comorbid conditions, and illness severity, and accounted for healthy user effect and indication bias using propensity analysis. We determined risk of severe sepsis and 90-day mortality. We measured markers inflammation (TNF, IL-6, IL-10), coagulation (antithrombin, Factor IX, plasminogen activator inhibitor, D-dimer, thrombin antithrombin complex), and lymphocyte cell surface protein expression during first week of hospitalization. There were no differences in severe sepsis risk between statin users and non-users for prior (30.8% vs. 30.7%, p=0.98) or continued statin use (30.2% vs. 30.8%, p=0.85) in univariate analyses, and after adjusting for patient characteristics and propensity for statin use. Ninety-day mortality was similar in prior statin users (9.2% vs. 12.0%, p=0.11) and lower in continued statin users (7.9% vs. 12.1%, p=0.02). After adjusting for patient characteristics and propensity for statin use, there was no mortality benefit for prior (OR=0.90 (0.63–1.29), p=0.57) or continued statin use (OR=0.73 (0.47–1.13), p=0.15). Only antithrombin activity over time was higher in statin subjects, yet the magnitude of difference was modest. There were no differences in other coagulation, inflammatory, or lymphocyte cell surface markers. Conclusions We found no evidence of a protective effect for statin use on clinical outcomes and only modest differences in circulating biomarkers in CAP, perhaps due to healthy user effects and indication bias. PMID:21516038

  12. Novel Polymorphisms in the Myosin Light Chain Kinase Gene Confer Risk for Acute Lung Injury

    Microsoft Academic Search

    Li Gao; Audrey Grant; Indrani Halder; Roy Brower; Jonathan Sevransky; James P. Maloney; Marc Moss; Carl Shanholtz; Charles R. Yates; Umberto Meduri; Mark D. Shriver; Roxann Ingersoll; Alan F. Scott; Terri H. Beaty; Jaideep Moitra; Shwu Fan Ma; Shui Q. Ye; Kathleen C. Barnes; Joe G. N. Garcia

    The genetic basis of acute lung injury (ALI) is poorly understood. The myosin light chain kinase (MYLK) gene encodes the nonmuscle myosin light chain kinase isoform, a multifunctional protein in- volved in the inflammatory response (apoptosis, vascular perme- ability,leukocytediapedesis).Toexamine MYLKasanovelcandidate gene in sepsis-associated ALI, we sequenced exons, exon-intron boundaries, and 2 kb of 5 UTR of the MYLK, which revealed

  13. Streptococcal M1 protein triggers chemokine formation, neutrophil infiltration, and lung injury in an NFAT-dependent manner.

    PubMed

    Zhang, Songen; Zhang, Su; Garcia-Vaz, Eliana; Herwald, Heiko; Gomez, Maria F; Thorlacius, Henrik

    2015-06-01

    Streptococcus pyogenes of the M1 serotype can cause STSS, which is associated with significant morbidity and mortality. The purpose of the present study was to examine the role of NFAT signaling in M1 protein-induced lung injury. NFAT-luc mice were treated with the NFAT inhibitor A-285222 before administration of the M1 protein. Neutrophil infiltration, edema, and CXC chemokines were quantified in the lung, 4 h after challenge with the M1 protein. Flow cytometry was used to determine Mac-1 expression. Challenge with the M1 protein increased NFAT-dependent transcriptional activity in the lung, spleen, and liver in NFAT-luc mice. Administration of the NFAT inhibitor A-285222 abolished M1 protein-evoked NFAT activation in the lung, spleen, and liver. M1 protein challenge induced neutrophil recruitment, edema, and CXC chemokine production in the lung, as well as up-regulation of Mac-1 on circulating neutrophils. Inhibition of NFAT activity attenuated M1 protein-induced neutrophil infiltration by 77% and edema formation by 50% in the lung. Moreover, administration of A-285222 reduced M1 protein-evoked pulmonary formation of CXC chemokine >80%. In addition, NFAT inhibition decreased M1 protein-triggered Mac-1 up-regulation on neutrophils. These findings indicate that NFAT signaling controls pulmonary infiltration of neutrophils in response to streptococcal M1 protein via formation of CXC chemokines and neutrophil expression of Mac-1. Thus, the targeting of NFAT activity might be a useful way to ameliorate lung injury in streptococcal infections. PMID:25583579

  14. Tissue Deposits of IgA-Binding Streptococcal M Proteins in IgA Nephropathy and Henoch-Schönlein Purpura

    PubMed Central

    Schmitt, Roland; Carlsson, Fredric; Mörgelin, Matthias; Tati, Ramesh; Lindahl, Gunnar; Karpman, Diana

    2010-01-01

    IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are diseases characterized by IgA deposits in the kidney and/or skin. Both may arise after upper respiratory tract infections, but the pathogenic mechanisms governing these diseases remain unclear. Patients with IgAN (n = 16) and HSP (n = 17) were included in this study aimed at examining whether IgA-binding M proteins of group A streptococci could be involved. As M proteins vary in sequence, the study focused on the IgA-binding-region (IgA-BR) of three different M proteins: M4, M22, and M60. Renal tissue from IgAN and HSP patients and skin from HSP patients were examined for deposits of streptococcal IgA-BR by immunohistochemistry and electron microscopy using specific antibodies, and a skin sample from a HSP patient was examined by mass spectrometry. IgA-BR deposits were detected in 10/16 IgAN kidneys and 7/13 HSP kidneys. Electron microscopy demonstrated deposits of IgA-BRs in the mesangial matrix and glomerular basement membrane, which colocalized with IgA. Skin samples exhibited IgA-BR deposits in 4/5 biopsies, a result confirmed by mass spectrometry in one patient. IgA-BR deposits were not detected in normal kidney and skin samples. Taken together, these results demonstrate IgA-BR from streptococcal M proteins in patient tissues. IgA-BR, would on gaining access to the circulation, encounter circulatory IgA and form a complex with IgA-Fc that could deposit in tissues and contribute to the pathogenesis of IgAN and HSP. PMID:20056836

  15. Streptococcal SpeB Cleaved PAR-1 Suppresses ERK Phosphorylation and Blunts Thrombin-Induced Platelet Aggregation

    PubMed Central

    Ender, Miriam; Andreoni, Federica; Zinkernagel, Annelies Sophie; Schuepbach, Reto Andreas

    2013-01-01

    Background The family of 4 related protease-activated receptors (PAR-1, 2, 3 & 4) expressed by mammalian cells allow to sense for and react to extracellular proteolytic activity. Since major human bacterial pathogens secret a wide array of protease(-s) we investigated whether they interfere with human PAR function. Methodology/Principal Findings Supernatants from cultures of major human bacterial pathogens were assayed for the presence of protease(-s) capable to cleave overexpressed human PAR-1, 2, 3 and 4 reporter constructs. Group A streptococcus (GAS) was found to secret a PAR-1-cleaving protease. Experiments involving genetical and pharmacological gain and loss of function identified streptococcal pyrogenic exotoxin B SpeB as the protease responsible. On the host’s side analysis of overexpressed PAR-1 carrying alanine substitutions and deletions showed the amino acid residue leucine44 on PAR-1’s extracellular N-terminus to be the only cleavage site. Complementary studies on endogenously expressed PAR-1 using PAR-1 blocking antibodies further supported our conclusion. Through PAR-1 cleavage SpeB efficiently blunted thrombin-induced induction of the ERK-pathway in endothelial cells and prevented platelets aggregation in response to thrombin. Conclusions/Significance Our results identify a novel function of the streptococcal virulence factor SpeB. By cleaving human PAR-1 at the N-terminal amino acid residue leucine44 SpeB rendered endothelial cells unresponsive to thrombin and prevented human platelets from thrombin-induced aggregation. These results suggest that by blunting PAR-1 signaling, SpeB modulates various innate host responses directed against invasive GAS potentially helping the invasive bacteria to escape. This may allow to tailor additional treatments in the future since upon invasion of the blood stream endothelial cells as well as platelets and mononuclear cells respond to PAR-1 agonists aiming to prevent further bacterial dissemination. PMID:24278414

  16. Hemodynamic effects of the laparoscopic pneumoperitoneum during sepsis in a porcine endotoxic shock model.

    PubMed Central

    Greif, W M; Forse, R A

    1998-01-01

    OBJECTIVE: The authors compared the hemodynamic effects of laparoscopic intervention with conventional laparotomy in an endotoxic shock model in the pig. SUMMARY BACKGROUND DATA: Laparoscopic techniques are being applied more frequently to severely ill patients to evaluate potential abdominal sources of sepsis. Although hemodynamic effects of laparoscopy are minimal in healthy patients, recent studies have shown more significant changes in patients with chronic cardiopulmonary disease. It is unclear whether these effects are applicable to acutely septic patients. METHODS: Twelve domestic pigs received intravenous lipopolysaccharide (LPS) injection and underwent surgical abdominal exploration using either laparoscopy or conventional laparotomy. For baseline comparison, four pigs underwent exploratory laparoscopy without intravenous LPS injection. Hemodynamic measurements and blood gas analyses were obtained using Swan-Ganz and arterial catheters. RESULTS: After LPS exposure, animals undergoing laparoscopic evaluation were significantly more hypercarbic (p < 0.01) and acidotic (p < 0.01) than those undergoing conventional laparotomy. Their mean pulmonary arterial pressure and pulmonary vascular resistance were greater as well (not significant). The cardiac index (p < 0.05) and stroke volume (p < 0.05) were decreased in the laparoscopic group. Their oxygen delivery was decreased and oxygen consumption increased, although these were not significantly different from those of the laparotomy group. The degree of acidosis was highly correlated with the cardiac index (correlation coefficient, r = 0.82). CONCLUSIONS: Animals exposed to LPS tolerate laparoscopy but with significant hemodynamic compromise. Much of this effect seems to be mediated by a cardiodepressive effect of acidosis. This study suggests that laparoscopic intervention, when used in septic patients, should be used with caution. PMID:9563532

  17. Advances in Intra-abdominal Sepsis: What Is New?

    PubMed

    Dietch, Zachary C; Shah, Puja M; Sawyer, Robert G

    2015-08-01

    We have reviewed the literature regarding recent advances in the management of intra-abdominal sepsis, with a focus on antimicrobial agents, duration of therapy, and source control. Several important developments in these areas are discussed in this review. The introduction of a new antimicrobial agent-ceftolozane/tazobactam-marks the first novel agent for treating intra-abdominal infections in a number of years, and its indications for use and supporting evidence are reviewed here. In addition, we discuss recent evidence that clarifies the importance of early source control for intra-abdominal infection and new data that suggests that an abbreviated course of antimicrobial therapy for intra-abdominal infection is equally effective as prolonged therapy. PMID:26099701

  18. Dysregulation of in vitro cytokine production by monocytes during sepsis.

    PubMed Central

    Munoz, C; Carlet, J; Fitting, C; Misset, B; Blériot, J P; Cavaillon, J M

    1991-01-01

    The production by monocytes of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNF alpha and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-1 alpha is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1 beta were lower than those of TNF alpha. Cell-associated IL-1 beta and TNF alpha were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-1 alpha production by monocytes in all patients, and of IL-1 beta, IL-6, and TNF alpha in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections. Images PMID:1939659

  19. Acquired factor VII deficiency associated with acute myeloid leukemia.

    PubMed

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics. PMID:24991944

  20. Anti-streptococcal, tubulin, and dopamine receptor 2 antibodies in children with PANDAS and Tourette syndrome: single-point and longitudinal assessments.

    PubMed

    Morris-Berry, C M; Pollard, M; Gao, S; Thompson, C; Singer, H S

    2013-11-15

    Single-point-in-time ELISA optical densities for three putative antibodies identified in Sydenham's chorea, the streptococcal group A carbohydrate antigen, N-acetyl-beta-d-glucosamine, tubulin, and the dopamine 2 receptor, showed no differences in children with PANDAS (n=44) or Tourette syndrome (n=40) as compared to controls (n=24). Anti-tubulin and D2 receptor antibodies assessed in serial samples from 12 PANDAS subjects obtained prior to a documented exacerbation, during the exacerbation (with or without a temporally associated streptococcal infection), and following the exacerbation, showed no evidence of antibody levels correlating with a clinical exacerbation. These data do not support hypotheses suggesting an autoimmune hypothesis in either TS or PANDAS. PMID:24080310

  1. Sensitivity and Specificity of Rapid Diagnostic Tests for Detection of Group B Streptococcal Antigen in Bacteremic Neonates

    Microsoft Academic Search

    DAVID N. GREENBERG; DAVID P. ASCHER; BRADLEY A. YODER; DONNA M. HENSLEY; HOWARD S. HEIMAN; ANDJULIAN F. KEITH

    1995-01-01

    Latexparticleagglutination(LPA)testingforantigentogroupBstreptococcus(GBS)hasbeenusefulinthe diagnosis of GBS sepsis in newborns. However, recent reports have demonstrated that the sensitivity of LPA assays may be as low as 27 to 54%. The purposes of the present study were to directly compare the abilities of four urine antigen assays to detect GBS antigen with clinical urine samples from neonates with GBS bacteremia and to evaluate the

  2. [Postnatal sepsis due to group A Streptococcus in a mother and her newborn].

    PubMed

    Jänisch, Stefanie; Germerott, Tanja; Bange, Franz-Christoph; Schmidt, Anke; Debertin, Anette Solveig

    2009-01-01

    Nowadays, postnatal sepsis caused by group A Streptococcus (Str. pyogenes) is a rare condition. However, the mortality due to this uncommon disease is still high, and it has been described in the literature more frequently in the last few years. The authors present the case of a female newborn who died 15 hours after spontaneous delivery in the 40th week of gestation. Autopsy revealed a lung edema and solid lung parenchyma with normal findings of the other organs on macroscopic examination. Additional bacteriological testing detected Streptococcus pyogenes in the child. Aspiration pneumonia and signs of sepsis were discovered in the histological examination. Three days postpartum, the mother was hospitalized with Streptococcus pyogenes sepsis. Streptococcus pyogenes colonization of the mother's vaginal flora was assumed to be the origin of the infection. The problem in this case was the macromorphological diagnosis of sepsis and pneumonia in the newborn. The importance of microbiological analysis as a matter of routine is emphasized. PMID:19938405

  3. Microbiological diagnosis of sepsis: the confounding effects of a "gold standard".

    PubMed

    Mancini, Nicasio; Burioni, Roberto; Clementi, Massimo

    2015-01-01

    The need of rapid and sensitive diagnostic techniques for sepsis is every day more compelling. Its morbidity and mortality loads are dramatically high, with one quarter of patients eventually dying. Several diagnostic progresses have been made in the last years using both molecular- and nonmolecular-based approaches, and they have to be broadly shared in the scientific community also under the technical point of view. The initial chapters of this book give a thorough overlook of the state of the art in the actual diagnosis of sepsis. The other chapters provide a broad range of protocols describing both already used and futuristic tools, covering both microbiological and nonmicrobiological aspects. The potential role of each described protocol is evidenced by a brief introduction on the specific topic of each chapter. A final chapter describing algorithms potentially useful in stratifying the risk of sepsis in each single patient and suggesting the future perspectives in the diagnosis of sepsis closes the book. PMID:25319774

  4. Neonatal sepsis and death caused by resistant Escherichia coli: Possible consequences of extended maternal ampicillin administration

    Microsoft Academic Search

    Dom A. Terrone; Brian K. Rinehart; Mark H. Einstein; Lauren B. Britt; James N. Martin; Kenneth G. Perry

    1999-01-01

    Objective: Our goal was to evaluate the relationship between neonatal death caused by sepsis associated with ampicillin-resistant organisms and length of antibiotic exposure. Study Design: All neonatal deaths from culture-positive sepsis over a 3-year period were examined. Infants who were delivered at either the University of Mississippi Medical Center or at Saint Barnabas Medical Center at ?24 weeks’ gestation and

  5. Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset

    Microsoft Academic Search

    Jia-Horng Jiang; Nan-Chang Chiu; Fu-Yang Huang; Hsin-An Kao; Chyong-Hsin Hsu; Han-Yang Hung; Jui-Hsing Chang; Chun-Chih Peng

    2004-01-01

    episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late on- set occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%).

  6. Seventy-Five Years of Neonatal Sepsis at Yale: 1928-2003

    Microsoft Academic Search

    Matthew J. Bizzarro; Craig Raskind; Robert S. Baltimore; Patrick G. Gallagher

    2010-01-01

    Objective. Yale-New Haven Hospital (Y- NHH) has maintained the longest running, single-center longitudinal database of neonatal sepsis, started in 1928. The objective of this study was to update this database with review of neonatal sepsis cases at Y-NHH to iden- tify longitudinal trends in demographics, pathogens, and outcome. Methods. Records of infants with positive blood cul- tures obtained while they

  7. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial

    Microsoft Academic Search

    Simon Nadel; Brahm Goldstein; Mark D Williams; Heidi Dalton; Mark Peters; William L Macias; Shamel A Abd-Allah; Howard Levy; Robinette Angle; Dazhe Wang; David P Sundin; Brett Giroir

    2007-01-01

    Summary Background Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to

  8. Score-based immunoglobulin G therapy of patients with sepsis: The SBITS study

    Microsoft Academic Search

    Karl Werdan; Günter Pilz; Oskar Bujdoso; Peter Fraunberger; Gertraud Neeser; Roland Erich Schmieder; Burkhard Viell; Walter Marget; Margret Seewald; Peter Walger; Ralph Stuttmann; Norbert Speichermann; Claus Peckelsen; Volkhard Kurowski; Hans-Heinrich Osterhues; Ljiljana Verner; Roswita Neumann; Ursula Müller-Werdan

    2007-01-01

    Objective: Intravenous immunoglobulin as an adjunctive treat- ment in sepsis was regarded as promising by a Cochrane meta- analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score- defined severe sepsis. Design: Randomized, double-blind, placebo-controlled, multi- center trial. Setting: Twenty-three medical and surgical

  9. Proven infection-related sepsis induces a differential stress response early after ICU admission

    Microsoft Academic Search

    Olivier Lesur; Jean-Francois Roussy; Frederic Chagnon; Nicole Gallo-Payet; Robert Dumaine; Philippe Sarret; Ahmed Chraibi; Lucie Chouinard; Bruno Hogue

    2010-01-01

    ABSTRACT: INTRODUCTION: Neuropeptides arginine-vasopressin (AVP), apelin (APL), and stromal-derived factor-1? (SDF-1?) are involved in the dysfunction of the corticotropic axis observed in septic ICU patients. Study aims were: (i) to portray a distinctive stress-related neuro-corticotropic systemic profile of early sepsis, (ii) to propose a combination data score, for aiding ICU physicians in diagnosing sepsis on admission. METHODS: This prospective one-center

  10. Effect of Sepsis Syndrome on Neonatal Oxygen Consumption and Energy Expenditure

    Microsoft Academic Search

    Jacqueline Bauer; Roland Hentschel; Otwin Linderkamp

    Objective. To evaluate oxygen consump- tion (VO2), carbon dioxide production, and energy expen- diture (EE) in full-term neonates with early-onset neo- natal septicemia daily for 7 days beginning at the day of clinical diagnosis of sepsis. Methods. A total of 17 spontaneously breathing full- term neonates, 10 with clinical signs of sepsis and 7 healthy neonates (control group), were enrolled

  11. Increased Serum Concentration of Soluble CD14 Is a Prognostic Marker in Gram-Positive Sepsis

    Microsoft Academic Search

    Heinz Burgmann; Stefan Winkler; Gottfried J. Locker; Elisabeth Presterl; Klaus Laczika; Thomas Staudinger; Sylvia Knapp; Florian Thalhammer; Christoph Wenisch; Konstantin Zedwitz-Liebenstein; Michael Frass; Wolfgang Graninger

    1996-01-01

    Increased serum sCD14 concentrations are associated with poor outcome in Gram-negative sepsis and trauma patients. In the present study serum sCD14 concentrations were measured in patients with Gram-positive sepsis and compared with Gram-negative septic and nonseptic intensive care unit patients. Furthermore, serum sCD14 concentration was correlated with patient's outcome. Serum samples of 28 Gram-positive (8 nonsurvivors\\/20 survivors) and 10 Gram-negative

  12. The Streptococcal Exotoxin Streptolysin O Activates Mast Cells To Produce Tumor Necrosis Factor Alpha by p38 Mitogen-Activated Protein Kinase- and Protein Kinase C-Dependent Pathways

    PubMed Central

    Stassen, Michael; Müller, Christian; Richter, Christoph; Neudörfl, Christine; Hültner, Lothar; Bhakdi, Sucharit; Walev, Iwan; Schmitt, Edgar

    2003-01-01

    Streptolysin O (SLO), a major virulence factor of pyogenic streptococci, binds to cholesterol in the membranes of eukaryotic cells and oligomerizes to form large transmembrane pores. While high toxin doses are rapidly cytocidal, low doses are tolerated because a limited number of lesions can be resealed. Here, we report that at sublethal doses, SLO activates primary murine bone marrow-derived mast cells to degranulate and to rapidly induce or enhance the production of several cytokine mRNAs, including tumor necrosis factor alpha (TNF-?). Mast cell-derived TNF-? plays an important protective role in murine models of acute inflammation, and the production of this cytokine was analyzed in more detail. Release of biologically active TNF-? peaked ?4 h after stimulation with SLO. Production of TNF-? was blunted upon depletion of protein kinase C by pretreatment of the cells with phorbol-12 myristate-13 acetate. Transient permeabilization of mast cells with SLO also led to the activation of the stress-activated protein kinases p38 mitogen-activated protein (MAP) kinase and c-jun N-terminal kinase (JNK), and inhibition of p38 MAP kinase markedly reduced production of TNF-?. In contrast, secretion of preformed granule constituents triggered by membrane permeabilization was not dependent on p38 MAP kinase or on protein kinase C. Thus, transcriptional activation of mast cells following transient permeabilization might contribute to host defense against infections via the beneficial effects of TNF-?. However, hyperstimulation of mast cells might also lead to overproduction of TNF-?, which would then promote the development of toxic streptococcal syndromes. PMID:14573633

  13. The streptococcal exotoxin streptolysin O activates mast cells to produce tumor necrosis factor alpha by p38 mitogen-activated protein kinase- and protein kinase C-dependent pathways.

    PubMed

    Stassen, Michael; Müller, Christian; Richter, Christoph; Neudörfl, Christine; Hültner, Lothar; Bhakdi, Sucharit; Walev, Iwan; Schmitt, Edgar

    2003-11-01

    Streptolysin O (SLO), a major virulence factor of pyogenic streptococci, binds to cholesterol in the membranes of eukaryotic cells and oligomerizes to form large transmembrane pores. While high toxin doses are rapidly cytocidal, low doses are tolerated because a limited number of lesions can be resealed. Here, we report that at sublethal doses, SLO activates primary murine bone marrow-derived mast cells to degranulate and to rapidly induce or enhance the production of several cytokine mRNAs, including tumor necrosis factor alpha (TNF-alpha). Mast cell-derived TNF-alpha plays an important protective role in murine models of acute inflammation, and the production of this cytokine was analyzed in more detail. Release of biologically active TNF-alpha peaked approximately 4 h after stimulation with SLO. Production of TNF-alpha was blunted upon depletion of protein kinase C by pretreatment of the cells with phorbol-12 myristate-13 acetate. Transient permeabilization of mast cells with SLO also led to the activation of the stress-activated protein kinases p38 mitogen-activated protein (MAP) kinase and c-jun N-terminal kinase (JNK), and inhibition of p38 MAP kinase markedly reduced production of TNF-alpha. In contrast, secretion of preformed granule constituents triggered by membrane permeabilization was not dependent on p38 MAP kinase or on protein kinase C. Thus, transcriptional activation of mast cells following transient permeabilization might contribute to host defense against infections via the beneficial effects of TNF-alpha. However, hyperstimulation of mast cells might also lead to overproduction of TNF-alpha, which would then promote the development of toxic streptococcal syndromes. PMID:14573633

  14. [Does the biocompatibility of the hemodialysis membrane influence the prognosis of acute renal insufficiency?].

    PubMed

    Tielemans, C; Gastaldello, K; Melot, C; Kahn, R J; Vanherweghem, J L

    1998-01-01

    Several recent publications have suggested that the use of cuprophane in the setting of acute renal failure is associated with a higher mortality (especially from sepsis) and a slower recovery of renal function in the survivors in comparison with more biocompatible membranes. We present here a critical review of these publications and point to several methodological bias that might invalidate their conclusions. However, while waiting further information, we would advocate to abandon the use of cuprophane to dialyze patients with acute renal failure. PMID:9592779

  15. The endothelial protein C receptor impairs the antibacterial response in murine pneumococcal pneumonia and sepsis.

    PubMed

    Schouten, Marcel; de Boer, J Daan; Kager, Liesbeth M; Roelofs, Joris J T H; Meijers, Joost C M; Esmon, Charles T; Levi, Marcel; van 't Veer, Cornelis; van der Poll, Tom

    2014-05-01

    Pneumococcal pneumonia is a frequent cause of gram-positive sepsis and has a high mortality. The endothelial protein C receptor (EPCR) has been implicated in both the activation of protein C (PC) and the anti-inflammatory actions of activated (A)PC. The aim of this study was to determine the role of the EPCR in murine pneumococcal pneumonia and sepsis. Wild-type (WT), EPCR knockout (KO) and Tie2-EPCR mice, which overexpress EPCR on the endothelium, were infected intranasally (pneumonia) or intravenously (sepsis) with viable Streptococcus pneumoniae and euthanised at 24 or 48 hours after initiation of the infection for analyses. Pneumonia did not alter constitutive EPCR expression on pulmonary endothelium but was associated with an influx of EPCR positive neutrophils into lung tissue. In pneumococcal pneumonia EPCR KO mice demonstrated diminished bacterial growth in the lungs and dissemination to spleen and liver, reduced neutrophil recruitment to the lungs and a mitigated inflammatory response. Moreover, EPCR KO mice displayed enhanced activation of coagulation in the early phase of disease. Correspondingly, in pneumococcal sepsis EPCR KO mice showed reduced bacterial growth in lung and liver and attenuated cytokine release. Conversely, EPCR-overexpressing mice displayed higher bacterial outgrowth in lung, blood, spleen and liver in pneumococcal sepsis. In conclusion, EPCR impairs antibacterial defense in both pneumococcal pneumonia and sepsis, which is associated with an enhanced pro-inflammatory response. PMID:24401906

  16. An integrated clinico-metabolomic model improves prediction of death in sepsis

    PubMed Central

    Langley, Raymond J.; Tsalik, Ephraim L.; van Velkinburgh, Jennifer C.; Glickman, Seth W.; Rice, Brandon J.; Wang, Chunping; Chen, Bo; Carin, Lawrence; Suarez, Arturo; Mohney, Robert P.; Freeman, Debra H.; Wang, Mu; You, Jinsam; Wulff, Jacob; Thompson, J. Will; Moseley, M. Arthur; Reisinger, Stephanie; Edmonds, Brian T.; Grinnell, Brian; Nelson, David R.; Dinwiddie, Darrell L.; Miller, Neil A.; Saunders, Carol J.; Soden, Sarah S.; Rogers, Angela J.; Gazourian, Lee; Fredenburgh, Laura E.; Massaro, Anthony F.; Baron, Rebecca M.; Choi, Augustine M.K.; Corey, G. Ralph; Ginsburg, Geoffrey S.; Cairns, Charles B.; Otero, Ronny M.; Fowler, Vance G.; Rivers, Emanuel P.; Woods, Christopher W.; Kingsmore, Stephen F.

    2014-01-01

    Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features, and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would die differed markedly from those who would survive. The different profiles of proteins and metabolites clustered into fatty acid transport and ?-oxidation, gluconeogenesis and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of seven metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis. PMID:23884467

  17. Synergistic Action of Staphylococcus aureus ?-Toxin on Platelets and Myeloid Lineage Cells Contributes to Lethal Sepsis.

    PubMed

    Powers, Michael E; Becker, Russell E N; Sailer, Anne; Turner, Jerrold R; Bubeck Wardenburg, Juliane

    2015-06-10

    Multi-organ failure contributes to mortality in bacterial sepsis. Platelet and immune cell activation contribute to organ injury during sepsis, but the mechanisms by which bacterial virulence factors initiate these responses remain poorly defined. We demonstrate that during lethal sepsis, Staphylococcus aureus ?-toxin simultaneously alters platelet activation and promotes neutrophil inflammatory signaling through interactions with its cellular receptor ADAM10. Platelet intoxication prevents endothelial barrier repair and facilitates formation of injurious platelet-neutrophil aggregates, contributing to lung and liver injury that is mitigated by ADAM10 deletion on platelets and myeloid lineage cells. While platelet- or myeloid-specific ADAM10 knockout does not alter sepsis mortality, double-knockout animals are highly protected. These results define a pathway by which a single bacterial toxin utilizes a widely expressed receptor to coordinate progressive, multi-organ disease in lethal sepsis. As an expression-enhancing ADAM10 polymorphism confers susceptibility to severe human sepsis, these studies highlight the importance of understanding molecular host-microbe interactions. PMID:26067604

  18. Microparticle alpha-2-macroglobulin enhances pro-resolving responses and promotes survival in sepsis

    PubMed Central

    Dalli, Jesmond; Norling, Lucy V; Montero-Melendez, Trinidad; Canova, Donata Federici; Lashin, Hazem; Pavlov, Anton M; Sukhorukov, Gleb B; Hinds, Charles J; Perretti, Mauro

    2014-01-01

    Incorporation of locally produced signaling molecules into cell-derived vesicles may serve as an endogenous mediator delivery system. We recently reported that levels alpha-2-macroglobulin (A2MG)-containing microparticles are elevated in plasma from patients with sepsis. Herein, we investigated the immunomodulatory actions of A2MG containing microparticles during sepsis. Administration of A2MG-enriched (A2MG-E)-microparticles to mice with microbial sepsis protected against hypothermia, reduced bacterial titers, elevated immunoresolvent lipid mediator levels in inflammatory exudates and reduced systemic inflammation. A2MG-E microparticles also enhanced survival in murine sepsis, an action lost in mice transfected with siRNA for LRP1, a putative A2MG receptor. In vitro, A2MG was functionally transferred onto endothelial cell plasma membranes from microparticles, augmenting neutrophil–endothelial adhesion. A2MG also modulated human leukocyte responses: enhanced bacterial phagocytosis, reactive oxygen species production, cathelicidin release, prevented endotoxin induced CXCR2 downregulation and preserved neutrophil chemotaxis in the presence of LPS. A significant association was also found between elevated plasma levels of A2MG-containing microparticles and survival in human sepsis patients. Taken together, these results identify A2MG enrichment in microparticles as an important host protective mechanism in sepsis. PMID:24357647

  19. Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective

    PubMed Central

    2012-01-01

    Sepsis represents a dysregulated host response to infection, the extent of which determines the severity of organ dysfunction and subsequent outcome. All trialled immunomodulatory strategies to date have resulted in either outright failure or inconsistent degrees of success. Intravenous immunoglobulin (IVIg) therapy falls into the latter category with opinion still divided as to its utility. This article provides a narrative review of the biological rationale for using IVIg in sepsis. A literature search was conducted using the PubMed database (1966 to February 2011). The strategy included the following text terms and combinations of these: IVIg, intravenous immune globulin, intravenous immunoglobulin, immunoglobulin, immunoglobulin therapy, pentaglobin, sepsis, inflammation, immune modulation, apoptosis. Preclinical and extrapolated clinical data of IVIg therapy in sepsis suggests improved bacterial clearance, inhibitory effects upon upstream mediators of the host response (for example, the nuclear factor kappa B (NF-?B) transcription factor), scavenging of downstream inflammatory mediators (for example, cytokines), direct anti-inflammatory effects mediated via Fc? receptors, and a potential ability to attenuate lymphocyte apoptosis and thus sepsis-related immunosuppression. Characterizing the trajectory of change in immunoglobulin levels during sepsis, understanding mechanisms contributing to these changes, and undertaking IVIg dose-finding studies should be performed prior to further large-scale interventional trials to enhance the likelihood of a successful outcome. PMID:22424150

  20. ?-hydroxy-?-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice.

    PubMed

    Supinski, Gerald S; Callahan, Leigh A

    2014-06-01

    Infections induce severe respiratory muscle weakness. Currently there are no treatments for this important clinical problem. We tested the hypothesis that ?-hydroxy-?-methylbutyrate (HMB) would prevent sepsis-induced diaphragm weakness. Four groups of adult male mice were studied: controls (saline-injected), sepsis (intraperitoneal lipopolysaccharide), sepsis+HMB (injected intravenously), and HMB. Diaphragm force generation and indices of caspase 3, calpain, 20S proteasomal subunit, and double-stranded RNA-dependent protein kinase (PKR) activation were assessed after 24h. Sepsis elicited large reductions in diaphragm specific force generation at all stimulation frequencies. Endotoxin also activated caspase 3, calpain, the 20S proteasomal subunit and PKR in the diaphragm. HMB blocked sepsis-induced caspase 3, 20S proteasomal and PKR activation, but did not prevent calpain activation. Most importantly, HMB administration significantly attenuated sepsis-induced diaphragm weakness, preserving muscle force generation at all stimulation frequencies (p<0.01). We speculate that HMB may prove to be an important therapy in infected patients, with the potential to increase diaphragm strength, to reduce the duration of mechanical ventilation and to decrease mortality in this patient population. PMID:24632527