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  1. Clinical analysis of cases of neonatal Streptococcus agalactiae sepsis.

    PubMed

    Zeng, S J; Tang, X S; Zhao, W L; Qiu, H X; Wang, H; Feng, Z C

    2016-01-01

    With the advent of antibiotic resistance, pathogenic bacteria have become a major threat in cases of neonatal sepsis; however, guidelines for treatment have not yet been standardized. In this study, 15 cases of neonatal Streptococcus agalactiae sepsis from our hospital were retrospectively analyzed. Of these, nine cases showed early-onset and six cases showed late-onset sepsis. Pathogens were characterized by genotyping and antibiotic sensitivity tests on blood cultures. Results demonstrated that in cases with early-onset sepsis, clinical manifestations affected mainly the respiratory tract, while late-onset sepsis was accompanied by intracranial infection. Therefore, we suggest including a cerebrospinal fluid examination when diagnosing neonatal sepsis. Bacterial genotyping indicated the bacteria were mainly type Ib, Ia, and III S. agalactiae. We recommend treatment with penicillin or ampicillin, since bacteria were resistant to clindamycin and tetracycline. In conclusion, our results provide valuable information for the clinical treatment of S. agalactiae sepsis in neonatal infants.

  2. Fatal Streptococcus pneumoniae Sepsis in a Patient With Celiac Disease-Associated Hyposplenism

    PubMed Central

    Ouseph, Madhu M.; Simons, Malorie; Treaba, Diana O.; Yakirevich, Evgeny; Green, Peter H.; Bhagat, Govind; Moss, Steven F.

    2016-01-01

    We present a 59-year-old male with poorly controlled celiac disease (CD) and fatal Streptococcus pneumoniae sepsis, describe the morphologic findings, and stress the need for monitoring splenic function and pneumococcal vaccination in these patients. PMID:27761478

  3. Sepsis

    MedlinePlus

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

  4. Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult.

    PubMed

    Hale, Andrew J; LaSalvia, Mary; Kirby, James E; Kimball, Allison; Baden, Rachel

    2016-01-01

    Asplenic patients are at increased risk for sepsis and fulminant infection. Sepsis in these patients is typically secondary to encapsulated bacteria, with Streptococcus pneumoniae being the most frequent pathogen. Rare complications of severe sepsis include purpura fulminans and bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). We present the case of a 36-year-old woman, healthy except for splenectomy years prior for idiopathic thrombocytopenic purpura treatment, who presented with fever. Upon presentation to our hospital, three hours after symptoms onset, she had purpura fulminans and shock. Despite timely antimicrobials and maximal resuscitative efforts, her disease progressed and she expired 12 hours after symptoms onset. Autopsy revealed bilateral adrenal hemorrhage; acute adrenal crisis likely contributed to her refractory shock. Prior to her presentation, she had not received guideline-based post-splenectomy care. Sepsis in asplenic patients can be fulminant and rapidly fatal. Streptococcus pneumoniae remains the most frequent cause, despite decreasing rates in recent years related to widespread pneumococcal vaccination. Guideline-based vaccinations and "pill-in-pocket" therapy can be life-saving for asplenic patients. Purpura fulminans represents an extreme manifestation of disseminated intravascular coagulation, is more common in asplenic patients, and portends a poor prognosis. Waterhouse-Friderichsen syndrome can be seen concurrently with purpura fulminans and further portends a poor prognosis; pre-mortem diagnosis requires a high index of suspicion. PMID:27583208

  5. Severe sepsis in women with group B Streptococcus in pregnancy: an exploratory UK national case–control study

    PubMed Central

    Kalin, Asli; Acosta, Colleen; Kurinczuk, Jennifer J; Brocklehurst, Peter; Knight, Marian

    2015-01-01

    Objective To estimate the incidence of severe maternal sepsis due to group B Streptococcus (GBS) in the UK, and to investigate the associated outcomes for mother and infant. Design National case–control study. Setting All UK consultant-led maternity units. Participants 30 women with confirmed or suspected severe GBS sepsis, and 757 control women. Main outcome measures Disease incidence, additional maternal morbidity, critical care admission, length of stay, infant infection, mortality. Results The incidences of confirmed and presumed severe maternal GBS sepsis were 1.00 and 2.75 per 100 000 maternities, respectively, giving an overall incidence of 3.75 per 100 000. Compared with controls, severe GBS sepsis was associated with higher odds of additional maternal morbidity (OR 12.35, 95% CI 3.96 to 35.0), requiring level 2 (OR 39.3, 95% CI 16.0 to 99.3) or level 3 (OR 182, 95% CI 21.0 to 8701) care and longer hospital stay (median stay in cases and controls was 7 days (range 3–29 days) and 2 days (range 0–16 days), respectively, p<0.001). None of the women died. Severe maternal GBS sepsis was associated with higher odds of infant sepsis (OR 32.7, 95% CI 8.99 to 119.0); 79% of infants, however, did not develop sepsis. There were no associated stillbirths or neonatal deaths. Conclusions Severe maternal GBS sepsis is a rare occurrence in the UK. It is associated with adverse maternal and neonatal outcomes. PMID:26450426

  6. Sepsis.

    PubMed

    Dean, Erin

    2016-09-01

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

  7. Sepsis.

    PubMed

    Dean, Erin

    2016-09-01

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

  8. Streptococcus pneumoniae sepsis as the initial presentation of systemic lupus erythematosus

    PubMed Central

    Erdem, Ilknur; Elbasan Omar, Senay; Ali, Ridvan Kara; Gunes, Hayati; Topkaya, Aynur Eren

    2016-01-01

    Objective Infections are among the most important causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE) but are rare initial presentation of the disease. Therefore, in this study, we describe a case of Streptococcus pneumoniae sepsis in a young woman with previously undiagnosed SLE. Case report A 23-year-old female patient was admitted to our outpatient clinic complaining of high fever (40°C), chills, fatigue, generalized myalgia, and cough with brown sputum for 5 days. Blood cultures grew gram-positive coccus defined as S. pneumoniae using standard procedures. Antinuclear antibody was positive at a titer of 1/1,000, and anti-double-stranded DNA was positive at 984 IU/mL. She was diagnosed with SLE. Her respiratory symptoms and pleural effusion were considered to be due to pulmonary manifestation of SLE. Conclusion The underlying immunosuppression caused by SLE could have predisposed the patient to invasive pneumococcal disease. It may also occur as a primary presenting feature, although a rare condition. PMID:27660485

  9. Streptococcus pneumoniae sepsis as the initial presentation of systemic lupus erythematosus

    PubMed Central

    Erdem, Ilknur; Elbasan Omar, Senay; Ali, Ridvan Kara; Gunes, Hayati; Topkaya, Aynur Eren

    2016-01-01

    Objective Infections are among the most important causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE) but are rare initial presentation of the disease. Therefore, in this study, we describe a case of Streptococcus pneumoniae sepsis in a young woman with previously undiagnosed SLE. Case report A 23-year-old female patient was admitted to our outpatient clinic complaining of high fever (40°C), chills, fatigue, generalized myalgia, and cough with brown sputum for 5 days. Blood cultures grew gram-positive coccus defined as S. pneumoniae using standard procedures. Antinuclear antibody was positive at a titer of 1/1,000, and anti-double-stranded DNA was positive at 984 IU/mL. She was diagnosed with SLE. Her respiratory symptoms and pleural effusion were considered to be due to pulmonary manifestation of SLE. Conclusion The underlying immunosuppression caused by SLE could have predisposed the patient to invasive pneumococcal disease. It may also occur as a primary presenting feature, although a rare condition.

  10. Sepsis

    MedlinePlus

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

  11. Molecular analysis of an outbreak of lethal postpartum sepsis caused by Streptococcus pyogenes.

    PubMed

    Turner, Claire E; Dryden, Matthew; Holden, Matthew T G; Davies, Frances J; Lawrenson, Richard A; Farzaneh, Leili; Bentley, Stephen D; Efstratiou, Androulla; Sriskandan, Shiranee

    2013-07-01

    Sepsis is now the leading direct cause of maternal death in the United Kingdom, and Streptococcus pyogenes is the leading pathogen. We combined conventional and genomic analyses to define the duration and scale of a lethal outbreak. Two postpartum deaths caused by S. pyogenes occurred within 24 h; one was characterized by bacteremia and shock and the other by hemorrhagic pneumonia. The women gave birth within minutes of each other in the same maternity unit 2 days earlier. Seven additional infections in health care and household contacts were subsequently detected and treated. All cluster-associated S. pyogenes isolates were genotype emm1 and were initially indistinguishable from other United Kingdom emm1 isolates. Sequencing of the virulence gene sic revealed that all outbreak isolates had the same unique sic type. Genome sequencing confirmed that the cluster was caused by a unique S. pyogenes clone. Transmission between patients occurred on a single day and was associated with casual contact only. A single isolate from one patient demonstrated a sequence change in sic consistent with longer infection duration. Transmission to health care workers was traced to single clinical contacts with index cases. The last case was detected 18 days after the first case. Following enhanced surveillance, the outbreak isolate was not detected again. Mutations in bacterial regulatory genes played no detectable role in this outbreak, illustrating the intrinsic ability of emm1 S. pyogenes to spread while retaining virulence. This fast-moving outbreak highlights the potential of S. pyogenes to cause a range of diseases in the puerperium with rapid transmission, underlining the importance of immediate recognition and response by clinical infection and occupational health teams.

  12. Fulminant neonatal sepsis due to Streptococcus alactolyticus - A case report and review.

    PubMed

    Toepfner, Nicole; Shetty, Sindhu; Kunze, Mirjam; Orlowska-Volk, Marzenna; Krüger, Markus; Berner, Reinhard; Hentschel, Roland

    2014-07-01

    Group D streptococci have rarely been associated with neonatal infections. We report a case of fulminant respiratory distress syndrome (RDS) caused by Streptococcus alactolyticus in a term neonate. Gram staining revealed gram-positive cocci and culture grew group D streptococci in samples taken from trachea, ear, and nasopharynx. Streptococcus alactolyticus was identified using automated microbial identification system (Vitek 2). Histopathology showed massive pulmonary inflammation with intra-alveolar granulocytosis and secondary pulmonary bleeding as etiology of fatal outcome. To our knowledge, this is first case presenting neonatal infection caused by Streptococcus alactolyticus.

  13. Coagulopathy in experimental sepsis with Streptococcus pneumoniae in rabbits: effect of drug therapy and splenectomy.

    PubMed

    Guckian, J C

    1976-08-01

    The cause of death in bacteremia due to Streptococcus pneumoniae remains unclear. The role of intravascular coagulation and splenectomy was investigated in rabbits with lethal pneumococcal bacteremia. The staphylococcal clumping titer in serum, a measure of fibrin degradation products, increased early and persisted until death. This titer correlated with the level of bacteremia. The partial thromboplastin time and platelet-rich plasma clotting time also increased as the disease worsened. However, the prothrombin time remained normal. 125I-labeled fibrinogen was cleared normally from the plasma of infected rabbits, whether intact or splenectomized. Similarly, the concentration of fibrogen in plasma remained normal, even though the level of fibrin degradation products increased, and no difference in these parameters was noted between intact and splenectomized rabbits. Fibrin deposition could not be detected in any of the organs studied. Neither the level of fibrin degradation products nor survival was affected by treatment with hydrocortisone, hexadimethrine, cytochrome c, carboxypeptidase B, epsilon-aminocaproic acid, or heparin. These data suggest that intravascular coagulation occurs in this experimental infection prior to the onset of shock but probably plays only a minor role in lethality.

  14. Early detection of neonatal group B streptococcus sepsis and the possible diagnostic utility of IL-6, IL-8, and CD11b in a human umbilical cord blood in vitro model

    PubMed Central

    Nakstad, Britt; Sonerud, Tonje; Solevåg, Anne Lee

    2016-01-01

    Background Group B streptococcus (GBS) infection remains a major cause of neonatal morbidity and mortality, and GBS III is the predominant strain in early-onset GBS neonatal sepsis. To avoid both over- and undertreatment of infants with nonspecific signs of infection, early diagnostic tools are warranted. The aim of this study was to identify biomarkers with high sensitivity and specificity in an early stage of GBS infection. A secondary aim was to assess the utility of a human umbilical cord blood (HUCB) model system of early-onset neonatal sepsis. Methods Umbilical cord blood samples from 20 healthy term pregnancies were stimulated for 2 hours with a GBS III isolate from a patient and a commercially available GBS Ia strain. Nonstimulated samples served as controls. Leukocyte surface markers (CD11b, CD64, toll-like receptor [TLR] 2, TLR4, and TLR6) were analyzed by flow cytometry and soluble biomarkers by enzyme-linked immunosorbent assay (interleukin [IL]-6 and -8; interferon-γ-inducing protein [IP]-10; and S100b). The area under the receiver operating characteristic curve (AUC) was calculated for the markers. Results GBS III gave the highest responses and AUC values for all biomarkers. Only IL-6 and IL-8 displayed an AUC approaching 0.8 for both GBS serotypes (P<0.001). IL-8 >5,292 pg/mL had both a sensitivity and a specificity of 1.00. IL-6 >197 pg/mL had both a sensitivity and a specificity of 0.95 for GBS III stimulation. CD11b on granulocytes and monocytes was the leukocyte surface marker with the highest AUC values for both GBS serotypes. Conclusion In agreement with previous studies, IL-6, IL-8, and potentially CD11b could be useful in diagnosing neonatal GBS infection in an early stage. Our HUCB early-onset neonatal sepsis model may be useful for evaluating biomarkers of neonatal sepsis. The HUCB of neonates with risk factors for sepsis might even be used for diagnostic purposes, but requires further study. PMID:27468243

  15. Neutropenic sepsis.

    PubMed

    Jones, Tracie

    2016-09-28

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

  16. Neonatal sepsis in Dubai, United Arab Emirates.

    PubMed

    Koutouby, A; Habibullah, J

    1995-06-01

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

  17. Streptococcus iniae and Streptococcus agalactiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus iniae and S. agalactiae are economically important Gram positive bacterial pathogens of cultured and wild fish with a worldwide distribution. Both bacteria are potential zoonotic pathogens and have been associated most often with infections in immunocompromised people. Streptococcus in...

  18. 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.

  19. Early-Onset Neonatal Sepsis

    PubMed Central

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

    2014-01-01

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

  20. Early-onset neonatal sepsis.

    PubMed

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

    2014-01-01

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

  1. Neonatal sepsis of vertical transmission: an epidemiological study from the "Grupo de Hospitales Castrillo".

    PubMed

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

    2000-01-01

    A prospective multicenter study was designed to assess the epidemiology of neonatal sepsis of vertical transmission in Spain. The study was carried out by the "Grupo de Hospitales Castrillo" that included the neonatal services of 19 tertiary care (reference) hospitals and 9 secondary care hospitals. Prospective data from infants with culture-proved neonatal sepsis, clinical sepsis and bacteremia were recorded for 1995 to 1997. In a total of 203,288 neonates, proven sepsis was diagnosed in 515 (rate of 2.5 per 1000 live births), clinical sepsis in 724 (rate of 3.6 per 1000 live births), and bacteremia of vertical transmission in 155 (rate of 0.76 per 1000 live births). Very low birth weight (VLBW) infants (< or = 1500 g) showed a significantly higher incidence of confirmed sepsis (26.5 per 1000 live births) and clinical sepsis (32.4 per 1000 live births) than infants weighing > 1500 g. Streptococcus agalactiae was the most frequent causative pathogen in cases of proven sepsis (51%) and bacteremia (33%), but Escherichia coli was the most frequently recovered organism in the VLBW group. The mortality rate of proven sepsis was significantly higher than that of clinical sepsis (8.7% versus 4.3%) (P < 0.01). In the VLBW cohort, there were no significant differences in the mortality rate between proven sepsis and clinical sepsis. In conclusion, clinical sepsis was the most frequent diagnosis, probably related to intrapartum chemoprophylaxis. Streptococcus agalactiae was the most frequent causative pathogen of culture-positive sepsis and bacteremia, whereas E. coli was the most significant in VLBW infants.

  2. Sepsis Questions and Answers

    MedlinePlus

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

  3. Recent advances in understanding the molecular basis of group B Streptococcus virulence

    PubMed Central

    Maisey, Heather C.; Doran, Kelly S.; Nizet, Victor

    2009-01-01

    Group B Streptococcus commonly colonises healthy adults without symptoms, yet under certain circumstances displays the ability to invade host tissues, evade immune detection and cause serious invasive disease. Consequently, Group B Streptococcus remains a leading cause of neonatal pneumonia, sepsis and meningitis. Here we review recent information on the bacterial factors and mechanisms that direct host–pathogen interactions involved in the pathogenesis of Group B Streptococcus infection. New research on host signalling and inflammatory responses to Group B Streptococcus infection is summarised. An understanding of the complex interplay between Group B Streptococcus and host provides valuable insight into pathogen evolution and highlights molecular targets for therapeutic intervention. PMID:18803886

  4. [Sepsis in Emergency Medicine].

    PubMed

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

    2016-07-01

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

  5. Early management of sepsis

    PubMed Central

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

    2014-01-01

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

  6. Exogenous arginine in sepsis.

    PubMed

    Luiking, Yvette C; Deutz, Nicolaas E P

    2007-09-01

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

  7. Sepsis-induced myopathy

    PubMed Central

    Callahan, Leigh Ann; Supinski, Gerald S.

    2014-01-01

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

  8. Neurology of Sepsis.

    PubMed

    Sweis, Rochelle; Ortiz, Jorge; Biller, José

    2016-03-01

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

  9. Implementing sepsis bundles

    PubMed Central

    Jozwiak, Mathieu; Monnet, Xavier

    2016-01-01

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

  10. The older adult experiencing sepsis.

    PubMed

    Englert, Nadine C; Ross, Carl

    2015-01-01

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

  11. Animal models of sepsis

    PubMed Central

    Fink, Mitchell P

    2014-01-01

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

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

    PubMed

    Reglinski, Mark; Sriskandan, Shiranee

    2014-01-01

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

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

    PubMed Central

    Reglinski, Mark; Sriskandan, Shiranee

    2014-01-01

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

  14. Sepsis-Associated Encephalopathy

    PubMed Central

    Cotena, Simona; Piazza, Ornella

    2012-01-01

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

  15. Sepsis in critical care.

    PubMed

    King, Joan E

    2007-03-01

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

  16. Essentials of sepsis management.

    PubMed

    Green, John M

    2015-04-01

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

  17. The resuscitation package in sepsis.

    PubMed

    Demertzis, Lee M; Kollef, Marin H

    2010-09-01

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

  18. Revisiting caspases in sepsis.

    PubMed

    Aziz, M; Jacob, A; Wang, P

    2014-01-01

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

  19. Nutrition and sepsis.

    PubMed

    Cohen, Jonathan; Chin, w Dat N

    2013-01-01

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

  20. Revisiting caspases in sepsis

    PubMed Central

    Aziz, M; Jacob, A; Wang, P

    2014-01-01

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

  1. Nutrition and sepsis.

    PubMed

    Cohen, Jonathan; Chin, w Dat N

    2013-01-01

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

  2. Sepsis Associated Encephalopathy.

    PubMed

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

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

  3. [Sepsis management -- antibiotic therapy].

    PubMed

    Welte, T

    2004-11-26

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

  4. Haemolytic uraemic syndrome associated with Pseudomonas aeruginosa sepsis.

    PubMed

    Narayanan, Parameswaran; Rustagi, Rashi S; Sivaprakasam, Prabha; Subramanian, Mahadevan; Parameswaran, Sreejith; Mandal, Jharna; Kaplan, B S

    2013-11-01

    Haemolytic uraemic syndrome (HUS) is a recognized complication of infection with Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae type 1. Infections with other micro-organisms, especially Streptococcus pneumoniae, have been cited as causes of HUS. In addition, influenza virus and other viruses may rarely be associated with this syndrome. A 2-year-old girl presented with severe Pseudomonas aeruginosa sepsis with renal failure and ecthyma gangrenosum. Further investigations revealed features of HUS. She was managed with antibiotics and other supportive measures including peritoneal dialysis, and subsequently made a full recovery. A possible role of neuraminidase in the pathogenesis of P. aeruginosa-associated HUS was proposed. This is the first reported case of P. aeruginosa sepsis leading to HUS.

  5. An unusual case of Streptococcus agalactiae meningitis in a patient with sys-temic lupus erythematosus

    PubMed Central

    Protonotariou, E; Arampatzi, A; Ourailoglou, V; Diza, E; Skoura, L

    2015-01-01

    Background: Streptococcus agalactiae (group B Streptococcus) is a major cause of sepsis and meningitis in neonates and an important cause of invasive disease in adults. Case description: We describe an unusual case of fatal bacterial meningitis caused by Streptococcus agalactiae in a young man suffering from systemic lupus erythematosus for over 20 years. The young man was transferred intubated in AHEPA University Hospital in a coma; twenty-four hours upon arrival and despite intense invasive treatment, he died from multiple organ failure. Conclusion: The risk of serious infections in patients with systemic lupus erythematosus even under treatment with moderate doses of corticosteroids is high. Hippokratia 2015; 19 (4):372-373.

  6. The encephalopathy of sepsis.

    PubMed

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

    1985-11-01

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

  7. 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

  8. Sepsis-associated hyperlactatemia.

    PubMed

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

    2014-01-01

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

  9. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePlus

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

  10. Muscle regeneration after sepsis.

    PubMed

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

    2016-01-01

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

  11. TLR2-induced IL-10 production impairs neutrophil recruitment to infected tissues during neonatal bacterial sepsis.

    PubMed

    Andrade, Elva B; Alves, Joana; Madureira, Pedro; Oliveira, Liliana; Ribeiro, Adília; Cordeiro-da-Silva, Anabela; Correia-Neves, Margarida; Trieu-Cuot, Patrick; Ferreira, Paula

    2013-11-01

    Sepsis is the third most common cause of neonatal death, with Group B Streptococcus (GBS) being the leading bacterial agent. The pathogenesis of neonatal septicemia is still unsolved. We described previously that host susceptibility to GBS infection is due to early IL-10 production. In this study, we investigated whether triggering TLR2 to produce IL-10 is a risk factor for neonatal bacterial sepsis. We observed that, in contrast to wild-type (WT) pups, neonatal TLR2-deficient mice were resistant to GBS-induced sepsis. Moreover, if IL-10 signaling were blocked in WT mice, they also were resistant to sepsis. This increased survival rate was due to an efficient recruitment of neutrophils to infected tissues that leads to bacterial clearance, thus preventing the development of sepsis. To confirm that IL-10 produced through TLR2 activation prevents neutrophil recruitment, WT pups were treated with the TLR2 agonist Pam3CSK4 prior to nebulization with the neutrophil chemotactic agent LTB4. Neutrophil recruitment into the neonatal lungs was inhibited in pups treated with Pam3CSK4. However, the migration was restored in Pam3CSK4-treated pups when IL-10 signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10-deficient mice). Our findings highlight that TLR2-induced IL-10 production is a key event in neonatal susceptibility to bacterial sepsis.

  12. Puerperal sepsis in the 21st century: progress, new challenges and the situation worldwide.

    PubMed

    Buddeberg, Bigna S; Aveling, Wynne

    2015-10-01

    Puerperal sepsis is one of the five leading causes of maternal mortality worldwide, and accounts for 15% of all maternal deaths. The WHO defined puerperal sepsis in 1992 as an infection of the genital tract occurring at any time between the rupture of membranes or labour and the 42nd day post partum; in which, two or more of the following are present: pelvic pain, fever, abnormal vaginal discharge and delay in the reduction of the size of the uterus. At the same time, the WHO introduced the term puerperal infections, which also include non-genital infections in the obstetric population. Recent epidemiological data shows that puerperal sepsis and non-genital tract infections are a major area of concern. In puerperal sepsis, group A streptococcus (GAS) is the most feared pathogen. Up to 30% of the population are asymptomatic carriers of GAS. GAS commonly causes throat infections. Women who died from GAS-positive sepsis all had signs of a throat infection themselves or one of their family members suffered from a throat infection. The pathway of infection is from the hands of the pregnant women or the mother to her perineum. In non-genital tract infections, influenza viruses and the HIV pandemic in the developing part of the world are responsible for many maternal deaths, and demand our attention. The physiological changes of pregnancy and the puerperium can obscure the signs and symptoms of sepsis in the obstetric population. A high level of suspicion is, therefore, needed in the care for the sick pregnant patient. If sepsis is suspected, timely administration of antibiotics, sepsis care bundles, multidisciplinary discussion and early involvement of senior staff members are important to improve outcome. PMID:26310266

  13. Sepsis From the Gut: The Enteric Habitat of Bacteria That Cause Late-Onset Neonatal Bloodstream Infections

    PubMed Central

    Carl, Mike A.; Ndao, I. Malick; Springman, A. Cody; Manning, Shannon D.; Johnson, James R.; Johnston, Brian D.; Burnham, Carey-Ann D.; Weinstock, Erica Sodergren; Weinstock, George M.; Wylie, Todd N.; Mitreva, Makedonka; Abubucker, Sahar; Zhou, Yanjiao; Stevens, Harold J.; Hall-Moore, Carla; Julian, Samuel; Shaikh, Nurmohammad; Warner, Barbara B.; Tarr, Phillip I.

    2014-01-01

    Background. Late-onset sepsis is a major problem in neonatology, but the habitat of the pathogens before bloodstream invasion occurs is not well established. Methods. We examined prospectively collected stools from premature infants with sepsis to find pathogens that subsequently invaded their bloodstreams, and sought the same organisms in stools of infants without sepsis. Culture-based techniques were used to isolate stool bacteria that provisionally matched the bloodstream organisms, which were then genome sequenced to confirm or refute commonality. Results. Of 11 children with late-onset neonatal bloodstream infections, 7 produced at least 1 stool that contained group B Streptococcus (GBS), Serratia marcescens, or Escherichia coli before their sepsis episode with provisionally matching organisms. Of 96 overlap comparison subjects without sepsis temporally associated with these cases, 4 were colonized with provisionally matching GBS or S. marcescens. Of 175 comparisons of stools from randomly selected infants without sepsis, 1 contained a GBS (this infant had also served as an overlap comparison subject and both specimens contained provisionally matching GBS). Genome sequencing confirmed common origin of provisionally matching fecal and blood isolates. The invasive E. coli were present in all presepticemic stools since birth, but gut colonization with GBS and S. marcescens occurred closer to time of bloodstream infection. Conclusions. The neonatal gut harbors sepsis-causing pathogens, but such organisms are not inevitable members of the normal microbiota. Surveillance microbiology, decolonization, and augmented hygiene might prevent dissemination of invasive bacteria between and within premature infants. PMID:24647013

  14. Life-threatening necrotizing myometritis, due to Group A streptococcus – still a life-threatening condition

    PubMed Central

    Boie, Sidsel; Krog, Jan; Tørring, Sofus; Bor, Isil Pinar

    2015-01-01

    Key Clinical Message Puerperal infection with Group A streptococcus (GAS) can present with few symptoms and rapidly progress to a life-threatening condition. Often, the infection can be treated with antibiotics. Delay in diagnosis increases risk of sepsis, multiorgan failure, and death. GAS infection is a differential diagnose for all postpartum women with unexplained symptoms. PMID:25984307

  15. Streptococcus anginosus ("Streptococcus milleri"): the unrecognized pathogen.

    PubMed Central

    Ruoff, K L

    1988-01-01

    "Streptococcus milleri" is an unofficial name that has been applied to a group of streptococci which, although basically similar, show various hemolytic, serological, and physiological characteristics. The species name Streptococcus anginosus has recently been recognized as the approved name for these organisms. Streptococci known as "S. milleri" have been implicated as etiologic agents in a variety of serious purulent infections, but because of their heterogeneous characteristics, these organisms may be unrecognized or misidentified by clinical laboratorians. This review describes the bacteriological aspects of organisms known as "S. milleri," their clinical significance, and the problems encountered with their identification in the clinical laboratory. PMID:3060239

  16. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

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

  17. Surviving sepsis in the critical care environment.

    PubMed

    Benedict, Lara

    2015-01-01

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

  18. Sepsis-associated encephalopathy.

    PubMed

    Gofton, Teneille E; Young, G Bryan

    2012-10-01

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

  19. Antimicrobial Peptides in Human Sepsis

    PubMed Central

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

    2015-01-01

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

  20. Capsular polysaccharide of Group B Streptococcus mediates biofilm formation in the presence of human plasma.

    PubMed

    Xia, Fan Di; Mallet, Adeline; Caliot, Elise; Gao, Cherry; Trieu-Cuot, Patrick; Dramsi, Shaynoor

    2015-01-01

    Group B Streptococcus (GBS) is an asymptomatic colonizer of human mucosal surfaces that is responsible for sepsis and meningitis in neonates. Bacterial persistence and pathogenesis often involves biofilm formation. We previously showed that biofilm formation in medium supplemented with glucose is mediated by the PI-2a pilus. Here, biofilm formation was tested in cell culture medium supplemented with human plasma. GBS strains were able to form biofilms in these conditions unlike Group A Streptococcus (GAS) or Staphylococcus aureus. Analysis of mutants impaired for various surface components revealed that the GBS capsule is a key component in this process.

  1. Streptococcus agalactiae infection in zebrafish larvae.

    PubMed

    Kim, Brandon J; Hancock, Bryan M; Del Cid, Natasha; Bermudez, Andres; Traver, David; Doran, Kelly S

    2015-02-01

    Streptococcus agalactiae (Group B Streptococcus, GBS) is an encapsulated, Gram-positive bacterium that is a leading cause of neonatal pneumonia, sepsis and meningitis, and an emerging aquaculture pathogen. The zebrafish (Danio rerio) is a genetically tractable model vertebrate that has been used to analyze the pathogenesis of both aquatic and human bacterial pathogens. We have developed a larval zebrafish model of GBS infection to study bacterial and host factors that contribute to disease progression. GBS infection resulted in dose dependent larval death, and GBS serotype III, ST-17 strain was observed as the most virulent. Virulence was dependent on the presence of the GBS capsule, surface anchored lipoteichoic acid (LTA) and toxin production, as infection with GBS mutants lacking these factors resulted in little to no mortality. Additionally, interleukin-1β (il1b) and CXCL-8 (cxcl8a) were significantly induced following GBS infection compared to controls. We also visualized GBS outside the brain vasculature, suggesting GBS penetration into the brain during the course of infection. Our data demonstrate that zebrafish larvae are a valuable model organism to study GBS pathogenesis. PMID:25617657

  2. Current epidemiology of sepsis in mainland China

    PubMed Central

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

    2016-01-01

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

  3. Fast Action Can Prevent Sepsis Death: CDC

    MedlinePlus

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

  4. Severe sepsis management are we doing enough?

    PubMed

    Ahrens, Tom; Vollman, Kathleen

    2003-10-01

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

  5. Sepsis caused by Flavimonas oryzihabitans.

    PubMed

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

    1994-07-01

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

  6. Sepsis caused by Flavimonas oryzihabitans.

    PubMed

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

    1994-07-01

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

  7. 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

  8. Epidemiologic trends of sepsis in western countries

    PubMed Central

    Suarez De La Rica, Alejandro; Gilsanz, Fernando

    2016-01-01

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

  9. Streptococcus bovis meningitis and hemorrhoids.

    PubMed

    Smith, Adam Hewitt; Sra, Harminder K; Bawa, Sandeep; Stevens, Richard

    2010-07-01

    We report a case of Streptococcus bovis (Streptococcus gallolyticus subsp. pasteurianus) meningitis, a rare cause of central nervous system (CNS) infection in an adult, and comment on the importance of investigation of the lower gastrointestinal tract to identify a portal of entry in cases of systemic Streptococcus bovis infection. PMID:20421434

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

    PubMed Central

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

    2016-01-01

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

  11. Significance, management and prevention of Streptococcus agalactiae infection during the perinatal period.

    PubMed

    Berner, Reinhard

    2004-06-01

    The highest annual death rate during the first five decades of life occurs in the first year, particularly during the perinatal period between the onset of labor and 72 h after birth. Invasive bacterial disease evoking the severe inflammatory response syndrome is a leading cause of perinatal morbidity and mortality. Group B streptococcus (Streptococcus agalactiae) is the most important pathogen in this period of life, although the concept of intrapartum antimicrobial prophylaxis has impressively reduced the rate of culture-proven invasive infection in neonates. This strategy, however, has considerable limitations since group B streptococcus-related stillbirths or prematurity and late-onset sepsis cannot be prevented. Moreover, the use of intrapartum antimicrobial prophylaxis has significantly increased the use of antibiotics during labor and therefore may select for intrapartum infections caused by other bacteria, including those resistant to antibiotics. Several advances in the development of vaccines and research on virulence factors and pathways involved in the immune response to group B streptococcus have been accomplished within the last years, including complete sequencing of the group B streptococcus genome. Development of effective vaccines and implementation of vaccination strategies will be one of the key challenges in the future for prevention of neonatal group B Streptococcus infections.

  12. Improving management of sepsis in the community.

    PubMed

    Culligan, Fiona

    2016-08-31

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

  13. Diagnosing sepsis - The role of laboratory medicine.

    PubMed

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

    2016-09-01

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

  14. Phenotypic differentiation of Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus strains within the "Streptococcus milleri group".

    PubMed Central

    Whiley, R A; Fraser, H; Hardie, J M; Beighton, D

    1990-01-01

    A biochemical scheme was developed by which strains of Streptococcus constellatus, Streptococcus intermedius, and Streptococcus anginosus can reliably be distinguished from within the "Streptococcus milleri group." Strains identified as S. intermedius were differentiated by the ability to produce detectable levels of alpha-glucosidase, beta-galactosidase, beta-D-fucosidase, beta-N-acetylgalactosaminidase, beta-N-acetylglucosaminidase, and sialidase with 4-methylumbelliferyl-linked fluorogenic substrates in microdilution trays after 3 h of incubation at 37 degrees C, together with the production of hyaluronidase. Strains of S. constellatus and S. anginosus were differentiated by the production of alpha-glucosidase and hyaluronidase by the former and the production of beta-glucosidase by the latter. The majority of strains of the S. milleri group obtained from dental plaque were identified as S. intermedius, as were most strains isolated from abscesses of the brain and liver. Strains of S. constellatus and S. anginosus were from a wider variety of infections, both oral and nonoral, than were strains of S. intermedius, with the majority of strains from urogenital infections being identified as S. anginosus. PMID:2380375

  15. Disseminated intravascular coagulation in sepsis.

    PubMed

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

    2005-10-01

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

  16. Serologic studies of Streptococcus intermedius, Streptococcus constellatus, and Streptococcus morbillorum by crossed immunoelectrophoresis.

    PubMed

    Coleman, R M; Lambe, D W

    1979-07-01

    A reference antigen-antibody system for Streptococcus intermedius, Streptococcus constellatus, and Streptococcus morbillorum was established with crossed immunoelectrophoresis. A comparison of S. intermedius, S. constellatus, and S. morbillorum with crossed immunoelectrophoresis and crossed immunoelectrophoresis with intermediate gel indicated that S. intermedius and S. constellatus are closely related antigenically with as many as six common cytoplasmic antigens. S. morbillorum was antigenically more distinct; antiserum of one strain of S. morbillorum was monospecific, indicating that specific serogroups of S. morbillorum exist. Crossed immunoelectrophoresis and tandem crossed immunoelectrophoresis revealed that S. intermedius, S. constellatus, and S. morbillorum also share some common antigens with Streptococcus sanguis and Streptococcus mitis, but S. intermedius, S. constellatus, and S. morbillorum are antigenically distinct from Streptococcus mutans and Streptococcus bovis.

  17. Sepsis: Medical errors in Poland.

    PubMed

    Rorat, Marta; Jurek, Tomasz

    2016-01-01

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

  18. Biosensor of endotoxin and sepsis

    NASA Astrophysics Data System (ADS)

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

    2001-09-01

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

  19. Sepsis: From Bench to Bedside

    PubMed Central

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

    2008-01-01

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

  20. Sepsis management in the deployed field hospital.

    PubMed

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

    2013-09-01

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

  1. Systems for Paediatric Sepsis: A Global Survey

    PubMed Central

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

    2014-01-01

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

  2. Autophagy in sepsis: Degradation into exhaustion?

    PubMed

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

    2016-07-01

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

  3. Sepsis management in the deployed field hospital.

    PubMed

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

    2013-09-01

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

  4. The Burden of Invasive Early-Onset Neonatal Sepsis in the United States, 2005–2008

    PubMed Central

    Weston, Emily J.; Pondo, Tracy; Lewis, Melissa M.; Martell-Cleary, Pat; Morin, Craig; Jewell, Brenda; Daily, Pam; Apostol, Mirasol; Petit, Sue; Farley, Monica; Lynfield, Ruth; Reingold, Art; Hansen, Nellie I.; Stoll, Barbara J.; Shane, Andi L.; Zell, Elizabeth; Schrag, Stephanie J.

    2011-01-01

    Background Sepsis in the first 3 days of life is a leading cause of morbidity and mortality among infants. Group B Streptococcus (GBS), historically the primary cause of early-onset sepsis, has declined through widespread use of intrapartum chemoprophylaxis. We estimated the national burden of invasive early-onset sepsis (EOS) cases and deaths in the era of GBS prevention. Methods Population-based surveillance for invasive EOS was conducted in 4 of CDC’s Active Bacterial Core surveillance (ABCs) sites from 2005–2008. We calculated incidence using state and national live birth files. Estimates of the national number of cases and deaths were calculated, standardizing by race and gestational age. Results ABCs identified 658 cases of EOS; 72 (10.9%) were fatal. Overall incidence remained stable during the three years (2005:0.77 cases/1,000 live births; 2008:0.76 cases/1,000 live births). GBS (~38%) was the most commonly reported pathogen followed by Escherichia coli (~24%). Black preterm infants had the highest incidence (5.14 cases/1,000 live births) and case fatality (24.4%). Non-black term infants had the lowest incidence (0.40 cases/1,000 live births) and case fatality (1.6%). The estimated national annual burden of EOS was approximately 3,320 cases (95% CI: 3,060–3,580) including 390 deaths (95% CI: 300–490). Among preterm infants, 1,570 cases (95% CI: 1,400–1,770; 47.3% of the overall) and 360 deaths (95% CI: 280–460; 92.3% of the overall) occurred annually. Conclusions The burden of invasive early-onset sepsis remains substantial in the era of GBS prevention and disproportionately affects preterm and black infants. Identification of strategies to prevent preterm births is needed to reduce the neonatal sepsis burden. PMID:21654548

  5. Improving the Odds of Surviving Sepsis

    MedlinePlus

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

  6. Estrogen sulfotransferase ablation sensitizes mice to sepsis

    PubMed Central

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

    2015-01-01

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

  7. Pseudomonas sepsis with Noma: an association?

    PubMed

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

    2005-08-01

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

  8. Pelvic sepsis after stapled hemorrhoidopexy

    PubMed Central

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

    2008-01-01

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

  9. Sepsis-induced acute kidney injury.

    PubMed

    Majumdar, Arghya

    2010-01-01

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

  10. Sepsis-associated encephalopathy: not just delirium

    PubMed Central

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

    2011-01-01

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

  11. Sepsis Induced by Cecal Ligation and Puncture

    PubMed Central

    Wen, Haitao

    2014-01-01

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

  12. Hemostasis and endothelial damage during sepsis.

    PubMed

    Johansen, Maria Egede

    2015-08-01

    The sepsis syndrome represents a disease continuum, including severe sepsis and septic shock associated with high mortality. One of the main problems in severe sepsis and septic shock, resulting in organ failure and death, are disturbances in the hemostasis due to sepsis-related coagulopathy. Sepsis-related coagulopathy affects not only traditional coagulation factors, but also the platelets and endothelium. Functional testing of the hemostatic system has found application in critical illness. Thrombelastography (TEG) provides an overview of the hemostatic system allowing for an evaluation of interactions between coagulation factors and platelets. Additionally, the role of the endothelium during sepsis can be explored through testing of biomarkers of endothelial damage. The three studies comprising this PhD thesis all investigate important aspects of the disturbed hemostasis during sepsis, including endothelial damage. Together, the specific findings from the three studies improve the existing understanding of sepsis-related coagulopathy, and the possible influences of some of the treatments offered these patients. The first study investigates the occurrence of antimicrobial-induced thrombocytopenia among critically ill patients. In sepsis, thrombocytopenia is a predictor of poor outcome, and reports, of mainly casuistic nature, have previously hypothesized that specific antimicrobial agents could induce in sepsis-related thrombocytopenia. This hypothesis was tested using a randomized designed set-up, encompassing 1147 critically ill patients, and no significant difference in risk of thrombocytopenia was observed among patients receiving large amounts of antimicrobials vs. patients receiving standard-of-care. As a consequence, the risk of antimicrobial-induced thrombocytopenia in the general population of critically ill patients seemingly does not represent a substantial problem and thrombocytopenia during critical illness is most likely due to other factors such

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

    PubMed Central

    Ang, Yuchen; Meier, Rudolf

    2010-01-01

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

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

    PubMed

    Schorr, Christa A; Dellinger, R Phillip

    2014-04-01

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

  15. 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

  16. 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.

  17. Sepsis

    MedlinePlus

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

  18. Sepsis

    MedlinePlus

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

  19. Fatal Streptococcus canis infections in intensively housed shelter cats.

    PubMed

    Pesavento, P A; Bannasch, M J; Bachmann, R; Byrne, B A; Hurley, K F

    2007-03-01

    Three independent, fatal outbreaks of Streptococcus canis infection occurred in a 2-year period in shelter cats. The outbreaks occurred in Northern California (Yolo County), Southern California (Kern County), and North Carolina (Guilford County). An estimation of the affected population is >150 cats among 3 affected shelters, with a mortality rate of up to 30%. Among 20 cats submitted for necropsy there were 2 distinct pathologic presentations. The first (shelters 1 and 2) was skin ulceration and chronic respiratory infection that progressed, in some cats, to necrotizing sinusitis and meningitis. The second (shelter 3) was rapid progression from necrotizing fasciitis with skin ulceration to toxic shock-like syndrome, sepsis, and death. S canis was the sole pathogen identified in most cases. Whether hypervirulent S canis strains exist is unknown; there is little understanding of how these bacteria cause invasive disease in cats.

  20. Fatal Streptococcus canis infections in intensively housed shelter cats.

    PubMed

    Pesavento, P A; Bannasch, M J; Bachmann, R; Byrne, B A; Hurley, K F

    2007-03-01

    Three independent, fatal outbreaks of Streptococcus canis infection occurred in a 2-year period in shelter cats. The outbreaks occurred in Northern California (Yolo County), Southern California (Kern County), and North Carolina (Guilford County). An estimation of the affected population is >150 cats among 3 affected shelters, with a mortality rate of up to 30%. Among 20 cats submitted for necropsy there were 2 distinct pathologic presentations. The first (shelters 1 and 2) was skin ulceration and chronic respiratory infection that progressed, in some cats, to necrotizing sinusitis and meningitis. The second (shelter 3) was rapid progression from necrotizing fasciitis with skin ulceration to toxic shock-like syndrome, sepsis, and death. S canis was the sole pathogen identified in most cases. Whether hypervirulent S canis strains exist is unknown; there is little understanding of how these bacteria cause invasive disease in cats. PMID:17317801

  1. Diagnostic Value of Presepsin for Sepsis

    PubMed Central

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

    2015-01-01

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

  2. Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae.

    PubMed

    Rego, Sara; Heal, Timothy J; Pidwill, Grace R; Till, Marisa; Robson, Alice; Lamont, Richard J; Sessions, Richard B; Jenkinson, Howard F; Race, Paul R; Nobbs, Angela H

    2016-07-29

    Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans Complementary crystallographic and biophysical characterization of BspA reveal a novel β-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections. PMID:27311712

  3. Dysglycemia and Glucose Control During Sepsis.

    PubMed

    Plummer, Mark P; Deane, Adam M

    2016-06-01

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

  4. Management of neonatal sepsis in term newborns

    PubMed Central

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

    2014-01-01

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

  5. Morganella morganii sepsis with massive hemolysis.

    PubMed

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

    2007-12-01

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

  6. Sepsis Resuscitation: Fluid Choice and Dose.

    PubMed

    Semler, Matthew W; Rice, Todd W

    2016-06-01

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

  7. Sepsis, venous return, and teleology.

    PubMed

    McNeilly, R G

    2014-11-01

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

  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

  9. A prospective treatment for sepsis

    PubMed Central

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Sepsis in Pregnancy: Identification and Management.

    PubMed

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

    2016-01-01

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

  13. Genetic manipulation of Streptococcus pyogenes (the Group A Streptococcus, GAS).

    PubMed

    Le Breton, Yoann; McIver, Kevin S

    2013-01-01

    Streptococcus pyogenes (the Group A Streptococcus, GAS) is a Gram-positive bacterium responsible for a wide spectrum of diseases ranging from mild superficial infections (pharyngitis, impetigo) to severe, often life-threatening invasive diseases (necrotizing fasciitis, streptococcal toxic shock syndrome) in humans. This unit describes molecular techniques for the genetic manipulation of S. pyogenes with detailed protocols for transformation, gene disruption, allelic exchange, transposon mutagenesis, and genetic complementation. PMID:24510894

  14. Identification of Streptococcus bovis and Streptococcus salivarius in clinical laboratories.

    PubMed Central

    Ruoff, K L; Ferraro, M J; Holden, J; Kunz, L J

    1984-01-01

    Streptococci identified as Streptococcus bovis, S. bovis variant, and Streptococcus salivarius were examined with respect to physiological and serological characteristics and cellular fatty acid content. Similarities in physiological reactions and problems encountered in serological analysis were noted, suggesting that an expanded battery of physiological tests is needed to definitively identify these streptococci. Cellular fatty acid analysis provided an accurate method for distinguishing S. salivarius from S. bovis and S. bovis variant. PMID:6490816

  15. Neonatal infectious diseases: evaluation of neonatal sepsis.

    PubMed

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

    2013-04-01

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

  16. Sepsis: From Pathophysiology to Individualized Patient Care

    PubMed Central

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

    2015-01-01

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

  17. Raftlin: a new biomarker in human sepsis.

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2007-01-01

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

  19. Streptococcus pneumoniae arginine synthesis genes promote growth and virulence in pneumococcal meningitis.

    PubMed

    Piet, Jurgen R; Geldhoff, Madelijn; van Schaik, Barbera D C; Brouwer, Matthijs C; Valls Seron, Mercedes; Jakobs, Marja E; Schipper, Kim; Pannekoek, Yvonne; Zwinderman, Aeilko H; van der Poll, Tom; van Kampen, Antoine H C; Baas, Frank; van der Ende, Arie; van de Beek, Diederik

    2014-06-01

    Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with pneumococcal meningitis. Pneumococci harboring these genes show increased growth in human blood and cerebrospinal fluid (CSF). Mouse models of meningitis and pneumonia showed that pneumococcal strains without arginine biosynthesis genes were attenuated in growth or cleared, from lung, blood and CSF. Thus, S. pneumoniae arginine synthesis genes promote growth and virulence in invasive pneumococcal disease.

  20. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection. PMID:25456681

  1. Streptococcus suis infection

    PubMed Central

    Feng, Youjun; Zhang, Huimin; Wu, Zuowei; Wang, Shihua; Cao, Min; Hu, Dan; Wang, Changjun

    2014-01-01

    Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial strains that represents a primary health problem in the swine industry worldwide. S. suis is also an emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis). Over the past few decades, continued efforts have made significant progress toward better understanding this zoonotic infectious entity, contributing in part to the elucidation of the molecular mechanism underlying its high pathogenicity. This review is aimed at presenting an updated overview of this pathogen from the perspective of molecular epidemiology, clinical diagnosis and typing, virulence mechanism, and protective antigens contributing to its zoonosis. PMID:24667807

  2. Plasma arginine correlations in trauma and sepsis.

    PubMed

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

    2006-02-01

    Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r(2) = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r(2) = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen

  3. A blueprint for a sepsis protocol.

    PubMed

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

    2005-04-01

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

  4. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    PubMed

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

    2016-07-01

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

  5. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    PubMed Central

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

    2016-01-01

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

  6. Year in review 2008: Critical Care - sepsis

    PubMed Central

    2009-01-01

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

  7. Endotoxins and other sepsis triggers.

    PubMed

    Opal, Steven M

    2010-01-01

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

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

    PubMed

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

    2015-01-01

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

  9. A Highly Arginolytic Streptococcus Species That Potently Antagonizes Streptococcus mutans

    PubMed Central

    Huang, Xuelian; Palmer, Sara R.; Ahn, Sang-Joon; Richards, Vincent P.; Williams, Matthew L.; Nascimento, Marcelle M.

    2016-01-01

    The ability of certain oral biofilm bacteria to moderate pH through arginine metabolism by the arginine deiminase system (ADS) is a deterrent to the development of dental caries. Here, we characterize a novel Streptococcus strain, designated strain A12, isolated from supragingival dental plaque of a caries-free individual. A12 not only expressed the ADS pathway at high levels under a variety of conditions but also effectively inhibited growth and two intercellular signaling pathways of the dental caries pathogen Streptococcus mutans. A12 produced copious amounts of H2O2 via the pyruvate oxidase enzyme that were sufficient to arrest the growth of S. mutans. A12 also produced a protease similar to challisin (Sgc) of Streptococcus gordonii that was able to block the competence-stimulating peptide (CSP)–ComDE signaling system, which is essential for bacteriocin production by S. mutans. Wild-type A12, but not an sgc mutant derivative, could protect the sensitive indicator strain Streptococcus sanguinis SK150 from killing by the bacteriocins of S. mutans. A12, but not S. gordonii, could also block the XIP (comX-inducing peptide) signaling pathway, which is the proximal regulator of genetic competence in S. mutans, but Sgc was not required for this activity. The complete genome sequence of A12 was determined, and phylogenomic analyses compared A12 to streptococcal reference genomes. A12 was most similar to Streptococcus australis and Streptococcus parasanguinis but sufficiently different that it may represent a new species. A12-like organisms may play crucial roles in the promotion of stable, health-associated oral biofilm communities by moderating plaque pH and interfering with the growth and virulence of caries pathogens. PMID:26826230

  10. Mitochondrial dysfunction and resuscitation in sepsis.

    PubMed

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

    2010-07-01

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

  11. Host innate immune responses to sepsis

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. Anticoagulant modulation of inflammation in severe sepsis.

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2003-08-01

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

  15. An Evidence Based Approach to Sepsis: Educational Program

    ERIC Educational Resources Information Center

    Perez, Dolores

    2015-01-01

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

  16. Ghrelin inhibits sympathetic nervous activity in sepsis.

    PubMed

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

    2007-12-01

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

  17. 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

  18. The Use of Fluids in Sepsis.

    PubMed

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

    2016-03-10

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

  19. Sepsis and septic shock: a review.

    PubMed

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

    2015-01-01

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

  20. The Use of Fluids in Sepsis

    PubMed Central

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

    2016-01-01

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

  1. 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%).

  2. Streptococcus Adherence and Colonization

    PubMed Central

    Nobbs, Angela H.; Lamont, Richard J.; Jenkinson, Howard F.

    2009-01-01

    Summary: Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed. PMID:19721085

  3. Development of primer sets for loop-mediated isothermal amplification that enables rapid and specific detection of Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae are the three main pathogens causing bovine mastitis, with great losses to the dairy industry. Rapid and specific loop-mediated isothermal amplification methods (LAMP) for identification and differentiation of these three ...

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

    PubMed

    Briegel, J; Möhnle, P

    2013-04-01

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

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

    PubMed

    Seeley, Eric J; Bernard, Gordon R

    2016-06-01

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

  6. Elucidating the role of genomics in neonatal sepsis.

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Real-Time Polymerase Chain Reaction for Detecting Bacterial DNA Directly from Blood of Neonates Being Evaluated for Sepsis

    PubMed Central

    Jordan, Jeanne A.; Durso, Mary Beth

    2005-01-01

    Speed is of the essence when evaluating an infant with symptoms consistent with sepsis. Because of the high morbidity and mortality associated with neonatal sepsis, infants receive multiple, broad-spectrum antibiotics before receiving finalized blood culture results. Incorporating an additional, reliable, yet rapid assay to detect bacteria directly from blood would facilitate timely diagnosis and appropriate care. To this end, we designed a real-time polymerase chain reaction (PCR) assay targeting the highly conserved 380 bases of 16S rDNA. DNA was extracted from whole-blood samples using a Qiagen column. The limit of detection for the TaqMan-based assay, using a Smartcycler instrument, was 40, 50, or 2000 colony-forming units per milliliter of blood (CFU/ml) of Escherichia coli, group B Streptococcus, and Listeria monocytogenes, respectively, when white blood cell counts were below 39,000/μl. Implementing this approach requires less than 4 hours for both sample preparation and real-time PCR compared with 1 to 2 days to detect growth in culture or 5 days to finalize no-growth culture results. There was an overall agreement between the results of culture and real-time PCR of 94.1% (80 of 85) in this study. These results suggest that molecular techniques can augment culture-based methods for diagnosing neonatal sepsis, especially in infants whose mothers have received intrapartum antibiotic prophylaxis. PMID:16258155

  9. Pathogenesis of Multiple Organ Failure in Sepsis.

    PubMed

    Rossaint, Jan; Zarbock, Alexander

    2015-01-01

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

  10. Immunomodulation during sepsis in organ transplanted children.

    PubMed

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

    2005-10-01

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

  11. Current treatment of sepsis and endotoxaemia.

    PubMed

    Periti, P

    2000-09-01

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

  12. [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.

  13. [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

  14. 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.

  15. Role of biomarkers in sepsis care.

    PubMed

    Samraj, Ravi S; Zingarelli, Basilia; Wong, Hector R

    2013-11-01

    Sepsis is one of the leading causes of mortality and morbidity, even with the current availability of extended-spectrum antibiotics and advanced medical care. Biomarkers offer a tool in facilitating early diagnosis, in identifying patient populations at high risk of complications, and in monitoring progression of the disease, which are critical assessments for appropriate therapy and improvement in patient outcomes. Several biomarkers are already available for clinical use in sepsis; however, their effectiveness in many instances is limited by the lack of specificity and sensitivity to characterize the presence of an infection and the complexity of the inflammatory and immune processes and to stratify patients into homogenous groups for specific treatments. Current advances in molecular techniques have provided new tools facilitating the discovery of novel biomarkers, which can vary from metabolites and chemical products present in body fluids to genes and proteins in circulating blood cells. The purpose of this review was to examine the current status of sepsis biomarkers, with special emphasis on emerging markers, which are undergoing validation and may transition into clinical practice for their informative value in diagnosis, prognosis, or response to therapy. We will also discuss the new concept of combination biomarkers and biomarker risk models, their existing challenges, and their potential use in the daily management of patients with sepsis.

  16. Translational research and biomarkers in neonatal sepsis.

    PubMed

    Delanghe, Joris R; Speeckaert, Marijn M

    2015-12-01

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

  17. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    PubMed Central

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  18. Recombination-deficient Streptococcus sanguis

    SciTech Connect

    Daneo-Moore, L.; Volpe, A.

    1985-05-01

    A UV-sensitive derivative was obtained from Streptococcus sanguis Challis. The organism could be transformed with a number of small streptococcal plasmids at frequencies equal to, or 1 logarithm below, the transformation frequencies for the parent organism. However, transformation with chromosomal DNA was greatly impaired in the UV-sensitive derivative.

  19. Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis.

    PubMed

    Stolk, Roeland F; van der Poll, Tom; Angus, Derek C; van der Hoeven, Johannes G; Pickkers, Peter; Kox, Matthijs

    2016-09-01

    Septic shock is a major cause of death worldwide and a considerable healthcare burden in the twenty-first century. Attention has shifted from damaging effects of the proinflammatory response to the detrimental role of antiinflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to reevaluate the current management of septic shock and to assess whether we are inadvertently compromising or altering the host immune response. In this perspective, we discuss the potential detrimental role of norepinephrine, the cornerstone treatment for septic shock, in sepsis-induced immunoparalysis. We provide a short overview of the current understanding of the immunologic pathophysiology of sepsis, followed by a detailed description of the immunomodulatory effects of norepinephrine and alternative vasopressors. We conclude that although the development of novel therapies aimed at reversing immunoparalysis is underway, the use of norepinephrine may aggravate the development, extent, and duration of sepsis-induced immunoparalysis. Current in vitro and animal data indicate that norepinephrine treatment exerts immunosuppressive and bacterial growth-promoting effects and may increase susceptibility toward infections. However, evidence in humans is circumstantial, as immunologic effects of norepinephrine have not been investigated properly in experimental or clinical studies. Alternatives such as vasopressin/selepressin, angiotensin II, and phenylephrine could have a fundamental advantage over norepinephrine with respect to their immunologic properties. However, also for these agents, in vivo immunologic data in humans are largely lacking. As such, human studies on the immunomodulatory properties of norepinephrine and viable alternatives are highly warranted. PMID:27398737

  20. Hospitalization Type and Subsequent Severe Sepsis

    PubMed Central

    Dickson, Robert P.; Rogers, Mary A. M.; Langa, Kenneth M.; Iwashyna, Theodore J.

    2015-01-01

    Rationale: Hospitalization is associated with microbiome perturbation (dysbiosis), and this perturbation is more severe in patients treated with antimicrobials. Objectives: To evaluate whether hospitalizations known to be associated with periods of microbiome perturbation are associated with increased risk of severe sepsis after hospital discharge. Methods: We studied participants in the U.S. Health and Retirement Study with linked Medicare claims (1998–2010). We measured whether three hospitalization types associated with increasing severity of probable dysbiosis (non–infection-related hospitalization, infection-related hospitalization, and hospitalization with Clostridium difficile infection [CDI]) were associated with increasing risk for severe sepsis in the 90 days after hospital discharge. We used two study designs: the first was a longitudinal design with between-person comparisons and the second was a self-controlled case series design using within-person comparison. Measurements and Main Results: We identified 43,095 hospitalizations among 10,996 Health and Retirement Study–Medicare participants. In the 90 days following non–infection-related hospitalization, infection-related hospitalization, and hospitalization with CDI, adjusted probabilities of subsequent admission for severe sepsis were 4.1% (95% confidence interval [CI], 3.8–4.4%), 7.1% (95% CI, 6.6–7.6%), and 10.7% (95% CI, 7.7–13.8%), respectively. The incidence rate ratio (IRR) of severe sepsis was 3.3-fold greater during the 90 days after hospitalizations than during other observation periods. The IRR was 30% greater after an infection-related hospitalization versus a non–infection-related hospitalization. The IRR was 70% greater after a hospitalization with CDI than an infection-related hospitalization without CDI. Conclusions: There is a strong dose–response relationship between events known to result in dysbiosis and subsequent severe sepsis hospitalization that is not present

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

    PubMed

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

    2015-11-01

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

  2. [Streptococcus pyogenes--much more than the aetiological agent of scarlet fever].

    PubMed

    Stock, Ingo

    2009-11-01

    The grampositive bacterium S. pyogenes (beta-haemolytic group A Streptococcus) is a natural colonizer of the human oropharynx mucous membrane and one of the most common agents of infectious diseases in humans. S. pyogenes causes the widest range of disease in humans among all bacterial pathogens. It is responsible for various skin infections such as impetigo contagiosa and erysipelas, and localized mucous membrane infections of the oropharynx (e. g. tonsillitis and pharyngitis). Betahaemolytic group A Streptococcus causes also invasive diseases such as sepses including puerperal sepsis. Additionally, S. pyogenes induces toxin-mediated syndromes, i. e. scarlet fever, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF). STSS and NF are severe, frequently fatal diseases that have emerged in Europe and Northern America during the last two decades. Finally, some immunpathological diseases such as acute rheumatic fever and glomerulonephritis also result from S. pyogenes infections. Most scientists recommend penicillins (benzylpenicillin, phenoxymethylpenicllin) as drugs of first choice for treatment of Streptococcus tonsillopharyngitis and scarlet fever. Erysipelas and some other skin infections should be treated with benzylpenicillin. Intensive care measurements are needed for treatment of severe toxin-mediated S. pyogenes diseases. These measurements include the elimination of internal bacterial foci, concomitant application of clindamycin and benzylpenicillin and suitable treatment of shock symptoms. Management of immunpathological diseases requires antiphlogistical therapy. Because of the wide distribution of S. pyogenes in the general population and the lack of an effective vaccine, possibilities for prevention allowing a suitable protection for diseases due to S. pyogenes are very limited.

  3. Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

    PubMed Central

    Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

    2016-01-01

    Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may

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

    PubMed Central

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

    2015-01-01

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

  5. Improving the management of sepsis in a district general hospital by implementing the 'Sepsis Six' recommendations.

    PubMed

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

    2015-01-01

    Sepsis is a common condition with a major global impact on healthcare resources and expenditure. The Surviving Sepsis Campaign has been vigorous in promoting internationally recognised pathways to improve the management of septic patients and decrease mortality. However, translating recommendations into practice is a challenging and complex task that requires a multi-faceted approach with sustained engagement from local stakeholders. Whilst working at a district general hospital in New Zealand, we were concerned by the seemingly inconsistent management of septic patients, often leading to long delays in the initiation of life-saving measures such as antibiotic, fluid, and oxygen administration. In our hospital there were no clear systems, protocols or guidelines in place for identifying and managing septic patients. We therefore launched the Sepsis Six resuscitation bundle of care in our hospital in an attempt to raise awareness amongst staff and improve the management of septic patients. We introduced a number of simple low-cost interventions that included educational sessions for junior doctors and nursing staff, as well as posters and modifications to phlebotomy trolleys that acted as visual reminders to implement the Sepsis Six bundle. Overall, we found there to a be a steady improvement in the delivery of the Sepsis Six bundle in septic patients with 63% of patients receiving appropriate care within one hour, compared to 29% prior to our interventions. However this did not translate to an improvement in patient mortality. This project forms part of an on going process to instigate a fundamental culture change among local healthcare professionals regarding the management of sepsis. Whilst we have demonstrated improved implementation of the Sepsis Six bundle, the key challenge remains to ensure that momentum of this project continues and forms a platform for sustainable clinical improvement in the long term. PMID:26734403

  6. Emerging resistant serotypes of invasive Streptococcus pneumoniae

    PubMed Central

    Elshafie, Sittana; Taj-Aldeen, Saad J

    2016-01-01

    Background Streptococcus pneumoniae is the leading cause of meningitis and sepsis. The aim of the study was to analyze the distribution, vaccine serotype coverage, and antibiotic resistance of S. pneumoniae serotypes isolated from patients with invasive diseases, after the introduction of pneumococcal 7-valent conjugated vaccine (PCV-7). Methods A total of 134 isolates were collected from blood and cerebrospinal fluid specimens at Hamad Hospital during the period from 2005 to 2009. Isolate serotyping was done using the Quellung reaction. The prevaccination period was considered before 2005. Results The most common serotypes for all age groups were 3 (12.70%), 14 (11.90%), 1 (11.90%), 19A (9.00%), 9V (5.20%), 23F (5.20%), and 19F (4.50%). Coverage rates for infant <2 years for PCV-7, the 10-valent conjugated vaccine (PCV-10), and the 13-valent conjugated vaccine (PCV-13) were 34.78%, 52.17%, and 78.26%, respectively. Coverage rates of these vaccines were 50%, 67.86%, and 75% for the 2–5 years age group; 27.12%, 40.68%, and 64.41% for the age group 6–64 years; and 25%, 33.33%, and 66.67% for the ≥65 years age group, respectively. The percentage of nonsusceptible isolates to penicillin, cefotaxime, and erythromycin were 43.86%, 16.66%, and 22.81%, respectively. Thirty-seven isolates (32.46%) were multidrug resistant (MDR) and belonged to serotypes 14, 19A, 19F, 23F, 1, 9V, 12F, 4, 6B, 3, and 15A. Compared to previous results before the introduction of PCV-7, there was a significant reduction in penicillin-nonsusceptable S. pneumoniae from 66.67% to 43.86%, and a slight insignificant reduction in erythromycin nonsusceptible strains from 27.60% to 22.8%, while there was a significant increase in cefotaxime nonsusceptible strains from 3.55% to 16.66%. Conclusion Invasive pneumococcal strains and the emergence of MDR serotypes is a global burden that must be addressed through multiple strategies, including vaccination, antibiotic stewardship, and continuous

  7. Gene repertoire evolution of Streptococcus pyogenes inferred from phylogenomic analysis with Streptococcus canis and Streptococcus dysgalactiae.

    PubMed

    Lefébure, Tristan; Richards, Vince P; Lang, Ping; Pavinski-Bitar, Paulina; Stanhope, Michael J

    2012-01-01

    Streptococcus pyogenes, is an important human pathogen classified within the pyogenic group of streptococci, exclusively adapted to the human host. Our goal was to employ a comparative evolutionary approach to better understand the genomic events concomitant with S. pyogenes human adaptation. As part of ascertaining these events, we sequenced the genome of one of the potential sister species, the agricultural pathogen S. canis, and combined it in a comparative genomics reconciliation analysis with two other closely related species, Streptococcus dysgalactiae and Streptococcus equi, to determine the genes that were gained and lost during S. pyogenes evolution. Genome wide phylogenetic analyses involving 15 Streptococcus species provided convincing support for a clade of S. equi, S. pyogenes, S. dysgalactiae, and S. canis and suggested that the most likely S. pyogenes sister species was S. dysgalactiae. The reconciliation analysis identified 113 genes that were gained on the lineage leading to S. pyogenes. Almost half (46%) of these gained genes were phage associated and 14 showed significant matches to experimentally verified bacteria virulence factors. Subsequent to the origin of S. pyogenes, over half of the phage associated genes were involved in 90 different LGT events, mostly involving different strains of S. pyogenes, but with a high proportion involving the horse specific pathogen S. equi subsp. equi, with the directionality almost exclusively (86%) in the S. pyogenes to S. equi direction. Streptococcus agalactiae appears to have played an important role in the evolution of S. pyogenes with a high proportion of LGTs originating from this species. Overall the analysis suggests that S. pyogenes adaptation to the human host was achieved in part by (i) the integration of new virulence factors (e.g. speB, and the sal locus) and (ii) the construction of new regulation networks (e.g. rgg, and to some extent speB).

  8. Gene Repertoire Evolution of Streptococcus pyogenes Inferred from Phylogenomic Analysis with Streptococcus canis and Streptococcus dysgalactiae

    PubMed Central

    Lefébure, Tristan; Richards, Vince P.; Lang, Ping; Pavinski-Bitar, Paulina; Stanhope, Michael J.

    2012-01-01

    Streptococcus pyogenes, is an important human pathogen classified within the pyogenic group of streptococci, exclusively adapted to the human host. Our goal was to employ a comparative evolutionary approach to better understand the genomic events concomitant with S. pyogenes human adaptation. As part of ascertaining these events, we sequenced the genome of one of the potential sister species, the agricultural pathogen S. canis, and combined it in a comparative genomics reconciliation analysis with two other closely related species, Streptococcus dysgalactiae and Streptococcus equi, to determine the genes that were gained and lost during S. pyogenes evolution. Genome wide phylogenetic analyses involving 15 Streptococcus species provided convincing support for a clade of S. equi, S. pyogenes, S. dysgalactiae, and S. canis and suggested that the most likely S. pyogenes sister species was S. dysgalactiae. The reconciliation analysis identified 113 genes that were gained on the lineage leading to S. pyogenes. Almost half (46%) of these gained genes were phage associated and 14 showed significant matches to experimentally verified bacteria virulence factors. Subsequent to the origin of S. pyogenes, over half of the phage associated genes were involved in 90 different LGT events, mostly involving different strains of S. pyogenes, but with a high proportion involving the horse specific pathogen S. equi subsp. equi, with the directionality almost exclusively (86%) in the S. pyogenes to S. equi direction. Streptococcus agalactiae appears to have played an important role in the evolution of S. pyogenes with a high proportion of LGTs originating from this species. Overall the analysis suggests that S. pyogenes adaptation to the human host was achieved in part by (i) the integration of new virulence factors (e.g. speB, and the sal locus) and (ii) the construction of new regulation networks (e.g. rgg, and to some extent speB). PMID:22666370

  9. Severe sepsis and septic shock: defining the clinical problem.

    PubMed

    Opal, Steven M

    2003-01-01

    It is generally acknowledged that severe sepsis/septic shock is a major problem in clinical medicine, yet the extent of the problem and its basic immunology remain poorly defined. The generation of accurate statistics about sepsis is confounded by the imprecise and highly variable terminology used to describe sepsis by clinicians around the world. The problem of sepsis is further complicated by the remarkably diverse spectrum of illness encompassed under the term 'sepsis'. Sepsis may range in severity from mild systemic inflammation without significant clinical consequences to multisystem failure in septic shock with an exceedingly high mortality rate. Sepsis connotes a clinical syndrome that may occur in any age group, in markedly different patient populations, and in response to a multitude of microbial pathogens from multiple different anatomical sites within the human body. A concerted effort has been made to standardize definitions of sepsis by the use of international committees and consensus opinions from panels of experts in sepsis research. While consensus definitions of sepsis have proven to be of value, the lack of uniformity in interpretation of these definitions continues to be problematic by clinicians and basic researchers alike. Recently, a new conceptual framework for understanding sepsis has been developed, called the PIRO concept (predisposition, infection, response and organ dysfunction). This has been conceptually modeled from the TNM classification (tumor size, nodal spread, metastases) which has been successfully used in defining treatment and prognostic indicators in clinical oncology. Further refinements in the definitions and predisposing factors of severe sepsis should improve the understanding and management of severe sepsis and septic shock in the near future.

  10. Sepsis in the severely immunocompromised patient.

    PubMed

    Kalil, Andre C; Opal, Steven M

    2015-06-01

    The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients.

  11. Sepsis in the severely immunocompromised patient.

    PubMed

    Kalil, Andre C; Opal, Steven M

    2015-06-01

    The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients. PMID:25939918

  12. Carbon monoxide in the treatment of sepsis.

    PubMed

    Nakahira, Kiichi; Choi, Augustine M K

    2015-12-15

    Carbon monoxide (CO), a low-molecular-weight gas, is endogenously produced in the body as a product of heme degradation catalyzed by heme oxygenase (HO) enzymes. As the beneficial roles of HO system have been elucidated in vitro and in vivo, CO itself has also been reported as a potent cytoprotective molecule. Whereas CO represents a toxic inhalation hazard at high concentration, low-dose exogenous CO treatment (~250-500 parts per million) demonstrates protective functions including but not limited to the anti-inflammatory and antiapoptotic effects in preclinical models of human diseases. Of note, CO exposure confers protection in animal models of sepsis by inhibiting inflammatory responses and also enhancing bacterial phagocytosis in leukocytes. These unique functions of CO including both dampening inflammation and promoting host defense mechanism are mediated by multiple pathways such as autophagy induction or biosynthesis of specialized proresolving lipid mediators. We suggest that CO gas may represent a novel therapy for patients with sepsis.

  13. Sepsis management: An evidence-based approach.

    PubMed

    Baig, Muhammad Akbar; Shahzad, Hira; Jamil, Bushra; Hussain, Erfan

    2016-03-01

    The Surviving Sepsis Campaign (SSC) guidelines have outlined an early goal directed therapy (EGDT) which demonstrates a standardized approach to ensure prompt and effective management of sepsis. Having said that, there are barriers associated with the application of evidence-based practice, which often lead to an overall poorer adherence to guidelines. Considering the global burden of disease, data from low- to middle-income countries is scarce. Asia is the largest continent but most Asian countries do not have a well-developed healthcare system and compliance rates to resuscitation and management bundles are as low as 7.6% and 3.5%, respectively. Intensive care units are not adequately equipped and financial concerns limit implementation of expensive treatment strategies. Healthcare policy-makers should be notified in order to alleviate financial restrictions and ensure delivery of standard care to septic patients.

  14. First Isolation of Streptococcus halichoeri and Streptococcus phocae from a Steller Sea Lion (Eumetopias jubatus) in South Korea.

    PubMed

    Lee, Kichan; Kim, Ji-Yeon; Jung, Suk Chan; Lee, Hee-Soo; Her, Moon; Chae, Chanhee

    2016-01-01

    Streptococcus species are emerging potential pathogens in marine mammals. We report the isolation and identification of Streptococcus halichoeri and Streptococcus phocae in a Steller sea lion (Eumetopias jubatus) in South Korea.

  15. First Isolation of Streptococcus halichoeri and Streptococcus phocae from a Steller Sea Lion (Eumetopias jubatus) in South Korea.

    PubMed

    Lee, Kichan; Kim, Ji-Yeon; Jung, Suk Chan; Lee, Hee-Soo; Her, Moon; Chae, Chanhee

    2016-01-01

    Streptococcus species are emerging potential pathogens in marine mammals. We report the isolation and identification of Streptococcus halichoeri and Streptococcus phocae in a Steller sea lion (Eumetopias jubatus) in South Korea. PMID:26555114

  16. Haemophilus influenzae sepsis resulting from pneumonia.

    PubMed

    Marinella, M A

    1997-01-01

    Haemophilus influenzae is a pleomorphic gram-negative bacterium that causes a myriad of infections in both adults and children. The organism frequently causes respiratory infections in patients with obstructive lung disease but may on occasion cause invasive infections including pneumonia with bacteremia. We report the case of a patient with underlying lung disease and metastatic malignancy in whom sepsis related to pneumonia caused by H. influenzae developed.

  17. GLYOXYLATE FERMENTATION BY STREPTOCOCCUS ALLANTOICUS

    PubMed Central

    Valentine, R. C.; Drucker, H.; Wolfe, R. S.

    1964-01-01

    Valentine, R. C. (University of Illinois, Urbana), H. Drucker, and R. S. Wolfe. Glyoxylate fermentation by Streptococcus allantoicus. J. Bacteriol. 87:241–246. 1964.—Extracts of Streptococcus allantoicus were found to degrade glyoxylate, yielding tartronic semialdehyde and CO2. Tartronic semialdehyde was prepared chemically, and its properties were compared with the enzymatic product: reduction by sodium borohydride yielded glycerate; heating at 100 C yielded glycolaldehyde and CO2; autoxidation yielded mesoxalic semialdehyde; periodate oxidation yielded glyoxylate and a compound presumed to be formate. Tartronic semialdehyde reductase was present in extracts of S. allantoicus and in a species of Pseudomonas grown on allantoin. A scheme for the synthesis of acetate from glyoxylate by S. allantoicus is discussed. PMID:14151040

  18. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

    2016-03-01

    Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future. PMID:26863125

  19. Reduction in maternal mortality due to sepsis.

    PubMed

    Chhabra, S; Kaipa, A; Kakani, A

    2005-02-01

    The present study was undertaken at a rural medical institute in India to analyse the trends in maternal mortality due to sepsis and the factors associated with change, if any. During the study period of 20 years, a total of 37,155 women delivered, 192 deaths occurred and forty deaths (20.83%) were due to sepsis and it's sequlae. It was revealed that there is a definite decrease in the proportion of deaths due to sepsis, to 10% in the last five years from 35% in earlier years. The change seems to be due to the advocacy of clean deliveries and reduction in case fatality because of alterations in medication and earlier surgical intervention. However the percentage contribution of septic abortion has remained the same. Septic abortion continues to exist inspite of all the current laws and discussion about the availability of a liberal law, which permits abortion almost on request. Most of the women who had died due to septic abortion were married (65%). Deaths due to septic abortion, are persisting even in married women and it is a matter of concern for health providers, policy makers and governments. PMID:15814392

  20. Sepsis and Meningitis due to Listeria Monocytogenes

    PubMed Central

    Aygen, Bilgehan; Esel, Duygu; Kayabas, Uner; Alp, Emine; Sumerkan, Bulent; Doganay, Mehmet

    2007-01-01

    Purpose This study focused on the effect of immuno-compromising conditions on the clinical presentation of severe listerial infection. Patients and Methods Nine human listeriosis cases seen from 1991-2002 were reviewed. All adult patients, from whose blood, peritoneal fluid or cerebrospinal fluid (CSF) the L. monocytogenes was isolated, were included in this retrospective study. Results Listeriosis presented as primary sepsis with positive blood cultures in 5 cases and meningitis with positive CSF cultures in 4 cases. All of these patients had at least one underlying disease, most commonly, hematologic malignancy, diabetes mellitus, amyloidosis and hepatic cirrhosis; 55.6% had received immunosuppressive or corticosteroid therapy within a week before the onset of listeriosis. The patients were adults with a mean age of 60 years. Fever, night sweats, chills and lethargy were the most common symptoms; high temperature (> 38℃), tachycardia, meningeal signs and poor conditions in general were the most common findings on admission. The mortality rate was 33.3% and was strictly associated with the severity of the underlying disease. Mortality differences were significant between sepsis (20%) and meningitis (50%) patients. Conclusion Listeriosis as an uncommon infection in our region and that immuno-suppressive therapy is an important pre-disposing factor of listeriosis. Sepsis and meningitis were more common in this group of patients and had the highest case-fatality rate for food-borne illnesses. PMID:17594151

  1. Coagulation in patients with severe sepsis.

    PubMed

    Levi, Marcel; Poll, Tom van der

    2015-02-01

    In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro)vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways. PMID:25590524

  2. The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

    PubMed

    Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

    2014-07-01

    Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

  3. Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

    PubMed Central

    Sassoon, Catherine S.; Zhu, Ercheng; Fang, Liwei; Subramanian, Veedamali S.; Said, Hamid M.

    2016-01-01

    Objective Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 (THTR-1) and thiamin transporter-2 (THTR-2)), and mitochondrial thiamin pyrophosphate transporter (MTPPT). Design Randomized, controlled study Setting Research laboratory at a Veterans Affairs Medical Center Subjects Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate and severe sepsis with equal number of animals in each group. Measurements and Main Results Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25 %, 50 % and 75 % of cecal length, defined as severe, moderate and mild sepsis, respectively. Control animals underwent laparotomy only. After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of THTR-1, THTR-2, and MTPPT proteins and mRNA were measured. Proinflammatory cytokines (IL-1β and IL-6), and adenosine triphosphate (ATP) were also measured. Sepsis inhibited [3H]thiamin uptake and the inhibition was a function of sepsis severity. Both cell membranes thiamin transporters and MTPPT expression levels were suppressed; also levels of ATP in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham operated controls. Conclusions For the first time we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and MTPPT, leading to ATP depletion. PMID:27065466

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

    PubMed Central

    Bodkin, Jennifer Victoria; Fernandes, Elizabeth Soares

    2013-01-01

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

  5. Factor v Leiden mutation in severe infection and sepsis.

    PubMed

    Levi, Marcel; Schouten, Marcel; van't Veer, Cees; van der Poll, Tom

    2011-11-01

    In severe infection and sepsis, activation of coagulation frequently occurs, which contributes to the development of multiple organ dysfunction. Factor V Leiden is a relatively common mutation resulting in a mild prohemostatic state and consequently with an increased tendency to develop thrombosis. Hypothetically, patients with factor V Leiden may suffer from more severe coagulopathy in cases of severe infection or sepsis. Aggravation of the procoagulant state in sepsis may subsequently result in more severe organ dysfunction and an increased risk of death. In this article we review the experimental and clinical evidence regarding the relationship between the presence of a factor V Leiden mutation and the incidence and outcome of sepsis.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Kim, Won-Young; Hong, Sang-Bum

    2016-04-01

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

  8. Evolutionary inactivation of a sialidase in group B Streptococcus

    PubMed Central

    Yamaguchi, Masaya; Hirose, Yujiro; Nakata, Masanobu; Uchiyama, Satoshi; Yamaguchi, Yuka; Goto, Kana; Sumitomo, Tomoko; Lewis, Amanda L.; Kawabata, Shigetada; Nizet, Victor

    2016-01-01

    Group B Streptococcus (GBS) is a leading cause of bacterial sepsis and meningitis in newborns. GBS possesses a protein with homology to the pneumococcal virulence factor, NanA, which has neuraminidase (sialidase) activity and promotes blood-brain barrier penetration. However, phylogenetic sequence and enzymatic analyses indicate the GBS NanA ortholog has lost sialidase function – and for this distinction we designate the gene and encoded protein nonA/NonA. Here we analyze NonA function in GBS pathogenesis, and through heterologous expression of active pneumococcal NanA in GBS, potential costs of maintaining sialidase function. GBS wild-type and ΔnonA strains lack sialidase activity, but forced expression of pneumococcal NanA in GBS induced degradation of the terminal sialic acid on its exopolysaccharide capsule. Deletion of nonA did not change GBS-whole blood survival or brain microvascular cell invasion. However, forced expression of pneumococcal NanA in GBS removed terminal sialic acid residues from the bacterial capsule, restricting bacterial proliferation in human blood and in vivo upon mouse infection. GBS expressing pneumococcal NanA had increased invasion of human brain microvascular endothelial cells. Thus, we hypothesize that nonA lost enzyme activity allowing the preservation of an effective survival factor, the sialylated exopolysaccharide capsule. PMID:27352769

  9. Characterization of Afb, a novel bifunctional protein in Streptococcus agalactiae

    PubMed Central

    Dehbashi, Sanaz; Pourmand, Mohammad Reza; Mashhadi, Rahil

    2016-01-01

    Background and Objectives: Streptococcus agalactiae is the leading cause of bacterial sepsis and meningitis in newborns and results in pneumonia and bacteremia in adults. A number of S. agalactiae components are involved in colonization of target cells. Destruction of peptidoglycan and division of covalently linked daughter cells is mediated by autolysins. In this study, autolytic activity and plasma binding ability of AFb novel recombinant protein of S. agalactiae was investigated. Materials and Methods: The gbs1805 gene was cloned and expressed. E. coli strains DH5α and BL21 were used as cloning and expression hosts, respectively. After purification, antigenicity and binding ability to plasma proteins of the recombinant protein was evaluated. Results: AFb, the 18KDa protein was purified successfully. The insoluble mature protein revealed the ability to bind to fibrinogen and fibronectin. This insoluble mature protein revealed that it has the ability to bind to fibrinogen and fibronectin plasma proteins. Furthermore, in silico analysis demonstrated the AFb has an autolytic activity. Conclusions: AFb is a novel protein capable of binding to fibrinogen and fibronectin. This findings lay a ground work for further investigation of the role of the bacteria in adhesion and colonization to the host. PMID:27092228

  10. Streptococcus tangierensis sp. nov. and Streptococcus cameli sp. nov., two novel Streptococcus species isolated from raw camel milk in Morocco.

    PubMed

    Kadri, Zaina; Vandamme, Peter; Ouadghiri, Mouna; Cnockaert, Margo; Aerts, Maarten; Elfahime, El Mostafa; Farricha, Omar El; Swings, Jean; Amar, Mohamed

    2015-02-01

    Biochemical and molecular genetic studies were performed on two unidentified Gram-stain positive, catalase and oxidase negative, non-hemolytic Streptococcus-like organisms recovered from raw camel milk in Morocco. Phenotypic characterization and comparative 16S rRNA gene sequencing demonstrated that the two strains were highly different from each other and that they did not correspond to any recognized species of the genus Streptococcus. Phylogenetic analysis based on 16S rRNA gene sequences showed the unidentified organisms each formed a hitherto unknown sub-line within the genus Streptococcus, displaying a close affinity with Streptococcus moroccensis, Streptococcus minor and Streptococcus ovis. DNA G+C content determination, MALDI-TOF mass spectrometry and biochemical tests demonstrated the bacterial isolates represent two novel species. Based on the phenotypic distinctiveness of the new bacteria and molecular genetic evidence, it is proposed to classify the two strains as Streptococcus tangierensis sp. nov., with CCMM B832(T) (=LMG 27683(T)) as the type strain, and Streptococcus cameli sp. nov., with CCMM B834(T) (=LMG 27685(T)) as the type strain.

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

    PubMed Central

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

    2015-01-01

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

  12. Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

    PubMed Central

    Landwehr-Kenzel, Sybille; Henneke, Philipp

    2014-01-01

    Streptococcus agalactiae (Group B streptococcus, GBS) is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis, and death at the beginning of life, in the elderly and in diabetic patients. Thus, GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days 7 and 90 of life are at risk of a particularly striking sepsis manifestation (late-onset disease), where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases are caused by one clone, GBS ST17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood–brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels, and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like glycerinaldehyde-3-phosphate-dehydrogenase-dependent induction of IL-10 and β-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are

  13. Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization.

    PubMed

    Patras, Kathryn A; Wescombe, Philip A; Rösler, Berenice; Hale, John D; Tagg, John R; Doran, Kelly S

    2015-09-01

    Streptococcus agalactiae (group B streptococcus [GBS]) colonizes the rectovaginal tract in 20% to 30% of women and during pregnancy can be transmitted to the newborn, causing severe invasive disease. Current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission, and GBS remains a leading cause of neonatal infection. We have investigated the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Comparison of the antibacterial activities of multiple S. salivarius strains by use of a deferred-antagonism test showed that S. salivarius strain K12 exhibited the broadest spectrum of activity against GBS. K12 effectively inhibited all GBS strains tested, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. Inhibition was dependent on the presence of megaplasmid pSsal-K12, which encodes the bacteriocins salivaricin A and salivaricin B; however, in coculture experiments, GBS growth was impeded by K12 independently of the megaplasmid. We also demonstrated that K12 adheres to and invades human vaginal epithelial cells at levels comparable to GBS. Inhibitory activity of K12 was examined in vivo using a mouse model of GBS vaginal colonization. Mice colonized with GBS were treated vaginally with K12. K12 administration significantly reduced GBS vaginal colonization in comparison to nontreated controls, and this effect was partially dependent on the K12 megaplasmid. Our results suggest that K12 may have potential as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy.

  14. Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization

    PubMed Central

    Patras, Kathryn A.; Wescombe, Philip A.; Rösler, Berenice; Hale, John D.; Tagg, John R.

    2015-01-01

    Streptococcus agalactiae (group B streptococcus [GBS]) colonizes the rectovaginal tract in 20% to 30% of women and during pregnancy can be transmitted to the newborn, causing severe invasive disease. Current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission, and GBS remains a leading cause of neonatal infection. We have investigated the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Comparison of the antibacterial activities of multiple S. salivarius strains by use of a deferred-antagonism test showed that S. salivarius strain K12 exhibited the broadest spectrum of activity against GBS. K12 effectively inhibited all GBS strains tested, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. Inhibition was dependent on the presence of megaplasmid pSsal-K12, which encodes the bacteriocins salivaricin A and salivaricin B; however, in coculture experiments, GBS growth was impeded by K12 independently of the megaplasmid. We also demonstrated that K12 adheres to and invades human vaginal epithelial cells at levels comparable to GBS. Inhibitory activity of K12 was examined in vivo using a mouse model of GBS vaginal colonization. Mice colonized with GBS were treated vaginally with K12. K12 administration significantly reduced GBS vaginal colonization in comparison to nontreated controls, and this effect was partially dependent on the K12 megaplasmid. Our results suggest that K12 may have potential as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy. PMID:26077762

  15. Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization.

    PubMed

    Patras, Kathryn A; Wescombe, Philip A; Rösler, Berenice; Hale, John D; Tagg, John R; Doran, Kelly S

    2015-09-01

    Streptococcus agalactiae (group B streptococcus [GBS]) colonizes the rectovaginal tract in 20% to 30% of women and during pregnancy can be transmitted to the newborn, causing severe invasive disease. Current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission, and GBS remains a leading cause of neonatal infection. We have investigated the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Comparison of the antibacterial activities of multiple S. salivarius strains by use of a deferred-antagonism test showed that S. salivarius strain K12 exhibited the broadest spectrum of activity against GBS. K12 effectively inhibited all GBS strains tested, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. Inhibition was dependent on the presence of megaplasmid pSsal-K12, which encodes the bacteriocins salivaricin A and salivaricin B; however, in coculture experiments, GBS growth was impeded by K12 independently of the megaplasmid. We also demonstrated that K12 adheres to and invades human vaginal epithelial cells at levels comparable to GBS. Inhibitory activity of K12 was examined in vivo using a mouse model of GBS vaginal colonization. Mice colonized with GBS were treated vaginally with K12. K12 administration significantly reduced GBS vaginal colonization in comparison to nontreated controls, and this effect was partially dependent on the K12 megaplasmid. Our results suggest that K12 may have potential as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy. PMID:26077762

  16. Group A Streptococcus endometritis following medical abortion.

    PubMed

    Gendron, Nicolas; Joubrel, Caroline; Nedellec, Sophie; Campagna, Jennifer; Agostini, Aubert; Doucet-Populaire, Florence; Casetta, Anne; Raymond, Josette; Poyart, Claire; Kernéis, Solen

    2014-07-01

    Medical abortion is not recognized as a high-risk factor for invasive pelvic infection. Here, we report two cases of group A Streptococcus (GAS; Streptococcus pyogenes) endometritis following medical abortions with a protocol of oral mifepristone and misoprostol. PMID:24829245

  17. Group A Streptococcus Endometritis following Medical Abortion

    PubMed Central

    Gendron, Nicolas; Joubrel, Caroline; Nedellec, Sophie; Campagna, Jennifer; Agostini, Aubert; Doucet-Populaire, Florence; Casetta, Anne; Raymond, Josette; Kernéis, Solen

    2014-01-01

    Medical abortion is not recognized as a high-risk factor for invasive pelvic infection. Here, we report two cases of group A Streptococcus (GAS; Streptococcus pyogenes) endometritis following medical abortions with a protocol of oral mifepristone and misoprostol. PMID:24829245

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

    PubMed Central

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

    2006-01-01

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

  19. New perspectives on immunomodulatory therapy for bacteraemia and sepsis.

    PubMed

    Opal, Steven M

    2010-12-01

    Systemic immune dysregulation is generally acknowledged to be the fundamental molecular mechanism that underlies the pathophysiology of severe sepsis and septic shock. In the presence of a systemic infection, microbial pathogens and their soluble mediators induce generalised immune activation and coagulation activation, leading to severe sepsis and septic shock. For decades, immune-based therapies have been devised with the specific intent of inhibiting the pro-inflammatory events that are thought to precipitate the septic process. Despite a clear therapeutic rationale based upon the available experimental evidence, anti-inflammatory therapies targeting the innate or acquired immune response have largely been unsuccessful in clinical trials of sepsis. Compelling evidence now exists that a prolonged state of sepsis-induced immune suppression follows the initial period of stabilisation and resuscitation in many critically ill patients. Sepsis-related immune suppression is evidenced by histological findings of markedly enhanced lymphocytic and monocytic apoptosis, poor response to neoantigens and recall antigens, and increased incidence of infections by opportunistic pathogens. Candidiasis, cytomegalovirus activation and secondary infections by relatively avirulent bacterial pathogens such as Stenotrophomonas and Acinetobacter spp. are commonplace in septic patients during prolonged Intensive Care Unit stays. Immunological tools to detect sepsis-induced immunosuppression are now available, and novel immunoadjuvants are in development to re-establish immune competence in sepsis patients. The intelligent use of immunomodulatory agents in sepsis will necessitate a personalised medicine approach to treat each patient at the appropriate time and with the optimal therapy.

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

    PubMed Central

    Koczera, Patrick

    2016-01-01

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

  1. Late mortality after sepsis: propensity matched cohort study

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Koczera, Patrick

    2016-01-01

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

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

    PubMed

    Nasa, Prashant; Juneja, Deven; Singh, Omender

    2012-02-01

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

  4. Endocarditis caused by unusual Streptococcus species (Streptococcus pluranimalium)

    PubMed Central

    Fotoglidis, A; Pagourelias, E; Kyriakou, P; Vassilikos, V

    2015-01-01

    Background Infective endocarditis in intravenous drug abusers is caused mainly by Staphylococcus species and usually affects the right heart valves. Case Description We report the case of a 37-years-old intravenous drug abuser, who was diagnosed with infective endocarditis of the mitral and aortic valve. An unusual Streptococcus species (Streptococcus pluranimalium) was isolated from surgical specimens (peripheral arterial emboli, valves’ vegetations) which, according to the literature, is related to animals’ diseases such as infective endocarditis in adult broiler parents, with no references existing regarding causing such disease in humans. This unusual coccus infection caused specific clinical features (sizable vegetation on mitral valve >2cm, smaller vegetations on aortic valve, systemic emboli), resistance to antimicrobial therapy, rapid progression of the disease (despite of medical therapy and surgical replacement of both valves), and finally the death of the patient two months after the initial presentation of infective endocarditis. Conclusion Unusual cases of infective endocarditis in intravenous drug abusers are emerging and are characterized by changing microbiological profile and varying clinical characteristics. Clinical doctors must be aware of these cases, especially when their patients present an atypical clinical course, and reappraise their medical management. Hippokratia 2015; 19 (2):182-185. PMID:27418771

  5. Cardiac Function and Dysfunction in Sepsis.

    PubMed

    Fenton, Kimberly E; Parker, Margaret M

    2016-06-01

    Cardiac function and dysfunction are important in the clinical outcomes of sepsis and septic shock. Cardiac dysfunction is not a single entity, but is a broad spectrum of syndromes that result in biventricular cardiac dysfunction manifested by both systolic and diastolic dysfunction and is influenced by cardiac loading conditions (ie, preload and afterload). Elucidating the underlying pathophysiology has proved to be complex. This article emphasizes the underlying pathophysiology of cardiac dysfunction and explores recent evidence related to diagnosis, including the utility of biomarkers, the role of echocardiography, and management goals and treatment. PMID:27229645

  6. Streptococcus milleri in the appendix.

    PubMed Central

    Poole, P M; Wilson, G

    1977-01-01

    The appendix was investigated as a possible habitat of Streptococcus milleri. Both normal and inflamed appendices were examined and the isolation rates compared. S. milleri was present in a quarter of the normal appendices and more than half of those associated with apendicitis--a difference that was statistically highly significant. The isolation rates throughout were indepencent of age. There was a pronounced connection between the presence of S. milleri in the appendix and the purulent manifestations of appendicitis. S. milleri was isolated from other abdominal sites associated with appendicitis. The frequency of isolation was increased by culture in an enrichment broth containing nalidixic acid and sulphadimidine. PMID:591633

  7. Streptococcus milleri in the appendix.

    PubMed

    Poole, P M; Wilson, G

    1977-10-01

    The appendix was investigated as a possible habitat of Streptococcus milleri. Both normal and inflamed appendices were examined and the isolation rates compared. S. milleri was present in a quarter of the normal appendices and more than half of those associated with apendicitis--a difference that was statistically highly significant. The isolation rates throughout were indepencent of age. There was a pronounced connection between the presence of S. milleri in the appendix and the purulent manifestations of appendicitis. S. milleri was isolated from other abdominal sites associated with appendicitis. The frequency of isolation was increased by culture in an enrichment broth containing nalidixic acid and sulphadimidine.

  8. Analysis of the coverage capacity of the StreptInCor candidate vaccine against Streptococcus pyogenes.

    PubMed

    De Amicis, Karine M; Freschi de Barros, Samar; Alencar, Raquel E; Postól, Edilberto; Martins, Carlo de Oliveira; Arcuri, Helen Andrade; Goulart, Cibelly; Kalil, Jorge; Guilherme, Luiza

    2014-07-01

    Streptococcus pyogenes is responsible for infections as pharyngitis, sepsis, necrotizing fasciitis and streptococcal toxic shock syndrome. The M protein is the major bacterial antigen and consists of both polymorphic N-terminal portion and a conserved region. In the present study, we analyzed the in vitro ability of StreptInCor a C-terminal candidate vaccine against S. pyogenes to induce antibodies to neutralize/opsonize the most common S. pyogenes strains in Sao Paulo by examining the recognition by sera from StreptInCor immunized mice. We also evaluated the presence of cross-reactive antibodies against human heart valve tissue. Anti-StreptInCor antibodies were able to neutralize/opsonize at least 5 strains, showing that immunization with StreptInCor is effective against several S. pyogenes strains and can prevent infection and subsequent sequelae without causing autoimmune reactions.

  9. Neonatal group B streptococcus disease in developing countries: are we ready to deploy a vaccine?

    PubMed

    Iroh Tam, Pui-Ying; Delair, Shirley F; Obaro, Stephen K

    2015-01-01

    Group B streptococcus (GBS) disease is the leading cause of neonatal sepsis in developed countries and has high case fatality rates. In developing countries, however, the burden of GBS is less clear; this is due to a lack of studies using optimal diagnostic, clinical and laboratory techniques and is complicated by the wide availability of non-prescription antibiotics to the general population and in peripartum patients. There is an urgent need for prospective, population-based surveillance to provide an accurate assessment of neonatal GBS disease burden in developing countries, which remains largely unrecognized, and consequently obscures the potential relevance of GBS vaccination in these populations. Preliminary data on GBS vaccines are promising as a preventive tool for neonatal GBS infection, more so than any other currently available public health initiative. However, how do we assess the true impact of a GBS vaccine without accurate surveillance data on the real burden of disease? PMID:26289974

  10. Neonatal group B streptococcus disease in developing countries: are we ready to deploy a vaccine?

    PubMed

    Iroh Tam, Pui-Ying; Delair, Shirley F; Obaro, Stephen K

    2015-01-01

    Group B streptococcus (GBS) disease is the leading cause of neonatal sepsis in developed countries and has high case fatality rates. In developing countries, however, the burden of GBS is less clear; this is due to a lack of studies using optimal diagnostic, clinical and laboratory techniques and is complicated by the wide availability of non-prescription antibiotics to the general population and in peripartum patients. There is an urgent need for prospective, population-based surveillance to provide an accurate assessment of neonatal GBS disease burden in developing countries, which remains largely unrecognized, and consequently obscures the potential relevance of GBS vaccination in these populations. Preliminary data on GBS vaccines are promising as a preventive tool for neonatal GBS infection, more so than any other currently available public health initiative. However, how do we assess the true impact of a GBS vaccine without accurate surveillance data on the real burden of disease?

  11. Scrum kidney: epidemic pyoderma caused by a nephritogenic Streptococcus pyogenes in a rugby team.

    PubMed

    Ludlam, H; Cookson, B

    1986-08-01

    In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match. PMID:2874337

  12. Science review: The brain in sepsis – culprit and victim

    PubMed Central

    Sharshar, Tarek; Hopkinson, Nicholas S; Orlikowski, David; Annane, Djillali

    2005-01-01

    On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free from blood-brain-barrier, interface between brain and bloodstream, in autonomic nuclei including the vagus nerve, and finally through the damaged endothelium. Recent observations have confirmed that sepsis is associated with excessive brain inflammation and neuronal apoptosis which clinical relevance remains to be explored. In parallel, damage within autonomic nervous and neuroendocrine systems may contribute to sepsis induced organ dysfunction. PMID:15693982

  13. How Can the Microbiologist Help in Diagnosing Neonatal Sepsis?

    PubMed Central

    Paolucci, Michela; Landini, Maria Paola; Sambri, Vittorio

    2012-01-01

    Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS) or later (late-onset neonatal sepsis—LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis. PMID:22319539

  14. 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

  15. Improving Sepsis Management in the Acute Admissions Unit.

    PubMed

    Adcroft, Laura

    2014-01-01

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

  16. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

    PubMed

    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection. PMID:27468649

  17. Sepsis-induced alterations in sleep of rats.

    PubMed

    Baracchi, Francesca; Ingiosi, Ashley M; Raymond, Richard M; Opp, Mark R

    2011-11-01

    Sepsis is a systemic immune response to infection that may result in multiple organ failure and death. Polymicrobial infections remain a serious clinical problem, and in the hospital, sepsis is the number-one noncardiac killer. Although the central nervous system may be one of the first systems affected, relatively little effort has been made to determine the impact of sepsis on the brain. In this study, we used the cecal ligation and puncture (CLP) model to determine the extent to which sepsis alters sleep, the EEG, and brain temperature (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye movement sleep (NREMS) during the dark period, but not during the light period. Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h following CLP surgery, after which REMS increases during dark periods for at least three nights. The EEG is dramatically altered shortly after sepsis induction, as evidenced by reductions in slow-frequency components. Furthermore, sleep is fragmented, indicating that the quality of sleep is diminished. Effects on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the duration of our recording period. Immunohistochemical assays focused on brain stem mechanisms responsible for alterations in REMS, as little information is available concerning infection-induced suppression of this sleep stage. Our immunohistochemical data suggest that REMS suppression after sepsis onset may be mediated, in part, by the brain stem GABAergic system. This study demonstrates for the first time that sleep and EEG patterns are altered during CLP-induced sepsis. These data suggest that the EEG may serve as a biomarker for sepsis onset. These data also contribute to our knowledge of potential mechanisms, whereby infections alter sleep and other central nervous system functions.

  18. Streptococcus agalactiae mastitis: a review.

    PubMed Central

    Keefe, G P

    1997-01-01

    Streptococcus agalactiae continues to be a major cause of subclinical mastitis in dairy cattle and a source of economic loss for the industry. Veterinarians are often asked to provide information on herd level control and eradication of S. agalactiae mastitis. This review collects and collates relevant publications on the subject. The literature search was conducted in 1993 on the Agricola database. Articles related to S. agalactiae epidemiology, pathogen identification techniques, milk quality consequences, and control, prevention, and therapy were included. Streptococcus agalactiae is an oblique parasite of the bovine mammary gland and is susceptible to treatment with a variety of antibiotics. Despite this fact, where state or provincial census data are available, herd prevalence levels range from 11% (Alberta, 1991) to 47% (Vermont, 1985). Infection with S. agalactiae is associated with elevated somatic cell count and total bacteria count and a decrease in the quantity and quality of milk products produced. Bulk tank milk culture has, using traditional milk culture techniques, had a low sensitivity for identifying S. agalactiae at the herd level. New culture methods, using selective media and large inocula, have substantially improved the sensitivity of bulk tank culture. Efficacy of therapy on individual cows remains high. Protocols for therapy of all infected animals in a herd are generally successful in eradicating the pathogen from the herd, especially if they are followed up with good udder hygiene techniques. PMID:9220132

  19. Vasopressin in sepsis and septic shock.

    PubMed

    Kampmeier, T G; Rehberg, S; Westphal, M; Lange, M

    2010-10-01

    Arginine vasopressin (AVP) and its synthetic, long-acting analog terlipressin (TP) are potent alternative vasoconstrictors in the treatment of septic patients with catecholamine-refractive vasodilatatory shock. The results from one large randomized clinical trial suggest that AVP plus norepinephrine (NE) infusion is as safe and effective as treatment with NE alone in patients with septic shock. Because the desired effects of vasopressin analogs are basically related to their vasopressinergic effects via the V1a receptor, more selective V1 agonists, such as TP, may be more potent in reversing sepsis-related arterial hypotension. In this regard, recent evidence from small-scale studies suggests that continuous low-dose infusion rather than intermittent bolus injection of TP is associated with fewer side effects, such as depression of cardiac output and rebound arterial hypotension. However, because clinical data on the administration of TP in patients with sepsis are limited, it should not currently be used beyond the scope of controlled trials. The optimal time point for the initiation of therapy with vasopressin analogs has yet to be determined. While AVP and TP are commonly used as last-resort therapies in severe septic shock, some evidence supports the initiation of treatment in a less severe state of the disease.

  20. Intestinal radiation syndrome: sepsis and endotoxin

    SciTech Connect

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-03-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.

  1. Hypomagnesemia in Critically Ill Sepsis Patients

    PubMed Central

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

    2015-01-01

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

  2. Use of Pyrosequencing of 16S rRNA Fragments to Differentiate between Bacteria Responsible for Neonatal Sepsis

    PubMed Central

    Jordan, Jeanne A.; Butchko, Allyson R.; Beth Durso, Mary

    2005-01-01

    Infants admitted to neonatal intensive care units for suspicion of bacterial sepsis receive at least two broad-spectrum antibiotics for a minimum of 48 to 72 hours to cover both gram-positive and gram-negative organisms while awaiting blood culture results. On average, bacterial growth becomes detectable within 12 to 24 hours, with an additional 24 to 48 hours required for identification. We have previously described using a 16S rRNA PCR assay for screening neonatal blood for bacterial DNA. Combining PCR with DNA sequencing could prove a faster means of detecting bacteria than culture-based identification. If successful, antibiotic therapy could be appropriately tailored sooner, thus sparing infants the administration of unnecessary antibiotics. Our goal was to assess the potential of pyrosequencing to differentiate between bacteria commonly associated with neonatal sepsis. To begin, full-length sequencing of the 380-bp 16S rRNA amplicons from representative bacteria was conducted (ABI 3100) and several databases queried. These included Staphylococcus sp., Streptococcus sp., Listeria sp., and numerous gram-negative rods. The sequences from clinical isolates were identical to those present in the published databases for the same bacteria. As a result, an informative 15 bases within the 380-bp amplicon was targeted for pyrosequencing following enrichment culture and PCR amplification. A total of 643 bacterial isolates commonly associated with neonatal sepsis, and 15 PCR-positive, culture-positive neonatal whole blood samples were analyzed by pyrosequencing. Results of DNA sequencing and culture identification were compared. In summary, we were successful at using PCR and pyrosequencing together to accurately differentiate between highly diverse bacterial groups. PMID:15681481

  3. Structural analysis of the lipoteichoic acids isolated from bovine mastitis Streptococcus uberis 233, Streptococcus dysgalactiae 2023 and Streptococcus agalactiae 0250.

    PubMed

    Czabańska, Anna; Neiwert, Olga; Lindner, Buko; Leigh, James; Holst, Otto; Duda, Katarzyna A

    2012-11-01

    Lipoteichoic acid (LTA) is an amphiphilic polycondensate located in the cell envelope of Gram-positive bacteria. In this study, LTAs were isolated from the three bovine mastitis species Streptococcus uberis 233, Streptococcus dysgalactiae 2023, and Streptococcus agalactiae 0250. Structural investigations of these LTAs were performed applying 1D and 2D nuclear magnetic resonance experiments as well as chemical analyses and mass spectrometry. Compositional analysis revealed the presence of glycerol (Gro), Glc, alanine (Ala), and 16:0, 16:1, 18:0, 18:1. The LTAs of the three Streptococcus strains possessed the same structure, that is, a lipid anchor comprised of α-Glcp-(1→2)-α-Glcp-(1→3)-1,2-diacyl-sn-Gro and the hydrophilic backbone consisting of poly(sn-Gro-1-phosphate) randomly substituted at O-2 of Gro by d-Ala.

  4. Structural analysis of the lipoteichoic acids isolated from bovine mastitis Streptococcus uberis 233, Streptococcus dysgalactiae 2023 and Streptococcus agalactiae 0250.

    PubMed

    Czabańska, Anna; Neiwert, Olga; Lindner, Buko; Leigh, James; Holst, Otto; Duda, Katarzyna A

    2012-11-01

    Lipoteichoic acid (LTA) is an amphiphilic polycondensate located in the cell envelope of Gram-positive bacteria. In this study, LTAs were isolated from the three bovine mastitis species Streptococcus uberis 233, Streptococcus dysgalactiae 2023, and Streptococcus agalactiae 0250. Structural investigations of these LTAs were performed applying 1D and 2D nuclear magnetic resonance experiments as well as chemical analyses and mass spectrometry. Compositional analysis revealed the presence of glycerol (Gro), Glc, alanine (Ala), and 16:0, 16:1, 18:0, 18:1. The LTAs of the three Streptococcus strains possessed the same structure, that is, a lipid anchor comprised of α-Glcp-(1→2)-α-Glcp-(1→3)-1,2-diacyl-sn-Gro and the hydrophilic backbone consisting of poly(sn-Gro-1-phosphate) randomly substituted at O-2 of Gro by d-Ala. PMID:23036931

  5. Antibody binding to Streptococcus mitis and Streptococcus oralis cell fractions

    PubMed Central

    Wirth, Katherine A.; Bowden, George H.; Richmond, Dorothy A.; Sheridan, Michael J.; Cole, Michael F.

    2008-01-01

    Summary Objective To determine which cell fraction(s) of Streptococcus mitis biovar 1 serve as the best source of antigens recognized by salivary SIgA antibodies in infants. Design Whole cells of 38 reference and wild-type isolates of Streptococcus mitis, S. oralis, S. gordonii, Enterococcus casseliflavus, and E. faecalis were fractionated into cell walls CW), protease-treated cell walls (PTCW), cell membranes (CM) and cell protein (CP). Whole cells and these fractions were tested for binding by rabbit anti-S. mitis SK145 and anti-S. oralis SK100 sera, and also by salivary SIgA antibodies from infants and adults. Results Anti-SK145 and anti-SK100 sera bound whole cells and fractions of all strains of S. mitis and S. oralis variably. Cluster analysis of antibody binding data placed the strains into S. mitis, S. oralis and ‘Non-S. mitis/non-S. oralis’ clusters. Antigens from CW and CM best discriminated S. mitis from S. oralis. CM bound the most infant salivary SIgA antibody and PTCW bound the least. In contrast, adult salivary SIgA antibody bound all of the cell fractions and at higher levels. Conclusions Presumably the relatively short period of immune stimulation and immunological immaturity in infants, in contrast to adults, result in low levels of salivary SIgA antibody that preferentially bind CM of S. mitis but not PTCW. By utilizing isolated cell walls and membranes as sources of antigens for proteomics it may be possible to identify antigens common to oral streptococci and dissect the fine specificity of salivary SIgA antibodies induced by oral colonization by S. mitis. PMID:17904095

  6. Mast Cell Stabilization Improves Survival by Preventing Apoptosis in Sepsis

    PubMed Central

    Ramos, Laura; Peña, Geber; Cai, Bolin; Deitch, E. A.; Ulloa, Luis

    2011-01-01

    Inhibiting single cytokines produced modest effects in clinical trials, in part because the cytokines werenot specific for sepsis, and sepsis may require cellular strategies. Previous studies reported that mast cells (MCs) fight infections in early sepsis. In this study, we report that MC stabilizers restrain serum TNF levels and improve survival in wild-type but not in MC-deficient mice. Yet, MC depletion in knockout mice attenuates serum TNF but does not improve survival in sepsis. Serum HMGB1 was the only factor correlating with survival. MC stabilizers inhibit systemic HMGB1 levels and rescue mice from established peritonitis. MC stabilizers fail to inhibit HMGB1 secretion from macrophages, but they prevent apoptosis and caspase-3 activation in sepsis. These results suggest that MC stabilization provides therapeutic benefits in sepsis by inhibiting extracellular release of HMGB1 from apoptotic cells. Our study provides the first evidence that MCs have major immunological implications regulating cell death in sepsis and represent a pharmacological target for infectious disorders in a clinically realistic time frame. PMID:20519642

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

    PubMed

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

    2015-05-01

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

  8. The role of arginine in infection and sepsis.

    PubMed

    Luiking, Yvette C; Poeze, Martijn; Ramsay, Graham; Deutz, Nicolaas E P

    2005-01-01

    Sepsis is a systemic response to an infection, with high morbidity and mortality rates. Metabolic changes during infection and sepsis could be related to changes in metabolism of the amino acid L-arginine. In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery because both endogenous de novo arginine production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine via the arginase and nitric oxide pathways. As a result, lowered plasma arginine levels are usually found. Arginine may therefore be considered as an essential amino acid in sepsis, and supplementation could be beneficial in sepsis by improving microcirculation and protein anabolism. L-Arginine supplementation in a hyperdynamic pig model of sepsis prohibits the increase in pulmonary arterial blood pressure, improves muscle and liver protein metabolism, and restores the intestinal motility pattern. Arguments raised against arginine supplementation are mainly pointed at stimulating nitric oxide (NO) production, with concerns about toxicity of increased NO and hemodynamic instability with refractory hypotension. NO synthase inhibition, however, increased mortality. Arginine supplementation in septic patients has transient effects on hemodynamics when supplied as a bolus but seems without hemodynamic side effects when supplied continuously. In conclusion, arginine could have an essential role in infection and sepsis.

  9. Challenges in the diagnosis and management of neonatal sepsis.

    PubMed

    Zea-Vera, Alonso; Ochoa, Theresa J

    2015-02-01

    Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries.

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

    PubMed

    Shah, Birju A; Padbury, James F

    2014-01-01

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

  11. Mortality in Sepsis and its relationship with Gender

    PubMed Central

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

    2015-01-01

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

  12. Colloids in sepsis: evenly distributed molecules surrounded by uneven questions.

    PubMed

    Zampieri, Fernando Godinho; Park, Marcelo; Azevedo, Luciano Cesar Pontes

    2013-05-01

    Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. These properties appear to be preserved even in patients with sepsis with increased capillary permeability. However, some colloids are associated with renal impairment and coagulation abnormalities. Starch use was associated with increased mortality in two large clinical trials. Also, starches probably have significant renal adverse effects and may be related to more need for renal replacement therapy in severe sepsis. Albumin is the only colloid that has been shown safe in patients with sepsis and that may be associated with improved outcomes on specific subpopulations. No trial so far found any robust clinical end point favoring colloid use in patients with sepsis. Because there is no proven benefit of the use of most colloids in patients with sepsis, its use should not be encouraged outside clinical trials. Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.

  13. Acute septicemia caused by Streptococcus gallolyticus subsp. pasteurianus in turkey poults.

    PubMed

    Saumya, Dona; Wijetunge, S; Dunn, Patricia; Wallner-Pendleton, Eva; Lintner, Valerie; Matthews, Tammy; Pierre, Traci; Kariyawasam, Subhashinie

    2014-06-01

    Streptococcus gallolyticus, previously known as Streptococcus bovis biotypes I and II/2, is a well-known cause of sepsis and meningitis in humans and birds. The present case report describes an outbreak of fatal septicemia associated with S. gallolyticus subsp. pasteurianus (S. bovis biotype II/2) in 11 turkey flocks in Pennsylvania between 2010 and 2013. Affected poults were 2-3 wk of age. Major clinical observation was sudden increase in mortality among turkey poults without any premonitory clinical signs. Postmortem examination findings revealed acute septicemia with lesions such as fibrinous pericarditis, meningitis, splenic multifocal fibrinoid necrosis, hepatitis, osteochondritis, myositis, and airsacculitis. Gram-positive cocci were isolated from several organs by routine bacterial culture. Biotyping identified bacteria as streptococci, whereas 16S ribosomal RNA gene sequencing identified them as S. gallolyticus subsp. pasteurianus. Antibiotic susceptibility profiles revealed that all the strains isolated were sensitive to penicillin and erythromycin with different sensitivity profiles for other antibacterial agents tested. The present study reports the first confirmed case of acute septicemia in turkey poults caused by S. gallolyticus subsp. pasteurianus.

  14. Epidemiology, clinical manifestations, and outcomes of Streptococcus suis infection in humans.

    PubMed

    Huong, Vu Thi Lan; Ha, Ngo; Huy, Nguyen Tien; Horby, Peter; Nghia, Ho Dang Trung; Thiem, Vu Dinh; Zhu, Xiaotong; Hoa, Ngo Thi; Hien, Tran Tinh; Zamora, Javier; Schultsz, Constance; Wertheim, Heiman Frank Louis; Hirayama, Kenji

    2014-07-01

    Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.

  15. Biofilm formation by Streptococcus agalactiae: influence of environmental conditions and implicated virulence factors

    PubMed Central

    Rosini, Roberto; Margarit, Immaculada

    2015-01-01

    Streptococcus agalactiae (Group B Streptococcus, GBS) is an important human pathogen that colonizes the urogenital and/or the lower gastro-intestinal tract of up to 40% of healthy women of reproductive age and is a leading cause of sepsis and meningitis in the neonates. GBS can also infect the elderly and immuno-compromised adults, and is responsible for mastitis in bovines. Like other Gram-positive bacteria, GBS can form biofilm-like three-dimensional structures that could enhance its ability to colonize and persist in the host. Biofilm formation by GBS has been investigated in vitro and appears tightly controlled by environmental conditions. Several adhesins have been shown to play a role in the formation of GBS biofilm-like structures, among which are the protein components of pili protruding outside the bacterial surface. Remarkably, antibodies directed against pilus proteins can prevent the formation of biofilms. The implications of biofilm formation in the context of GBS asymptomatic colonization and dissemination to cause invasive disease remain to be investigated in detail. PMID:25699242

  16. Update on the management of neonatal sepsis in horses.

    PubMed

    Palmer, Jon

    2014-08-01

    Despite advances in neonatal intensive care sepsis, severe sepsis and septic shock remain the biggest killers of neonatal foals. Management of this severe syndrome remains difficult, requiring intensive intervention. Key aspects of management include infection control, hemodynamic support, immunomodulatory interventions, and metabolic/endocrine support. Infection control largely consists of early antimicrobial therapy, plasma transfusions, and local therapy for the infected focus. In cases with severe sepsis or septic shock, hemodynamic support with fluids, vasoactive agents, and respiratory support insuring oxygen delivery to vital organs is important. Nutritional support is important, but close monitoring is needed to avoid hyperglycemia and hypoglycemia.

  17. Potential of surface acoustic wave biosensors for early sepsis diagnosis.

    PubMed

    Csete, Marie; Hunt, William D

    2013-08-01

    Early diagnosis of sepsis is a difficult problem for intensivists and new biomarkers for early diagnosis have been difficult to come by. Here we discuss the potential of adapting a technology from the electronics industry, surface acoustic wave (SAW) sensors, for diagnosis of multiple markers of sepsis in real time, using non-invasive assays of exhaled breath condensate. The principles and advantages of the SAW technology are reviewed as well as a proposed plan for adapting this flexible technology to early sepsis detection. PMID:23471596

  18. Challenges with Diagnosing and Managing Sepsis in Older Adults.

    PubMed

    Clifford, Kalin M; Dy-Boarman, Eliza A; Haase, Krystal K; Maxvill, Kristen; Pass, Steven E; Alvarez, Carlos A

    2016-01-01

    Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis and offers recommendations for monitoring and treating sepsis in the older adult population.

  19. Metabolism, Metabolomics, and Nutritional Support of Patients with Sepsis.

    PubMed

    Englert, Joshua A; Rogers, Angela J

    2016-06-01

    Sepsis is characterized by profound changes in systemic and cellular metabolism that disrupt normal metabolic homeostasis. These metabolic changes can serve as biomarkers for disease severity. Lactate, a metabolite of anaerobic metabolism, is the most widely used ICU biomarker and it is incorporated into multiple management algorithms. Technological advances now make broader metabolic profiling possible, with early studies identifying metabolic changes associated with sepsis mortality. Finally, given the marked changes in metabolism in sepsis and the association of worse prognosis in patients with severe metabolic derangements, we summarize the seminal trials conducted to optimize nutrition in the ICU. PMID:27229648

  20. A plasmid in Streptococcus pneumoniae.

    PubMed Central

    Smith, M D; Guild, W R

    1979-01-01

    Plasmid deoxyribonucleic acid has been detected in three related laboratory strains of Streptococcus pneumoniae. Strains D39S, R36, and R36NC each contain a minimum of two copies per cell of a 2.0-megadalton plasmid (pDP1). A plasmid twice as large as this smaller one is also present in much lower quantity in these strains, but neither plasmid is present in four strains related to these or in a drug-resistant clinical isolate from Paris. The plasmid yield was not amplified in the presence of chloramphenicol. No phenotype has been correlated with the presence of pDP1, which has existed in strains carried for many years in laboratory collections. Images PMID:33961

  1. Safety assessment of dairy microorganisms: Streptococcus thermophilus.

    PubMed

    Delorme, Christine

    2008-09-01

    Streptococcus thermophilus is a major dairy starter used in yogurt and cheese production. In Streptococcus genus, S. thermophilus is the only one food species among commensal and opportunistic pathogen species. Comparative genomics suggest that this species recently emerged and evolved by combination of loss-of-function and horizontal gene transfer events. These gene transfer events detected in S. thermophilus have originated from other dairy species and might contribute to its adaptation to the milk environment.

  2. Infections Associated with Streptococcus intermedius in Children.

    PubMed

    Faden, Howard S

    2016-09-01

    Streptococcus intermedius is a viridans Streptococcus belonging to the Anginosus group. In the past 7 years, it has been associated with abscesses in 48 children, 40% of whom had complicated and/or life-threatening illness. It was the sole pathogen in 35 cases. Seventy-five percent of the infections occurred in winter and spring. None occurred in infants younger than 1 year.

  3. Vasoactive agents for the treatment of sepsis

    PubMed Central

    Chen, Kun

    2016-01-01

    The article describes some commonly used vasoactive agents in patients with septic shock. Depending on their distinct pharmacological properties, their effects on vascular bed and cardiac function are different. For example, dopamine has equivalent effect on heart and vasculature, which can result in increases in cardiac output, mean arterial pressure and heart rate. Dobutamine is considered as inodilator because it has potent effect on cardiac systole and vasculature. Patients with sepsis and septic shock sometimes have coexisting cardiac dysfunction that justifies the use of dobutamine. Levosimendan is a relatively new agent exerting its inodilator effect by increasing sensitivity of myocardium to calcium. Some preliminary studies showed a promising result of levosimendan on reducing mortality. PMID:27713891

  4. 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.

  5. Sepsis: From Pattern to Mechanism and Back

    PubMed Central

    An, Gary; Namas, Rami A.; Vodovotz, Yoram

    2013-01-01

    Sepsis is a clinical entity in which complex inflammatory and physiological processes are mobilized, not only across a range of cellular and molecular interactions, but also in clinically relevant physiological signals accessible at the bedside. There is a need for a mechanistic understanding that links the clinical phenomenon of physiologic variability with the underlying patterns of the biology of inflammation, and we assert that this can be facilitated through the use of dynamic mathematical and computational modeling. An iterative approach of laboratory experimentation and mathematical/computational modeling has the potential to integrate cellular biology, physiology, control theory, and systems engineering across biological scales, yielding insights into the control structures that govern mechanisms by which phenomena, detected as biological patterns, are produced. This approach can represent hypotheses in the formal language of mathematics and computation, and link behaviors that cross scales and domains, thereby offering the opportunity to better explain, diagnose, and intervene in the care of the septic patient. PMID:23140124

  6. [Community acquired sepsis by Serratia rubidaea].

    PubMed

    Okada, Takanori; Yokota, Eisuke; Matsumoto, Isao

    2002-02-01

    A 48-year-old male who had a past history of alcoholic pancreatitis and diabetes mellitus was admitted to our hospital due to chills and vomiting, on August 13, 1998. His body temperature was 38.0 degrees C, and he had the disturbance of consciousness, tachypnea, tachycardia and hepatomegaly with tenderness. Laboratory findings showed highly inflammatory reactions, DIC and hepatorenal dysfunction. Abdominal CT and US revealed multiple liver abscess with portal vein thrombus. Serratia rubidaea was detected in the blood culture. SBT/CPZ and TOB were administered and he recovered. This is a rare case of Serratia rubidaea sepsis. It is also necessary to pay attention to Serratia infections as well as S. marcescens.

  7. Sepsis, parenteral vaccination and skin disinfection

    PubMed Central

    Cook, Ian F.

    2016-01-01

    ASBSTRACT Disinfection should be required for all skin penetrative procedures including parenteral administration of vaccines. This review analyses medically attended infectious events following parenteral vaccination in terms of their microbiological aetiology and pathogenesis. Like ‘clean’ surgical site infections, the major pathogens responsible for these events were Staphylococcal species, implicating endogenous con-tamination as a significant source of infection. As 70% isopropyl alcohol swabbing has been shown to effectively disinfect the skin, it would be medico-legally difficult to defend a case of sepsis with the omission of skin disinfection unless the very low risk of this event was adequately explained to the patient and documented prior to vaccination. There was a significant cost-benefit for skin disinfection and cellulitis. Skin disinfection in the context of parenteral vaccination represents a new paradigm of medical practice; the use of a low cost intervention to prevent an event of very low prevalence but of significant cost. PMID:27295449

  8. Interprofessional sepsis education module: a pilot study.

    PubMed

    Chung, Han-Oh; Medina, Damien; Fox-Robichaud, Alison

    2016-03-01

    Although there is an increasing emphasis on interprofessional collaboration for safer health care systems, there remains a paucity of opportunities for postgraduate trainees to engage in formal interprofessional education (IPE). Current opportunities for interprofessional learning, such as simulation sessions, typically do not provide true IPE because they often utilize actors or confederates as support staff, making residents the only stakeholders in the education experience. Here, we describe a flexible educational module designed to provide genuine IPE for physicians, nurses, and respiratory therapists. We outline how simulation, feedback, and group discussions can be used to teach interprofessional team communication, collaboration, and crew resource management skills-while, at the same time, also teaching a highly relevant medical topic (sepsis management) and thus resulting in learner engagement and motivation.

  9. 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

  10. Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons.

    PubMed

    Frej, Cecilia; Linder, Adam; Happonen, Kaisa E; Taylor, Fletcher B; Lupu, Florea; Dahlbäck, Björn

    2016-06-01

    Sphingosine 1-phosphate (S1P) is an important regulator of vascular integrity and immune cell migration, carried in plasma by high-density lipoprotein (HDL)-associated apolipoprotein M (apoM) and by albumin. In sepsis, the protein and lipid composition of HDL changes dramatically. The aim of this study was to evaluate changes in S1P and its carrier protein apoM during sepsis. For this purpose, plasma samples from both human sepsis patients and from an experimental Escherichia coli sepsis model in baboons were used. In the human sepsis cohort, previously studied for apoM, plasma demonstrated disease-severity correlated decreased S1P levels, the profile mimicking that of plasma apoM. In the baboons, a similar disease-severity dependent decrease in plasma levels of S1P and apoM was observed. In the lethal E. coli baboon sepsis, S1P decreased already within 6-8 hrs, whereas the apoM decrease was seen later at 12-24 hrs. Gel filtration chromatography of plasma from severe human or baboon sepsis on Superose 6 demonstrated an almost complete loss of S1P and apoM in the HDL fractions. S1P plasma concentrations correlated with the platelet count but not with erythrocytes or white blood cells. The liver mRNA levels of apoM and apoA1 decreased strongly upon sepsis induction and after 12 hr both were almost completely lost. In conclusion, during septic challenge, the plasma levels of S1P drop to very low levels. Moreover, the liver synthesis of apoM decreases severely and the plasma levels of apoM are reduced. Possibly, the decrease in S1P contributes to the decreased endothelial barrier function observed in sepsis. PMID:26990127

  11. 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.

  12. Isolation of Streptococcus tigurinus - a novel member of Streptococcus mitis group from a case of periodontitis.

    PubMed

    Dhotre, Shree V; Mehetre, Gajanan T; Dharne, Mahesh S; Suryawanshi, Namdev M; Nagoba, Basavraj S

    2014-08-01

    Streptococcus tigurinus is a new member of the Streptococcus viridians group and is closely related to Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pseudopneumoniae, Streptococcus oralis, and Streptococcus infantis. The type strain AZ_3a(T) of S. tigurinus was originally isolated from a patient with infective endocarditis. Accurate identification of S. tigurinus is facilitated only by newer molecular methods like 16S rRNA gene analysis. During the course of study on bacteraemia and infective endocarditis with reference to periodontitis and viridians group of streptococci, a strain of S. tigurinus isolated from subgingival plaque of a patient with periodontitis identified by 16S rRNA gene analysis, which was originally identified as Streptococcus pluranimalium by Vitek 2. Confirmation by 16S rRNA gene analysis showed 99.39% similarity (1476/1485 bp) with S. tigurinus AZ_3a(T) (AORU01000002). To the best of our knowledge, this is the first report of isolation of S. tigurinus from the oral cavity of a periodontitis patient.

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

    PubMed Central

    2010-01-01

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

  14. Paradoxical Roles of the Neutrophil in Sepsis: Protective and Deleterious

    PubMed Central

    Sônego, Fabiane; Castanheira, Fernanda Vargas e Silva; Ferreira, Raphael Gomes; Kanashiro, Alexandre; Leite, Caio Abner Vitorino Gonçalves; Nascimento, Daniele Carvalho; Colón, David Fernando; Borges, Vanessa de Fátima; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2016-01-01

    Sepsis, an overwhelming inflammatory response syndrome secondary to infection, is one of the costliest and deadliest medical conditions worldwide. Neutrophils are classically considered to be essential players in the host defense against invading pathogens. However, several investigations have shown that impairment of neutrophil migration to the site of infection, also referred to as neutrophil paralysis, occurs during severe sepsis, resulting in an inability of the host to contain and eliminate the infection. On the other hand, the neutrophil antibacterial arsenal contributes to tissue damage and the development of organ dysfunction during sepsis. In this review, we provide an overview of the main events in which neutrophils play a beneficial or deleterious role in the outcome of sepsis. PMID:27199981

  15. Clinical Decision Support for Early Recognition of Sepsis.

    PubMed

    Amland, Robert C; Hahn-Cover, Kristin E

    2016-01-01

    Sepsis is an inflammatory response triggered by infection, with a high in-hospital mortality rate. Early recognition and treatment can reverse the inflammatory response, with evidence of improved patient outcomes. One challenge clinicians face is identifying the inflammatory syndrome against the background of the patient's infectious illness and comorbidities. An approach to this problem is implementation of computerized early warning tools for sepsis. This multicenter retrospective study sought to determine clinimetric performance of a cloud-based computerized sepsis clinical decision support system (CDS), understand the epidemiology of sepsis, and identify opportunities for quality improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013. Of 13% patients screened-in, 51% were already suspected to have an infection when the system activated. This study focused on a patient cohort screened-in before infection was suspected; median time from arrival to CDS activation was 3.5 hours, and system activation to diagnostic collect was another 8.6 hours. PMID:25385815

  16. Development of an e-learning package for sepsis care.

    PubMed

    Davis, Anna; Henderson, James; Langmack, Gill

    Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis.

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

    PubMed

    Zheng, Yijun; Zhu, Duming

    2016-01-01

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

  18. Biomarkers for sepsis: a review with special attention to India.

    PubMed

    Nelson, George E; Mave, Vidya; 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.

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

    PubMed Central

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

    2015-01-01

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

  20. Penetration of Streptococcus sobrinus and Streptococcus sanguinis into dental enamel.

    PubMed

    Kneist, Susanne; Nietzsche, Sandor; Küpper, Harald; Raser, Gerhard; Willershausen, Brita; Callaway, Angelika

    2015-10-01

    The aim of this pilot study was to assess the difference in virulence of acidogenic and aciduric oral streptococci in an in vitro caries model using their penetration depths into dental enamel. 30 caries-free extracted molars from 11- to 16-year-olds were cleaned ultrasonically for 1 min with de-ionized water and, after air-drying, embedded in epoxy resin. After 8-h of setting at room temperature, the specimens were ground on the buccal side with SiC-paper 1200 (particle size 13-16 μm). Enamel was removed in circular areas sized 3 mm in diameter; the mean depth of removed enamel was 230 ± 60 μm. 15 specimens each were incubated anaerobically under standardized conditions with 24 h-cultures of Streptococcus sanguinis 9S or Streptococcus sobrinus OMZ 176 in Balmelli broth at 37 ± 2 °C; the pH-values of the broths were measured at the beginning and end of each incubation cycle. After 2, 4, 6, 8, and 10 weeks 3 teeth each were fixed in 2.5% glutaraldehyde in cacodylate buffer for 24 h, washed 3× and dehydrated 30-60min by sequential washes through a series of 30-100% graded ethanol. The teeth were cut in half longitudinally; afterward, two slits were made to obtain fracture surfaces in the infected area. After critical-point-drying the fragments were gold-sputtered and viewed in a scanning electron microscope at magnifications of ×20-20,000. After 10 weeks of incubation, penetration of S. sanguinis of 11.13 ± 24.04 μm below the break edges into the enamel was observed. The invasion of S. sobrinus reached depths of 87.53 ± 76.34 μm. The difference was statistically significant (paired t test: p = 0.033). The experimental penetration depths emphasize the importance of S. sanguinis versus S. sobrinus in the context of the extended ecological plaque hypothesis.

  1. Penetration of Streptococcus sobrinus and Streptococcus sanguinis into dental enamel.

    PubMed

    Kneist, Susanne; Nietzsche, Sandor; Küpper, Harald; Raser, Gerhard; Willershausen, Brita; Callaway, Angelika

    2015-10-01

    The aim of this pilot study was to assess the difference in virulence of acidogenic and aciduric oral streptococci in an in vitro caries model using their penetration depths into dental enamel. 30 caries-free extracted molars from 11- to 16-year-olds were cleaned ultrasonically for 1 min with de-ionized water and, after air-drying, embedded in epoxy resin. After 8-h of setting at room temperature, the specimens were ground on the buccal side with SiC-paper 1200 (particle size 13-16 μm). Enamel was removed in circular areas sized 3 mm in diameter; the mean depth of removed enamel was 230 ± 60 μm. 15 specimens each were incubated anaerobically under standardized conditions with 24 h-cultures of Streptococcus sanguinis 9S or Streptococcus sobrinus OMZ 176 in Balmelli broth at 37 ± 2 °C; the pH-values of the broths were measured at the beginning and end of each incubation cycle. After 2, 4, 6, 8, and 10 weeks 3 teeth each were fixed in 2.5% glutaraldehyde in cacodylate buffer for 24 h, washed 3× and dehydrated 30-60min by sequential washes through a series of 30-100% graded ethanol. The teeth were cut in half longitudinally; afterward, two slits were made to obtain fracture surfaces in the infected area. After critical-point-drying the fragments were gold-sputtered and viewed in a scanning electron microscope at magnifications of ×20-20,000. After 10 weeks of incubation, penetration of S. sanguinis of 11.13 ± 24.04 μm below the break edges into the enamel was observed. The invasion of S. sobrinus reached depths of 87.53 ± 76.34 μm. The difference was statistically significant (paired t test: p = 0.033). The experimental penetration depths emphasize the importance of S. sanguinis versus S. sobrinus in the context of the extended ecological plaque hypothesis. PMID:25805186

  2. Heart Rate Variability in Porcine Progressive Peritonitis-Induced Sepsis

    PubMed Central

    Jarkovska, Dagmar; Valesova, Lenka; Chvojka, Jiri; Benes, Jan; Sviglerova, Jitka; Florova, Blanka; Nalos, Lukas; Matejovic, Martin; Stengl, Milan

    2016-01-01

    Accumulating evidence suggests that heart rate variability (HRV) alterations could serve as an indicator of sepsis progression and outcome, however, the relationships of HRV and major pathophysiological processes of sepsis remain unclear. Therefore, in this experimental study HRV was investigated in a clinically relevant long-term porcine model of severe sepsis/septic shock. HRV was analyzed by several methods and the parameters were correlated with pathophysiological processes of sepsis. In 16 anesthetized, mechanically ventilated, and instrumented domestic pigs of either gender, sepsis was induced by fecal peritonitis. Experimental subjects were screened up to the refractory shock development or death. ECG was continuously recorded throughout the experiment, afterwards RR intervals were detected and HRV parameters computed automatically using custom made measurement and analysis MATLAB routines. In all septic animals, progressive hyperdynamic septic shock developed. The statistical measures of HRV, geometrical measures of HRV and Poincaré plot analysis revealed a pronounced reduction of HRV that developed quickly upon the onset of sepsis and was maintained throughout the experiment. The frequency domain analysis demonstrated a decrease in the high frequency component and increase in the low frequency component together with an increase of the low/high frequency component ratio. The reduction of HRV parameters preceded sepsis-associated hemodynamic changes including heart rate increase or shock progression. In a clinically relevant porcine model of peritonitis-induced progressive septic shock, reduction of HRV parameters heralded sepsis development. HRV reduction was associated with a pronounced parasympathetic inhibition and a shift of sympathovagal balance. Early reduction of HRV may serve as a non-invasive and sensitive marker of systemic inflammatory syndrome, thereby widening the therapeutic window for early interventions. PMID:26779039

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

    PubMed

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

    2014-01-01

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

  4. A Review of GM-CSF Therapy in Sepsis.

    PubMed

    Mathias, Brittany; Szpila, Benjamin E; Moore, Frederick A; Efron, Philip A; Moldawer, Lyle L

    2015-12-01

    Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune-activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID:26683913

  5. A Review of GM-CSF Therapy in Sepsis

    PubMed Central

    Mathias, Brittany; Szpila, Benjamin E.; Moore, Frederick A.; Efron, Philip A.; Moldawer, Lyle L.

    2015-01-01

    Abstract Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune-activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID

  6. Opsonic Fibronectin Deficiency and Sepsis: Cause or Effect?

    PubMed Central

    Lanser, Marc E.; Saba, Thomas M.

    1982-01-01

    Opsonic fibronectin is known to modulate macrophage (RE cell) and neutrophil Phagocytic function. Its depletion has been documented following trauma, burn, and operation in patients with rapid restoration of normal levels unless bacteremia and/or wound sepsis intervenes. Sepsis is associated with a secondary phase of opsonic fibronectin deficiency. We have observed in burn patients that this secondary phase of opsonic fibronectin depletion following trauma and burn is seen two to three days prior to the onset of clinical sepsis, raising the question of whether this deficiency sensitized the host to the subsequent development of sepsis or whether its deplection was merely an unsuspected sensitive indication of preclinical sepsis. To address the possibility that opsonic fibronectin deficiency might lower resistance to sepsis, Sprague-Dawley rats (200 gm) were partially depleted (35%) of their opsonic fibronectin prior to intraperitoneal inoculation with Staphylococcus aureus. Mortality to S. aureus peritonitis was significantly (p < 0.05) increased in animals with fibronectin deficiency. Furthermore, in control animals, nonsurvival was also associated with significantly (p < 0.05) lower initial fibronectin levels than survival. However, peritonitis itself also resulted in an early (within one hour) depletion of opsonic fibronectin followed by a marked “hyperopsonemia” within 12 hours in both groups. Thus, opsonic fibronectin depletion decreases resistance to sepsis, and the development of sepsis itself will initiate opsonic fibronectin deficiency. Host defense against infection may depend on early restoration and maintenance of normal opsonic fibronectin levels following trauma, burn, and operation, as well as the ability of the host to mount an appropriate hyperopsonemic elevation of fibronectin levels in response to infection. PMID:7059244

  7. Development and Validation of an Automated Sepsis Risk Assessment System.

    PubMed

    Back, Ji-Sun; Jin, Yinji; Jin, Taixian; Lee, Sun-Mi

    2016-10-01

    Aggressive resuscitation can decrease sepsis mortality, but its success depends on early detection of sepsis. The purpose of this study was to develop and verify an Automated Sepsis Risk Assessment System (Auto-SepRAS), which would automatically assess the sepsis risk of inpatients by applying data mining techniques to electronic health records (EHR) data and provide daily updates. The seven predictors included in the Auto-SepRAS after initial analysis were admission via the emergency department, which had the highest odds ratio; diastolic blood pressure; length of stay; respiratory rate; heart rate; and age. Auto-SepRAS classifies inpatients into three risk levels (high, moderate, and low) based on the predictive values from the sepsis risk-scoring algorithm. The sepsis risk for each patient is presented on the nursing screen of the EHR. The AutoSepRAS was implemented retrospectively in several stages using EHR data and its cut-off scores adjusted. Overall discrimination power was moderate (AUC>.80). The Auto-SepRAS should be verified or updated continuously or intermittently to maintain high predictive performance, but it does not require invasive tests or data input by nurses that would require additional time. Nurses are able to provide patients with nursing care appropriate to their risk levels by using the sepsis risk information provided by the Auto-SepRAS. In particular, with early detection of changes related to sepsis, nurses should be able to help in providing rapid initial resuscitation of high-risk patients. © 2016 Wiley Periodicals, Inc.

  8. Functional outcomes of general medical patients with severe sepsis

    PubMed Central

    2013-01-01

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

  9. Manatí Medical Center Sepsis Management Epidemiological Study.

    PubMed

    Morales Serrano, Tamara; Ramos, Shirley; Lara Gonzalez, Yanira; Torres Colberg, Heileene; Vera Quiñones, Alexis; Miranda Santiago, Roberto; Amill, Samuel; Otero, Marielys; Cintron, Vielka; Villarreal Morales, Martha Lissete

    2015-01-01

    Sepsis is the combination of infection and physiological changes known as the systemic inflammatory response syndrome. There have been improvements in mortality rates and outcomes of septic patients based on "Surviving Sepsis Campaign" guidelines. Current management of sepsis at our Institution follows no specific mandatory protocols. This study aimed to verify the incidence and outcome of sepsis in Manati Medical Center, Puerto Rico. An observational retrospective study was conducted. All the Emergency Department admissions from May 1/ to October 31/ 2013 were screened for sepsis per ICD-9 code. For all included patients, demographic and clinical data at ED admission were collected. During this period 8931 patients were admitted and 148 met criteria for sepsis and related conditions. The overall mortality rate was 43.91%. Mortality increased with age, from 10.52% among ≤ 44 years old to 68.75% in those ≥ 85 years old. The main infection sources were respiratory (32.66%) and urinary tract (24.62%). Mean age among non-survivors was 10.8 years higher than the survivor group (95% Cl 5.2-1 6.5, p < 0.05). Multivariate analysis showed an increased fatality rate associated to severity of sepsis (HR 1.33; 95% Cl; 1.03-1.72, p = 0.02) and the APACHE2 score (HR 1.05; 95% Cl, 1.01-1.09 p = 0.03). Our data suggests that sepsis is an important problem to consider. We strongly encourage an institutional standardized protocol to diminish the mortality impact. Our results will allow adequate preventive strategies to improve early diagnosis, mortality rates and outcomes of septic patients.

  10. 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

  11. NUTRITION THERAPY IN SEPSIS: CHARACTERIZATION AND IMPLICATIONS FOR CLINICAL PROGNOSIS.

    PubMed

    Machado, Raquel Rodrigues Campos; Caruso, Lúcia; Lima, Patricia de Azevedo; Damasceno, Nágila Raquel Teixeira; Soriano, Francisco Garcia

    2015-09-01

    Introducción: la respuesta inflamatoria causada por sepsis provoca cambios metabolicos que pueden provocar una perdida de masa magra significativa en pacientes septicos. Debido a ello, cuando el tracto digestivo es funcional la terapia nutricional (NT) debe iniciarse dentro de las 48 horas de tratamiento intensivo para reducir la perdida de proteina. Objetivo: evaluar la terapia nutricional enteral (TNE) en pacientes septicos adultos con TNE exclusivo para ≥ 72 horas y duracion de ≥ 7 dias de estancia en la Unidad de Cuidados Intensivos y su relacion con el pronostico clinico. Métodos: se analizaron prospectivamente la adecuacion de la nutricion enteral administrada, los factores asociados con la falta de conformidad, la tolerancia gastrointestinal y el resultado. Se utilizaron pruebas estadisticas de chi-cuadrado y la t de Student, asi como las correlaciones de Mann-Whitney y Spearman y Pearson (p < 0,05). Se ha realizado un modelo de regresion logistica multiple mediante el metodo paso a paso para evaluar la asociacion entre factores de prediccion de la evolucion clinica. Resultados: 53 pacientes, 67,9% hombres y 52,8% ancianos se inscribieron en este estudio. El tiempo promedio para el inicio de ENT fue de 30 (23,5) horas, y el 88,7% de los pacientes alcanzaron el objetivo nutricional en 48 horas. El volumen medio entregado en relacion con el prescrito fue 78,9%. Cuando la muestra se estratifico segun calorias prescritas/administradas, los pacientes que recibieron < 80% tenian una tasa de mortalidad mas alta (p = 0,001) y el consumo de calorias ≥ 80% fue el factor determinante en el pronostico clinico de los pacientes (p = 0,021). Conclusión: los pacientes septicos recibieron nutricion enteral precoz. El objetivo nutricional y el volumen medio entregado en relacion con el volumen prescrito cumplen las directrices de cuidados intensivos. El soporte nutricional se asocio con el resultado clinico y la ingesta calorica ≥ 80% para determinar el pronostico

  12. 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

  13. Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability

    PubMed Central

    Li, Yicong; Hadden, Coedy; Cooper, Anthonya; Ahmed, Asli; Wu, Hong; Lupashin, Vladimir V.; Mayeux, Philip R.; Kilic, Fusun

    2016-01-01

    Hyperpermeability of the endothelial barrier and resulting microvascular leakage are a hallmark of sepsis. Our studies describe the mechanism by which serotonin (5-HT) regulates the microvascular permeability during sepsis. The plasma 5-HT levels are significantly elevated in mice made septic by cecal ligation and puncture (CLP). 5-HT-induced permeability of endothelial cells was associated with the phosphorylation of p21 activating kinase (PAK1), PAK1-dependent phosphorylation of vimentin (P-vimentin) filaments, and a strong association between P-vimentin and ve-cadherin. These findings were in good agreement with the findings with the endothelial cells incubated in serum from CLP mice. In vivo, reducing the 5-HT uptake rates with the 5-HT transporter (SERT) inhibitor, paroxetine blocked renal microvascular leakage and the decline in microvascular perfusion. Importantly, mice that lack SERT showed significantly less microvascular dysfunction after CLP. Based on these data, we propose that the increased endothelial 5-HT uptake together with 5-HT signaling disrupts the endothelial barrier function in sepsis. Therefore, regulating intracellular 5-HT levels in endothelial cells represents a novel approach in improving sepsis-associated microvascular dysfunction and leakage. These new findings advance our understanding of the mechanisms underlying cellular responses to intracellular/extracellular 5-HT ratio in sepsis and refine current views of these signaling processes during sepsis. PMID:26956613

  14. Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability.

    PubMed

    Li, Yicong; Hadden, Coedy; Cooper, Anthonya; Ahmed, Asli; Wu, Hong; Lupashin, Vladimir V; Mayeux, Philip R; Kilic, Fusun

    2016-01-01

    Hyperpermeability of the endothelial barrier and resulting microvascular leakage are a hallmark of sepsis. Our studies describe the mechanism by which serotonin (5-HT) regulates the microvascular permeability during sepsis. The plasma 5-HT levels are significantly elevated in mice made septic by cecal ligation and puncture (CLP). 5-HT-induced permeability of endothelial cells was associated with the phosphorylation of p21 activating kinase (PAK1), PAK1-dependent phosphorylation of vimentin (P-vimentin) filaments, and a strong association between P-vimentin and ve-cadherin. These findings were in good agreement with the findings with the endothelial cells incubated in serum from CLP mice. In vivo, reducing the 5-HT uptake rates with the 5-HT transporter (SERT) inhibitor, paroxetine blocked renal microvascular leakage and the decline in microvascular perfusion. Importantly, mice that lack SERT showed significantly less microvascular dysfunction after CLP. Based on these data, we propose that the increased endothelial 5-HT uptake together with 5-HT signaling disrupts the endothelial barrier function in sepsis. Therefore, regulating intracellular 5-HT levels in endothelial cells represents a novel approach in improving sepsis-associated microvascular dysfunction and leakage. These new findings advance our understanding of the mechanisms underlying cellular responses to intracellular/extracellular 5-HT ratio in sepsis and refine current views of these signaling processes during sepsis.

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

    PubMed Central

    Mohsen, Abdel Hakeem Abdel; Kamel, Bothina Ahmed

    2015-01-01

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

  16. Circulating MicroRNAs as Biomarkers for Sepsis.

    PubMed

    Benz, Fabian; Roy, Sanchari; Trautwein, Christian; Roderburg, Christoph; Luedde, Tom

    2016-01-09

    Sepsis represents a major cause of lethality during intensive care unit (ICU) treatment. Pharmacological treatment strategies for sepsis are still limited and mainly based on the early initiation of antibiotic and supportive treatment. In this context, numerous clinical and serum based markers have been evaluated for the diagnosis, the severity, and the etiology of sepsis. However until now, few of these factors could be translated into clinical use. MicroRNAs (miRNAs) do not encode for proteins but regulate gene expression by inhibiting the translation or transcription of their target mRNAs. Recently it was demonstrated that miRNAs are released into the circulation and that the spectrum of circulating miRNAs might be altered during various pathologic conditions, such as inflammation, infection, and sepsis. By using array- and single PCR-based methods, a variety of deregulated miRNAs, including miR-25, miR-133a, miR-146, miR-150, and miR-223, were described in the context of sepsis. Some of the miRNAs correlated with the disease stage, as well as patients' short and long term prognosis. Here, we summarize the current findings on the role of circulating miRNAs in the diagnosis and staging of sepsis in critically ill patients. We compare data from patients with findings from animal models and, finally, highlight the challenges and drawbacks that currently prevent the use of circulating miRNAs as biomarkers in clinical routine.

  17. HMGB1 Mediates Anemia of Inflammation in Murine Sepsis Survivors

    PubMed Central

    Valdés-Ferrer, Sergio I; Papoin, Julien; Dancho, Meghan E; Olofsson, Peder S; Li, Jianhua; Lipton, Jeffrey M; Avancena, Patricia; Yang, Huan; Zou, Yong-Rui; Chavan, Sangeeta S; Volpe, Bruce T; Gardenghi, Sara; Rivella, Stefano; Diamond, Betty; Andersson, Ulf; Steinberg, Bettie M; Blanc, Lionel; Tracey, Kevin J

    2015-01-01

    Patients surviving sepsis develop anemia, but the molecular mechanism is unknown. Here we observed that mice surviving polymicrobial gram-negative sepsis develop hypochromic, microcytic anemia with reticulocytosis. The bone marrow of sepsis survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in the spleen is defective during terminal differentiation. Circulating tumor necrosis factor (TNF) and interleukin (IL)-6 are elevated for 5 d after the onset of sepsis, and serum high-mobility group box 1 (HMGB1) levels are increased from d 7 until at least d 28. Administration of recombinant HMGB1 to healthy mice mediates anemia with extramedullary erythropoiesis and significantly elevated reticulocyte counts. Moreover, administration of anti-HMGB1 monoclonal antibodies after sepsis significantly ameliorates the development of anemia (hematocrit 48.5 ± 9.0% versus 37.4 ± 6.1%, p < 0.01; hemoglobin 14.0 ± 1.7 versus 11.7 ± 1.2 g/dL, p < 0.01). Together, these results indicate that HMGB1 mediates anemia by interfering with erythropoiesis, suggesting a potential therapeutic strategy for anemia in sepsis. PMID:26736178

  18. Improving time to antibiotics and implementing the "Sepsis 6".

    PubMed

    McGregor, Calum

    2014-01-01

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

  19. Identification of adults with sepsis in the prehospital environment: a systematic review

    PubMed Central

    Smyth, Michael A; Brace-McDonnell, Samantha J; Perkins, Gavin D

    2016-01-01

    Objective Early identification of sepsis could enable prompt delivery of key interventions such as fluid resuscitation and antibiotic administration which, in turn, may lead to improved patient outcomes. Limited data indicate that recognition of sepsis by paramedics is often poor. We systematically reviewed the literature on prehospital sepsis screening tools to determine whether they improved sepsis recognition. Design Systematic review. The electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed were systematically searched up to June 2015. In addition, subject experts were contacted. Setting Prehospital/emergency medical services (EMS). Study selection All studies addressing identification of sepsis (including severe sepsis and septic shock) among adult patients managed by EMS. Outcome measures Recognition of sepsis by EMS clinicians. Results Owing to considerable variation in the methodological approach adopted and outcome measures reported, a narrative approach to data synthesis was adopted. Three studies addressed development of prehospital sepsis screening tools. Six studies addressed paramedic diagnosis of sepsis with or without use of a prehospital sepsis screening tool. Conclusions Recognition of sepsis by ambulance clinicians is poor. The use of screening tools, based on the Surviving Sepsis Campaign diagnostic criteria, improves prehospital sepsis recognition. Screening tools derived from EMS data have been developed, but they have not yet been validated in clinical practice. There is a need to undertake validation studies to determine whether prehospital sepsis screening tools confer any clinical benefit. PMID:27496231

  20. 21 CFR 866.3740 - Streptococcus spp. serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus spp. serological reagents. (a) Identification. Streptococcus spp. serological reagents are devices... streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by...

  1. 21 CFR 866.3740 - Streptococcus spp. serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus spp. serological reagents. (a) Identification. Streptococcus spp. serological reagents are devices... streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by...

  2. Galactokinase activity in Streptococcus thermophilus

    SciTech Connect

    Hutkins, R.; Morris, H.A.; McKay, L.L.

    1985-10-01

    ATP-dependent phosphorylation of (/sup 14/C)galactose by 11 strains of streptococcus thermophilus indicated that these organisms possessed the Leloir enzyme, galactokinase (galK). Activities were 10 times higher in fully induced, galactose-fermenting (Gal/sup +/) strains than in galactose-nonfermenting (Gal/sup -/) strains. Lactose-grown, Gal/sup -/ cells released free galactose into the medium and were unable to utilize residual galactose or to induce galK above basal levels. Gal/sup +/ S. thermophilus 19258 also released galactose into the medium, but when lactose was depleted, growth on galactose commenced, and galK increased from 0.025 to 0.22 ..mu..mol of galactose phosphorylated per min per mg of protein. When lactose was added to galactose-grown cells of S. thermophilus 19258, galK activity rapidly decreased. These results suggest that galK in Gal/sup +/ S. thermophilus is subject to an induction-repression mechanism, but that galK cannot be induced in Gal/sup -/ strains.

  3. Macrolide Resistance in Streptococcus pneumoniae

    PubMed Central

    Schroeder, Max R.; Stephens, David S.

    2016-01-01

    Streptococcus pneumoniae is a common commensal and an opportunistic pathogen. Suspected pneumococcal upper respiratory infections and pneumonia are often treated with macrolide antibiotics. Macrolides are bacteriostatic antibiotics and inhibit protein synthesis by binding to the 50S ribosomal subunit. The widespread use of macrolides is associated with increased macrolide resistance in S. pneumoniae, and the treatment of pneumococcal infections with macrolides may be associated with clinical failures. In S. pneumoniae, macrolide resistance is due to ribosomal dimethylation by an enzyme encoded by erm(B), efflux by a two-component efflux pump encoded by mef (E)/mel(msr(D)) and, less commonly, mutations of the ribosomal target site of macrolides. A wide array of genetic elements have emerged that facilitate macrolide resistance in S. pneumoniae; for example erm(B) is found on Tn917, while the mef (E)/mel operon is carried on the 5.4- or 5.5-kb Mega element. The macrolide resistance determinants, erm(B) and mef (E)/mel, are also found on large composite Tn916-like elements most notably Tn6002, Tn2009, and Tn2010. Introductions of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV-7 and PCV-13) have decreased the incidence of macrolide-resistant invasive pneumococcal disease, but serotype replacement and emergence of macrolide resistance remain an important concern. PMID:27709102

  4. Streptococcus orisasini sp. nov. and Streptococcus dentasini sp. nov., isolated from the oral cavity of donkeys.

    PubMed

    Takada, Kazuko; Saito, Masanori; Tsudukibashi, Osamu; Hiroi, Takachika; Hirasawa, Masatomo

    2013-08-01

    Four Gram-positive, catalase-negative, coccoid isolates that were obtained from donkey oral cavities formed two distinct clonal groups when characterized by phenotypic and phylogenetic studies. From the results of biochemical tests, the organisms were tentatively identified as a streptococcal species. Comparative 16S rRNA gene sequencing studies confirmed the organisms to be members of the genus Streptococcus. Two of the isolates were related most closely to Streptococcus ursoris with 95.6 % similarity based on the 16S rRNA gene and to Streptococcus ratti with 92.0 % similarity based on the 60 kDa heat-shock protein gene (groEL). The other two isolates, however, were related to Streptococcus criceti with 95.0 and 89.0 % similarities based on the 16S rRNA and groEL genes, respectively. From both phylogenetic and phenotypic evidence, the four isolates formed two distinct clonal groups and are suggested to represent novel species of the genus Streptococcus. The names proposed for these organisms are Streptococcus orisasini sp. nov. (type strain NUM 1801(T) = JCM 17942(T) = DSM 25193(T)) and Streptococcus dentasini sp. nov. (type strain NUM 1808(T) = JCM 17943(T) = DSM 25137(T)).

  5. Distribution of Streptococcus troglodytae and Streptococcus dentirousetti in chimpanzee oral cavities.

    PubMed

    Miyanohara, Mayu; Imai, Susumu; Okamoto, Masaaki; Saito, Wataru; Nomura, Yoshiaki; Momoi, Yasuko; Tomonaga, Masaki; Hanada, Nobuhiro

    2013-05-01

    The aim of this study was to analyze the distribution and phenotypic properties of the indigenous streptococci in chimpanzee (Pan troglodytes) oral cavities. Eleven chimpanzees (aged from 9 to 44 years, mean ± SD, 26.9 ± 12.6 years) in the Primate Research Institute of Kyoto University were enrolled in this research and brushing bacterial samples collected from them. Streptococci were isolated from the oral cavities of all chimpanzees. The isolates (n = 46) were identified as thirteen species by 16S rRNA genes analysis. The predominant species was Streptococcus sanguinis of mitis streptococci from five chimpanzees (45%). Mutans streptococci were isolated from six chimpanzees (55%). The predominant species in the mutans streptococci were Streptococcus troglodytae from four chimpanzees (36%), this species having been proposed as a novel species by us, and Streptococcus dentirousetti from three chimpanzees (27%). Streptococcus mutans was isolated from one chimpanzee (9%). However, Streptococcus sobrinus, Streptococcus macacae and Streptococcus downei, which are indigenous to human and monkey (Macaca fasciclaris) oral habitats, were not isolated. Of the mutans streptococci, S. troglodytae, S. dentirousetti, and S. mutans possessed strong adherence activity to glass surface.

  6. Late-onset neonatal sepsis: recent developments

    PubMed Central

    Dong, Ying; Speer, Christian P

    2015-01-01

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

  7. [Immunology and sepsis syndrome in burn trauma].

    PubMed

    Ipaktchi, K; Vogt, P M

    2009-05-01

    Despite significant advances in burn surgery and critical care, severe burn trauma defined as injuries covering more than 25% of the total body surface area, is still associated with high mortality and morbidity. Burn trauma is a whole body injury where peripheral dermal injury rapidly results in systemic inflammation and inflammatory core organ damage. The severe disturbance of internal homeostasis involves all vital organ systems and obligates early referral to specialized burn centers. Treatment of severely burned patients is a multifaceted challenge directed by pathophysiologic events which progress from local skin destruction, disruption of physicochemical and microvascular barriers to breakdown of peripheral and central circulation, organ failure and ultimately death. While early intensive care focuses on maintenance of tissue oxygenation and perfusion, surgical treatment deals with management of the burn wounds as a source of inflammation and infection. Here wound debridement and coverage is essential to abrogate systemic effects of inflammation and limit pathogen invasion. While control of early burn stages minimizes mortality due to burn shock, subsequent burn sepsis continues to be a formidable challenge for physicians and the main cause of burn mortality.

  8. 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.

  9. ATP-driven calcium transport in membrane vesicles of Streptococcus sanguis. [Streptococcus sanguis; Streptococcus faecalis; Escherichia coli

    SciTech Connect

    Houng, H.; Lynn, A.R.; Rosen, B.P.

    1986-11-01

    Calcium transport was investigated in membrane vesicles prepared from the oral bacterium Streptococcus sanguis. Procedures were devised for the preparation of membrane vesicles capable of accumulation /sup 45/Ca/sup 2 +/. Uptake was ATP dependent and did not require a proton motive force. Calcium transport in these vesicles was compared with /sup 45/Ca/sup 2 +/ accumulation in membrane vesicles from Streptococcus faecalis and Escherichia coli. The data support the existence of an ATP-driven calcium pump in S. sanguis similar to that in S. faecalis. This pump, which catalyzes uptake into membrane vesicles, would be responsible for extrusion of calcium from intact cells.

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

    PubMed Central

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

    2009-01-01

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

  11. Serum Procalcitonine Levels as an Early Diagnostic Indicator of Sepsis

    PubMed Central

    Beqja-Lika, Anila; Bulo-Kasneci, Anyla; Refatllari, Etleva; Heta-Alliu, Nevila; Rucaj-Barbullushi, Alma; Mone, Iris; Mitre, Anila

    2013-01-01

    Introduction: Prompt and accurate diagnosis of sepsis is of high importance for clinicians. Procalcitonine (PCT) and C-reactive protein (CRP) have been proposed as markers for this purpose. Our aim was to evaluate the levels of PCT and CRP in early sepsis and its correlation with severity of sepsis. Methods: Levels of PCT and CRP were taken from 60 patients with sepsis criteria and 39 patients with SIRS symptoms from the University Hospital Center “Mother Teresa” in Tirana, Albania during 2010-2012. Sensitivity, specificity and predictive values for PCT and CRP were calculated. Results: PCT and CRP levels increased in parallel with the severity of the clinical conditions of the patients. The mean PCT level in patients with sepsis was 11.28 ng/ml versus 0.272 ng/ml in patients with SIRS symptoms, with a sensitivity of 97.4% and a specificity of 96.6% for PCT >0.5ng/ml. The mean CRP level in septic patients was 146.58 mg/l vs. 34.4 mg/l in patients with SIRS, with a sensitivity of 98.6% for sepsis and a specificity of 75 % for CRP >11mg/l. Conclusion: PCT and CRP values are useful markers to determine early diagnosis and severity of an infection. In the present study, PCT was found to be a more accurate diagnostic parameter for differentiating SIRS from sepsis and may be helpful in the follow-up of critically ill patients. PMID:23687457

  12. Impact of sepsis on CD4 T cell immunity

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-07-01

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

  15. Global fibrinolytic capacity in pediatric patients with sepsis and disseminated intravascular coagulation.

    PubMed

    Bay, Ali; Oner, Ahmet Faik; Kose, Dogan; Dogan, Murat

    2006-10-01

    There are many complex pathophysiologic changes of the coagulation system in sepsis. The fibrinolytic system was evaluated in septic children using the global fibrinolytic capacity (GFC), a new technique reflecting the overall fibrinolytic activity. The study consisted of 24 children with sepsis, 36 children with sepsis plus disseminated intravascular coagulation (DIC), and 20 healthy age-matched control individuals. Compared with controls, 86% of sepsis patients and 87% of sepsis plus DIC patients had decreased GFC levels. Between the sepsis plus DIC and sepsis groups there was no significant difference in terms of GFC levels. While 19 patients (52.7%) died in the sepsis plus DIC group, only three patients (12.5%) died in the sepsis group. When survivors and nonsurvivors were compared in terms of coagulation tests, there were significant differences for protein C, antithrombin, platelet, fibrinogen, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and white blood cell values. In conclusion, the level of GFC reduced in most of the pediatric sepsis patients but no difference was observed between patients with sepsis and patients with sepsis plus DIC. While inhibition of fibrinolysis is an important finding in sepsis, the mortality is mainly associated with the presence of end-organ damage and the status of coagulation parameters.

  16. Biomarkers of endothelial cell activation in early sepsis

    PubMed Central

    Skibsted, Simon; Jones, Alan E; Puskarich, Michael A.; Arnold, Ryan; Sherwin, Robert; Trzeciak, Stephen; Schuetz, Philipp; Aird, William C.; Shapiro, Nathan I

    2013-01-01

    PURPOSE To investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that: 1) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis; and, that sFlt-1, holds promise as novel prognostic markers in sepsis. METHODS A prospective, multicenter, observational study of a convenience sample of Emergency Department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED, and subsequently assayed endothelial-related biomarkers, namely sFlt-1, sE-Selectin, sICAM-1, sVCAM-1, and PAI-1. Outcomes were organ dysfunction and in-hospital mortality. RESULTS We enrolled at a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%) and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant inter-correlation between all biomarkers, strongest between sFlt1 and PAI-1 (r=0.61, P < 0.001) and PAI-1 and sE-selectin and sICAM-1 (r=0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with SOFA score (r=0.58, P < 0.001). sFlt-1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87. CONCLUSIONS This multi-center validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. Additionally, sFLT-1 holds promise as a novel sepsis severity biomarker. PMID:23524845

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

    PubMed

    Lee, Soon Min; Chang, Meayoung; Kim, Ki-Soo

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

    Sepsis is a common condition with a major global impact on healthcare resources and expenditure. The Surviving Sepsis Campaign has been vigorous in promoting internationally recognised pathways to improve the management of septic patients and decrease mortality. However, translating recommendations into practice is a challenging and complex task that requires a multi-faceted approach with sustained engagement from local stakeholders. Whilst working at a district general hospital in New Zealand, we were concerned by the seemingly inconsistent management of septic patients, often leading to long delays in the initiation of life-saving measures such as antibiotic, fluid, and oxygen administration. In our hospital there were no clear systems, protocols or guidelines in place for identifying and managing septic patients. We therefore launched the Sepsis Six resuscitation bundle of care in our hospital in an attempt to raise awareness amongst staff and improve the management of septic patients. We introduced a number of simple low-cost interventions that included educational sessions for junior doctors and nursing staff, as well as posters and modifications to phlebotomy trolleys that acted as visual reminders to implement the Sepsis Six bundle. Overall, we found there to a be a steady improvement in the delivery of the Sepsis Six bundle in septic patients with 63% of patients receiving appropriate care within one hour, compared to 29% prior to our interventions. However this did not translate to an improvement in patient mortality. This project forms part of an on going process to instigate a fundamental culture change among local healthcare professionals regarding the management of sepsis. Whilst we have demonstrated improved implementation of the Sepsis Six bundle, the key challenge remains to ensure that momentum of this project continues and forms a platform for sustainable clinical improvement in the long term. PMID:26734403

  19. Galactose metabolism by Streptococcus mutans.

    PubMed

    Abranches, Jacqueline; Chen, Yi-Ywan M; Burne, Robert A

    2004-10-01

    The galK gene, encoding galactokinase of the Leloir pathway, was insertionally inactivated in Streptococcus mutans UA159. The galK knockout strain displayed only marginal growth on galactose, but growth on glucose or lactose was not affected. In strain UA159, the sugar phosphotransferase system (PTS) for lactose and the PTS for galactose were induced by growth in lactose and galactose, although galactose PTS activity was very low, suggesting that S. mutans does not have a galactose-specific PTS and that the lactose PTS may transport galactose, albeit poorly. To determine if the galactose growth defect of the galK mutant could be overcome by enhancing lactose PTS activity, the gene encoding a putative repressor of the operon for lactose PTS and phospho-beta-galactosidase, lacR, was insertionally inactivated. A galK and lacR mutant still could not grow on galactose, although the strain had constitutively elevated lactose PTS activity. The glucose PTS activity of lacR mutants grown in glucose was lower than in the wild-type strain, revealing an influence of LacR or the lactose PTS on the regulation of the glucose PTS. Mutation of the lacA gene of the tagatose pathway caused impaired growth in lactose and galactose, suggesting that galactose can only be efficiently utilized when both the Leloir and tagatose pathways are functional. A mutation of the permease in the multiple sugar metabolism operon did not affect growth on galactose. Thus, the galactose permease of S. mutans is not present in the gal, lac, or msm operons. PMID:15466549

  20. Streptococcus pneumoniae NanC

    PubMed Central

    Owen, C. David; Lukacik, Petra; Potter, Jane A.; Sleator, Olivia; Taylor, Garry L.; Walsh, Martin A.

    2015-01-01

    Streptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from α2–3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-β-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind α2–3- and α2–6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold. PMID:26370075

  1. Iron acquisition and regulation systems in Streptococcus species.

    PubMed

    Ge, Ruiguang; Sun, Xuesong

    2014-05-01

    Gram-positive Streptococcus species are responsible for millions of cases of meningitis, bacterial pneumonia, endocarditis, erysipelas and necrotizing fasciitis. Iron is essential for the growth and survival of Streptococcus in the host environment. Streptococcus species have developed various mechanisms to uptake iron from an environment with limited available iron. Streptococcus can directly extract iron from host iron-containing proteins such as ferritin, transferrin, lactoferrin and hemoproteins, or indirectly by relying on the employment of specialized secreted hemophores (heme chelators) and small siderophore molecules (high affinity ferric chelators). This review presents the most recent discoveries in the iron acquisition system of Streptococcus species - the transporters as well as the regulators.

  2. A clinical perspective of sepsis-associated delirium.

    PubMed

    Tsuruta, Ryosuke; Oda, Yasutaka

    2016-01-01

    The term sepsis-associated encephalopathy (SAE) has been applied to animal models, postmortem studies in patients, and severe cases of sepsis. SAE is considered to include all types of brain dysfunction, including delirium, coma, seizure, and focal neurological signs. Clinical data for sepsis-associated delirium (SAD) have been accumulating since the establishment of definitions of coma or delirium and the introduction of validated screening tools. Some preliminary studies have examined the etiology of SAD. Neuroinflammation, abnormal cerebral perfusion, and neurotransmitter imbalances are the main mechanisms underlying the development of SAD. However, there are still no specific diagnostic blood, electrophysiological, or imaging tests or treatments specific for SAD. The duration of delirium in intensive care patients is associated with long-term functional disability and cognitive impairment, although this syndrome usually reverses after the successful treatment of sepsis. Once the respiratory and hemodynamic states are stabilized, patients with severe sepsis or septic shock should receive rehabilitation as soon as possible because early initiation of rehabilitation can reduce the duration of delirium. We expect to see further pathophysiological data and the development of novel treatments for SAD now that reliable and consistent definitions of SAD have been established. PMID:27011789

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

    PubMed

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

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

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

    PubMed

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

    1992-07-01

    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.

  5. The role of MBL2 gene polymorphism in sepsis incidence

    PubMed Central

    Liu, Lei; Ning, Bo

    2015-01-01

    Aim: This case-control study was aimed to explore the role of mannose-binding lectin 2 (MBL2) gene rs1800450 polymorphism (codon 54 A/B, G230A) in the development of sepsis in Han Chinese. Methods: MBL2 rs1800450 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MBL serum level was detected by enzyme-linked immunosorbent assay (ELISA). Associations between rs1800450 and sepsis susceptibility was detected by Chi-square test and represented by odds ratios (ORs) and 95% confidence intervals (CIs). Correlation of rs1800450 genotypes and MBL serum level was assessed using t test. Result: Variant A allele frequency was significantly observed in cases than that in controls, indicating a significant association with the susceptibility of sepsis (OR = 1.979, 95% CI = 1.200-3.262). GA genotype also relate to the onset of sepsis (OR = 2.090, 95% CI = 1.163-3.753). MBL serum concentrations were significantly different between case and control groups (P<0.001). Meanwhile, variant allele carriers had lower serum level compared with wild homozygous (P<0.001). Conclusion: Variant A allele in MBL2 gene rs1800450 polymorphism might increase the risk of sepsis via decrease the MBL serum level. PMID:26823854

  6. Impaired Granuloma Formation in Sepsis: Impact of Monocytopenia

    PubMed Central

    Alingrin, Julie; Coiffard, Benjamin; Textoris, Julien; Belenotti, Pauline; Daumas, Aurélie; Leone, Marc; Mege, Jean-Louis

    2016-01-01

    Granulomas are a collection of immune cells considered to be protective in infectious diseases. The in vitro generation of granulomas is an interesting substitution to invasive approaches of granuloma study. The monitoring of immune response through the determination of in vitro granuloma formation in patients with severe sepsis may be critical to individualize treatments. We compared the in vitro generation of granulomas by co-culturing circulating mononuclear cells from 19 patients with severe sepsis, 9 patients cured from Q fever and 12 healthy subjects as controls, and Sepharose beads coated either with BCG or Coxiella burnetii extracts to analyze both immune and innate granulomas, respectively. We showed that the great majority of patients with severe sepsis were unable to form granulomas in response to BCG and C. burnetii extracts whereas more than 80% of healthy controls and patients cured from Q fever formed granulomas. We also found that monocytopenia and defective production of tumor necrosis factor were associated with reduced formation of granulomas in patients with severe sepsis even if TNF did not seem to be involved in the defective granuloma formation. Taken together, these results suggest that the deficiency of granuloma formation may be a measurement of altered recruitment and activation of monocytes and lymphocytes in patients with severe sepsis. PMID:27441846

  7. Multi-analytical Approaches Informing the Risk of Sepsis

    NASA Astrophysics Data System (ADS)

    Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael

    Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.

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

    PubMed

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

    2015-01-28

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

  9. Use of miRNAs as biomarkers in sepsis.

    PubMed

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

    2015-01-01

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

  10. [Usefulness of Presepsin Measurement: A New Biomarker for Sepsis].

    PubMed

    Okamura, Yoshikazu

    2015-01-01

    Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, and it is one of the major causes of mortality of critical care patients. Since it has been reported that early, optimal treatment of patients is important to reduce mortality from sepsis, a sepsis marker with a high sensitivity and specificity is required. Presepsin (P-SEP) was discovered as a new marker whose levels elevated specifically in the blood of patients with sepsis in Japan in 2002. Presepsin is a 13-kDa glycoprotein that is a truncated N-terminal fragment of CD14. Since one of the production mechanisms of presepsin is related to the phagocytosis of bacteria, the biological characteristics of presepsin are different from those of other inflammatory markers. Presepsin has three features in comparison with procalcitonin(PCT), C-reactive protein(CRP), and interleukin-6 (IL-6): 1) Presepsin can be detected earlier after the onset of infection; 2) Presepsin is not affected by severe trauma, severe burn, or invasive surgical procedures, which lead to SIRS, more than PCT, CRP, or IL-6; 3) Presepsin levels reflect the clinical condition of septic patients. Although clinical evidence is not sufficient at present, presepsin may be a strong tool for the development of novel treatment strategies for sepsis.

  11. Impaired Granuloma Formation in Sepsis: Impact of Monocytopenia.

    PubMed

    Alingrin, Julie; Coiffard, Benjamin; Textoris, Julien; Belenotti, Pauline; Daumas, Aurélie; Leone, Marc; Mege, Jean-Louis

    2016-01-01

    Granulomas are a collection of immune cells considered to be protective in infectious diseases. The in vitro generation of granulomas is an interesting substitution to invasive approaches of granuloma study. The monitoring of immune response through the determination of in vitro granuloma formation in patients with severe sepsis may be critical to individualize treatments. We compared the in vitro generation of granulomas by co-culturing circulating mononuclear cells from 19 patients with severe sepsis, 9 patients cured from Q fever and 12 healthy subjects as controls, and Sepharose beads coated either with BCG or Coxiella burnetii extracts to analyze both immune and innate granulomas, respectively. We showed that the great majority of patients with severe sepsis were unable to form granulomas in response to BCG and C. burnetii extracts whereas more than 80% of healthy controls and patients cured from Q fever formed granulomas. We also found that monocytopenia and defective production of tumor necrosis factor were associated with reduced formation of granulomas in patients with severe sepsis even if TNF did not seem to be involved in the defective granuloma formation. Taken together, these results suggest that the deficiency of granuloma formation may be a measurement of altered recruitment and activation of monocytes and lymphocytes in patients with severe sepsis. PMID:27441846

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

    PubMed Central

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

    2013-01-01

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

  13. [Real-time PCR detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae DNA in clinical specimens].

    PubMed

    Vacková, Z; Lžičařová, D; Stock, N K; Kozáková, J

    2015-10-01

    The study aim was to implement a molecular real-time polymerase chain reaction (PCR) assay recommended by the CDC (Centers for Disease Control and Prevention) for the detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical (culture negative) specimens from patients with suspected invasive bacterial disease. Clinical specimens are referred to the National Reference Laboratory (NRL) for Meningococcal Infections, Unit for Airborne Bacterial Infections, Centre for Epidemiology and Microbiology, National Institute of Public Health from various regions of the Czech Republic. Clinical specimens are, in particular, cerebrospinal fluid, anti-coagulated blood or serum and, exceptionally, post-mortem specimens. The NRL has implemented molecular diagnosis of these bacterial pathogens involved in meningitis and sepsis from clinical specimens since 1999. The first diagnostic method was semi-nested PCR followed by electrophoretic analysis. In 2014, a molecular qualitative real-time PCR assay was implemented.

  14. In silico prediction of conserved vaccine targets in Streptococcus agalactiae strains isolated from fish, cattle, and human samples.

    PubMed

    Pereira, U P; Soares, S C; Blom, J; Leal, C A G; Ramos, R T J; Guimarães, L C; Oliveira, L C; Almeida, S S; Hassan, S S; Santos, A R; Miyoshi, A; Silva, A; Tauch, A; Barh, D; Azevedo, V; Figueiredo, H C P

    2013-01-01

    Streptococcus agalactiae (Lancefield group B; group B streptococci) is a major pathogen that causes meningoencephalitis in fish, mastitis in cows, and neonatal sepsis and meningitis in humans. The available prophylactic measures for conserving human and animal health are not totally effective and have limitations. Effective vaccines against the different serotypes or genotypes of pathogenic strains from the various hosts would be useful. We used an in silico strategy to identify conserved vaccine candidates in 15 genomes of group B streptococci strains isolated from human, bovine, and fish samples. The degree of conservation, subcellular localization, and immunogenic potential of S. agalactiae proteins were investigated. We identified 36 antigenic proteins that were conserved in all 15 genomes. Among these proteins, 5 and 23 were shared only by human or fish strains, respectively. These potential vaccine targets may help develop effective vaccines that will help prevent S. agalactiae infection. PMID:24065646

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

    PubMed Central

    Riley, Carley; Wheeler, Derek S.

    2012-01-01

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

  16. Australian Enterococcal Sepsis Outcome Progamme, 2011.

    PubMed

    Coombs, Geoffrey W; Pearson, Julie C; Le, Tam; Daly, Denise A; Robinson, James O; Gottlieb, Thomas; Howden, Benjamin P; Johnson, Paul D R; Bennett, Catherine M; Stinear, Timothy P; Turnidge, John D

    2014-09-01

    From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium. PMID:25391408

  17. Streptococcus tigurinus, a novel member of the Streptococcus mitis group, causes invasive infections.

    PubMed

    Zbinden, Andrea; Mueller, Nicolas J; Tarr, Philip E; Eich, Gerhard; Schulthess, Bettina; Bahlmann, Anna S; Keller, Peter M; Bloemberg, Guido V

    2012-09-01

    We recently described the novel species Streptococcus tigurinus sp. nov. belonging to the Streptococcus mitis group. The type strain AZ_3a(T) of S. tigurinus was originally isolated from a patient with infective endocarditis. According to its phenotypic and molecular characteristics, S. tigurinus is most closely related to Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pseudopneumoniae, Streptococcus oralis, and Streptococcus infantis. Accurate identification of S. tigurinus is facilitated by 16S rRNA gene analysis. We retrospectively analyzed our 16S rRNA gene molecular database, which contains sequences of all clinical samples obtained in our institute since 2003. We detected 17 16S rRNA gene sequences which were assigned to S. tigurinus, including sequences from the 3 S. tigurinus strains described previously. S. tigurinus originated from normally sterile body sites, such as blood, cerebrospinal fluid, or heart valves, of 14 patients and was initially detected by culture or broad-range 16S rRNA gene PCR, followed by sequencing. The 14 patients had serious invasive infections, i.e., infective endocarditis (n = 6), spondylodiscitis (n = 3), bacteremia (n = 2), meningitis (n = 1), prosthetic joint infection (n = 1), and thoracic empyema (n = 1). To evaluate the presence of Streptococcus tigurinus in the endogenous oral microbial flora, we screened saliva specimens of 31 volunteers. After selective growth, alpha-hemolytic growing colonies were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and subsequent molecular methods. S. tigurinus was not identified among 608 strains analyzed. These data indicate that S. tigurinus is not widely distributed in the oral cavity. In conclusion, S. tigurinus is a novel agent of invasive infections, particularly infective endocarditis.

  18. Antagonistic action of Streptococcus salivarius and Streptococcus faecalis to Mycobacterium tuberculosis.

    PubMed Central

    Darling, C L; Hart, G D

    1976-01-01

    Streptococcus salivarius and Streptococcus faecalis were found to inhibit the growth of Mycobacterium tuberculosis on Löwenstein-Jensen and Middlebrook 7H11 agars, but not on the latter medium when antibacterial drugs were added. S. faecalis was found to be more inhibitory than S. salivarius to 15 strains of M. tuberculosis. S. salivarius produced little or no inhibition of growth of Runyon group III organisms but was very antagonistic to Runyon group I mycobacteria. Images PMID:824304

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

    PubMed

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

    1982-05-01

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

  20. [Reinstating cloxacilin for empiric antibiotic in late-onset sepsis].

    PubMed

    Sandoval, Alejandra; Cofré, Fernanda; Delpiano, Luis; Izquierdo, Giannina; Labraña, Yenis; Reyes, Alejandra

    2015-04-01

    Vancomycin has been used for more than 50 years in neonatal intensive care units (NICUs) as the therapy of choice for late-onset sepsis, mainly because Coagulase negative Staphylococci (CoNS) are common and mostly resistant to oxacyllin despitelow virulence and unusual association with fulminant sepsis. CUs due to several factors including its high pharmacokinetic variability, difficulty in reaching therapeutic plasmatic drug concentrations and progressively increasing minimum inhibitory concentrations (MIC). The increase of CoNS with higher MICs as well as the rise of infections caused by resistant gram-negative bacilli and candida should move to reconsider Vancomycin as first line treatment. Infections in neonates have a different behavior than in other populations and we consoder of utmost importance to consider the use of oxacyllin as first line antimicrobial therapy for late-onset sepsis. PMID:26065451

  1. Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis

    PubMed Central

    Liu, Lingling; Yu, Yonghao; Wang, Guolin

    2014-01-01

    Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-κB and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis. PMID:24829918

  2. Host response biomarkers in sepsis: the role of procalcitonin.

    PubMed

    Vincent, Jean-Louis; Van Nuffelen, Marc; Lelubre, Christophe

    2015-01-01

    Procalcitonin is the prohormone of calcitonin and present in minute quantities in health. However, during infection, its levels rise considerably and are correlated with the severity of the infection. Several assays have been developed for measurement of procalcitonin levels; in this article, we will briefly present the PCT-sensitive Kryptor(®) test (Brahms, Hennigsdorf, Germany), one of the most widely used assays for procalcitonin in recent studies. Many studies have demonstrated the value of procalcitonin levels for diagnosing sepsis and assessing disease severity. Procalcitonin levels have also been successfully used to guide antibiotic administration. However, procalcitonin is not specific for sepsis, and values need to be interpreted in the context of a full clinical examination and the presence of other signs and symptoms of sepsis.

  3. Streptococcus loxodontisalivarius sp. nov. and Streptococcus saliviloxodontae sp. nov., isolated from oral cavities of elephants.

    PubMed

    Saito, Masanori; Shinozaki-Kuwahara, Noriko; Hirasawa, Masatomo; Takada, Kazuko

    2014-09-01

    Four Gram-stain-positive, catalase-negative, coccoid-shaped organisms were isolated from elephant oral cavities. The isolates were tentatively identified as streptococcal species based on the results of biochemical tests. Comparative 16S rRNA gene sequencing studies confirmed the organisms to be members of the genus Streptococcus. Two isolates (NUM 6304(T) and NUM 6312) were related most closely to Streptococcus salivarius with 96.8 % and 93.1 % similarity based on the 16S rRNA gene and the RNA polymerase β subunit encoding gene (rpoB), respectively, and to Streptococcus vestibularis with 83.7 % similarity based on the 60 kDa heat-shock protein gene (groEL). The other two isolates (NUM 6306(T) and NUM 6318) were related most closely to S. vestibularis with 97.0 % and 82.9 % similarity based on the 16S rRNA and groEL genes, respectively, and to S. salivarius with 93.5 % similarity based on the rpoB gene. Based on phylogenetic and phenotypic evidence, these isolates are suggested to represent novel species of the genus Streptococcus, for which the names Streptococcus loxodontisalivarius sp. nov. (type strain NUM 6304(T) = JCM 19287(T) = DSM 27382(T)) and Streptococcus saliviloxodontae sp. nov. (type strain NUM 6306(T) = JCM 19288(T) = DSM 27513(T)) are proposed.

  4. Streptococcus moroccensis sp. nov. and Streptococcus rifensis sp. nov., isolated from raw camel milk.

    PubMed

    Kadri, Zaina; Amar, Mohamed; Ouadghiri, Mouna; Cnockaert, Margo; Aerts, Maarten; El Farricha, Omar; Vandamme, Peter

    2014-07-01

    Two catalase- and oxidase-negative Streptococcus-like strains, LMG 27682(T) and LMG 27684(T), were isolated from raw camel milk in Morocco. Comparative 16S rRNA gene sequencing assigned these bacteria to the genus Streptococcus with Streptococcus rupicaprae 2777-2-07(T) as their closest phylogenetic neighbour (95.9% and 95.7% similarity, respectively). 16S rRNA gene sequence similarity between the two strains was 96.7%. Although strains LMG 27682(T) and LMG 27684(T) shared a DNA-DNA hybridization value that corresponded to the threshold level for species delineation (68%), the two strains could be distinguished by multiple biochemical tests, sequence analysis of the phenylalanyl-tRNA synthase (pheS), RNA polymerase (rpoA) and ATP synthase (atpA) genes and by their MALDI-TOF MS profiles. On the basis of these considerable phenotypic and genotypic differences, we propose to classify both strains as novel species of the genus Streptococcus, for which the names Streptococcus moroccensis sp. nov. (type strain, LMG 27682(T)  = CCMM B831(T)) and Streptococcus rifensis sp. nov. (type strain, LMG 27684(T)  = CCMM B833(T)) are proposed.

  5. Fatal sepsis caused by an unusual Klebsiella species that was misidentified by an automated identification system.

    PubMed

    Seki, Masafumi; Gotoh, Kazuyoshi; Nakamura, Shota; Akeda, Yukihiro; Yoshii, Tadashi; Miyaguchi, Shinichi; Inohara, Hidenori; Horii, Toshihiro; Oishi, Kazunori; Iida, Tetsuya; Tomono, Kazunori

    2013-05-01

    This is a description of fatal sepsis caused by infection with Klebsiella variicola, which is an isolate genetically related to Klebsiella pneumoniae. The patient's condition was incorrectly diagnosed as common sepsis caused by K. pneumoniae, which was identified using an automated identification system, but next-generation sequencing and the non-fermentation of adonitol finally identified the cause of sepsis as K. variicola.

  6. Proteolytic inactivation of plasma C1- inhibitor in sepsis.

    PubMed

    Nuijens, J H; Eerenberg-Belmer, A J; Huijbregts, C C; Schreuder, W O; Felt-Bersma, R J; Abbink, J J; Thijs, L G; Hack, C E

    1989-08-01

    Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis. Because C1 inhibitor (C1-Inh) regulates the activation of both cascade systems, we studied the characteristics of plasma C1-Inh in 48 patients with severe sepsis on admission to the Intensive Care Unit at the Free University of Amsterdam. The ratio between the level of functional and antigenic C1-Inh (functional index) was significantly reduced in the patients with sepsis compared with healthy volunteers (P = 0.004). The assessment of modified (cleaved), inactive C1-Inh (iC1-Inh), and complexed forms of C1-Inh (nonfunctional C1-Inh species) revealed that the reduced functional index was mainly due to the presence of iC1-Inh. On SDS-PAGE, iC1-Inh species migrated with a lower apparent molecular weight (Mr 98,000, 91,000, and 86,000) than native C1-Inh (Mr 110,000). Elevated iC1-Inh levels (greater than or equal to 0.13 microM) were found in 81% of all patients, sometimes up to 1.6 microM. Levels of iC1-Inh on admission appeared to be of prognostic value: iC1-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003). The mortality in 15 patients with iC1-Inh levels up to 0.2 microM was 27%, but in 12 patients with plasma iC1-Inh exceeding 0.44 microM, the mortality was 83%. The overall mortality in the patients with sepsis was 56%. We propose that the cleavage of C1-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis.

  7. Diagnostic and prognostic biomarkers of sepsis in critical care.

    PubMed

    Kibe, Savitri; Adams, Kate; Barlow, Gavin

    2011-04-01

    Sepsis is a leading cause of mortality in critically ill patients. Delay in diagnosis and initiation of antibiotics have been shown to increase mortality in this cohort. However, differentiating sepsis from non-infectious triggers of the systemic inflammatory response syndrome (SIRS) is difficult, especially in critically ill patients who may have SIRS for other reasons. It is this conundrum that predominantly drives broad-spectrum antimicrobial use and the associated evolution of antibiotic resistance in critical care environments. It is perhaps unsurprising, therefore, that the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine. Procalcitonin (PCT) has emerged as the most studied and promising sepsis biomarker. For diagnostic and prognostic purposes in critical care, PCT is an advance on C-reactive protein and other traditional markers of sepsis, but is not accurate enough for clinicians to dispense with clinical judgement. There is stronger evidence, however, that measurement of PCT has a role in reducing the antibiotic exposure of critical care patients. For units intending to incorporate PCT assays into routine clinical practice, the cost-effectiveness of this is likely to depend on the pre-implementation length of an average antibiotic course and the subsequent impact of implementation on emerging antibiotic resistance. In most of the trials to date, the average baseline duration of the antibiotic course was longer than is currently standard practice in many UK critical care units. Many other biomarkers are currently being investigated. To be highly useful in clinical practice, it may be necessary to combine these with other novel biomarkers and/or traditional markers of sepsis.

  8. Arginine, citrulline and nitric oxide metabolism in sepsis.

    PubMed

    Kao, Christina C; Bandi, Venkata; Guntupalli, Kalpalatha K; Wu, Manhong; Castillo, Leticia; Jahoor, Farook

    2009-06-02

    Arginine has vasodilatory effects, via its conversion by NO synthase into NO, and immunomodulatory actions which play important roles in sepsis. Protein breakdown affects arginine availability and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore affect NO synthesis in patients with sepsis. The objective of the present study was to investigate whole-body in vivo arginine and citrulline metabolism and NO synthesis rates, and their relationship to protein breakdown in patients with sepsis or septic shock and in healthy volunteers. Endogenous leucine flux, an index of whole-body protein breakdown rate, was measured in 13 critically ill patients with sepsis or septic shock and seven healthy controls using an intravenous infusion of [1-13C]leucine. Arginine flux, citrulline flux and the rate of conversion of arginine into citrulline (an index of NO synthesis) were measured with intravenous infusions of [15N2]guanidino-arginine and [5,5-2H2]citrulline. Plasma concentrations of nitrite plus nitrate, arginine, citrulline and asymmetric dimethylarginine were measured. Compared with controls, patients had a higher leucine flux and higher NO metabolites, but arginine flux, plasma asymmetric dimethylarginine concentration and the rate of NO synthesis were not different. Citrulline flux and plasma arginine and citrulline were lower in patients than in controls. Arginine production was positively correlated with the protein breakdown rate. Whole-body arginine production and NO synthesis were similar in patients with sepsis and septic shock and healthy controls. Despite increased proteolysis in sepsis, there is a decreased arginine plasma concentration, suggesting inadequate de novo synthesis secondary to decreased citrulline production.

  9. Heparanase mediates renal dysfunction during early sepsis in mice

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

  11. Development of an anti-endotoxin vaccine for sepsis.

    PubMed

    Cross, Alan S

    2010-01-01

    Gram-negative bacterial lipopolysaccharide (LPS, endotoxin) is an important initiator of sepsis, a clinical syndrome that is a leading cause of death in intensive care units. Vaccines directed against core LPS structures that are widely conserved among Gram-negative bacteria (GNB) have been developed for the treatment and/or prevention of sepsis. Killed whole bacterial vaccines (E. coli O111:B4, J5 [Rc chemotype] mutant and S. minnesota, Re chemotype) protected mice against experimental sepsis. Human J5 immune antisera reduced the mortality from GNB sepsis in a large controlled clinical trial; however, subsequent clinical studies with antiendotoxin antibodies did not demonstrate protective efficacy in sepsis. Multiple clinical studies have since demonstrated a correlation between the level of circulating antibodies to LPS core and morbidity and mortality in different clinical settings. We therefore developed a subunit vaccine by combining detoxified J5 LPS (J5 dLPS) with the outer membrane protein (OMP) from group B N. meningitidis. This vaccine was highly efficacious in experimental models of sepsis and progressed to phase 1 clinical trial. While well-tolerated, this vaccine induced only 3-4-fold increases in anti-J5 dLPS antibody. Addition of the TLR9 agonist, oligodeoxynucleotide with a CpG motif, as adjuvant to the vaccine increased antibody levels in mice and the vaccine/CpG combination will progress to phase 1 human study. Additional vaccines in which the core glycolipid was either conjugated to carrier protein or incorporated into liposomes have been developed, but have not progressed to clinical trial. Should an antiendotoxin vaccine become available, a new immunization strategy directed towards distinct populations at risk will be required. PMID:20593272

  12. 9230 FECAL ENTEROCOCCUS/STREPTOCOCCUS GROUPS

    EPA Science Inventory

    In 1903 the genus name Enterococcus was proposed for gram-positive, catalase-negative, coccoid-shaped bacterial of intestinal origin. Several years later, it was suggested that the genus name be changed to Streptococcus because of the organisms' ability to form chains of coccoid...

  13. Nontypeable Streptococcus pneumoniae as an Otopathogen

    PubMed Central

    Xu, Qingfu; Kaur, Ravinder; Casey, Janet R.; Sabharwal, Vishakha; Pelton, Stephen; Pichichero, Michael E.

    2014-01-01

    Among 34 Spn sequential isolates from middle ear fluid we found a case of a nontypeable Streptococcus pneumoniae (NT-Spn) in a child with AOM. The strain was pneumolysin PCR positive and capsule gene PCR negative. Virulence of the NT-Spn was confirmed in a chinchilla model of AOM. PMID:21251566

  14. Streptococcus-Zebrafish Model of Bacterial Pathogenesis

    PubMed Central

    Neely, Melody N.; Pfeifer, John D.; Caparon, Michael

    2002-01-01

    Due to its small size, rapid generation time, powerful genetic systems, and genomic resources, the zebrafish has emerged as an important model of vertebrate development and human disease. Its well-developed adaptive and innate cellular immune systems make the zebrafish an ideal model for the study of infectious diseases. With a natural and important pathogen of fish, Streptococcus iniae, we have established a streptococcus- zebrafish model of bacterial pathogenesis. Following injection into the dorsal muscle, zebrafish developed a lethal infection, with a 50% lethal dose of 103 CFU, and died within 2 to 3 days. The pathogenesis of infection resembled that of S. iniae in farmed fish populations and that of several important human streptococcal diseases and was characterized by an initial focal necrotic lesion that rapidly progressed to invasion of the pathogen into all major organ systems, including the brain. Zebrafish were also susceptible to infection by the human pathogen Streptococcus pyogenes. However, disease was characterized by a marked absence of inflammation, large numbers of extracellular streptococci in the dorsal muscle, and extensive myonecrosis that occurred far in advance of any systemic invasion. The genetic systems available for streptococci, including a novel method of mutagenesis which targets genes whose products are exported, were used to identify several mutants attenuated for virulence in zebrafish. This combination of a genetically amenable pathogen with a well-defined vertebrate host makes the streptococcus-zebrafish model of bacterial pathogenesis a powerful model for analysis of infectious disease. PMID:12065534

  15. Pediatric autoimmune neuropsychiatric disorders after streptococcus infection.

    PubMed

    Maini, Baljeet; Bathla, Manish; Dhanjal, Gurdeep S; Sharma, Prem D

    2012-10-01

    Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) is a group of disorders recently recognized as a clinical entity. A case of PANDAS is described here, which remitted after 1 month of treatment. Recent Group A beta-hemolytic streptococcus infection should be considered in a child who presents with a sudden explosive onset of tics or obsessive compulsive symptoms. PMID:23372243

  16. Streptococcus suis Serotype 2 Capsule In Vivo.

    PubMed

    Auger, Jean-Philippe; Meekhanon, Nattakan; Okura, Masatoshi; Osaki, Makoto; Gottschalk, Marcelo; Sekizaki, Tsutomu; Takamatsu, Daisuke

    2016-10-01

    Many Streptococcus suis isolates from porcine endocarditis in slaughterhouses have lost their capsule and are considered avirulent. However, we retrieved capsule- and virulence-recovered S. suis after in vivo passages of a nonencapsulated strain in mice, suggesting that nonencapsulated S. suis are still potentially hazardous for persons in the swine industry. PMID:27648583

  17. Streptococcus equi subsp. zooepidemicus meningitis in Peru.

    PubMed

    Mori, Nicanor; Guevara, Jose M; Tilley, Drake H; Briceno, Jesus A; Zunt, Joseph R; Montano, Silvia M

    2013-02-01

    A 59-year-old man with a history of fever, unsteadiness, hemiparesis, motor aphasia and consciousness disturbance was hospitalized for Streptococcus equi subsp. zooepidemicus meningitis. He denied contact with farm animals, but had a practice of consuming unpasteurized goats' cheese from an uncertain source.

  18. Streptococcus suis Serotype 2 Capsule In Vivo

    PubMed Central

    Auger, Jean-Philippe; Meekhanon, Nattakan; Okura, Masatoshi; Osaki, Makoto; Gottschalk, Marcelo; Sekizaki, Tsutomu

    2016-01-01

    Many Streptococcus suis isolates from porcine endocarditis in slaughterhouses have lost their capsule and are considered avirulent. However, we retrieved capsule- and virulence-recovered S. suis after in vivo passages of a nonencapsulated strain in mice, suggesting that nonencapsulated S. suis are still potentially hazardous for persons in the swine industry. PMID:27648583

  19. Revisitingmolecular serotyping of Streptococcus pneumoniae

    PubMed Central

    2015-01-01

    Background Ninety-two Streptococcus pneumoniae serotypes have been described so far, but the pneumococcal conjugate vaccine introduced in the Brazilian basic vaccination schedule in 2010 covers only the ten most prevalent in the country. Pneumococcal serotype-shifting after massive immunization is a major concern and monitoring this phenomenon requires efficient and accessible serotyping methods. Pneumococcal serotyping based on antisera produced in animals is laborious and restricted to a few reference laboratories. Alternatively, molecular serotyping methods assess polymorphisms in the cps gene cluster, which encodes key enzymes for capsular polysaccharides synthesis in pneumococci. In one such approach, cps-RFLP, the PCR amplified cps loci are digested with an endonuclease, generating serotype-specific fingerprints on agarose gel electrophoresis. Methods In this work, in silico and in vitro approaches were combined to demonstrate that XhoII is the most discriminating endonuclease for cps-RFLP, and to build a database of serotype-specific fingerprints that accommodates the genetic diversity within the cps locus of 92 known pneumococci serotypes. Results The expected specificity of cps-RFLP using XhoII was 76% for serotyping and 100% for serogrouping. The database of cps-RFLP fingerprints was integrated to Molecular Serotyping Tool (MST), a previously published web-based software for molecular serotyping. In addition, 43 isolates representing 29 serotypes prevalent in the state of Minas Gerais, Brazil, from 2007 to 2013, were examined in vitro; 11 serotypes (nine serogroups) matched the respective in silico patterns calculated for reference strains. The remaining experimental patterns, despite their resemblance to their expected in silico patterns, did not reach the threshold of similarity score to be considered a match and were then added to the database. Conclusion The cps-RFLP method with XhoII outperformed the antisera-based and other molecular serotyping

  20. Sepsis attenuates the anabolic response to skeletal muscle contraction

    PubMed Central

    Steiner, Jennifer L.; Lang, Charles H.

    2014-01-01

    Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ~24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the non-stimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 substrates S6K1 Thr389 (8-fold), S6K1 Thr421/Ser424 (7-fold) and 4E-BP1 Ser65 (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr389 (67%), S6K1 Thr421/Ser424 (46%) and 4E-BP1 Ser65 (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr56 phosphorylation was decreased similarly by muscle contraction in both groups. MAPK signaling was discordant following muscle contraction in septic muscle; phosphorylation of ERK Thr202/Tyr204 and p38 Thr180/Tyr182 was increased similarly in both CON and CLP mice while sepsis prevented the contraction-induced phosphorylation of JNK Thr183/Tyr185 and c-JUN Ser63. The expression of IL-6 and TNF-α mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR-mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent. PMID:25423127

  1. Cold agglutinin disease in sepsis: A rare entity

    PubMed Central

    Garg, Ravinder; Kukar, Neetu; Bajwa, Sukhminder Jit Singh; Kaur, Shaminder

    2015-01-01

    Cold agglutinin disease (CAgD) is a type of autoimmune hemolytic anemia which generally occurs in adults and is characterized by the presence of IgM antibodies directed against polysaccharide antigens on red blood cell surface. A 16-year-old male, having clinical picture of sepsis and anemia, presented to the Emergency Department of our Institute in an Hemodynamically unstable condition. Investigation profile revealed hemolysis due to CAgD, which responded to corticosteroids, antibiotics and supportive treatment. This case highlights the importance of recognizing this entity in such type of cases presenting with sepsis and anemia. PMID:26229347

  2. Endothelial and Microcirculatory Function and Dysfunction in Sepsis.

    PubMed

    Colbert, James F; Schmidt, Eric P

    2016-06-01

    The microcirculation is a series of arterioles, capillaries, and venules that performs essential functions of oxygen and nutrient delivery, customized to the unique physiologic needs of the supplied organ. The homeostatic microcirculatory response to infection can become harmful if overactive and/or dysregulated. Pathologic microcirculatory dysfunction can be directly visualized by intravital microscopy or indirectly measured via detection of circulating biomarkers. Although several treatments have been shown to protect the microcirculation during sepsis, they have not improved patient outcomes when applied indiscriminately. Future outcomes-oriented studies are needed to test sepsis therapeutics when personalized to a patient's microcirculatory dysfunction. PMID:27229643

  3. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    PubMed

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

    2016-06-01

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

  4. Community-, Healthcare- and Hospital-Acquired Severe Sepsis Hospitalizations in the University HealthSystem Consortium

    PubMed Central

    Page, David B.; Donnelly, John P.; Wang, Henry E.

    2015-01-01

    Objectives Severe sepsis poses a major burden on the U.S. healthcare system. Previous epidemiologic studies have not differentiated community-acquired severe sepsis from healthcare-associated severe sepsis or hospital-acquired severe sepsis hospitalizations. We sought to compare and contrast community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis hospitalizations in a national hospital sample. Setting United States Interventions None Measurements & Main Results Prevalence of community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis, adjusted hospital mortality, length of hospitalization, length of stay in an ICU, and hospital costs. Among 3,355,753 hospital discharges, there were 307,491 with severe sepsis, including 193,081 (62.8%) community-acquired severe sepsis, 79,581 (25.9%) healthcare-associated severe sepsis, and 34,829 (11.3%) hospital-acquired severe sepsis. Hospital-acquired severe sepsis and healthcare-associated severe sepsis exhibited higher in-hospital mortality than community-acquired severe sepsis (hospital-acquired [19.2%] vs healthcare-associated [12.8%] vs community-acquired [8.6%]). Hospital-acquired severe sepsis had greater resource utilization than both healthcare-associated severe sepsis and community-acquired severe sepsis, with higher median length of hospital stay (hospital acquired [17 d] vs healthcare associated [7 d] vs community-acquired [6 d]), median length of ICU stay (hospital-acquired [8 d] vs healthcare-associated [3 d] vs community-acquired [3 d]), and median hospital costs (hospital-acquired [$38,369] vs healthcare-associated [$8,796] vs community-acquired [$7,024]). Conclusions In this series, severe sepsis hospitalizations included CA-SS (62.8%), HCA-SS (25.9%) and HA-SS (11.3%) cases. HA-SS was associated with both higher mortality and resource utilization than CA-SS and HCA-SS. PMID:26110490

  5. Sepsis, severe sepsis, and septic shock: current evidence for emergency department management.

    PubMed

    Booker, Ethan

    2011-05-01

    In the middle of a busy shift, a patient arrives by ambulance from a local long-term care facility with a report of altered mental status. You enter the room to find a chronically ill-appearing 85-year-old man with fever, tachycardia, and hypotension, and it is instantly apparent that this patient is septic. What is not clear is what the source is, what modifications in treatment might be necessary based on preexisting microbial resistance, and which of the array of invasive resuscitation techniques are appropriate when meaningful recovery is questionable and efforts may not be desired by the patient and family. You order IV fluids and broad-spectrum antibiotics; send lab tests, including lactate and cultures of blood, urine, and sputum; and begin to review his extensive history to discuss goals of care with his family and primary doctor. While reviewing these issues, a 54-year-old woman with a history of asthma is brought straight back from triage with respiratory distress. You listen to her lungs, expecting wheezes, but hear decreased lung sounds at the right base, preserved air movement elsewhere, and her skin radiates heat. Now, on the monitor, she has a heart rate of 135 beats per minute, blood pressure of 90/60 mm Hg, O2 saturation of 86%, and a temperature of 39.4 degrees C (103 degrees F). You again identify sepsis and instruct your team that you will be using your department's severe sepsis protocol. Equipment for monitoring and procedures is assembled, your staff provides preprinted order and monitoring flow sheets, and the ICU is alerted. Within an hour, the patient is intubated, has a central line placed, and has received IV fluids, broad-spectrum antibiotics and norepinephrine, and you are pleased to see a MAP of 67 mm Hg, a lactate decreasing from an initial value of 7.0, CVP of 10, and ScvO2 of 78%.

  6. Interleukin-17A Contributes to the Control of Streptococcus pyogenes Colonization and Inflammation of the Female Genital Tract

    PubMed Central

    Carey, Alison J.; Weinberg, Jason B.; Dawid, Suzanne R.; Venturini, Carola; Lam, Alfred K.; Nizet, Victor; Caparon, Michael G.; Walker, Mark J.; Watson, Michael E.; Ulett, Glen C.

    2016-01-01

    Postpartum women are at increased risk of developing puerperal sepsis caused by group A Streptococcus (GAS). Specific GAS serotypes, including M1 and M28, are more commonly associated with puerperal sepsis. However, the mechanisms of GAS genital tract infection are not well understood. We utilized a murine genital tract carriage model to demonstrate that M1 and M28 GAS colonization triggers TNF-α, IL-1β, and IL-17A production in the female genital tract. GAS-induced IL-17A significantly influences streptococcal carriage and alters local inflammatory responses in two genetically distinct inbred strains of mice. An absence of IL-17A or the IL-1 receptor was associated with reduced neutrophil recruitment to the site of infection; and clearance of GAS was significantly attenuated in IL-17A−/− mice and Rag1−/− mice (that lack mature lymphocytes) but not in mice deficient for the IL-1 receptor. Together, these findings support a role for IL-17A in contributing to the control of streptococcal mucosal colonization and provide new insight into the inflammatory mediators regulating host-pathogen interactions in the female genital tract. PMID:27241677

  7. Novel predictors of sepsis outperform the American Burn Association sepsis criteria in the burn intensive care unit patient.

    PubMed

    Mann-Salinas, Elizabeth A; Baun, Mara M; Meininger, Janet C; Murray, Clinton K; Aden, James K; Wolf, Steven E; Wade, Charles E

    2013-01-01

    The purpose of this study was to determine whether systemic inflammatory response syndrome (SIRS) and American Burn Association (ABA) criteria predict sepsis in the burn patient and develop a model representing the best combination of novel clinical sepsis predictors. A retrospective, case-controlled, within-patient comparison of burn patients admitted to a single intensive care unit from January 2005 to September 2010 was made. Blood culture results were paired with documented sepsis: positive-sick, negative-sick (collectively defined as sick), and negative-not sick. Data for all predictors were collected for the 72 hours before blood culture. Variables were evaluated using regression and area under the curve (AUC) analyses. Fifty-nine subjects represented 177 culture periods. SIRS criteria were not discriminative: 98% of the subjects met criteria. ABA sepsis criteria were different on the day before (P = .004). The six best-fit variables identified for the model included heart rate > 130 beats per min, mean arterial pressure < 60 mm Hg, base deficit < -6 mEq/L, temperature < 36°C, use of vasoactive medications, and glucose > 150 mg/dl. The model was significant in predicting positive-sick and sick, with an AUC of 0.775 (P < .001) and 0.714 (P < .001), respectively; comparatively, the ABA criteria AUC was 0.619 (P = .028) and 0.597 (P = .035), respectively. Usefulness of the ABA criteria to predict sepsis is limited to the day before blood culture is obtained. A significant contribution of this research is the identification of six novel sepsis predictors for the burn patient.

  8. Streptococcus agalactiae: prevalence of antimicrobial resistance in vaginal and rectal swabs in Italian pregnant women.

    PubMed

    Matani, Chiara; Trezzi, Michele; Matteini, Alice; Catalani, Carlotta; Messeri, Daniela; Catalani, Corrado

    2016-09-01

    Intrapartum antibiotic prophylaxis (IAP) reduces both the vertical transmission of Streptococcus agalactiae or Group B Streptococcus (GBS) and the early onset of neonatal sepsis. However, existing guidelines do not recommend that antimicrobial susceptibility testing (AST) be routinely performed. Penicillin or ampicillin are indicated as first-choice antibiotics, cefazolin being an alternative in the case of history of mild allergic reactions, and vancomycin or clindamycin an alternative in the event of severe reactions. We performed a cross-sectional analysis to identify the presence of any bacterial resistance towards the antibiotics most frequently used for IAP in pregnant women with GBS positive vaginal-rectal swabs, in the Pistoia area of central Italy. Of the 255 tested samples, 65 (25.5%) were positive for GBS. Sensitivity to glycopeptides was over 90%, but lower to ampicillin and penicillin (87.10% and 87.93% respectively). Resistance towards clindamycin and erythromycin was as high as 43.75% and 32.20%. All tested GBS proved susceptible to moxifloxacin, linezolid and tigecycline. Our observed prevalence is aligned or slightly higher than data reported in other series. The less than full effectiveness and low percentages of ampicillin and penicillin sensitivity observed give cause for concern. We confirmed the increase in clindamycin and erythromycin resistance. Glycopeptides can be used as second-line antibiotics, but the complete AST of GBS should always be performed before IAP. Given that gentamicin is used synergically with penicillin when treating chorioamnionitis, it needs to be always included in the AST. This is the first study on the GBS sensitivity profile in Tuscany. Further investigation on a larger scale is required prior to implementing any changes in the current guidelines. PMID:27668902

  9. Molecular and antimicrobial susceptibility profiling of atypical Streptococcus species from porcine clinical specimens.

    PubMed

    Moreno, Luisa Z; Matajira, Carlos E C; Gomes, Vasco T M; Silva, Ana Paula S; Mesquita, Renan E; Christ, Ana Paula G; Sato, Maria Inês Z; Moreno, Andrea M

    2016-10-01

    The Streptococcus species present broad phenotypic variation, making identification difficult using only traditional microbiological methods. Even though Streptococcus suis is the most important species for the worldwide swine industry, other Streptococcus species appear to be able to cause disease in swine and could represent a higher underestimated risk for porcine health. The aim of this study was to identify Streptococcus-like isolates by MALDI-TOF MS and 16S rRNA sequencing and further molecular and antibiotic susceptibility characterization of the atypical Streptococcus species capable of causing disease in swine. Fifty presumptive Streptococcus isolates from diseased pigs isolated from different Brazilian States between 2002 and 2014 were evaluated. Among the studied isolates, 26% were identified as Streptococcus hyovaginalis, 24% as Streptococcus plurianimalium, 12% as Streptococcus alactolyticus, 10% as Streptococcus hyointestinalis, and the remaining isolates belonged to Streptococcus henryi (6%), Streptococcus thoraltensis (6%), Streptococcus gallolyticus (6%), Streptococcus gallinaceus (4%), Streptococcus sanguinis (4%), and Streptococcus mitis (2%). The Streptococcus isolates were successfully identified by spectral cluster analysis and 16S rRNA sequencing with 96% of concordance between the techniques. The SE-AFLP analysis also supported Streptococcus species distinction and enabled further observation of higher genetic heterogeneity intra-species. The identified Streptococcus species presented variable MIC values to β-lactams, enrofloxacin and florfenicol, and high resistance rates to tetracyclines and macrolides, which appear to be directly related to the industry's antimicrobial usage and resistance selection.

  10. Impact of antibiotic resistance on the treatment of sepsis.

    PubMed

    Turnidge, John

    2003-01-01

    Antibiotics are essential to the treatment of bacterial sepsis as they reduce the bacterial burden. The impact of bacterial resistance has recently been studied and found to be important in a range of conditions. Resistance to antibiotics can be defined genotypically, phenotypically and clinically through pharmacokinetic/pharmacodynamic studies and their correlations with clinical outcomes. Although the kinetics of antibiotics has been shown to be favourably altered in sepsis, a range of studies in sepsis has revealed that for most pathogens resistance contributes to significant increases in mortality. This has been clearly demonstrated in bacteraemia, including community- and hospital-acquired infection, and with bacteraemia caused by vancomycin-resistant enterococci, methicillin-resistant staphylococci and extended-spectrum producing Gram-negative bacteria. Significant mortality increases have also been seen with ventilator-associated pneumonia and serious infections requiring admission to intensive care. Gentotypic and phenotypic resistance in coagulase-negative staphylococci causing bacteraemia, and in invasive pneumococcal disease has not shown differences in mortality. In the latter case, dosage regimens have to date been adequate to overcome laboratory-defined resistance. Early indications are that de-escalating therapy from broad-spectrum initial coverage after results of cultures and susceptibility tests become available does not jeopardize outcomes, and further prospective studies are warranted. There is now convincing evidence that broad-spectrum initial therapy to cover the likely pathogens and their resistances pending culture results is mandatory in sepsis to minimize adverse outcomes.

  11. 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.

  12. 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

  13. Time for a neonatal–specific consensus definition for sepsis

    PubMed Central

    Wynn, James L.; Wong, Hector R.; Shanley, Thomas P.; Bizzarro, Matthew J.; Saiman, Lisa; Polin, Richard A.

    2014-01-01

    Objective To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. Study selection The review focused primarily on pediatric literature relevant to the topic of interest. Conclusions Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates. PMID:24751791

  14. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

    PubMed

    Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela; Galindo-Sevilla, Norma

    2016-01-01

    The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.

  15. Arginine, citrulline and nitric oxide metabolism in sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

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

    PubMed

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

    2011-01-01

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

  17. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis.

    PubMed

    Hasvold, J; Bradford, L; Nelson, C; Harrison, C; Attar, M; Stillwell, T

    2013-01-01

    Neonatal sepsis is a significant cause of morbidity and mortality among term and preterm infants. Ampicillin and gentamicin are standard empiric therapy for early onset sepsis. Four cases of neonatal sepsis secondary to Escherichia coli (E. coli) found to be gentamicin resistant occurred within a five week period in one neonatal intensive care unit (NICU). To determine whether these cases could be tied to a single vector of transmission, and to more broadly evaluate the incidence of gentamicin resistant strains of E. coli in the neonatal population at our institution compared to other centers, we reviewed the charts of the four neonates (Infants A through D) and their mothers. The E. coli isolates were sent for Pulse Field Gel Electrophoresis (PFGE) to evaluate for genetic similarity between strains. We also reviewed all positive E. coli cultures from one NICU over a two year period. Infants A and B had genetically indistinguishable strains which matched that of urine and placental cultures of Infant B's mother. Infant C had a genetically distinct organism. Infant D, the identical twin of Infant C, did not have typing performed. Review of all cultures positive for E. coli at our institution showed a 12.9 percent incidence of gentamicin-resistance. A review of other studies showed that rates of resistance vary considerably by institution. We conclude that gentamicin-resistant E. coli is a relatively uncommon cause of neonatal sepsis, but should remain a consideration in patients who deteriorate despite initiation of empiric antibiotics. PMID:24246520

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

    PubMed Central

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

    2014-01-01

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

  19. Early onset neonatal sepsis due to Morganella morganii.

    PubMed

    Dutta, Sourabh; Narang, Anil

    2004-11-01

    Two neonates, both 32-weekers, developed Morganella morganii sepsis on the first day of life. They presented within a day of each other, primarily with respiratory signs. In both cases there was a history of spontaneous premature rupture of membranes, exposure to a single dose of ampicillin ante-partum, and similar antibiograms. No common source could be identified.

  20. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

    PubMed

    Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela; Galindo-Sevilla, Norma

    2016-01-01

    The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation. PMID:27293317

  1. Sepsis Patient Detection and Monitor Based on Auto-BN.

    PubMed

    Jiang, Yu; Sha, Lui; Rahmaniheris, Maryam; Wan, Binhua; Hosseini, Mohammad; Tan, Pengliu; Berlin, Richard B

    2016-04-01

    Sepsis is a life-threatening condition caused by an inappropriate immune response to infection, and is a leading cause of elderly death globally. Early recognition of patients and timely antibiotic therapy based on guidelines improve survival rate. Unfortunately, for those patients, it is often detected late because it is too expensive and impractical to perform frequent monitoring for all the elderly. In this paper, we present a risk driven sepsis screening and monitoring framework to shorten the time of onset detection without frequent monitoring of all the elderly. Within this framework, the sepsis ultimate risk of onset probability and mortality is calculated based on a novel temporal probabilistic model named Auto-BN, which consists of time dependent state, state dependent property, and state dependent inference structures. Then, different stages of a patient are encoded into different states, monitoring frequency is encoded into the state dependent property, and screening content is encoded into different state dependent inference structures. In this way, the screening and monitoring frequency and content can be automatically adjusted when encoding the sepsis ultimate risk into the guard of state transition. This allows for flexible manipulation of the tradeoff between screening accuracy and frequency. We evaluate its effectiveness through empirical study, and incorporate it into existing medical guidance system to improve medical healthcare.

  2. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis

    PubMed Central

    Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela

    2016-01-01

    The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation. PMID:27293317

  3. Surviving Sepsis Puerto Rico: A Call For Action.

    PubMed

    Vigo, Ronald; Matos, Miguel Laforet; Turbay, Tamid

    2015-01-01

    There are 1.7 million sepsis-related hospitalizations each year making it the sixth most common cause for hospitalization in the United States. Not only are this hospitalizations common, they are expensive to our medical system with $15.3 billion spent yearly (3) and hospitalizations lasting 75% longer than for other conditions. In 2001, Rivers et al published in the NEJM the results of his study "Early Goal Directed Therapy (EGDT) in The Treatment of Severe Sepsis and Septic Shock". EGDT demonstrated a 16.5% decrease in mortality in septic patients (4). In 2002 the Surviving Sepsis Campaign began as a collaboration between the Society of Critical Care Medicine and European Society of Intensive Care Medicine with goals of reducing worldwide sepsis related mortality by 25% in the next 5 years. Despite the proven benefit of early identification and management, knowledge regarding the topic in Puerto Rico remains scarce. In a study performed in PR by Fernandez et al. in 2006, only an alarming 31.4% of doctors from different specialties correctly identified SIRS criteria. Our goal is to educate physicians about the importance of early identification and treatment of the septic patient. A campaign to increase awareness and improve care is essential and we propose treatment protocols for our Puerto Rican hospitals to help reduce morbidity, mortality, length of stay and costs. PMID:26434083

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2016-09-16

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

  8. Considerations in the pharmacologic treatment and prevention of neonatal sepsis.

    PubMed

    Stockmann, Chris; Spigarelli, Michael G; Campbell, Sarah C; Constance, Jonathan E; Courter, Joshua D; Thorell, Emily A; Olson, Jared; Sherwin, Catherine M T

    2014-02-01

    The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis. PMID:24218112

  9. Membrane TLR Signaling Mechanisms in the Gastrointestinal Tract during Sepsis

    PubMed Central

    Buchholz, Bettina M.; Bauer, Anthony J.

    2010-01-01

    Our bacterial residents are deadly Janus-faced indwellers which can lead to a septic-induced systemic inflammatory response syndrome and multiple organ failure. Over half of ICU patients suffer from infections and sepsis remains among the top ten causes of death in the United States. Severe ileus frequently accompanies sepsis setting up an insidious cycle of gut-derived microbial translocation and the copious intestinal production of potent systemic inflammatory mediators. Few therapeutic advances have occurred to prevent/treat the sequelae of sepsis. Here, we selectively review studies on cellular membrane bound Toll-like receptor (TLR) mechanisms of ileus. Virtually no data exists on Gram-positive/TLR2 signaling mechanisms of ileus, however, TLR2 is highly inducible by numerous inflammatory mediators and studies using clinically relevant scenarios of Gram-positive sepsis are needed. Specific Gram-negative/TLR4 signaling pathways are being elucidated using a “reverse engineering” approach and have revealed that endotoxin induced ileus is dually mediated by classical leukocyte inflammatory signaling and by a MyD88-dependent non-bone marrow derived mechanism, but the specific roles of individual cell populations are still unknown. Like TLR2, little is also know of the role of flagellin/TLR5 signaling in ileus. But, much can be learned by understanding TLR signaling in other systems. Clearly, the use of polymicrobial models provide important clinical relevancy but simultaneous activation of virtually all pattern recognition receptors make it impossible to discretely study specific signaling pathways. We believe that dissection of individual TLR pathways, which can then be intelligently re-assembled in a meaningful manner, will provide insight into treatments for sepsis induced ileus. PMID:20377787

  10. Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation.

    PubMed

    Sivula, Mirka; Pettilä, Ville; Niemi, Tomi T; Varpula, Marjut; Kuitunen, Anne H

    2009-09-01

    Severe sepsis induces coagulopathy, which may lead to disseminated intravascular coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation monitor, which has been validated in human endotoxemia model. We assessed thromboelastometry in severe sepsis and overt DIC and investigated its applicability in differentiating sepsis-related coagulation disturbances. Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria of overt DIC on admission. Ten healthy persons served as controls. Coagulation parameters, clotting time, clot formation time (CFT), alpha angle, maximal clot firmness (MCF) and lysis index at 60 min, were registered. In patients with overt DIC, EXTEM MCF, CFT and alpha angle differed from that in both healthy controls and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT 184, 88 and 73 s; and alpha angle 58, 72 and 76 degrees , respectively, P < 0.01 for all). In patients without DIC, the trend was toward hypercoagulation in EXTEM and FIBTEM MCF (68 vs. 63 mm, P = 0.042 and 23 vs. 15 mm, P = 0.034, respectively). Receiver operating characteristic curves showed that MCF, CFT and alpha angle discriminated patients with overt DIC moderately (area under curve 0.891, 0.815 and 0.828, respectively, P < 0.001 for all). Traditional coagulation assays showed progressively worsening coagulopathy from controls to septic patients without DIC and further to those with overt DIC. We conclude that thromboelastometry may be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.

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

    PubMed

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

    2014-01-01

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

  12. 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

    2015-01-23

    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.

  13. Rapid rewarming after therapeutic hypothermia worsens outcome in sepsis

    PubMed Central

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

    2014-01-01

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

  14. IMPACT OF SEPSIS CLASSIFICATION AND MULTIDRUG RESISTANCE STATUS ON OUTCOME AMONG PATIENTS TREATED WITH APPROPRIATE THERAPY

    PubMed Central

    Burnham, Jason P.; Lane, Michael A.; Kollef, Marin H.

    2015-01-01

    Objective To assess the impact of sepsis classification and multidrug resistance status on outcome in patients receiving appropriate initial antibiotic therapy. Design A retrospective cohort study. Setting Barnes-Jewish Hospital, a 1250-bed teaching hospital. Patients Individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock that received appropriate initial antimicrobial therapy between June 2009 and December 2013. Interventions Clinical outcomes were compared according to multidrug resistance status, sepsis classification, demographics, severity of illness, comorbidities, and antimicrobial treatment. Measurements and Main Results We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were non-survivors. Mortality increased significantly with increasing severity of sepsis (3.5%, 9.9%, and 28.6%, for sepsis, severe sepsis, and septic shock, respectively, p<0.05). Time to antimicrobial therapy was not significantly associated with outcome. APACHE II was more predictive of mortality than age-adjusted Charlson comorbidity index. Multidrug resistance status did not result in excess mortality. Length of intensive care unit and hospital stay increased with more severe sepsis. In multivariate logistic regression analysis, African-American race, sepsis severity, APACHE II score, solid organ cancer, cirrhosis, and transfer from an outside hospital were all predictors of mortality. Conclusions Our results support sepsis severity, but not multidrug resistance status as being an important predictor of death when all patients receive appropriate initial antibiotic therapy. Future sepsis trials should attempt to provide appropriate antimicrobial therapy and take sepsis severity into careful account when determining outcomes. PMID:25855900

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

    PubMed Central

    Wiener, Renda Soylemez

    2014-01-01

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

  16. Developing oral probiotics from Streptococcus salivarius.

    PubMed

    Wescombe, Philip A; Hale, John D F; Heng, Nicholas C K; Tagg, John R

    2012-12-01

    Considerable human illness can be linked to the development of oral microbiota disequilibria. The predominant oral cavity commensal, Streptococcus salivarius has emerged as an important source of safe and efficacious probiotics, capable of fostering more balanced, health-associated oral microbiota. Strain K12, the prototype S. salivarius probiotic, originally introduced to counter Streptococcus pyogenes infections, now has an expanded repertoire of health-promoting applications. K12 and several more recently proposed S. salivarius probiotics are now being applied to control diverse bacterial consortia infections including otitis media, halitosis and dental caries. Other potential applications include upregulation of immunological defenses against respiratory viral infections and treatment of oral candidosis. An overview of the key steps required for probiotic development is also presented. PMID:23231486

  17. Acute Mastoiditis Caused by Streptococcus pneumoniae.

    PubMed

    Obringer, Emily; Chen, Judy L

    2016-05-01

    Acute mastoiditis (AM) is a relatively rare complication of acute otitis media (AOM). The most common pathogens include Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Pneumococcal vaccination and changes in antibiotic prescribing recommendations for AOM may change the incidence of AM in the future. Diagnosis of AM can be made based on clinical presentation, but computed tomography of the temporal bone with contrast should be considered if there is concern for complicated AM. Both extracranial and intracranial complications of AM may occur. Previously, routine cortical mastoidectomy was recommended for AM treatment, but new data suggest that a more conservative treatment approach can be considered, including intravenous (IV) antibiotics alone or IV antibiotics with myringotomy. [Pediatr Ann. 2016;45(5):e176-e179.]. PMID:27171806

  18. 21 CFR 866.3740 - Streptococcus spp. serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus... derived from clinical specimens. The identification aids in the diagnosis of diseases caused by...

  19. 21 CFR 866.3740 - Streptococcus spp. serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus... derived from clinical specimens. The identification aids in the diagnosis of diseases caused by...

  20. 21 CFR 866.3740 - Streptococcus spp. serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3740 Streptococcus... derived from clinical specimens. The identification aids in the diagnosis of diseases caused by...

  1. C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean?

    PubMed Central

    Gucyetmez, Bulent; Atalan, Hakan K.

    2016-01-01

    Objectives Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis. Methods A total of 2777 patients admitted to the ICU of two centers between 2006–2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-), non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-), culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients’ demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded. Results 1257 patients were categorized as non-sepsis SIRS (816, 64.9%) and sepsis (441, 35.1%). In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2–4.6), 1.7 (1.2–2.4), 1.6 (1.2–2.1), 2.3 (1.4–3.8), 1.5 (1.1–2.1) times by the APACHE II≥13, SOFA score≥4, CRP≥4.0, LymC<0.45 and PLTC<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027). The likelihood of sepsis was increased 18.1 (8.4–38.7) times by the combination of CRP≥4.0, lymC<0.45 and PLTC<150 (P<0.001). Conclusions While WBCC, NeuC, Neu%, NLCR and EoC are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, LymC and PLTC can be used to determine the likelihood of sepsis. PMID:26863002

  2. Recombination-deficient mutant of Streptococcus faecalis

    SciTech Connect

    Yagi, Y.; Clewell, D.B.

    1980-08-01

    An ultraviolet radiation-sensitive derivative of Streptococcus faecalis strain JH2-2 was isolated and found to be deficient in recombination, using a plasmid-plasmid recombination system. The strain was sensitive to chemical agents which interact with deoxyribonucleic acid and also underwent deoxyribonucleic acid degradation after ultraviolet irradiation. Thus, the mutant has properties similar to those of recA strains of Escherichia coli.

  3. Dual Functions of Streptococcus salivarius Urease

    PubMed Central

    Chen, Yi-Ywan M.; Weaver, Cheryl A.; Burne, Robert A.

    2000-01-01

    A urease-deficient derivative of Streptococcus salivarius 57.I was constructed by allelic exchange at the ureC locus. The wild-type strain was protected against acid killing through hydrolysis of physiologically relevant concentrations of urea, whereas the mutant was not. Also, S. salivarius could use urea as a source of nitrogen for growth exclusively through a urease-dependent pathway. PMID:10913107

  4. Genomics, evolution, and molecular epidemiology of the Streptococcus bovis/Streptococcus equinus complex (SBSEC).

    PubMed

    Jans, Christoph; Meile, Leo; Lacroix, Christophe; Stevens, Marc J A

    2015-07-01

    The Streptococcus bovis/Streptococcus equinus complex (SBSEC) is a group of human and animal derived streptococci that are commensals (rumen and gastrointestinal tract), opportunistic pathogens or food fermentation associates. The classification of SBSEC has undergone massive changes and currently comprises 7 (sub)species grouped into four branches based on sequences identities: the Streptococcus gallolyticus, the Streptococcus equinus, the Streptococcus infantarius and the Streptococcus alactolyticus branch. In animals, SBSEC are causative agents for ruminal acidosis, potentially laminitis and infective endocarditis (IE). In humans, a strong association was established between bacteraemia, IE and colorectal cancer. Especially the SBSEC-species S. gallolyticus subsp. gallolyticus is an emerging pathogen for IE and prosthetic joint infections. S. gallolyticus subsp. pasteurianus and the S. infantarius branch are further associated with biliary and urinary tract infections. Knowledge on pathogenic mechanisms is so far limited to colonization factors such as pili and biofilm formation. Certain strain variants of S. gallolyticus subsp. macedonicus and S. infantarius subsp. infantarius are associated with traditional dairy and plant-based food fermentations and display traits suggesting safety. However, due to their close relationship to virulent strains, their use in food fermentation has to be critically assessed. Additionally, implementing accurate and up-to-date taxonomy is critical to enable appropriate treatment of patients and risk assessment of species and strains via recently developed multilocus sequence typing schemes to enable comparative global epidemiology. Comparative genomics revealed that SBSEC strains harbour genomics islands (GI) that seem acquired from other streptococci by horizontal gene transfer. In case of virulent strains these GI frequently encode putative virulence factors, in strains from food fermentation the GI encode functions that are

  5. Genomics, evolution, and molecular epidemiology of the Streptococcus bovis/Streptococcus equinus complex (SBSEC).

    PubMed

    Jans, Christoph; Meile, Leo; Lacroix, Christophe; Stevens, Marc J A

    2015-07-01

    The Streptococcus bovis/Streptococcus equinus complex (SBSEC) is a group of human and animal derived streptococci that are commensals (rumen and gastrointestinal tract), opportunistic pathogens or food fermentation associates. The classification of SBSEC has undergone massive changes and currently comprises 7 (sub)species grouped into four branches based on sequences identities: the Streptococcus gallolyticus, the Streptococcus equinus, the Streptococcus infantarius and the Streptococcus alactolyticus branch. In animals, SBSEC are causative agents for ruminal acidosis, potentially laminitis and infective endocarditis (IE). In humans, a strong association was established between bacteraemia, IE and colorectal cancer. Especially the SBSEC-species S. gallolyticus subsp. gallolyticus is an emerging pathogen for IE and prosthetic joint infections. S. gallolyticus subsp. pasteurianus and the S. infantarius branch are further associated with biliary and urinary tract infections. Knowledge on pathogenic mechanisms is so far limited to colonization factors such as pili and biofilm formation. Certain strain variants of S. gallolyticus subsp. macedonicus and S. infantarius subsp. infantarius are associated with traditional dairy and plant-based food fermentations and display traits suggesting safety. However, due to their close relationship to virulent strains, their use in food fermentation has to be critically assessed. Additionally, implementing accurate and up-to-date taxonomy is critical to enable appropriate treatment of patients and risk assessment of species and strains via recently developed multilocus sequence typing schemes to enable comparative global epidemiology. Comparative genomics revealed that SBSEC strains harbour genomics islands (GI) that seem acquired from other streptococci by horizontal gene transfer. In case of virulent strains these GI frequently encode putative virulence factors, in strains from food fermentation the GI encode functions that are

  6. Evaluation of Group B Streptococcus Differential Agar for detection and isolation of Streptococcus agalactiae.

    PubMed

    Bou, G; Figueira, M; Canle, D; Cartelle, M; Eiros, J M; Villanueva, R

    2005-08-01

    In total, 320 vaginal or rectal swabs were cultured on Granada medium (GM) or Group B Streptococcus Differential Agar (GBSDA), and were also inoculated into LIM broth (Todd-Hewitt broth supplemented with selective antibiotics), for detection of group B Streptococcus (GBS). Overall, GBS isolates were detected on 53 of the 320 swabs; 47 of these isolates grew on both GM and GBSDA, five only on GBSDA, and one only following subculture from LIM broth. GBSDA appears to be a valid alternative to GM for the growth of GBS isolates from pregnant women.

  7. Association of the immature platelet fraction with sepsis diagnosis and severity

    PubMed Central

    Hubert, Rodolfo Monteiro Enz; Rodrigues, Melina Veiga; Andreguetto, Bruna Dolci; Santos, Thiago M.; de Fátima Pereira Gilberti, Maria; de Castro, Vagner; Annichino-Bizzacchi, Joyce M.; Dragosavac, Desanka; Carvalho-Filho, Marco Antonio; De Paula, Erich Vinicius

    2015-01-01

    Management of Sepsis would greatly benefit from the incorporation of simple and informative new biomarkers in clinical practice. Ideally, a sepsis biomarker should segregate infected from non-infected patients, provide information about prognosis and organ-specific damage, and be accessible to most healthcare services. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Recently, a study performed in critically-ill patients suggested that IPF could be a more accurate sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this retrospective study we evaluated the performance of IPF and IRF as biomarkers of sepsis diagnosis and severity. 41 patients admitted to two intensive care units were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non-complicated sepsis. Significantly higher IPF levels were observed in patients with severe sepsis/septic shock. IPF correlated with sepsis severity scores and presented the highest diagnostic accuracy for the presence of sepsis of all studied clinical and laboratory parameters. No significant differences were observed in IRF levels. Our results suggest that IPF levels could be used as a biomarker of sepsis diagnosis and severity. PMID:25620275

  8. Association of the immature platelet fraction with sepsis diagnosis and severity.

    PubMed

    Enz Hubert, Rodolfo Monteiro; Rodrigues, Melina Veiga; Andreguetto, Bruna Dolci; Santos, Thiago M; de Fátima Pereira Gilberti, Maria; de Castro, Vagner; Annichino-Bizzacchi, Joyce M; Dragosavac, Desanka; Carvalho-Filho, Marco Antonio; De Paula, Erich Vinicius

    2015-01-26

    Management of Sepsis would greatly benefit from the incorporation of simple and informative new biomarkers in clinical practice. Ideally, a sepsis biomarker should segregate infected from non-infected patients, provide information about prognosis and organ-specific damage, and be accessible to most healthcare services. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Recently, a study performed in critically-ill patients suggested that IPF could be a more accurate sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this retrospective study we evaluated the performance of IPF and IRF as biomarkers of sepsis diagnosis and severity. 41 patients admitted to two intensive care units were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non-complicated sepsis. Significantly higher IPF levels were observed in patients with severe sepsis/septic shock. IPF correlated with sepsis severity scores and presented the highest diagnostic accuracy for the presence of sepsis of all studied clinical and laboratory parameters. No significant differences were observed in IRF levels. Our results suggest that IPF levels could be used as a biomarker of sepsis diagnosis and severity.

  9. A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains

    PubMed Central

    Zaccaria, Edoardo; Cao, Rui; Wells, Jerry M.; van Baarlen, Peter

    2016-01-01

    Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates. PMID:26999052

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

    PubMed Central

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

    2010-01-01

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

  11. Clinical outcome and predictors of mortality in children with sepsis, severe sepsis, and septic shock from Rohtak, Haryana: A prospective observational study

    PubMed Central

    Kaur, Gurpreet; Vinayak, Nikhil; Mittal, Kundan; Kaushik, Jaya Shankar; Aamir, Mohammad

    2014-01-01

    Background: Information regarding early predictive factors for mortality and morbidity in sepsis is limited from developing countries. Methods: A prospective observational study was conducted to determine the clinical outcome and predictors of mortality in children with sepsis, severe sepsis, and septic shock. Children aged 1 month to 14 years admitted to a tertiary care pediatric intensive care unit (PICU) with a diagnosis of sepsis, severe sepsis, or septic shock were enrolled in the study. Hemodynamic and laboratory parameters which discriminate survivors from nonsurvivors were evaluated. Results: A total of 50 patients (30 [60%] males) were enrolled in the study, of whom 21 (42%) were discharged (survivors) and rest 29 (58%) expired (nonsurvivor). Median (interquartile range) age of enrolled patients were 18 (6, 60) months. Mortality was not significantly predicted individually by any factor including age (odds ratio [OR] [95% confidence interval [CI

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

    PubMed

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

    2011-11-01

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

  13. 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

  14. Recombination between Streptococcus suis ICESsu32457 and Streptococcus agalactiae ICESa2603 yields a hybrid ICE transferable to Streptococcus pyogenes.

    PubMed

    Marini, Emanuela; Palmieri, Claudio; Magi, Gloria; Facinelli, Bruna

    2015-07-01

    Integrative conjugative elements (ICEs) are mobile genetic elements that reside in the chromosome but retain the ability to undergo excision and to transfer by conjugation. Genes involved in drug resistance, virulence, or niche adaptation are often found among backbone genes as cargo DNA. We recently characterized in Streptococcus suis an ICE (ICESsu32457) carrying resistance genes [tet(O/W/32/O), tet(40), erm(B), aphA, and aadE] in the 15K unstable genetic element, which is flanked by two ∼1.3kb direct repeats. Remarkably, ∼1.3-kb sequences are conserved in ICESa2603 of Streptococcus agalactiae 2603V/R, which carry heavy metal resistance genes cadC/cadA and mer. In matings between S. suis 32457 (donor) and S. agalactiae 2603V/R (recipient), transconjugants were obtained. PCR experiments, PFGE, and sequence analysis of transconjugants demonstrated a tandem array between ICESsu32457 and ICESa2603. Matings between tandem array-containing S. agalactiae 2603V/R (donor) and Streptococcus pyogenes RF12 (recipient) yielded a single transconjugant containing a hybrid ICE, here named ICESa2603/ICESsu32457. The hybrid formed by recombination of the left ∼1.3-kb sequence of ICESsu32457 and the ∼1.3-kb sequence of ICESa2603. Interestingly, the hybrid ICE was transferable between S. pyogenes strains, thus demonstrating that it behaves as a conventional ICE. These findings suggest that both tandem arrays and hybrid ICEs may contribute to the evolution of antibiotic resistance in streptococci, creating novel mobile elements capable of disseminating new combinations of antibiotic resistance genes.

  15. Diversity of human small intestinal Streptococcus and Veillonella populations.

    PubMed

    van den Bogert, Bartholomeus; Erkus, Oylum; Boekhorst, Jos; de Goffau, Marcus; Smid, Eddy J; Zoetendal, Erwin G; Kleerebezem, Michiel

    2013-08-01

    Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points.

  16. Draft Genome Sequence of Streptococcus agalactiae PR06

    PubMed Central

    MZ, Irma Syakina; Teh, L. K.

    2013-01-01

    Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium that was first recognized as a causative agent of bovine mastitis. S. agalactiae has subsequently emerged as a significant cause of human diseases. Here, we report the draft genome sequence of S. agalactiae PR06, which was isolated from a septicemic patient in a local hospital in Malaysia. PMID:23766409

  17. Human Streptococcus agalactiae isolate in Nile tilapia (Oreochromis niloticus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus agalactiae, the Lancefield group B Streptococcus (GBS), long recognized as a mammalian pathogen, is an emerging pathogen to fish. We show that a GBS serotype Ia, multilocus sequence type ST-7 isolate from a human neonatal meningitis clinical case causes disease signs and mortality in N...

  18. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?

    PubMed Central

    de Lima, Lúcio Flávio Peixoto

    2016-01-01

    Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named “metabolic resuscitation”, would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to “mitochondrial resuscitation” are expected to increase driven by genomics and metabolomics. PMID:27501325

  19. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?

    PubMed

    Leite, Heitor Pons; de Lima, Lúcio Flávio Peixoto

    2016-07-01

    Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named "metabolic resuscitation", would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to "mitochondrial resuscitation" are expected to increase driven by genomics and metabolomics. PMID:27501325

  20. Randomized Controlled Trial of Calcitriol in Severe Sepsis

    PubMed Central

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

    2014-01-01

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

  1. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?

    PubMed

    Leite, Heitor Pons; de Lima, Lúcio Flávio Peixoto

    2016-07-01

    Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named "metabolic resuscitation", would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to "mitochondrial resuscitation" are expected to increase driven by genomics and metabolomics.

  2. Clavanin bacterial sepsis control using a novel methacrylate nanocarrier

    PubMed Central

    Saúde, Amanda CM; Ombredane, Alicia S; Silva, Osmar N; Barbosa, João ARG; Moreno, Susana E; Guerra Araujo, Ana Claudia; Falcão, Rosana; Silva, Luciano P; Dias, Simoni C; Franco, Octávio L

    2014-01-01

    Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT® L 100-55 and RS 30 D solution (3:1 w:w). Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections. PMID:25382976

  3. Case Report of Sepsis in Neonates Fed Expressed Mother's Milk.

    PubMed

    Smith, Sandra L; Serke, Laura

    2016-01-01

    Mother's milk is the recommended food for premature infants cared for in the NICU. In the cases presented in this article, mothers pumped their milk into food-grade aseptic plastic containers. Milk was refrigerated before use. In Case 1, an infant developed Pseudomonas aeruginosa sepsis. In Case 2, an infant developed methicillin-resistant Staphylococcus aureus. Both cases were attributed to contaminated mother's milk. Proper cleaning and sterilization of pump parts is essential to prevent milk contamination. PMID:27486089

  4. Surviving sepsis--a 3D integrative educational simulator.

    PubMed

    Ježek, Filip; Tribula, Martin; Kulhánek, Tomáš; Mateják, Marek; Privitzer, Pavol; Šilar, Jan; Kofránek, Jiří; Lhotská, Lenka

    2015-08-01

    Computer technology offers greater educational possibilities, notably simulation and virtual reality. This paper presents a technology which serves to integrate multiple modalities, namely 3D virtual reality, node-based simulator, Physiomodel explorer and explanatory physiological simulators employing Modelica language and Unity3D platform. This emerging tool chain should allow the authors to concentrate more on educational content instead of application development. The technology is demonstrated through Surviving sepsis educational scenario, targeted on Microsoft Windows Store platform. PMID:26737091

  5. Update in sepsis and acute kidney injury 2014.

    PubMed

    Schortgen, Frédérique; Asfar, Pierre

    2015-06-01

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

  6. 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.

  7. Host response biomarker in sepsis: suPAR detection.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna

    2015-01-01

    Recent studies of our group have shown that suPAR may complement APACHE II score for risk assessment in sepsis. suPAR may be measured in serum of patients by an enzyme immunosorbent assay developed by Virogates (suPARnostic™). Production of suPAR from circulating neutrophils and monocytes may be assessed after isolation of neutrophils and monocytes and ex vivo culture. This is followed by measurement of suPAR in culture supernatants.

  8. Surviving sepsis--a 3D integrative educational simulator.

    PubMed

    Ježek, Filip; Tribula, Martin; Kulhánek, Tomáš; Mateják, Marek; Privitzer, Pavol; Šilar, Jan; Kofránek, Jiří; Lhotská, Lenka

    2015-08-01

    Computer technology offers greater educational possibilities, notably simulation and virtual reality. This paper presents a technology which serves to integrate multiple modalities, namely 3D virtual reality, node-based simulator, Physiomodel explorer and explanatory physiological simulators employing Modelica language and Unity3D platform. This emerging tool chain should allow the authors to concentrate more on educational content instead of application development. The technology is demonstrated through Surviving sepsis educational scenario, targeted on Microsoft Windows Store platform.

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

    PubMed Central

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

    2016-01-01

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

  10. Linking the sepsis triad of inflammation, coagulation, and suppressed fibrinolysis to infants.

    PubMed

    Short, Mary A

    2004-10-01

    Sepsis continues to be a significant cause of morbidity and mortality in hospitalized newborns and premature infants. The pathophysiology and disease state of sepsis appear to be similar between adults and children. Both groups display symptoms that indicate a systemic inflammatory response leading to coagulopathy, hypotension, inadequate perfusion of peripheral tissues and organs, and, ultimately, organ failure and death. By presenting a comparison of adult and neonatal pathophysiology, as well as a supporting literature review and clinical evidence, this article links the pathways of inflammation, activation of coagulation, and impaired fibrinolysis, known as the sepsis cascade, to neonatal sepsis. Knowledge of the pathophysiology has important clinical and research implications. Unlike traditional antimicrobial therapy, new potential therapies, currently under investigation for the treatment of sepsis, target the cellular response rather than the invading organism. A more complete understanding of the pathophysiology of sepsis may also lead to diagnostic tools with improved sensitivity and specificity for early recognition and treatment.

  11. A Systematic Review of Rhubarb (a Traditional Chinese Medicine) Used for the Treatment of Experimental Sepsis.

    PubMed

    Lai, Fang; Zhang, Yan; Xie, Dong-Ping; Mai, Shu-Tao; Weng, Yan-Na; Du, Jiong-Dong; Wu, Guang-Ping; Zheng, Jing-Xia; Han, Yun

    2015-01-01

    Sepsis is a global major health problem in great need for more effective therapy. For thousands of years, Rhubarb had been used for various diseases including severe infection. Pharmacological studies and trials reported that Rhubarb may be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on Rhubarb for sepsis. The present study is the first systematic review of Rhubarb used for the treatment of experimental sepsis in both English and Chinese literatures by identifying 27 studies from 7 databases. It showed that Rhubarb might be effective in reducing injuries in gastrointestinal tract, lung, and liver induced by sepsis, and its potential mechanisms might include reducing oxidative stress and inflammation, ameliorating microcirculatory disturbance, and maintaining immune balance. Yet the positive findings should be interpreted with caution due to poor methodological quality. In a word, Rhubarb might be a promising candidate that is worth further clinical and experimental trials for sepsis therapy.

  12. Novel Streptococcus infantarius subsp. infantarius variants harboring lactose metabolism genes homologous to Streptococcus thermophilus.

    PubMed

    Jans, Christoph; Gerber, Andrea; Bugnard, Joséphine; Njage, Patrick Murigu Kamau; Lacroix, Christophe; Meile, Leo

    2012-08-01

    Streptococcus infantarius subsp. infantarius belongs to the Streptococcus bovis/Streptococcus equinus complex (SBSEC) commonly associated with human and animal infections. We elucidated the lactose metabolism of S. infantarius subsp. infantarius predominant in African fermented milk products. S. infantarius subsp. infantarius isolates (n = 192) were identified in 88% of spontaneously fermented camel milk suusac samples (n = 24) from Kenya and Somalia at log₁₀ 8.2-8.5 CFU mL⁻¹. African S. infantarius isolates excreted stoichiometric amounts of galactose when grown on lactose, exhibiting a metabolism similar to Streptococcus thermophilus and distinct from their type strain. African S. infantarius subsp. infantarius CJ18 harbors a regular gal operon with 99.7-100% sequence identity to S. infantarius subsp. infantarius ATCC BAA-102(T) and a gal-lac operon with 91.7-97.6% sequence identity to S. thermophilus, absent in all sequenced SBSEC strains analyzed. The expression and functionality of lacZ was demonstrated in a β-galactosidase assay. The gal-lac operon was identified in 100% of investigated S. infantarius isolates (n = 46) from suusac samples and confirmed in Malian fermented cow milk isolates. The African S. infantarius variant potentially evolved through horizontal gene transfer of an S. thermophilus-homologous lactose pathway. Safety assessments are needed to identify any putative health risks of this novel S. infantarius variant. PMID:22475940

  13. Influence of pH on inhibition of Streptococcus mutans by Streptococcus oligofermentans.

    PubMed

    Liu, Ying; Chu, Lei; Wu, Fei; Guo, Lili; Li, Mengci; Wang, Yinghui; Wu, Ligeng

    2014-02-01

    Streptococcus oligofermentans is a novel strain of oral streptococcus that can specifically inhibit the growth of Streptococcus mutans. The aims of this study were to assess the growth of S. oligofermentans and the ability of S. oligofermentans to inhibit growth of Streptococcus mutans at different pH values. Growth inhibition was investigated in vitro using an interspecies competition assay. The 4-aminoantipyine method was used to measure the initial production rate and the total yield of hydrogen peroxide in S. oligofermentans. S. oligofermentans grew best at pH 7.0 and showed the most pronounced inhibitory effect when it was inoculated earlier than S. mutans. In terms of the total yield and the initial production rate of hydrogen peroxide by S. oligofermentans, the effects of the different culture pH values were as follows: pH 7.0 > 6.5 > 6.0 > 7.5 > 5.5 = 8.0 (i.e. there was no significant difference between pH 5.5 and pH 8.0). Environmental pH and the sequence of inoculation significantly affected the ability of S. oligofermentans to inhibit the growth of S. mutans. The degree of inhibition may be attributed to the amount of hydrogen peroxide produced.

  14. Novel Streptococcus infantarius subsp. infantarius variants harboring lactose metabolism genes homologous to Streptococcus thermophilus.

    PubMed

    Jans, Christoph; Gerber, Andrea; Bugnard, Joséphine; Njage, Patrick Murigu Kamau; Lacroix, Christophe; Meile, Leo

    2012-08-01

    Streptococcus infantarius subsp. infantarius belongs to the Streptococcus bovis/Streptococcus equinus complex (SBSEC) commonly associated with human and animal infections. We elucidated the lactose metabolism of S. infantarius subsp. infantarius predominant in African fermented milk products. S. infantarius subsp. infantarius isolates (n = 192) were identified in 88% of spontaneously fermented camel milk suusac samples (n = 24) from Kenya and Somalia at log₁₀ 8.2-8.5 CFU mL⁻¹. African S. infantarius isolates excreted stoichiometric amounts of galactose when grown on lactose, exhibiting a metabolism similar to Streptococcus thermophilus and distinct from their type strain. African S. infantarius subsp. infantarius CJ18 harbors a regular gal operon with 99.7-100% sequence identity to S. infantarius subsp. infantarius ATCC BAA-102(T) and a gal-lac operon with 91.7-97.6% sequence identity to S. thermophilus, absent in all sequenced SBSEC strains analyzed. The expression and functionality of lacZ was demonstrated in a β-galactosidase assay. The gal-lac operon was identified in 100% of investigated S. infantarius isolates (n = 46) from suusac samples and confirmed in Malian fermented cow milk isolates. The African S. infantarius variant potentially evolved through horizontal gene transfer of an S. thermophilus-homologous lactose pathway. Safety assessments are needed to identify any putative health risks of this novel S. infantarius variant.

  15. Curcumin modulates leukocyte and platelet adhesion in murine sepsis

    PubMed Central

    Vachharajani, Vidula; Wang, Si-Wei; Mishra, Nilamadhab; El-Gazzar, Mohammad; Yoza, Barbara; McCall, Charles

    2010-01-01

    Objective Circulating cell-endothelial cell interaction in sepsis is a rate-determining factor in organ dysfunction, and interventions targeting this process have a potential therapeutic value. In this project, we examined whether curcumin, an active ingredient of turmeric and an anti-inflammatory agent, could disrupt interactions between circulating blood cells and endothelium and improve survival in a murine model of sepsis. Methods Mice were subjected to cecal ligation and puncture (CLP) to induce sepsis vs. sham surgery. We studied leukocyte and platelet adhesion in cerebral microcirculation using intravital fluorescent video microscopy technique, blood brain barrier dysfunction using Evans Blue leakage method, P-selectin expression using dual radiolabeling technique and survival in mice subjected to Sham, CLP and CLP with curcumin pre-treatment (CLP+Curcumin). Results Curcumin significantly attenuated leukocyte and platelet adhesion in cerebral microcirculation, Evans Blue leakage in the brain tissue and improved survival in mice with CLP. P-selectin expression in mice with CLP+Curcumin was significantly attenuated compared to CLP in various microcirculatory beds including brain. Reduction in platelet adhesion was predominantly via modulation of endothelium by curcumin. Conclusion Curcumin pre-treatment modulates leukocyte and platelet adhesion and blood brain barrier dysfunction in mice with CLP via P-selectin expression and improves survival in mice with CLP. PMID:20690979

  16. The role of genetics and antibodies in sepsis

    PubMed Central

    Giamarellos-Bourboulis, Evangelos J.

    2016-01-01

    During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production. PMID:27713886

  17. Evaluating the Near-Term Infant for Early Onset Sepsis

    PubMed Central

    Jordan, Jeanne A.; Durso, Mary Beth; Butchko, Allyson R.; Jones, Judith G.; Brozanski, Beverly S.

    2006-01-01

    Although the rate of early onset sepsis in the near-term neonate is low (one to eight of 1000 cases), the rate of mortality and morbidity is high. As a result, infants receive multiple, broad-spectrum antibiotic therapy, many for up to 7 days despite blood cultures showing no growth. Maternal intrapartum antibiotic prophylaxis and small blood volume collections from infants are cited as reasons for the lack of confidence in negative culture results. Incorporating an additional, more rapid test could facilitate a more timely diagnosis in these infants. To this end, a 16S rDNA polymerase chain reaction (PCR) assay was compared to blood culturing for use as a tool in evaluating early onset sepsis. Of 1751 neonatal intensive care unit admissions that were screened, 1233 near-term infants met inclusion criteria. Compared to culture, PCR demonstrated excellent analytical specificity (1186 of 1216, 97.5%) and negative predictive value (1186 of 1196, 99.2%); however, PCR failed to detect a significant number of culture-proven cases. These findings underscore the cautionary stance that should be taken at this time when considering the use of a molecular amplification test for diagnosing neonatal sepsis. The experience gained from this study illustrates the need for changes in sample collection and preparation techniques so as to improve analytical sensitivity of the assay. PMID:16825509

  18. Zwitterionic chitosan for the systemic treatment of sepsis.

    PubMed

    Cho, Eun Jung; Doh, Kyung-Oh; Park, Jinho; Hyun, Hyesun; Wilson, Erin M; Snyder, Paul W; Tsifansky, Michael D; Yeo, Yoon

    2016-01-01

    Severe sepsis and septic shock are life-threatening conditions, with Gram-negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cationic charge, the very properties responsible for their interactions with LPS. We hypothesize that a chitosan derivative zwitterionic chitosan (ZWC), previously shown to suppress the production of pro-inflammatory cellular mediators in LPS-challenged macrophages, will have protective effects in an animal model of sepsis induced by systemic injection of LPS. In this study, we evaluate whether ZWC attenuates the fatal effect of LPS in C57BL/6 mice and investigate the mechanism by which ZWC counteracts the LPS effect using a PMJ2-PC peritoneal macrophage cell line. Unlike its parent compound with low water solubility, intraperitoneally administered ZWC is readily absorbed with no local residue or adverse tissue reaction at the injection site. Whether administered at or prior to the LPS challenge, ZWC more than doubles the animals' median survival time. ZWC appears to protect the LPS-challenged organisms by forming a complex with LPS and thus attenuating pro-inflammatory signaling pathways. These findings suggest that ZWC have utility as a systemic anti-LPS agent. PMID:27412050

  19. Delayed emergency myelopoiesis following polymicrobial sepsis in neonates.

    PubMed

    Cuenca, Alex G; Cuenca, Angela L; Gentile, Lori F; Efron, Philip A; Islam, Saleem; Moldawer, Lyle L; Kays, David W; Larson, Shawn D

    2015-05-01

    Neonates have increased susceptibility to infection, which leads to increased mortality. Whether or not this as a result of implicit deficits in neonatal innate immune function or recapitulation of innate immune effector cell populations following infection is unknown. Here, we examine the process of emergency myelopoiesis whereby the host repopulates peripheral myeloid cells lost following the initial infectious insult. As early inflammatory responses are often dependent upon NF-κB and type I IFN signaling, we also examined whether the absence of MyD88, TRIF or MyD88 and TRIF signaling altered the myelopoietic response in neonates to polymicrobial sepsis. Following neonatal polymicrobial septic challenge, hematopoietic stem cell (HSC) expansion in bone marrow and the spleen were both attenuated and delayed in neonates compared with adults. Similar reductions in other precursors were observed in neonates. Similar to adult studies, the expansion of progenitor stem cell populations was also seen in the absence of MyD88 and/or TRIF signaling. Overall, neonates have impaired emergency myelopoiesis in response to sepsis compared with young adults. Despite reports that this expansion may be related to TLR signaling, our data suggest that other factors may be important, as TRIF(-/-) and MyD88(-/-) neonatal HSCs are still able to expand in response to polymicrobial neonatal sepsis.

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

    PubMed

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

    2009-06-01

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

  1. Zwitterionic chitosan for the systemic treatment of sepsis

    PubMed Central

    Cho, Eun Jung; Doh, Kyung-Oh; Park, Jinho; Hyun, Hyesun; Wilson, Erin M.; Snyder, Paul W.; Tsifansky, Michael D.; Yeo, Yoon

    2016-01-01

    Severe sepsis and septic shock are life-threatening conditions, with Gram-negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cationic charge, the very properties responsible for their interactions with LPS. We hypothesize that a chitosan derivative zwitterionic chitosan (ZWC), previously shown to suppress the production of pro-inflammatory cellular mediators in LPS-challenged macrophages, will have protective effects in an animal model of sepsis induced by systemic injection of LPS. In this study, we evaluate whether ZWC attenuates the fatal effect of LPS in C57BL/6 mice and investigate the mechanism by which ZWC counteracts the LPS effect using a PMJ2-PC peritoneal macrophage cell line. Unlike its parent compound with low water solubility, intraperitoneally administered ZWC is readily absorbed with no local residue or adverse tissue reaction at the injection site. Whether administered at or prior to the LPS challenge, ZWC more than doubles the animals’ median survival time. ZWC appears to protect the LPS-challenged organisms by forming a complex with LPS and thus attenuating pro-inflammatory signaling pathways. These findings suggest that ZWC have utility as a systemic anti-LPS agent. PMID:27412050

  2. Sepsis: Something Old, Something New, and a Systems View

    PubMed Central

    Namas, Rami; Zamora, Ruben; Namas, Rajaie; An, Gary; Doyle, John; Dick, Thomas E.; Jacono, Frank J.; Androulakis, Ioannis P.; Nieman, Gary F.; Chang, Steve; Billiar, Timothy R.; Kellum, John A.; Angus, Derek C.; Vodovotz, Yoram

    2011-01-01

    Sepsisis a clinical syndrome characterized by a multi-system response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation, which, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, pro-inflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis, and focus specifically on the biological cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multi-dimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology. PMID:21798705

  3. 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-α 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

  4. Antiviral Prevention of Sepsis Induced Cytomegalovirus Reactivation in Immunocompetent Mice

    PubMed Central

    Forster, Meghan R.; Trgovcich, Joanne; Zimmerman, Peter; Chang, Alexander; Miller, Cortland; Klenerman, Paul; Cook, Charles H.

    2009-01-01

    Introduction Immunocompetent patients can reactivate latent cytomegalovirus (CMV) during critical illness and reactivation is associated with significantly worse outcomes. Prior to clinical trials in humans to prove causality, we sought to determine an optimal antiviral treatment strategy. Methods Mice latently infected with murine CMV (MCMV) received a septic reactivation trigger and were randomized to receive one of four ganciclovir regimens or saline. Lungs were evaluated for viral transcriptional reactivation and fibrosis after each regimen. Influences of ganciclovir on early sepsis induced pulmonary inflammation and T-cell activation were studied after sepsis induction. Results All ganciclovir regimens reduced measurable MCMV transcriptional reactivation, and 10mg/day for 7 or 21 days was most effective. Lower dose (5mg/kg/day) or delayed therapy were associated with significant breakthrough reactivation. Higher doses of ganciclovir given early were associated with the lowest incidence of pulmonary fibrosis, and delay of therapy for 1 week was associated with significantly worse pulmonary fibrosis. Although bacterial sepsis induced activation of MCMV-specific pulmonary T-cells, this activation was not influenced by ganciclovir. Conclusion These results suggest that antiviral treatment trials in humans should use 10mg/kg/day ganciclovir administered as early as possible in at-risk patients to minimize reactivation events and associated pulmonary injury PMID:20004216

  5. Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed

    Tulli, G

    2003-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

    Dellinger, R Phillip

    2015-04-01

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

  11. [Experience in the treatment of severe forms of sepsis by extracorporeal therapy and hyperbaric oxygenation].

    PubMed

    Zhidkov, K P; Klechikov, V Z; Bogatyr', M N

    1997-01-01

    The results of multiple modality treatment of 81 patients with sepsis complicated by multiple organ failure are assessed. In 40 patients the traditional therapy of sepsis was supplemented with extracorporeal methods (hemoperfusion, autotransfusion of UV-exposed blood, and perfusion of xenospleen slices) and hyperbaric oxygenation (HBO) sessions. In the patients treated traditionally the mortality was 94%, whereas addition of extracorporeal treatment and HBO decreased this value to 40%. Hence, extracorporeal treatment and HBO are recommended for the treatment of sepsis.

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

    2014-01-01

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

  14. Association between PAI-1 polymorphisms and plasma PAI-1 level with sepsis in severely burned patients.

    PubMed

    Chi, Y F; Chai, J K; Yu, Y M; Luo, H M; Zhang, Q X; Feng, R

    2015-01-01

    We investigated the association between plasminogen activator inhibitor-1 (PAI-1) polymorphisms and plasma PAI-1 level with sepsis in severely burned patients. A total of 182 patients with burn areas lager than 30% of the body surface area were enrolled in this study. Peripheral blood samples were obtained from 103 patients with sepsis (sepsis group) and 79 patients without sepsis (control group). An allele-specific polymerase chain reaction assay was used to determine PAI-1 polymorphism 4G/5G distribution. Plasma PAI-1 levels were detected using an enzyme-linked immunosorbent assay. The frequency of the 4G/4G genotype and the 4G allele frequency in the sepsis group were 42.7 and 62.1% respectively, which were significantly higher than those in the control group (P < 0.05). Sepsis patients had a significantly higher plasma PAI-1 level than the control group (P < 0.05). Compared with the 5G/5G genotype, PAI-1 concentrations were significantly higher in the 4G/4G genotype (P < 0.05). The study indicates that the 4G/5G promoter polymorphism of PAI-1 gene may be related to the susceptibility to burn sepsis and that the 4G/4G genotype may be an important genetic risk factor of burn sepsis. Additionally, PAI-1 concentrations in the serum are increased in patients with burn sepsis.

  15. Development and Validation of a Disease Severity Scoring Model for Pediatric Sepsis

    PubMed Central

    HU, Li; ZHU, Yimin; CHEN, Mengshi; LI, Xun; LU, Xiulan; LIANG, Ying; TAN, Hongzhuan

    2016-01-01

    Background: Multiple severity scoring systems have been devised and evaluated in adult sepsis, but a simplified scoring model for pediatric sepsis has not yet been developed. This study aimed to develop and validate a new scoring model to stratify the severity of pediatric sepsis, thus assisting the treatment of sepsis in children. Methods: Data from 634 consecutive patients who presented with sepsis at Children’s hospital of Hunan province in China in 2011–2013 were analyzed, with 476 patients placed in training group and 158 patients in validation group. Stepwise discriminant analysis was used to develop the accurate discriminate model. A simplified scoring model was generated using weightings defined by the discriminate coefficients. The discriminant ability of the model was tested by receiver operating characteristic curves (ROC). Results: The discriminant analysis showed that prothrombin time, D-dimer, total bilirubin, serum total protein, uric acid, PaO2/FiO2 ratio, myoglobin were associated with severity of sepsis. These seven variables were assigned with values of 4, 3, 3, 4, 3, 3, 3 respectively based on the standardized discriminant coefficients. Patients with higher scores had higher risk of severe sepsis. The areas under ROC (AROC) were 0.836 for accurate discriminate model, and 0.825 for simplified scoring model in validation group. Conclusions: The proposed disease severity scoring model for pediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which has important clinical significance in evaluating the severity of pediatric sepsis and predicting its progress. PMID:27516993

  16. Risk Factors and Prevention of Late Onset Sepsis in Premature Infants

    PubMed Central

    Downey, L Corbin; Smith, P Brian; Benjamin, Daniel K

    2010-01-01

    Late-onset sepsis in premature infants is a major cause of morbidity, mortality, and increased medical costs. Risk factors include low birth weight, low gestational age, previous antimicrobial exposure, poor hand hygiene, and central venous catheters. Methods studied to prevent late-onset sepsis include early feedings, immune globulin administration, prophylactic antimicrobial administration, and improved hand hygiene. In this review, we will outline the risk factors for development of late-onset sepsis and evidence supporting methods for prevention of late-onset sepsis in premature infants. PMID:20116186

  17. Angiopoietin-1, angiopoietin-2 and bicarbonate as diagnostic biomarkers in children with severe sepsis.

    PubMed

    Wang, Kun; Bhandari, Vineet; Giuliano, John S; O Hern, Corey S; Shattuck, Mark D; Kirby, Michael

    2014-01-01

    Severe pediatric sepsis continues to be associated with high mortality rates in children. Thus, an important area of biomedical research is to identify biomarkers that can classify sepsis severity and outcomes. The complex and heterogeneous nature of sepsis makes the prospect of the classification of sepsis severity using a single biomarker less likely. Instead, we employ machine learning techniques to validate the use of a multiple biomarkers scoring system to determine the severity of sepsis in critically ill children. The study was based on clinical data and plasma samples provided by a tertiary care center's Pediatric Intensive Care Unit (PICU) from a group of 45 patients with varying sepsis severity at the time of admission. Canonical Correlation Analysis with the Forward Selection and Random Forests methods identified a particular set of biomarkers that included Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), and Bicarbonate (HCO[Formula: see text]) as having the strongest correlations with sepsis severity. The robustness and effectiveness of these biomarkers for classifying sepsis severity were validated by constructing a linear Support Vector Machine diagnostic classifier. We also show that the concentrations of Ang-1, Ang-2, and HCO[Formula: see text] enable predictions of the time dependence of sepsis severity in children.

  18. Identification of microRNA as sepsis biomarker based on miRNAs regulatory network analysis.

    PubMed

    Huang, Jie; Sun, Zhandong; Yan, Wenying; Zhu, Yujie; Lin, Yuxin; Chen, Jiajai; Shen, Bairong; Wang, Jian

    2014-01-01

    Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroRNAs (miRNAs) are small noncoding RNAs which pair the sites in mRNAs to regulate gene expression in eukaryotes. They play a key role in inflammatory response, and have been validated to be potential sepsis biomarker recently. In the present work, we apply a miRNA regulatory network based method to identify novel microRNA biomarkers associated with the early diagnosis of sepsis. By analyzing the miRNA expression profiles and the miRNA regulatory network, we obtained novel miRNAs associated with sepsis. Pathways analysis, disease ontology analysis, and protein-protein interaction network (PIN) analysis, as well as ROC curve, were exploited to testify the reliability of the predicted miRNAs. We finally identified 8 novel miRNAs which have the potential to be sepsis biomarkers.

  19. Sepsis following cancer surgery: the need for early recognition and standardised clinical care.

    PubMed

    Hiong, A; Thursky, K A; Teh, B W; Haeusler, G M; Slavin, M A; Worth, L J

    2016-01-01

    Despite the implementation of multimodal bundles of care in hospitalised patients, post-operative sepsis in patients with cancer still accounts for a significant burden of illness and substantial healthcare costs. Patients undergoing surgery for cancer are at particular risk of sepsis due to underlying malignancy, being immunocompromised associated with cancer management and the complexity of surgical procedures performed. In this review, we evaluate the burden of illness and risks for sepsis following surgery for cancer. Current evidence supporting standardised strategies for sepsis management (including early recognition and resuscitation) is examined together with challenges in implementing quality improvement programs.

  20. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

    PubMed

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-04-01

    Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  1. Reactive oxygen species-associated molecular signature predicts survival in patients with sepsis.

    PubMed

    Bime, Christian; Zhou, Tong; Wang, Ting; Slepian, Marvin J; Garcia, Joe G N; Hecker, Louise

    2016-06-01

    Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)-associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies. PMID:27252846

  2. Paramedic Recognition of Sepsis in the Prehospital Setting: A Prospective Observational Study

    PubMed Central

    Travers, Andrew H.; Cain, Edward; Campbell, Samuel G.; Jensen, Jan L.; Petrie, David A.; Erdogan, Mete; Patrick, Gredi; Patrick, Ward

    2016-01-01

    Background. Patients with sepsis benefit from early diagnosis and treatment. Accurate paramedic recognition of sepsis is important to initiate care promptly for patients who arrive by Emergency Medical Services. Methods. Prospective observational study of adult patients (age ≥ 16 years) transported by paramedics to the emergency department (ED) of a Canadian tertiary hospital. Paramedic identification of sepsis was assessed using a novel prehospital sepsis screening tool developed by the study team and compared to blind, independent documentation of ED diagnoses by attending emergency physicians (EPs). Specificity, sensitivity, accuracy, positive and negative predictive value, and likelihood ratios were calculated with 95% confidence intervals. Results. Overall, 629 patients were included in the analysis. Sepsis was identified by paramedics in 170 (27.0%) patients and by EPs in 71 (11.3%) patients. Sensitivity of paramedic sepsis identification compared to EP diagnosis was 73.2% (95% CI 61.4–83.0), while specificity was 78.8% (95% CI 75.2–82.2). The accuracy of paramedic identification of sepsis was 78.2% (492/629, 52 true positive, 440 true negative). Positive and negative predictive values were 30.6% (95% CI 23.8–38.1) and 95.9% (95% CI 93.6–97.5), respectively. Conclusion. Using a novel prehospital sepsis screening tool, paramedic recognition of sepsis had greater specificity than sensitivity with reasonable accuracy. PMID:27051533

  3. Probiotics for Preventing Late-Onset Sepsis in Preterm Neonates

    PubMed Central

    Zhang, Guo-Qiang; Hu, Hua-Jian; Liu, Chuan-Yang; Shakya, Shristi; Li, Zhong-Yue

    2016-01-01

    Abstract The effect of probiotics on late-onset sepsis (LOS) in preterm neonates remains controversial. The authors systematically reviewed the literature to investigate whether enteral probiotic supplementation reduced the risk of LOS in preterm neonates in neonatal intensive care units. PubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) regarding the effect of probiotics in preterm neonates. The primary outcome was culture-proven bacterial and/or fungal sepsis. The Mantel–Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Twenty-seven trials were included in our review, and 25 trials involving 6104 preterm neonates were statistically analyzed. Pooled analysis indicated that enteral probiotic supplementation significantly reduced the risk of any sepsis (25 RCTs; RR 0.83, 95% CI 0.73–0.94; I2 = 26%), bacterial sepsis (11 RCTs; RR 0.82, 95% CI 0.71–0.95; I2 = 0%), and fungal sepsis (6 RCTs; RR 0.57, 95% CI 0.41–0.78; I2 = 0%). This beneficial effect remains in very low birth weight infants (<1500 g) (19 RCTs; RR 0.86, 95% CI 0.75–0.97; I2 = 18%), but not in extremely low birth weight infants (<1000 g) (3 RCTs; RR 0.73, 95% CI 0.45–1.19; I2 = 53%). All the included trials reported no systemic infection caused by the supplemental probiotic organisms. Current evidence indicates that probiotic supplementation is safe, and effective in reducing the risk of LOS in preterm neonates in neonatal intensive care units. Further studies are needed to address the optimal probiotic organism, dosing, timing, and duration. High-quality and adequately powered RCTs regarding the efficacy and safety of the use of probiotics in extremely low birth weight infants are still warranted. PMID:26937897

  4. Ferrous iron transport in Streptococcus mutans

    SciTech Connect

    Evans, S.L.; Arcenaeux, J.E.L.; Byers, B.R.; Martin, M.E.; Aranha, H.

    1986-12-01

    Radioiron uptake from /sup 59/FeCl/sub 3/ by Streptococcus mutans OMZ176 was increased by anaerobiosis, sodium ascorbate, and phenazine methosulfate (PMS), although there was a 10-min lag before PMS stimulation was evident. The reductant ascorbate may have provided ferrous iron. The PMS was reduced by the cells, and the reduced PMS then may have generated ferrous iron for transport; reduced PMS also may have depleted dissolved oxygen. It was concluded that S. mutans transports only ferrous iron, utilizing reductants furnished by glucose metabolism to reduce iron prior to its uptake.

  5. Colonisation endpoints in Streptococcus pneumoniae vaccine trials.

    PubMed

    Auranen, Kari; Rinta-Kokko, Hanna; Goldblatt, David; Nohynek, Hanna; O'Brien, Katherine L; Satzke, Catherine; Simell, Birgit; Tanskanen, Antti; Käyhty, Helena

    2013-12-17

    Evaluating vaccine efficacy for protection against colonisation (VEcol) with bacterial pathogens is an area of growing interest. In this article, we consider estimation of VEcol for colonisation with Streptococcus pneumoniae (the pneumococcus). Colonisation is a common, recurrent and multi-type endpoint that requires both careful definition of the vaccine efficacy parameter and the corresponding method of estimation. We review recent developments in the area and provide practical guidelines for choosing the estimand and the estimation method in trials with a colonisation endpoint. We concentrate on methods that are based on a cross-sectional study design, in which only one nasopharyngeal sample is obtained per study subject.

  6. Streptococcus agalactiae pyomyositis in diabetes mellitus.

    PubMed

    Panikkath, Deepa; Tantrachoti, Pakpoom; Panikkath, Ragesh; Nugent, Kenneth

    2016-07-01

    Pyomyositis is an acute infectious disorder affecting the skeletal muscle. Although seen more commonly in the tropics, cases are being reported in temperate countries, including the United States. We report a case of nontropical pyomyositis in a 58-year-old diabetic man who presented with a vague chest wall swelling. His initial clinical presentation and imaging findings suggested an intramuscular hematoma. He later developed fever with increased swelling, and pyomyositis was diagnosed after an aspiration of the swelling yielded Streptococcus agalactiae. Aspiration of the abscess and the use of appropriate antibiotics led to complete resolution of the disease. We discuss possible factors in diabetics that might predispose them to pyomyositis. PMID:27365874

  7. Streptococcus anginosus infections: crossing tissue planes.

    PubMed

    Sunwoo, Bernie Y; Miller, Wallace T

    2014-10-01

    Streptococcus anginosus has long been recognized to cause invasive pyogenic infections. This holds true for thoracic infections where S. anginosus has a propensity for abscess and empyema formation. Early diagnosis is important given the significant morbidity and mortality associated with thoracic S. anginosus infections. Yet, distinguishing thoracic S. anginosus clinically is difficult. We present three cases of thoracic S. anginosus that demonstrated radiographic extension across tissue planes, including the interlobar fissure, diaphragm, and chest wall. Few infectious etiologies are known to cross tissue planes. Accordingly, we propose S. anginosus be considered among the differential diagnosis of potential infectious etiologies causing radiographic extension across tissue planes.

  8. Update on Streptococcus equi subsp equi infections.

    PubMed

    Mallicote, Martha

    2015-04-01

    There are few diseases that ignite as much fervor among horse owners as strangles. Streptococcus equi subsp equi (strangles) infections frequently require the treating veterinarian to manage not only the clinical cases but also the biosecurity and provision of information to all involved parties. Although the disease is typically characterized by low mortality and high morbidity, restrictions of horse movement that result from appropriate quarantine procedures often frustrate the involved parties. The aims of this article are to provide clinically relevant information for diagnosis, treatment, and biosecurity management of strangles infection.

  9. Acid tolerance mechanisms utilized by Streptococcus mutans

    PubMed Central

    Matsui, Robert; Cvitkovitch, Dennis

    2010-01-01

    Since its discovery in 1924 by J Clarke, Streptococcus mutans has been the focus of rigorous research efforts due to its involvement in caries initiation and progression. Its ability to ferment a range of dietary carbohydrates can rapidly drop the external environmental pH, thereby making dental plaque inhabitable to many competing species and can ultimately lead to tooth decay. Acid production by this oral pathogen would prove suicidal if not for its remarkable ability to withstand the acid onslaught by utilizing a wide variety of highly evolved acid-tolerance mechanisms. The elucidation of these mechanisms will be discussed, serving as the focus of this review. PMID:20210551

  10. Distribution of pilus islands and alpha-like protein genes of group B Streptococcus colonized in pregnant women in Beijing, China.

    PubMed

    Lu, B; Wang, D; Zhou, H; Zhu, F; Li, D; Zhang, S; Shi, Y; Cui, Y; Huang, L; Wu, H

    2015-06-01

    Group B Streptococcus (GBS) is one of the major pathogens of severe newborn sepsis and meningitis. Understanding its regional molecular epidemiology is helpful for regulating efficient prevention practice. A total of 160 GBS strains were collected from colonized pregnant women in six hospital settings in Beijing, China. Polymerase chain reaction (PCR) assays were used to identify the pilus island (PI), alp genes profiling of the alpha-like protein family, and capsular polysaccharide (cps) serotyping. The clonal relationships between strains were investigated using multilocus sequence typing (MLST). All isolates carried at least one pilus island. The most frequently detected pilus island was PI-2a alone (70 isolates, 43.8 %). The most prevalent alp gene was rib (60 isolates, 37.5 %). Moreover, a strong association was noted between alp genes, serotyping, and pilus island profiles. The GBS isolates under study hinted similar molecular epidemical characteristics in Beijing to those reported worldwide, but having their regional distributional features. PMID:25669160

  11. Feasibility of Modified Surviving Sepsis Campaign Guidelines in a Resource-Restricted Setting Based on a Cohort Study of Severe S. Aureus Sepsis

    PubMed Central

    Srisomang, Pramot; Teparrukkul, Prapit; Lorvinitnun, Pichet; Wongyingsinn, Mingkwan; Chierakul, Wirongrong; Hongsuwan, Maliwan; West, T. Eoin; Day, Nicholas P.; Limmathurotsakul, Direk; Peacock, Sharon J.

    2012-01-01

    Background The Surviving Sepsis Campaign (SSC) guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting. Methods and Findings We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53%) of who died within 28 days. One third of patients were treated in intensive care units (ICUs). Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis. Conclusion It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries. PMID:22363410

  12. [Infectious aortitis caused by Streptococcus pneumoniae].

    PubMed

    Zizi, O; Jiber, H; Bouarhroum, A

    2016-02-01

    Infectious aortitis is a rare clinical entity that most often manifests itself by an aortic aneurysm. The syphilitic or tubercular forms can be subacute. When it is caused by Salmonella sp., Staphylococcus sp. or Streptococcus pneumoniae, the aortitis is acute with alarming symptoms. Germs found in most cases are Salmonella and Staphylococcus aureus. S. pneumoniae rarely causes infectious aortitis. We report the case of a 75-year-old patient seen in an emergency setting for sudden-onset abdominal pain with fever. An abdominal angio-computed tomography (CT) scan showed a sacciform infrarenal abdominal aortic aneurysm, with an inflammatory aspect and periaortic hematoma. Surgical cure was undertaken because of the impending rupture. An interposition aortic replacement graft was implanted. Blood cultures and bacteriological study of the aortic wall isolated a S. pneumoniae. The anatomical pathology study reported fibrin clot leukocyte remodeling of the aortic wall. An intravenous antibiotic regimen was started. Several organisms, including Streptococcus, can cause infectious aortitis. We found 36 cases described in the literature in addition to our patient. PMID:26775836

  13. Diverse virulent pneumophages infect Streptococcus mitis.

    PubMed

    Ouennane, Siham; Leprohon, Philippe; Moineau, Sylvain

    2015-01-01

    Streptococcus mitis has emerged as one of the leading causes of bacterial endocarditis and is related to Streptococcus pneumoniae. Antibiotic resistance has also increased among strains of S. mitis and S. pneumoniae. Phages are being reinvestigated as alternatives to antibiotics for managing infections. In this study, the two virulent phages Cp-1 (Podoviridae) and Dp-1 (Siphoviridae), previously isolated from S. pneumoniae, were found to also infect S. mitis. Microbiological assays showed that both pneumophages could not only replicate in S. mitis but also produced more visible plaques on this host. However, the burst size and phage adsorption data were lower in S. mitis as compared to S. pneumoniae. A comparison of the genomes of each phage grown on both hosts produced identical nucleotide sequences, confirming that the same phages infect both bacterial species. We also discovered that the genomic sequence of podophage Cp-1 of the Félix d'Hérelle collection is different than the previously reported sequence and thus renamed SOCP. PMID:25692983

  14. Diverse Virulent Pneumophages Infect Streptococcus mitis

    PubMed Central

    Ouennane, Siham; Leprohon, Philippe; Moineau, Sylvain

    2015-01-01

    Streptococcus mitis has emerged as one of the leading causes of bacterial endocarditis and is related to Streptococcus pneumoniae. Antibiotic resistance has also increased among strains of S. mitis and S. pneumoniae. Phages are being reinvestigated as alternatives to antibiotics for managing infections. In this study, the two virulent phages Cp-1 (Podoviridae) and Dp-1 (Siphoviridae), previously isolated from S. pneumoniae, were found to also infect S. mitis. Microbiological assays showed that both pneumophages could not only replicate in S. mitis but also produced more visible plaques on this host. However, the burst size and phage adsorption data were lower in S. mitis as compared to S. pneumoniae. A comparison of the genomes of each phage grown on both hosts produced identical nucleotide sequences, confirming that the same phages infect both bacterial species. We also discovered that the genomic sequence of podophage Cp-1 of the Félix d’Hérelle collection is different than the previously reported sequence and thus renamed SOCP. PMID:25692983

  15. Occurrence of Streptococcus macedonicus in Italian cheeses.

    PubMed

    Pacini, Federico; Cariolato, Diego; Andrighetto, Christian; Lombardi, Angiolella

    2006-08-01

    A new approach for the detection and enumeration of Streptococcus macedonicus in cheese was developed. The method which is based on a first screening of cheeses by a PCR assay specific for S. macedonicus followed by plating positive samples on a differential medium (SM medium) was applied to 51 samples derived from PDO and traditional Italian cheeses. Streptococcus macedonicus was found in 16 of the 51 samples examined in the present work. With the exclusion of an Asiago cheese sample in which very high numbers of S. macedonicus (7.13 log CFU g(-1)) were found, the counts of S. macedonicus in SM medium ranged from 2.48 to 4.70 log CFU g(-1). In the same cheeses, total streptococci enumerated onto M17 agar were found at higher concentrations with values up to 7.88 log CFU g(-1). The system developed was particularly useful for the differential count of S. macedonicus in cheese and allowed to evaluate the occurrence of this species within the complex microbial lactic acid bacteria (LAB) population, which is typical of traditional cheeses. Results showed that in the examined cheeses S. macedonicus cannot be considered as a dominant LAB species.

  16. Does Celiac Disease Influence Survival in Sepsis? A Nationwide Longitudinal Study

    PubMed Central

    Röckert Tjernberg, Anna; Bonnedahl, Jonas; Ludvigsson, Jonas F.

    2016-01-01

    Background Individuals with celiac disease (CD) are at increased risk of sepsis. The aim of this study was to examine whether CD influences survival in sepsis of bacterial origin. Methods Nationwide longitudinal registry-based study. Through data on small intestinal biopsies from Sweden’s 28 pathology departments, we identified 29,096 individuals with CD (villous atrophy, Marsh stage III). Each individual with CD was matched with five population-based controls. Among these, 5,470 had a record of sepsis according to the Swedish Patient Register (1,432 celiac individuals and 4,038 controls). Finally we retrieved data on mortality in sepsis patients through the Swedish Cause of Death Registry. Results CD was associated with a 19% increase in overall mortality after sepsis (95% confidence interval (CI) = 1.09–1.29), with the highest relative risk occurring in children (adjusted hazard ratio (aHR) = 1.62; 95%CI = 0.67–3.91). However, aHR for death from sepsis was lower (aHR = 1.10) and failed to reach statistical significance (95%CI = 0.72–1.69). CD did not influence survival within 28 days after sepsis (aHR = 0.98; 95%CI = 0.80–1.19). Conclusions Although individuals with CD seem to be at an increased risk of overall death after sepsis, that excess risk does not differ from the general excess mortality previously seen in celiac patients in Sweden. CD as such does not seem to influence short-term or sepsis-specific survival in individuals with sepsis and therefore is not an independent risk factor for poor prognosis in sepsis. PMID:27124735

  17. Role of nicotine on cognitive and behavioral deficits in sepsis-surviving rats.

    PubMed

    Leite, Franco B; Prediger, Rui D; Silva, Mônica V; de Sousa, João Batista; Carneiro, Fabiana P; Gasbarri, Antonella; Tomaz, Carlos; Queiroz, Amadeu J; Martins, Natália T; Ferreira, Vania M

    2013-04-24

    Sepsis and its complications are important causes of mortality in intensive care units and sepsis survivors may present long-term cognitive and emotional impairments, including memory deficits and anxiety symptoms. In the present study, we investigated whether repeated nicotine administration can affect the behavioral changes in sepsis-surviving rats. Male Wistar rats were divided in two groups: sham-operated and experimental sepsis induced by cecal ligation and puncture (CLP). The animals were injected subcutaneously with nicotine (0.1 mg/kg) or vehicle once a day during 1 week before and/or 1 week after sepsis induction. Thirty minutes after the last administration (i.e., 7 days after surgery), the animals were tested in the open field, elevated plus-maze and step-down inhibitory avoidance tasks. The repeated nicotine treatment did not affect the survival rate in the sepsis group (50%). Moreover, no significant changes on locomotor activity were observed in the sepsis group while the treatment with nicotine during 1 week after surgery reduced the locomotion of sepsis-surviving rats in the open field. It is important to note that both schedules of nicotine treatment (prior and/or after CLP) improved the sepsis-induced anxiogenic-like responses. Interestingly, nicotine was able to improve short- and long-term inhibitory avoidance memory impairments, observed in sepsis survivors, only when administered during 2 consecutive weeks (i.e., prior and after CLP). Taken together, these results indicate that repeated nicotine administration does not alter the survival rate in rats submitted to CLP and provide new evidence that nicotine can improve long-lasting memory impairments and anxiogenic-like responses in sepsis-surviving animals.

  18. The Impact of HIV Co-Infection on the Genomic Response to Sepsis.

    PubMed

    Huson, Michaëla A M; Scicluna, Brendon P; van Vught, Lonneke A; Wiewel, Maryse A; Hoogendijk, Arie J; Cremer, Olaf L; Bonten, Marc J M; Schultz, Marcus J; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Grobusch, Martin P; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis.

  19. The Impact of HIV Co-Infection on the Genomic Response to Sepsis

    PubMed Central

    Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

  20. Neonatal Sepsis 2004–2013: The Rise and Fall of Coagulase-Negative Staphylococci

    PubMed Central

    Bizzarro, Matthew J.; Shabanova, Veronika; Baltimore, Robert S.; Dembry, Louise-Marie; Ehrenkranz, Richard A.; Gallagher, Patrick G.

    2015-01-01

    Objectives To evaluate data for the period 2004–2013 to identify changes in demographics, pathogens, and outcomes in a single, level IV neonatal intensive care unit (NICU). Study design Sepsis episodes were identified prospectively and additional information obtained retrospectively from infants with sepsis while in the NICU from 2004–2013. Demographics, hospital course, and outcome data were collected and analyzed. Sepsis was categorized as early (≤3 days of life) or late-onset (>3 days of life). Results Four hundred and fifty two organisms were identified from 410 episodes of sepsis in 340 infants. Ninety percent of cases were late-onset. Rates of early-onset sepsis remained relatively static throughout the study period (0.9 per 1000 live births). The majority (60%) of infants with early-onset sepsis were very low birth weight for the first time in decades, and E. coli (45%) replaced GBS (36%) as the most common organism associated with early-onset sepsis. Rates of late-onset sepsis, particularly due to coagulase-negative staphylococci (CoNS), decreased significantly after implementation of several infection prevention initiatives. CoNS was responsible for 31% of all cases from 2004–2009 but accounted for no cases of late-onset sepsis after 2011. Conclusions The epidemiology and microbiology of early- and late-onset sepsis continue to change, impacted by targeted infection prevention efforts. We believe the decrease in sepsis indicates that these interventions have been successful, but additional surveillance and strategies based on evolving trends are necessary. PMID:25919728

  1. Bacteremia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates.

    PubMed Central

    Ruoff, K L; Miller, S I; Garner, C V; Ferraro, M J; Calderwood, S B

    1989-01-01

    Two biotypes of Streptococcus bovis can be identified by laboratory testing and can be distinguished from the phenotypically similar organism Streptococcus salivarius. We assessed the clinical relevance of careful identification of these organisms in 68 patients with streptococcal bacteremia caused by these similar species. S. bovis was more likely to be clinically significant when isolated from blood (89%) than was S. salivarius (23%). There was a striking association between S. bovis I bacteremia and underlying endocarditis (94%) compared with that of S. bovis II bacteremia (18%). Bacteremia with S. bovis I was also highly correlated with an underlying colonic neoplasm (71% of patients overall, 100% of those with thorough colonic examinations) compared with bacteremia due to S. bovis II or S. salivarius (17% overall, 25% of patients with thorough colonic examinations). We conclude that careful identification of streptococcal bacteremic isolates as S. bovis biotype I provides clinically important information and should be more widely applied. PMID:2915024

  2. Comparative Genomics of Carriage and Disease Isolates of Streptococcus pneumoniae Serotype 22F Reveals Lineage-Specific Divergence and Niche Adaptation

    PubMed Central

    Cleary, David W.; Devine, Vanessa T.; Jefferies, Johanna M.C.; Webb, Jeremy S.; Bentley, Stephen D.; Gladstone, Rebecca A.; Faust, Saul N.; Clarke, Stuart C.

    2016-01-01

    Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom’s childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin-–antitoxin systems, were also observed. PMID:27016484

  3. Quantification of functional and inactivated alpha 2-macroglobulin in sepsis.

    PubMed

    Abbink, J J; Nuijens, J H; Eerenberg, A J; Huijbregts, C C; Strack van Schijndel, R J; Thijs, L G; Hack, C E

    1991-01-23

    Alpha 2-macroglobulin (alpha 2 M) in vitro inhibits numerous proteinases that are generated during inflammatory reactions and therefore, probably plays an important role in diseases such as sepsis. To monitor the state of alpha 2 M in sepsis, we developed novel assays for functional and inactive alpha 2M. Functional alpha 2M in plasma was measured by quantitating the binding of alpha 2M to solid-phase trypsin. Inactive alpha 2M (i alpha 2M) was assessed with a monoclonal antibody, mcAb M1, that specifically reacts with a neodeterminant exposed on i alpha 2M. This mcAb in combination with chromogenic substrates was used to detect alpha 2M-proteinase complexes. Functional alpha 2M was reduced in plasma from 48 patients with clinical sepsis compared to healthy controls (p less than 0.0001). Levels of functional alpha 2M on admission and the lowest levels encountered in 23 patients with shock were lower than in 25 normotensive patients (p = 0.023 and p = 0.009, respectively). Increased levels of i alpha 2M (greater than 30 nM) at least on one occasion were found in only 4 of the 48 patients, being not different in hypotensive compared with normotensive patients, and not in patients who died compared with those who survived. Levels of functional alpha 2M correlated significantly with levels of factor XII and prekallikrein suggesting that decreases in alpha 2M at least in part were due to contact activation. Indeed, in two patients with increased i alpha 2M, complexes between alpha 2M and kallikrein were demonstrated in addition to plasmin- and thrombin-alpha 2M complexes.

  4. 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

  5. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

  6. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been desc...

  7. Oral lactoferrin for the 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...

  8. 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...

  9. Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  10. Maturity aggravates sepsis-associated skeletal muscle catabolism in growing pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synthesis and accretion of muscle protein is elevated in neonates and decreases with development. During sepsis, muscle protein synthesis is reduced, but the effect of development on the metabolic response to sepsis in skeletal muscle is not well understood. Fasted 7- and 26-d-old pigs were infused ...

  11. Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  12. 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

  13. 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.

  14. Novel relationships between oxidative stress and angiogenesis-related factors in sepsis: New biomarkers and therapies.

    PubMed

    Vera, Sergio; Martínez, Rolando; Gormaz, Juan Guillermo; Gajardo, Abraham; Galleguillos, Fernanda; Rodrigo, Ramón

    2015-06-01

    Sepsis is a systemic uncontrolled inflammatory response in the presence of an infection. It remains a major cause of morbidity and mortality in hospitalized patients. According to its severity, sepsis can progress to three different states: severe sepsis, septic shock, and multiple organ dysfunction syndrome, related to organ dysfunction and/or tissue hypoperfusion. Different processes underlie its pathophysiology; among them are oxidative stress, endothelial and mitochondrial dysfunction, and angiogenesis-related factors. However, no studies have integrated these elements in sepsis. The main difficulty in sepsis is its diagnosis. Currently, the potential of inflammatory biomarkers in septic patients remains weak. In this context, the research into new biomarkers is essential to aid with sepsis diagnosis and prognostication. Furthermore, even though the current management of severe forms of sepsis has been effective, morbimortality remains elevated. Therefore, it is essential to explore alternative approaches to therapy development. The aim of this review is to present an update of evidence supporting the role of oxidative stress and angiogenesis-related factors in the pathophysiology of the different forms of sepsis. It proposes a novel convergence between both elements in their role in the disease, and it will cover their utility as new diagnostic tools, predictors of outcome, and as novel therapeutic targets.

  15. Don't Go Chasing Waterfalls: Excessive Fluid Resuscitation in Severe Sepsis and Septic Shock.

    PubMed

    Chen, Leon

    2016-01-01

    Aggressive fluid resuscitation is the mainstay therapy in modern sepsis management. Its efficacy was demonstrated in the landmark study by Emmanuel Rivers in 2001. However, more recent evidence largely shows that a positive fluid balance increases mortality in critically ill patients with sepsis. This article examines the theoretical benefits of fluid resuscitation and physiological responses to it that may negatively affect patients' outcome.

  16. Reappraisal of the taxonomy of Streptococcus suis serotypes 20, 22 and 26: Streptococcus parasuis sp. nov.

    PubMed

    Nomoto, R; Maruyama, F; Ishida, S; Tohya, M; Sekizaki, T; Osawa, Ro

    2015-02-01

    In order to clarify the taxonomic position of serotypes 20, 22 and 26 of Streptococcus suis, biochemical and molecular genetic studies were performed on isolates (SUT-7, SUT-286(T), SUT-319, SUT-328 and SUT-380) reacted with specific antisera of serotypes 20, 22 or 26 from the saliva of healthy pigs as well as reference strains of serotypes 20, 22 and 26. Comparative recN gene sequencing showed high genetic relatedness among our isolates, but marked differences from the type strain S. suis NCTC 10234(T), i.e. 74.8-75.7 % sequence similarity. The genomic relatedness between the isolates and other strains of species of the genus Streptococcus, including S. suis, was calculated using the average nucleotide identity values of whole genome sequences, which indicated that serotypes 20, 22 and 26 should be removed taxonomically from S. suis and treated as a novel genomic species. Comparative sequence analysis revealed 99.0-100 % sequence similarities for the 16S rRNA genes between the reference strains of serotypes 20, 22 and 26, and our isolates. Isolate STU-286(T) had relatively high 16S rRNA gene sequence similarity with S. suis NCTC 10234(T) (98.8 %). SUT-286(T) could be distinguished from S. suis and other closely related species of the genus Streptococcus using biochemical tests. Due to its phylogenetic and phenotypic similarities to S. suis we propose naming the novel species Streptococcus parasuis sp. nov., with SUT-286(T) ( = JCM 30273(T) = DSM 29126(T)) as the type strain.

  17. Laboratory growth and maintenance of Streptococcus pyogenes (the Group A Streptococcus, GAS).

    PubMed

    Gera, Kanika; McIver, Kevin S

    2013-10-02

    Streptococcus pyogenes is a Gram-positive bacterium that strictly infects humans. It is the causative agent of a broad spectrum of diseases accounting for millions of infections and at least 517,000 deaths each year worldwide. It is a nutritionally fastidious organism that ferments sugars to produce lactic acid and has strict requirements for growth. To aid in the study of this organism, this unit describes the growth and maintenance of S. pyogenes.

  18. Comparison of genes required for H2O2 resistance in Streptococcus gordonii and Streptococcus sanguinis.

    PubMed

    Xu, Yifan; Itzek, Andreas; Kreth, Jens

    2014-12-01

    Hydrogen peroxide (H2O2) is produced by several members of the genus Streptococcus mainly through the pyruvate oxidase SpxB under aerobic growth conditions. The acute toxic nature of H2O2 raises the interesting question of how streptococci cope with intrinsically produced H2O2, which subsequently accumulates in the microenvironment and threatens the closely surrounding population. Here, we investigate the H2O2 susceptibility of oral Streptococcus gordonii and Streptococcus sanguinis and elucidate potential mechanisms of how they protect themselves from the deleterious effect of H2O2. Both organisms are considered primary colonizers and occupy the same intraoral niche making them potential targets for H2O2 produced by other species. We demonstrate that S. gordonii produces relatively more H2O2 and has a greater ability for resistance to H2O2 stress. Functional studies show that, unlike in Streptococcus pneumoniae, H2O2 resistance is not dependent on a functional SpxB and confirms the important role of the ferritin-like DNA-binding protein Dps. However, the observed increased H2O2 resistance of S. gordonii over S. sanguinis is likely to be caused by an oxidative stress protection machinery present even under anaerobic conditions, while S. sanguinis requires a longer period of time for adaptation. The ability to produce more H2O2 and be more resistant to H2O2 might aid S. gordonii in the competitive oral biofilm environment, since it is lower in abundance yet manages to survive quite efficiently in the oral biofilm.

  19. Laboratory Growth and Maintenance of Streptococcus pyogenes (The Group A Streptococcus, GAS)

    PubMed Central

    Gera, Kanika; McIver, Kevin S.

    2013-01-01

    Streptococcus pyogenes is a Gram-positive bacterium that strictly infects humans. It is the causative agent of a broad spectrum of diseases accounting for millions of infections and at least 517, 000 deaths each year worldwide (Carapetis et al., 2005). It is a nutritionally fastidious organism that ferments sugars to produce lactic acid and has strict requirements for growth. To aid in the study of this organism, this unit describes the growth and maintenance of S. pyogenes. PMID:24510893

  20. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    PubMed Central

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  1. Neonatal Conjunctivitis Leading to Neonatal Sepsis--A Case Report.

    PubMed

    Dey, A C; Hossain, M I; Dey, S K; Mannan, M A; Shahidullah, M

    2016-01-01

    Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day. PMID:26931268

  2. Hyperferritinemic Sepsis: An Opportunity for Earlier Diagnosis and Intervention?

    PubMed Central

    Halstead, E. Scott; Rajasekaran, Surender; Fitzgerald, Julie C.; Weiss, Scott L.

    2016-01-01

    We describe a case of an infant with HSV meningitis and septic shock who demonstrated a remarkably high serum ferritin level. Aggressive pediatric intensive care and the administration of high-dose glucocorticoids were not able to reverse the multiple organ dysfunctions. Subsequent autopsy identified the presence of hemophagocytosis, thus the patient fulfilled hemophagocytic lymphohistiocytosis (HLH) criteria post-mortem. This case highlights that serum ferritin may be an important early indicator of mortality in sepsis due to a cytokine storm similar to macrophage activation syndrome and HLH. PMID:27532033

  3. Neonatal Conjunctivitis Leading to Neonatal Sepsis--A Case Report.

    PubMed

    Dey, A C; Hossain, M I; Dey, S K; Mannan, M A; Shahidullah, M

    2016-01-01

    Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day.

  4. Phage 3396 from a Streptococcus dysgalactiae subsp. equisimilis pathovar may have its origins in streptococcus pyogenes.

    PubMed

    Davies, Mark R; McMillan, David J; Van Domselaar, Gary H; Jones, Malcolm K; Sriprakash, Kadaba S

    2007-04-01

    Streptococcus dysgalactiae subsp. equisimilis strains (group G streptococcus [GGS]) are largely defined as commensal organisms, which are closely related to the well-defined human pathogen, the group A streptococcus (GAS). While lateral gene transfers are emerging as a common theme in these species, little is known about the mechanisms and role of these transfers and their effect on the population structure of streptococci in nature. It is now becoming evident that bacteriophages are major contributors to the genotypic diversity of GAS and, consequently, are pivotal to the GAS strain structure. Furthermore, bacteriophages are strongly associated with altering the pathogenic potential of GAS. In contrast, little is know about phages from GGS and their role in the population dynamics of GGS. In this study we report the first complete genome sequence of a GGS phage, Phi3396. Exhibiting high homology to the GAS phage Phi315.1, the chimeric nature of Phi3396 is unraveled to reveal evidence of extensive ongoing genetic diversity and dissemination of streptococcal phages in nature. Furthermore, we expand on our recent findings to identify inducible Phi3396 homologues in GAS from a region of endemicity for GAS and GGS infection. Together, these findings provide new insights into not only the population structure of GGS but also the overall population structure of the streptococcal genus and the emergence of pathogenic variants.

  5. A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines.

    PubMed

    Fujishima, Seitaro; Gando, Satoshi; Saitoh, Daizoh; Mayumi, Toshihiko; Kushimoto, Shigeki; Shiraishi, Shin-Ichiro; Ogura, Hiroshi; Takuma, Kiyotsugu; Kotani, Joji; Ikeda, Hiroto; Yamashita, Norio; Suzuki, Koichiro; Tsuruta, Ryosuke; Takeyama, Naoshi; Araki, Tsunetoshi; Suzuki, Yasushi; Miki, Yasuo; Yamaguchi, Yoshihiro; Aikawa, Naoki

    2014-02-01

    To elucidate the standard Surviving Sepsis Campaign (SSC) guidelines-based quality of care and mortality related to severe sepsis in Japan, we conducted a multicenter, prospective, observational study using a new web-based database between June 1, 2010, and December 31, 2011. A total of 1104 patients with severe sepsis were enrolled from 39 Japanese emergency and critical care centers. All-cause hospital mortality was 29.3% in patients with severe sepsis and 40.7% in patients with septic shock. Pulmonary, renal, hepatic, and hematological dysfunctions were associated with significantly higher mortality, and hematological dysfunction, especially coagulopathy, was associated with the highest odds ratio for mortality. Compliance with severe sepsis bundles in our study was generally low compared with that in a previous international sepsis registry study, and glycemic control was associated with lowest odds ratio for mortality. Despite higher complication rates of multiple organ dysfunction syndrome and low compliance with severe sepsis bundles on the whole, mortality in our study was similar to that in the international sepsis registry study. From these results, we concluded that our prospective multicenter study was successful in evaluating SSC guidelines-based standard quality of care and mortality related to severe sepsis in Japan. Although mortality in Japan was equivalent to that reported worldwide in the above-mentioned international sepsis registry study, compliance with severe sepsis bundles was low. Thus, there is scope for improvement in the initial treatment of severe sepsis and septic shock in Japanese emergency and critical care centers.

  6. Identification of Lipoprotein Homologues of Pneumococcal PsaA in the Equine Pathogens Streptococcus equi and Streptococcus zooepidemicus

    PubMed Central

    Harrington, Dean J.; Greated, Joanne S.; Chanter, Neil; Sutcliffe, Iain C.

    2000-01-01

    Streptococcus equi and Streptococcus zooepidemicus are major etiological agents of upper and lower airway disease in horses. Despite the considerable animal suffering and economic burden associated with these diseases, the factors that contribute to the virulence of these equine pathogens have not been extensively investigated. Here we demonstrate the presence of a homologue of the Streptococcus pneumoniae PsaA protein in both of these equine pathogens. Inhibition of signal peptide processing by the antibiotic globomycin confirmed the lipoprotein nature of the mature proteins, and surface exposure was confirmed by their release from intact cells by mild trypsinolysis. PMID:10992520

  7. T-cell mediated immunity and the role of TRAIL in sepsis-induced immunosuppression

    PubMed Central

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

    2013-01-01

    Sepsis is the leading cause of death in most intensive care units, and the death of septic patients usually does not result from the initial septic event but rather from subsequent nosocomial infections. Patients who survive severe sepsis often display severely compromised immune function. Not only is there significant apoptosis of lymphoid and myeloid cells that depletes critical components of the immune system during sepsis, there is also decreased function of the remaining immune cells. Studies in animals and humans suggest the immune defects that occur during sepsis may be critical to the pathogenesis and subsequent mortality. This review is focused on sepsis-induced alterations with the CD8 T-cell compartment that can affect the control of secondary heterologous infections. Understanding how a septic event directly influences CD8 T-cell populations through apoptotic death and homeostatic proliferation and indirectly by immune-mediated suppression will provide valuable starting points for developing new treatment options. PMID:23510024

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

    PubMed Central

    Dyagilev, Kirill; Saria, Suchi

    2015-01-01

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

  9. [Serum lactate as a biomarker of severe sepsis in children with cancer, neutropenia and fever].

    PubMed

    Pacheco-Rosas, Daniel Octavio; Huelgas-Plaza, Ana Celia; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: la neutropenia es una complicación frecuente secundaria a la quimioterapia en los pacientes con cáncer, en quienes la prevalencia de sepsis es de 12.9 a 17.4 % y la letalidad es de 16 %. El objetivo de este estudio fue determinar la utilidad del lactato como biomarcador de sepsis grave en niños con cáncer, fiebre y neutropenia. MÉTODOS: se realizó un estudio de prueba diagnóstica fase II. Se midieron los niveles del lactato al ingreso. Los episodios de neutropenia se clasificaron en tres grupos: I, con sepsis II, sin sepsis; III, pacientes neutropénicos sin fiebre (controles). Se calculó sensibilidad, especificidad, valores predictivos positivo y negativo e índices de verosimilitud. El estándar de oro fue el diagnóstico clínico de sepsis grave.

  10. Sepsis through the eyes of an engineer -- why treatments have succeeded and failed.

    PubMed

    Jopling, Jeffrey; Buchman, Timothy G

    2012-01-01

    The sepsis syndrome is an old phenomenon. A destructive response to a system disturbance, it manifests as widespread inflammation. Over the past two centuries, biomedical research has identified triggers and described components of the pathways that underlie the sepsis syndrome. Attempts at translating these findings into preventive and therapeutic interventions have met with varying levels of success. In this chapter, we examine the history of sepsis science through an engineering lens. Patterned attempts to intervene in the natural history of the sepsis syndrome will be discussed in parallel with similar, hypothetical adjustments made to a model system from the engineering canon. This juxtaposition will facilitate our review of the history of sepsis science. Using the logic of systems engineering and network science, we propose a way forward.

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

    PubMed

    Maley, Jason H; Mikkelsen, Mark E

    2016-06-01

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

  12. The effect of HIV infection on the host response to bacterial sepsis.

    PubMed

    Huson, Michaëla A M; Grobusch, Martin P; van der Poll, Tom

    2015-01-01

    Bacterial sepsis is an important cause of morbidity and mortality in patients with HIV. HIV causes increased susceptibility to invasive infections and affects sepsis pathogenesis caused by pre-existing activation and exhaustion of the immune system. We review the effect of HIV on different components of immune responses implicated in bacterial sepsis, and possible mechanisms underlying the increased risk of invasive bacterial infections. We focus on pattern recognition receptors and innate cellular responses, cytokines, lymphocytes, coagulation, and the complement system. A combination of factors causes increased susceptibility to infection and can contribute to a disturbed immune response during a septic event in patients with HIV. HIV-induced perturbations of the immune system depend on stage of infection and are only in part restored by combination antiretroviral therapy. Immunomodulatory treatments currently under development for sepsis might be particularly beneficial to patients with HIV co-infection because many pathogenic mechanisms in HIV and sepsis overlap. PMID:25459220

  13. Procession to pediatric bacteremia and sepsis: covert operations and failures in diplomacy.

    PubMed

    Bateman, Stacey L; Seed, Patrick C

    2010-07-01

    Despite advances in diagnosis and treatment, bacterial sepsis remains a major cause of pediatric morbidity and mortality, particularly among neonates, the critically ill, and the growing immunocompromised patient population. Sepsis is the end point of a complex and dynamic series of events in which both host and microbial factors drive high morbidity and potentially lethal physiologic alterations. In this article we provide a succinct overview of the events that lead to pediatric bloodstream infections (BSIs) and sepsis, with a focus on the molecular mechanisms used by bacteria to subvert host barriers and local immunity to gain access to and persist within the systemic circulation. In the events preceding and during BSI and sepsis, Gram-positive and Gram-negative pathogens use a battery of factors for translocation, inhibition of immunity, molecular mimicry, intracellular survival, and nutrient scavenging. Gaps in understanding the molecular pathogenesis of bacterial BSIs and sepsis are highlighted as opportunities to identify and develop new therapeutics.

  14. Genomics and pharmacogenomics of sepsis: so close and yet so far.

    PubMed

    Russell, James A

    2016-01-01

    Sapru et al. show in this issue of Critical Care that variants of thrombomodulin and the endothelial protein C receptor, but not protein C, are associated with mortality and organ dysfunction (ventilation-free and organ failure-free days) in ARDS. Hundreds of gene variants have been found prognostic in sepsis. However, none of these prognostic genomic biomarkers are used clinically. Predictive biomarker discovery (pharmacogenomics) usually follows a candidate gene approach, utilizing knowledge of drug pathways. Pharmacogenomics could be applied to enhance efficacy and safety of drugs used for treatment of sepsis (e.g., norepinephrine, epinephrine, vasopressin, and corticosteroids). Pharmacogenomics can enhance drug development in sepsis, which is very important because there is no approved drug for sepsis. Pharmacogenomics biomarkers must pass three milestones: scientific, regulatory, and commercial. Huge challenges remain but great opportunities for pharmacogenomics of sepsis are on the horizon. PMID:27384443

  15. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of glyceraldehyde-3-phosphate dehydrogenase from Streptococcus agalactiae NEM316

    PubMed Central

    Nagarajan, Revathi; Ponnuraj, Karthe

    2014-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential enzyme involved in glycolysis. Despite lacking the secretory signal sequence, this cytosolic enzyme has been found localized at the surface of several bacteria and fungi. As a surface protein, GAPDH exhibits various adhesive functions, thereby facilitating colonization and invasion of host tissues. Streptococcus agalactiae, also known as group B streptococcus (GBS), binds onto the host using its surface adhesins and causes sepsis and pneumonia in neonates. GAPDH is one of the surface adhesins of GBS binding to human plasminogen and is a virulent factor associated with host colonization. Although the surface-associated GAPDH has been shown to bind to a variety of host extracellular matrix (ECM) molecules in various bacteria, the molecular mechanism underlying their interaction is not fully understood. To investigate this, structural studies on GAPDH of S. agalactiae were initiated. The gapC gene of S. agalactiae NEM316 encoding GAPDH protein was cloned into pET-28a vector, overexpressed in Escherichia coli BL21(DE3) cells and purified to homogeneity. The purified protein was crystallized using the hanging-drop vapour-diffusion method. The GAPDH crystals obtained in two different crystallization conditions diffracted to 2.8 and 2.6 Å resolution, belonging to two different space groups P21 and P212121, respectively. The structure was solved by molecular replacement and structure refinement is now in progress. PMID:25005093

  16. Group B Streptococcus β-hemolysin/Cytolysin Breaches Maternal-Fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

    PubMed Central

    Randis, Tara M.; Gelber, Shari E.; Hooven, Thomas A.; Abellar, Rosanna G.; Akabas, Leor H.; Lewis, Emma L.; Walker, Lindsay B.; Byland, Leah M.; Nizet, Victor; Ratner, Adam J.

    2014-01-01

    Background. Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. Methods. We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection. Results. Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. Conclusions. Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis. PMID:24474814

  17. High Incidence of Macrolide and Tetracycline Resistance among Streptococcus Agalactiae Strains Isolated from Clinical Samples in Tehran, Iran

    PubMed Central

    EMANEINI, Mohammad; MIRSALEHIAN, Akbar; BEIGVIERDI, Reza; FOOLADI, Abbas Ali Imani; ASADI, Fatemeh; JABALAMELI, Fereshteh; TAHERIKALANI, Morovat

    2014-01-01

    Background: Streptococcus agalactiae or Group B Streptococci (GBS) is an important bacterial pathogen that causes a wide range of infections including neonatal sepsis, meningitis, pneumonia and soft tissue or urinary tract infections. Material and methods: One hundred and fifteen isolates of Streptococcus agalactiae collected from urine specimens of patients attending a hospital in Tehran. All isolates were screened for their capsular types and genes encoding resistance to the macrolide and tetracycline antibiotics by PCR and multiplex PCR–based methods. Results: Most of isolates belonged to capsular types III (49%), V (19%), II (16%), and Ib (6%). Twelve isolates (10%) were nontypable. All isolates were susceptible to penicillin and Quinupristin-dalfopristin, but were resistant to clindamycin (35%), chloramphenicol (45%), erythromycin (35%), linezolid (1%) and tetracycline (96%). The most prevalent antimicrobial resistance gene was tetM found in 93% of the isolates followed by ermTR, ermB, and tetK, found in 23%, 16%, and 16% of isolates, respectively. The genes, tetL, tetO, ermA, ermC and mefA were not detected in any of the S. agalactiae isolates. Of the 110 tetracycline resistant S. agalactiae, 89 isolates harbored the tetM gene alone and eighteen isolates carried the tetM gene with the tetK gene. All erythromycin-resistant isolates exhibited cMLSB resistance phenotype, 22 isolates harbored the ermTR gene alone and five isolates carried the ermTR gene with the ermB gene. The rate of coexistence of genes encoding the erythromycin and tetracycline resistance determinants was 34%. Conclusion: The present study demonstrated that S. agalactiae isolates obtained from urine samples showed a high rate of resistance to tetracycline, chloramphenicol and macrolide antibiotics and were commonly associated with the resistance genes temM, ermTR or ermB. PMID:25705271

  18. Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus: S. pyogenes super-infection.

    PubMed

    Klonoski, Joshua M; Hurtig, Heather R; Juber, Brian A; Schuneman, Margaret J; Bickett, Thomas E; Svendsen, Joshua M; Burum, Brandon; Penfound, Thomas A; Sereda, Grigoriy; Dale, James B; Chaussee, Michael S; Huber, Victor C

    2014-09-01

    Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection. PMID:25077423

  19. Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus: S. pyogenes super-infection.

    PubMed

    Klonoski, Joshua M; Hurtig, Heather R; Juber, Brian A; Schuneman, Margaret J; Bickett, Thomas E; Svendsen, Joshua M; Burum, Brandon; Penfound, Thomas A; Sereda, Grigoriy; Dale, James B; Chaussee, Michael S; Huber, Victor C

    2014-09-01

    Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection.

  20. Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus:S. pyogenes super-infection

    PubMed Central

    Klonoski, Joshua M.; Hurtig, Heather R.; Juber, Brian A.; Schuneman, Margaret J.; Bickett, Thomas E.; Svendsen, Joshua M.; Burum, Brandon; Penfound, Thomas A.; Sereda, Grigoriy; Dale, James B.; Chaussee, Michael S.; Huber, Victor C.

    2014-01-01

    Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection. PMID:25077423