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Sample records for acute streptococcal sepsis

  1. 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 ?-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

  2. Group G streptococcal sepsis, septic arthritis and myositis in a patient with severe oral ulcerations

    PubMed Central

    Deng, Wu; Farricielli, Laurie

    2014-01-01

    Lancefield group G streptococci (GGS) are a relatively less common cause of streptococcal infections but the incidence of which has been reported to increase in the recent years. Similar to group A streptococci, GGS produce localised and invasive infections. Streptococcal myositis is a very rare but highly fatal infection of muscles generally caused by group A streptococci. We report a case of sepsis, migrating septic arthritis and diffuse myositis caused by ?-haemolytic GGS. It is an unusual case of diffuse ?-haemolytic GGS myositis involving multiple muscle groups in a patient who demonstrated no skin lesions or sign of streptococcal toxic shock syndrome. The patient responded well to intravenous antibiotics without surgical intervention and experienced full recovery. PMID:24469838

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

    PubMed Central

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

    1995-01-01

    Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis. Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection. This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens. Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families. Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05). The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets. Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response. All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion. These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s). Images PMID:7593594

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

  6. Sepsis-Associated Acute Kidney Injury

    PubMed Central

    Alobaidi, Rashid; Basu, Rajit K.; Goldstein, Stuart L.; Bagshaw, Sean M.

    2015-01-01

    Summary Acute kidney injury (AKI) is an epidemic problem. Sepsis has long been recognized as a foremost precipitant of AKI. Sepsis-associated AKI (SA-AKI) portends a high burden of morbidity and mortality in both children and adults with critical illness. Although our understanding of its pathophysiology is incomplete, SA-AKI likely represents a distinct subset of AKI contributed to by a unique constellation of hemodynamic, inflammatory, and immune mechanisms. SA-AKI poses significant clinical challenges for clinicians. To date, no singular effective therapy has been developed to alter the natural history of SA-AKI. Rather, current strategies to alleviate poor outcomes focus on clinical risk identification, early detection of injury, modifying clinician behavior to avoid harm, early appropriate antimicrobial therapy, and surveillance among survivors for the longer-term sequelae of kidney damage. Recent evidence has confirmed that patients no longer die with AKI, but from AKI. To improve the care and outcomes for sufferers of SA-AKI, clinicians need a robust appreciation for its epidemiology and current best-evidence strategies for prevention and treatment. PMID:25795495

  7. Sepsis-associated acute kidney injury.

    PubMed

    Alobaidi, Rashid; Basu, Rajit K; Goldstein, Stuart L; Bagshaw, Sean M

    2015-01-01

    Acute kidney injury (AKI) is an epidemic problem. Sepsis has long been recognized as a foremost precipitant of AKI. Sepsis-associated AKI (SA-AKI) portends a high burden of morbidity and mortality in both children and adults with critical illness. Although our understanding of its pathophysiology is incomplete, SA-AKI likely represents a distinct subset of AKI contributed to by a unique constellation of hemodynamic, inflammatory, and immune mechanisms. SA-AKI poses significant clinical challenges for clinicians. To date, no singular effective therapy has been developed to alter the natural history of SA-AKI. Rather, current strategies to alleviate poor outcomes focus on clinical risk identification, early detection of injury, modifying clinician behavior to avoid harm, early appropriate antimicrobial therapy, and surveillance among survivors for the longer-term sequelae of kidney damage. Recent evidence has confirmed that patients no longer die with AKI, but from AKI. To improve the care and outcomes for sufferers of SA-AKI, clinicians need a robust appreciation for its epidemiology and current best-evidence strategies for prevention and treatment. PMID:25795495

  8. Sepsis

    MedlinePLUS

    ... NIGMS NIGMS Home > Science Education > Sepsis Fact Sheet Sepsis Fact Sheet Tagline (Optional) Middle/Main Content Area En español What is sepsis? Sepsis is a serious medical condition caused by ...

  9. Improving Sepsis Management in the Acute Admissions Unit

    PubMed Central

    Adcroft, Laura

    2014-01-01

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

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

    PubMed Central

    Kafle, Sumitra; Nath, Navdeep

    2014-01-01

    Severe sepsis still remains a major cause of morbidity and mortality, claiming between 36,000 to 64,000 lives annually in the UK, with a mortality rate of 35%.[1,2] The project aims to measure the management of severely septic patients in acute medical unit (AMU) in a district general hospital against best practice guidelines, before and after a set of interventions aiming to optimise patient management and outcomes. All new admissions who met the criteria for sepsis in AMU over a two week period were evaluated. Those who met the criteria for severe sepsis were further analysed. The criteria evaluated were time to first administration of oxygen, intravenous fluids, antibiotics, the taking of blood cultures, other relevant bloods tests (including lactate) and urine output monitoring. A re-audit was completed after the introduction of a set of interventions which included a “sepsis box.” A total of 32 patients (19 Males, 13 Females) were identified in the pre-intervention group. Twenty-two of these patients met the criteria for severe sepsis. Only 15 out of 32 (47%) had their lactate measured. Ten out of 22 (45%) received fluids within an hour. Twelve out of 22 (55%) had their blood culture sample taken after administration of antibiotics and only 12 out of 22 (55%) had antibiotics administrated within an hour of medical assessment. Post-intervention the results however improved dramatically. A total of 30 patients were identified in the post-intervention group (12 Males, 18 Females). Antibiotics administration within an hour went up by 22%. Lactate was performed in 26/30 (87%) patients presented with sepsis compared to 47% in the pre-intervention group. Similarly, identification of severe sepsis, and administration of intravenous fluids also showed improvement ultimately improving patient safety. Following the initial success, the trial was repeated over three months period, which showed sustainable improvement. PMID:26734299

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

    PubMed Central

    2011-01-01

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

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

    PubMed

    Uziel, Yosef; Perl, Liat; Barash, Judith; Hashkes, Philip J

    2011-01-01

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

  13. Sepsis

    MedlinePLUS

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

  14. Sepsis.

    PubMed

    2016-02-01

    Essential facts Each year in the UK there are an estimated 150,000 cases of sepsis, and 44,000 people die as a result of the condition (UK Sepsis Trust). Sepsis is triggered by an infection that causes the immune system to attack the body's own tissues. If not treated quickly, it can lead to multiple organ failure and death. PMID:26838630

  15. Emerging Therapeutic Targets of Sepsis-Associated Acute Kidney Injury

    PubMed Central

    Swaminathan, Sundararaman; Rosner, Mitchell H.; Okusa, Mark D.

    2015-01-01

    Sepsis-associated acute kidney injury (SA-AKI) is linked to high morbidity and mortality. Thus far singular approaches to target specific pathways known to contribute to the pathogenesis of SA-AKI have failed. Because of the complexity of the pathogenesis of SA-AKI, a reassessment necessitates integrative approaches to therapeutics of SA-AKI that include general supportive therapies such as the use of vasopressors, fluids, antimicrobial and target specific and time dependent therapeutics. There has been recent progress in our understanding of the pathogenesis and treatment of SA-AKI including temporal nature of pro- and anti-inflammatory processes. In this review, we will discuss the clinical and experimental basis of emerging therapeutic approaches that focus on targeting early proinflammatory and late anti-inflammatory processes as well as therapeutics that may enhance cellular survival and recovery. Lastly we include ongoing clinical trials in sepsis. PMID:25795498

  16. Emerging therapeutic targets of sepsis-associated acute kidney injury.

    PubMed

    Swaminathan, Sundararaman; Rosner, Mitchell H; Okusa, Mark D

    2015-01-01

    Sepsis-associated acute kidney injury (SA-AKI) is linked to high morbidity and mortality. To date, singular approaches to target specific pathways known to contribute to the pathogenesis of SA-AKI have failed. Because of the complexity of the pathogenesis of SA-AKI, a reassessment necessitates integrative approaches to therapeutics of SA-AKI that include general supportive therapies such as the use of vasopressors, fluids, antimicrobials, and target-specific and time-dependent therapeutics. There has been recent progress in our understanding of the pathogenesis and treatment of SA-AKI including the temporal nature of proinflammatory and anti-inflammatory processes. In this review, we discuss the clinical and experimental basis of emerging therapeutic approaches that focus on targeting early proinflammatory and late anti-inflammatory processes, as well as therapeutics that may enhance cellular survival and recovery. Finally, we include ongoing clinical trials in sepsis. PMID:25795498

  17. Posterior Reversible Encephalopathy Syndrome and Acute Post-Streptococcal Glomerulonephritis Mimicking Breakthrough Seizures

    PubMed Central

    Abdool, Kamille; Ramcharan, Kanterpersad; Bhagwandass, Neal; Persad, Navindra; Temull, Vasant; Seegobin, Karan; Mike, Cassie

    2015-01-01

    We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated anti-streptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI) demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed. PMID:26294945

  18. 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. PMID:26141259

  19. Update in sepsis and acute kidney injury 2014.

    PubMed

    Schortgen, Frdrique; Asfar, Pierre

    2015-06-01

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

  20. Sepsis

    MedlinePLUS

    ... blood cells is abnormal. They also do lab tests that check for signs of infection. People with sepsis are usually treated in hospital intensive care units. Doctors try to treat the infection, sustain the ...

  1. ACUTE DIALYSIS QUALITY INITIATIVE (ADQI) XIV SEPSIS PHENOTYPES AND TARGETS FOR BLOOD PURIFICATION IN SEPSIS: THE BOGOT CONSENSUS.

    PubMed

    Kellum, John A; Gmez, Hernando; Gmez, Alonso; Murray, Patrick; Ronco, Claudio

    2016-03-01

    Despite widespread use, there is currently no consensus on how extracorporeal blood purification therapies should be applied or studied in patients with sepsis. One major obstacle has been the lack of clear descriptions of specific sepsis phenotypes tied to mechanisms that would permit the identification of molecular targets. Current evidence suggests that sepsis-related morbidity and mortality involve widely different clinical phenotypes that variably include mitochondrial dysfunction, abnormalities of vascular biology including endothelial dysfunction and coagulopathy, epithelial dysfunction, and immune suppression and dysregulation. While most cases of sepsis involve some element of all of these pathobiologic processes, the magnitude of each varies greatly from patient to patient in part as a result of the pathogen and in part related to host-specific factors. Thus, the purpose of the fourteenth international consensus conference of acute dialysis quality initiative was to develop consensus for a conceptual model of sepsis-induced organ failure that can be treated by extracorporeal blood purification and possibly also with drugs or other therapies. We assembled a group of experts from around the world and used a modified Delphi method to reach consensus. Specific findings and recommendations for future research are provided in the four accompanying papers. PMID:26871663

  2. New streptococcal serotypes causing pyoderma and acute glomerulonephritis types 59,60, and 61.

    PubMed

    Dillon, H C; Dillon, M S

    1974-06-01

    Three new streptococcal M serotypes, types 59, 60, and 61; have been described. They were first isolated from patients with pyoderma and acute glomerulonephritis (AGN), seen during epidemiological studies in Alabama. A possible antigenic relationship between types 59 and 61 was suggested by their T-agglutination reactions; a more specific T antiserum prepared for type 59 was useful in separating these two types, as well as other strains known to share T antigens 11, 12, and 5/27/44. On the basis of precipitin tests, a common antigenic determinant among types 59, 61, and 49 was suggested. This is of interest in view of the relation between these types and AGN. Type 59 has been relatively more widespread in distribution than type 61, but neither have been related to epidemic AGN. Type 60, first identified as "T-4," thus being related to previously described M types which share this antigen, is of great interest in terms of the epidemiology of AGN. Most strains in our collection were recovered from patients with pyoderma and AGN or from their infected siblings. Recently, the type was found to be prevalent among patients with pyoderma and AGN seen in Trinidad. Data reported in relation to these new types further illustrate the dichotomy in M serotypes common to pyoderma and AGN on the one hand and those types found in collections of patients with pharyngitis on the other hand. The high rate of non-M-typable streptococci among pyoderma collections, encountered earlier, is best explained by lack of suitable reference antisera available for prevalent pyoderma serotypes. PMID:4208529

  3. Group B streptococcal late-onset sepsis with submandibular phlegmon in a premature infant after beginning of breast-feeding.

    PubMed

    Bertini, Giovanna; Dani, Carlo

    2008-03-01

    The case of a premature intra-uterine growth retardation (IUGR) infant, born from caesarean section to a mother with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and admitted to NICU for low birth weight is reported. The baby girl was fed with pasteurized maternal milk, and she had a normal growth. Before discharge, at the age of 23 days of life, she started to be breast-fed from the mother. Suddenly, the infant presented inconsolable crying, and then she appeared pale, hypothermic, and irritable. Eventually she showed apneic spells and hyperglycemia. A purple rash in the left submandibular area was noted. This rash rapidly progressed to painful hardening of the area. The neck ultrasonography revealed the presence of non-vascularized oval mass in the left submandibular area with an irregular sonostructure. The diagnosis of sepsis and submandibular phlegmon was confirmed by a positive blood culture for serotype III group B Streptococcus agalactiae. The polymerase chain reaction (PCR) assay for group B Streptococcus showed the presence of the same serotype in mother's milk. At 24 months of age the infant's neurodevelopment was normal. PMID:18297577

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-02-01

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

  7. Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats.

    PubMed

    Zhao, Hongyu; Zhao, Min; Wang, Yu; Li, Fengchun; Zhang, Zhigang

    2016-02-01

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-? B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-?B and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI. PMID:26385569

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  10. [Invasive streptococcal infections].

    PubMed

    Kosina, P; Plísek, S; Dostál, V; Morávková, M; Cermák, P; Preis, J; Lukes, A; Kracmarová, R; Krausová, J

    2007-12-01

    The severity of streptococcal infections depends upon different virulence of individual strains of its causative agent. The most important species are beta-haemolytic group A streptococci (GAS). Clinical manifestations include skin affections, respiratory tract infections and, in particular, serious systemic invasive infections. The pathogenicity of GAS is derived from cell wall components and extracellular products, especially toxins with properties of the so-called superantigens. Less invasive forms of the disease are include necrotizing fasciitis, myositis, pneumonia, sepsis without focus, arthritis, meningitis, puerperal sepsis, streptococcal toxic shock syndrome (STSS) and severe course of erysipelas and cellulitis with blood culture positive for GAS. In most cases, soft tissue infections dominate, often accompanied by chronic diseases of lower extremities in elderly patients. The other clinical forms are rather rare. In children, the condition is clearly frequently related to chickenpox. The generally accepted therapeutic management comprises comprehensive intensive care, early administration of penicillin in combination with clindamycin, and surgical intervention. The use of intravenous immunoglobulins (IVIG), elimination methods and hyperbaric oxygen are under discussion. The slight increase in cases and ineffective prevention require rapid assessment of diagnosis and adequate treatment as a protracted course of the condition is connected with a high mortality rate. PMID:18320500

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

    PubMed Central

    2014-01-01

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

  12. Azithromycin versus penicillin V in the treatment of paediatric patients with acute streptococcal pharyngitis/tonsillitis. Paediatric Azithromycin Study Group.

    PubMed

    O'Doherty, B

    1996-09-01

    The efficacy and safety of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis/tonsillitis in paediatric patients were compared in a double-blind, double-dummy prospective study. A total of 489 children (age range, 2-13 years) were randomized to receive treatment with penicillin V (125-250 mg 4 x daily for 10 days) or azithromycin in an oral suspension (10 or 20 mg/kg 1 x daily for 3 days). Only patients with baseline cultures positive for Streptococcus pyogenes and complete clinical and microbiological assessments at the end of the therapy and follow-up one month later were included in the efficacy analysis. A satisfactory clinical response (cure or improvement) was recorded in 99% of the 10 mg/kg azithromycin group, 100% of the 20 mg/kg azithromycin group, and 97% of the penicillin V group at the end of therapy (day 12-14). At the follow-up evaluation (day 28-30), relapse rates in patients cured or improved at the end of therapy were 6%, 5%, and 2%, respectively. Bacteriological eradication rates at the end of therapy were 98% in both azithromycin groups and 92% in patients who received penicillin V (p = 0.011); pathogen recurrence was recorded at follow-up in 4% of the 20 mg/kg azithromycin group and in 6% of both the 10 mg/kg azithromycin and penicillin V groups. Treatment-related adverse events, the majority of mild to moderate severity, occurred in 13% of patients in the 20 mg/kg azithromycin group, 9% in the 10 mg/kg azithromycin group, and 5% in the penicillin V group. Azithromycin in a dosage of 10 or 20 mg/kg/day one daily for three days was as safe and effective as penicillin V administered four times daily in the treatment of paediatric patients with acute pharyngitis/tonsillitis. PMID:8922571

  13. Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome

    PubMed Central

    2013-01-01

    Introduction Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis. Methods This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS. Results Using the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days. Conclusions Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury. PMID:24156650

  14. Chitinase-like Proteins are Candidate Biomarkers for Sepsis-induced Acute Kidney Injury*

    PubMed Central

    Maddens, B.; Ghesquire, B.; Vanholder, R.; Demon, D.; Vanmassenhove, J.; Gevaert, K.; Meyer, E.

    2012-01-01

    Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 3648 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI. PMID:22233884

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

    PubMed

    Iwashita, Yoshiaki; Imai, Hiroshi

    2015-01-01

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

  16. Vitamin D deficiency and risk of acute lung injury in severe sepsis and severe trauma: a case-control study

    PubMed Central

    2014-01-01

    Background The aim of this study was to determine the association between 25-hydroxyvitamin D (25-OHD) levels at the onset of critical illness and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with sepsis or trauma. Methods We performed two nested case-control studies of 478 patients with sepsis and trauma with or without ALI/ARDS admitted to the medical, surgical and trauma ICUs of a tertiary-care center. Cases consisted of patients with either sepsis or trauma and ALI/ARDS; controls consisted of equivalent numbers of matched patients with either sepsis or trauma alone. We measured serum 25-OHD levels the morning after ICU admission and used multivariable regression to assess the relationship between 25-OHD and diagnosis of ALI/ARDS during the first four ICU days, controlling for age, gender, diabetes, smoking status and season. Results 25-OHD levels did not differ between cases with ALI/ARDS and controls in either the sepsis or trauma cohorts. Using a conditional logistic regression model, sepsis patients during the winter season with higher 25-OHD levels were more likely to develop acute lung injury (odds ratio 1.68, 95% confidence interval of 1.05 to 2.69, P = 0.03). This association did not hold for the trauma cohort in either season. Sepsis and trauma patients had a lower risk of hospital mortality at higher 25-OHD levels but neither relationship reached significance. Higher one-year mortality after trauma was associated with lower 25-OHD levels (HR 0.50, CI 0.35,0.72 P = 0.001). Conclusions Serum 25-OHD measured early after admission to intensive care is not associated with the development of acute lung injury, hospital or one-year mortality in critically ill patients with sepsis although lower 25-OHD levels were associated with higher one-year mortality in patients with severe trauma. PMID:24559079

  17. Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and systemic inflammatory mediator release in acute experimental sepsis

    PubMed Central

    2012-01-01

    Introduction Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. Methods In the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed. Results HU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals. Conclusion CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis. PMID:22420504

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

    PubMed

    Tetta, C; Bellomo, R; Ronco, C

    2003-03-01

    Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the nonselective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extracorporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials that lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. Additionally, we will review novel information related to other blood purification techniques using large pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance. PMID:12662203

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

    PubMed

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

    2013-12-01

    Sepsis is an acute inflammatory condition that can result in multiple organ failure and acute lung injury. Growth arrest-specific protein 6 (Gas6) is a broad regulator of the innate immune response involved with the nuclear factor ?B signaling pathway. We hypothesized that Gas6 could have a protective role in attenuating the severity of acute lung injury and sepsis. Male mice were subjected to sepsis by cecal ligation and puncture (CLP) after which recombinant murine Gas6 (rmGas6; 5 ?g/mouse) or normal saline (vehicle) was administered intravenously. Blood and lung tissues were collected at 20 h after CLP for various measurements. Treatment with rmGas6 significantly reduced serum levels of the injury markers aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as proinflammatory cytokines interleukin 6 (IL-6) and IL-17, compared with the vehicle group (P < 0.05). The parenchyma of the lungs damaged by CLP was attenuated by rmGas6 treatment. Lung mRNA levels of tumor necrosis factor ?, IL-1?, IL-6, IL-17, and macrophage inflammatory protein 2 (MIP-2) were decreased by 60%, 86%, 82%, 93%, and 82%, respectively, with rmGas6 treatment as determined by real-time reverse transcriptase-polymerase chain reaction (P < 0.05). The degradation of I?B-? induced by CLP in the lungs was inhibited by rmGas6 treatment. The number of neutrophils and myeloperoxidase activity in the lungs were significantly reduced in the rmGas6 group. Moreover, rmGas6 reduced the in vitro migration of differentiated human promyelocytic HL60 cells by 64%. Finally, the 10-day survival rate of mice subjected to CLP was increased from 31% in the vehicle group to 67% in the rmGas6 group (P < 0.05). Thus, Gas6 has potential to be developed as a novel therapeutic agent to treat patients with sepsis and acute lung injury. PMID:23881260

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    DeRubertis, Frederick R.; Woeber, Kenneth A.

    1973-01-01

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

  2. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis.

    PubMed

    Lin, Wei-Chieh; Chen, Chang-Wen; Huang, Yu-Wen; Chao, Lee; Chao, Julie; Lin, Yee-Shin; Lin, Chiou-Feng

    2015-01-01

    Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various animal models and cultured cells. Here, we demonstrate that kallistatin levels were positively correlated with the concentration of total protein in bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower ratio of kallistatin to total protein in BALF showed a significant trend toward elevated neutrophil counts (P = 0.002) in BALF and increased mortality (P = 0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin in lung by gene transfer with human kallistatin-encoding plasmid ameliorated acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression compared to the control mice. Mouse survival was improved by kallistatin gene transfer or recombinant human kallistatin treatment after LPS challenge. In LPS-stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis, down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen species (ROS) and inhibited ROS-mediated NF-κB activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-κB inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. PMID:26198099

  3. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis

    PubMed Central

    Lin, Wei-Chieh; Chen, Chang-Wen; Huang, Yu-Wen; Chao, Lee; Chao, Julie; Lin, Yee-Shin; Lin, Chiou-Feng

    2015-01-01

    Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various animal models and cultured cells. Here, we demonstrate that kallistatin levels were positively correlated with the concentration of total protein in bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower ratio of kallistatin to total protein in BALF showed a significant trend toward elevated neutrophil counts (P?=?0.002) in BALF and increased mortality (P?=?0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin in lung by gene transfer with human kallistatin-encoding plasmid ameliorated acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression compared to the control mice. Mouse survival was improved by kallistatin gene transfer or recombinant human kallistatin treatment after LPS challenge. In LPS-stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis, down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen species (ROS) and inhibited ROS-mediated NF-?B activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-?B inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. PMID:26198099

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

    PubMed

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

    2015-01-01

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

  5. Pre-B-Cell Colony-Enhancing Factor and Its Clinical Correlates With Acute Lung Injury and Sepsis

    PubMed Central

    Lee, Kathleen A.

    2011-01-01

    Background: Pre-B-cell colony-enhancing factor (PBEF) is a potential biomarker for acute lung injury (ALI) in sepsis. We aimed to determine the clinical correlates for elevated plasma PBEF upon ICU admission for severe sepsis and the usefulness of PBEF to predict ALI development and sepsis mortality. Methods: This is a prospective cohort of patients admitted to the medical ICU with severe sepsis. Patients without available blood samples or who were not enrolled within 24 h of admission were excluded. Plasma collected within 24 h of ICU admission was measured for PBEF concentrations by enzyme-linked immunosorbent assay. Patients were followed for ALI development as defined by the American-European Consensus Conference and for all-cause hospital mortality. Results: Between September 30, 2008, and March 10, 2009, 113 patients were enrolled, and 50 (44%) developed ALI. Elevated PBEF levels significantly correlated with higher APACHE (Acute Physiology and Chronic Health Evaluation) III scores (R2 = 0.08, P = .003) and failure to reach early sepsis goals within 6 h of severe sepsis (P = .003). PBEF did not differ by ALI status (P = .58). The mortality rate was 46%. Nonsurvivors had higher PBEF levels than survivors (2.53 ng/mL; interquartile range [IQR], 1.07-8.16 vs 1.44 ng/mL; IQR, 0.84-2.81; P = .02). After adjusting for severity of illness, PBEF levels were no longer significantly associated with mortality (OR, 1.44 per 10-fold increase; 95% CI, 0.69-3.03, P = .34). Conclusions: In this study, elevated PBEF did not correlate with lung injury in sepsis. However, it was associated with sepsis mortality mainly due to its association with greater severity of illness on ICU admission. PMID:21565968

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  8. The effect of Lactobacillus bacteria supplement on sepsis and its complications in patients with acute burns.

    PubMed

    Koren, Lior; Gurfinkel, Reuven; Glezinger, Ronen; Perry, Zvi Howard; Lev-Ari, Sandra; Rosenberg, Lior

    2007-08-01

    Sepsis as a result of bacterial translocation from the gastrointestinal tract (GIT) is a known associate of morbidity and mortality in patients with severe burns. This translocation is influenced by the GIT flora. Oral consumption of Lactobacillus bacteria was previously shown to reduce translocation. We conducted a retrospective cohort study on a series of 56 patients with burns admitted to Soroka University Medical Center in Beer-Sheva, Israel. Those 56 patients included 28 who were given lactobacillus supplements and 28 who were not. The parameters that were compared between the groups evaluated the level of sepsis and its complications. The parameters of morbidity during hospitalization were significantly higher in the treatment group; however, their mortality was lower. That difference in mortality between the groups was not significant as a whole (p=0.071), but it was significant in the subgroup analysis of 41-70% total body surface area burned. In that subgroup there were zero cases of death in the treatment group versus five cases in the control group (p=0.005). Our findings suggest that in acute burns, lactobacillus bacteria food additives may be clinically beneficial in patients with total burned body surface area of 41-70%. PMID:17482370

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

    Chen, Lin

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

    Background Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis and sepsis-associated ARDS is associated with significant morbidity and mortality. To date, no study has directly examined the epidemiology of ARDS in severe sepsis from the earliest presentation to the health care system, the Emergency Department (ED). Methods Single-center retrospective, observational cohort study of 778 adults with severe sepsis presenting to the ED. The primary outcome was the development of ARDS requiring mechanical ventilation during the first 5 hospital days. ARDS was defined using the Berlin definition. We used multivariable logistic regression to identify risk factors associated independently with ARDS development. Results The incidence of ARDS was 6.2% (48 of 778 patients) in the entire cohort. ARDS development varied across the continuum of care: 0.9% of patients fulfilled criteria for ARDS in the ED, 1.4% admitted to the ward developed ARDS, and 8.9% admitted to the ICU developed ARDS. ARDS developed a median of 1 day after admission and was associated with a four-fold higher risk of in-hospital mortality (14% vs. 60%, p<0.001). Independent risk factors associated with increased risk of ARDS development included: intermediate (23.9 mmol/L) (p=0.04) and high (? 4) serum lactate levels (p=0.008), lung injury prediction score (LIPS) (p<0.001) and microbiologically-proven infection (p=0.01). Conclusions In patients presenting to the ED with severe sepsis, the rate of sepsis-associated ARDS development varied across the continuum of care. ARDS developed rapidly and was associated with significant mortality. Elevated serum lactate levels in the ED and a recently validated clinical prediction score were independently associated with the development of ARDS in severe sepsis. PMID:23903852

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

    PubMed Central

    Venot, Marion; Weis, Lise; Clech, Christophe; Darmon, Michael; Allaouchiche, Bernard; Goldgran-Toldano, Dany; Garrouste-Orgeas, Mait; Adrie, Christophe; Timsit, Jean-Franois; Azoulay, Elie

    2015-01-01

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

  13. Definitions and pathophysiology of sepsis.

    PubMed

    Sagy, Mayer; Al-Qaqaa, Yasir; Kim, Paul

    2013-01-01

    Mortality rates for sepsis and septic shock have not improved in the past decade. The Surviving Sepsis Campaign (SSC) guidelines released in 2012 emphasize early recognition and treatment of sepsis, in an effort to reduce the burden of sepsis worldwide. This series of review articles will discuss the pathophysiology of sepsis; comorbidities, such as multiorgan dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), and endocrine issues; and finally, management of sepsis and septic shock. PMID:24295606

  14. Acute-Phase Deaths from Murine Polymicrobial Sepsis Are Characterized by Innate Immune Suppression Rather Than Exhaustion.

    PubMed

    Chiswick, Evan L; Mella, Juan R; Bernardo, John; Remick, Daniel G

    2015-10-15

    Sepsis, a leading cause of death in the United States, has poorly understood mechanisms of mortality. To address this, our model of cecal ligation and puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes. By 24 h, however, Die-P mice have increased bacterial burden, despite increased neutrophil recruitment, suggesting Die-P phagocytes have impaired bacterial killing. Peritoneal cells were used to study multiple bactericidal processes: bacterial killing, reactive oxygen species (ROS) generation, and phagocytosis. Total phagocytosis and intraphagosomal processes were determined with triple-labeled Escherichia coli, covalently labeled with ROS- and pH-sensitive probes, and an ROS/pH-insensitive probe for normalization. Although similar proportions of Live-P and Die-P phagocytes responded to exogenous stimuli, Die-P phagocytes showed marked deficits in all parameters measured, thus suggesting immunosuppression rather than exhaustion. This contradicts the prevailing sepsis paradigm that acute-phase sepsis deaths (<5 d) result from excessive inflammation, whereas chronic-phase deaths (>5 d) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first 6 h. PMID:26371253

  15. Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis.

    PubMed

    Weber, Georg F; Chousterman, Benjamin G; He, Shun; Fenn, Ashley M; Nairz, Manfred; Anzai, Atsushi; Brenner, Thorsten; Uhle, Florian; Iwamoto, Yoshiko; Robbins, Clinton S; Noiret, Lorette; Maier, Sarah L; Znnchen, Tina; Rahbari, Nuh N; Schlch, Sebastian; Klotzsche-von Ameln, Anne; Chavakis, Triantafyllos; Weitz, Jrgen; Hofer, Stefan; Weigand, Markus A; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K

    2015-03-13

    Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis. PMID:25766237

  16. Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury

    PubMed Central

    Ma, Shwu-Fan; Xie, Lishi; Pino-Yanes, Maria; Sammani, Saad; Wade, Michael S.; Letsiou, Eleftheria; Siegler, Jessica; Wang, Ting; Infusino, Giovanni; Kittles, Rick A.; Flores, Carlos; Zhou, Tong; Prabhakar, Bellur S.; Moreno-Vinasco, Liliana; Villar, Jesus; Jacobson, Jeffrey R.; Dudek, Steven M.

    2011-01-01

    The role of thyroid hormone metabolism in clinical outcomes of the critically ill remains unclear. Using preclinical models of acute lung injury (ALI), we assessed the gene and protein expression of type 2 deiodinase (DIO2), a key driver for synthesis of biologically active triiodothyronine, and addressed potential association of DIO2 genetic variants with ALI in a multiethnic cohort. DIO2 gene and protein expression levels in murine lung were validated by microarrays and immunoblotting. Lung injury was assessed by levels of bronchoalveolar lavage protein and leukocytes. Single-nucleotide polymorphisms were genotyped and ALI susceptibility association assessed. Significant increases in both DIO2 gene and D2 protein expression were observed in lung tissues from murine ALI models (LPS- and ventilator-induced lung injury), with expression directly increasing with the extent of lung injury. Mice with reduced levels of DIO2 expression (by silencing RNA) demonstrated reduced thyroxine levels in plasma and increased lung injury (increased bronchoalveolar lavage protein and leukocytes), suggesting a protective role for DIO2 in ALI. The G (Ala) allele of the Thr92Ala coding single-nucleotide polymorphism (rs225014) was protective in severe sepsis and severe sepsisassociated ALI after adjustments for age, sex, and genetic ancestry in a logistic regression model in European Americans. Our studies indicate that DIO2 is a novel ALI candidate gene, the nonsynonymous Thr92Ala coding variant of which confers ALI protection. Increased DIO2 expression may dampen the ALI inflammatory response, thereby strengthening the premise that thyroid hormone metabolism is intimately linked to the integrated response to inflammatory injury in critically ill patients. PMID:21685153

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

    PubMed

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

    2013-02-01

    The updated Guidelines on Prevention of Perinatal Group B Streptococcal Disease, issued by the Centers for Disease Control and Prevention, actually represent the mainstay in the prevention of neonatal early-onset group B streptococcal (GBS) sepsis. According to these guidelines, patients with possible preterm delivery are screened for GBS colonization and offered intrapartum prophylaxis only if they enter preterm labor or experience preterm premature rupture of the membranes. Nonetheless, the fulfillment of these recommendations seems to be suboptimal in clinical practice, as it is heavily influenced by the knowledge of the colonization status. We report here 2 cases of blood culture-proven, early-onset neonatal GBS sepsis involving preterm infants delivered by mothers who had midtrimester cervical insufficiency and bulging membranes. Midtrimester acute cervical insufficiency strongly predicts preterm delivery. These women are liable to miss intrapartum antibiotic prophylaxis because they typically have shorter labor, and the test results for GBS status are unlikely to be available before delivery. We believe that women with midtrimester cervical insufficiency and bulging membranes should be screened for GBS infection soon after hospital admittance if the gestational age is close to the threshold of fetal viability. A timely diagnosis of GBS colonization may not only increase the number of patients receiving targeted intrapartum antibiotic prophylaxis but would also allow consideration of the administration of antepartum antibiotic prophylaxis. Indeed, as further outlined in this report, GBS intraamniotic infection may dramatically occur before the onset of preterm labor or preterm premature rupture of the membranes. PMID:23296432

  18. Glycyrrhizic Acid Attenuates Sepsis-Induced Acute Kidney Injury by Inhibiting NF-κB Signaling Pathway

    PubMed Central

    Zhao, Hongyu; Zhao, Min; Wang, Yu; Li, Fengchun; Zhang, Zhigang

    2016-01-01

    Glycyrrhizic acid (GA) is a major active ingredient in licorice. In our study, the effects of GA on acute kidney injury (AKI) in rats and its underlying molecular mechanisms were investigated. The sepsis model was produced by caecal ligation and puncture (CLP) in rats. The molecular and histological experiments were performed in the kidney tissues and serum samples of rats. According to the results obtained, GA alleviated sepsis-induced AKI by improving the pathological changes, decreasing the levels of blood urea nitrogen (BUN), creatinine (Cre), and increasing the survival rate of rats with AKI significantly. The production of inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, was markedly inhibited by GA. Moreover, treatment with GA inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression levels of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in kidney tissues. Furtherly, the apoptosis in kidney tissue induced by AKI was suppressed by GA. Finally, GA could inhibit the activation of NF-κB signaling pathway. Our study suggests that GA alleviates sepsis-induced AKI by inhibiting the NF-κB signaling pathway, which provides a strong evidence for a new approach for treating sepsis-induced AKI. PMID:26904148

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

    PubMed Central

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

    2015-01-01

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

  20. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

    PubMed

    McGill, F; Heyderman, R S; Michael, B D; Defres, S; Beeching, N J; Borrow, R; Glennie, L; Gaillemin, O; Wyncoll, D; Kaczmarski, E; Nadel, S; Thwaites, G; Cohen, J; Davies, N W S; Miller, A; Rhodes, A; Read, R C; Solomon, T

    2016-04-01

    Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. PMID:26845731

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

    PubMed

    Jin, Li-Yan; Li, Cong-Feng; Zhu, Guang-Fa; Wu, Chun-Ting; Wang, Jun; Yan, Shu-Feng

    2014-08-01

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

  2. [Microbiology of streptococcal infections].

    PubMed

    Peuckert, W

    1985-01-01

    Since the discovery of streptococci by the surgeon of Vienna, Theodor Billroth, more than 100 years ago, they have proved to be a bacterial group of great medical and epidemiological importance. The classification in growth-characteristics on blood culture mediums (alpha-, beta- and gamma-hemolysis) has been detached by the evidence of group specific cell wall antigens. The antigene extraction described by Lancefield can distinguish at least 21 serogroups (A-T). They have also taken over the historical names (S. pyogenes, S. agalactiae etc.). In addition to group relationship the antigen structure of the streptococci cell wall (carbohydrates, peptidoglycanes, M-T-R-proteins and others) is responsible for antigenetic and pathogenetic conditions. Some species of streptococci do also excrete exotoxines (streptolysin, hyaluronidase, bacteriocines, erythrogenic toxins) with antigenetic and pathogenetic significance. Infections with streptococci of the serogroup A, B, D and H are numerously and medically significant. There is a great interest in infections due to A streptococci (pharygitis, impetigo, erysipel, scarlatin fever). The known non-purulent diseases following A streptococci infections (acute rheumatoid fever, acute glomerulonephritis) are streptococcal specific reactions for the individual. Some antigens of the cell wall and also some exotoxines react in human beings as autoantigenes. Human beings are the most important reservoir for streptococci. Nearly 20% of a population have A streptococci in their upper respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3974168

  3. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation.

    PubMed

    Campos, Renata; Shimizu, Maria Helosa Massola; Volpini, Rildo Aparecido; de Bragana, Ana Carolina; Andrade, Lucia; Lopes, Fernanda Degobbi Tenrio Quirino Dos Santos; Olivo, Clarice; Canale, Daniele; Seguro, Antonio Carlos

    2012-04-01

    Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the ?-subunit of the epithelial sodium channel (?-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, ?-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis. PMID:22268121

  4. Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep.

    PubMed

    Murakami, Kazunori; McGuire, Roy; Cox, Robert A; Jodoin, Jeffrey M; Bjertnaes, Lars J; Katahira, Jiro; Traber, Lillian D; Schmalstieg, Frank C; Hawkins, Hal K; Herndon, David N; Traber, Daniel L

    2002-09-01

    Pseudomonas pneumonia is a common complication of smoke inhalation injury. Airway casts formed from clotted mucous occur frequently in this condition. A recent report shows that intravenous heparin improves oxygenation and reduces lung damage in a sheep model of smoke inhalation. We hypothesized that nebulized heparin could be an effective means of reducing cast formation. Female sheep (n = 19) were surgically prepared for a study of acute lung injury (ALI). After a tracheotomy, 48 breaths of cotton smoke (<40 degrees C) were inflated into the airway. Afterwards, live Pseudomonas aeruginosa (5 x 10(11) CFU) was instilled into the lung. All sheep were mechanically ventilated with 100% O2 and were divided into four groups: a heparin-nebulized group (n = 5; animals received aerosolized heparin [10,000 I.U.] 1 h after the bacterial instillation and subsequently every 4 h thereafter), an intravenous heparin group (n = 5,300 U/kg/23 h, infusion was started 1 h after the injury), a saline-nebulization group (n = 5; animals received inhaled nebulized saline), and a sham injury group (n = 4, treated in the same fashion, but no injury). The animals were sacrificed after 24 h of mechanical ventilation, and lung samples were harvested. Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes and a corresponding drop in PaO2. These changes were significantly attenuated in the heparin groups. Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin. These data suggest that nebulized inhaled heparin is a beneficial therapy for sepsis-induced ALI. PMID:12353924

  5. Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis

    PubMed Central

    Ginde, Adit A.; Blatchford, Patrick J.; Trzeciak, Stephen; Hollander, Judd E.; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M.; Moretti, Eugene; Nguyen, H. Bryant; Gunnerson, Kyle J.; Milzman, David; Gaieski, David F.; Goyal, Munish; Cairns, Charles B.; Rivers, Emanuel P.; Shapiro, Nathan I.

    2014-01-01

    Objective To evaluate age-related differences in inflammation biomarkers during the first 72 hours of hospitalization for sepsis. Methods This was a secondary analysis of a prospective observational cohort of adult patients (n=855) from ten, urban, academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. We analyzed six inflammation-related biomarkerschemokine (CC-motif) ligand-23 (CCL-23); C-reactive protein (CRP); interleukin-1 receptor antagonist (IL-1ra); neutrophil gelatinase-associated lipocalin (NGAL); peptidoglycan recognition protein (PGRP); and tumor necrosis factor receptor-1a (TNFR-1a)measured at presentation and 3, 6, 12, 24, 48, or 72 hours later. Results The median age was 56 (IQR 4372) years and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 1834 years had severe sepsis or septic shock compared to 71% for those aged ?65 years (p<0.001). In longitudinal models adjusting for demographics, co-morbidities, and infection source, older age was associated with higher baseline values for CCL-23, IL-1ra, NGAL, and TNFR-1a (all p<0.05). However, older adults had higher mean values during the entire 72-hour period only for NGAL and TNFR-1a, and higher final 72-hour values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Conclusion While older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 hours of hospitalization. PMID:24978893

  6. Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

    PubMed

    Ginde, Adit A; Blatchford, Patrick J; Trzeciak, Stephen; Hollander, Judd E; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M; Moretti, Eugene; Nguyen, H Bryant; Gunnerson, Kyle J; Milzman, David; Gaieski, David F; Goyal, Munish; Cairns, Charles B; Rivers, Emanuel P; Shapiro, Nathan I

    2014-08-01

    The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization. PMID:24978893

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

    PubMed

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

    2015-09-01

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

  8. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury in mice.

    PubMed

    Takaoka, Yuki; Goto, Shigeru; Nakano, Toshiaki; Tseng, Hui-Peng; Yang, Shih-Ming; Kawamoto, Seiji; Ono, Kazuhisa; Chen, Chao-Long

    2014-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related enzyme in the glycolytic pathway. Recently, it has been reported that GAPDH has other physiological functions, such as apoptosis, DNA repair and autophagy. Some in vitro studies have indicated immunological aspects of GAPDH function, although there is no definite study discussing the advantage of GAPDH as a therapeutic target. Here, we show that GAPDH has an anti-inflammatory function by using a lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury (ALI) mouse model, which is referred to as acute respiratory distress syndrome (ARDS) in humans. GAPDH pre-injected mice were protected from septic death, and their serum levels of proinflammatory cytokines were significantly suppressed. In lung tissue, LPS-induced acute injury and neutrophil accumulation were strongly inhibited by GAPDH pre-injection. Pulmonary, proinflammatory cytokine gene expression and serum chemokine expression in GAPDH pre-injected mice were also reduced. These data suggest the therapeutic potential of GAPDH for sepsis-related ALI/ARDS. PMID:24902773

  9. Acute administration of antibiotics modulates intestinal capillary perfusion and leukocyte adherence during experimental sepsis.

    PubMed

    Al-Banna, N A; Pavlovic, D; Bac, V H; Utpatel, K; Janke, E; Rippke, J N; Borowiak, M; Cerny, V; Spassov, A; Johnston, B; Issekutz, T B; Lehmann, C H

    2013-06-01

    Antibiotic treatment represents a mainstay of therapy for clinical sepsis. Distinct from their antimicrobial effects, antibiotics may impact the inflammatory process in sepsis, e.g. within the intestinal microcirculation. The impact of seven antibiotics relevant to clinical sepsis on intestinal leukocyte recruitment and capillary perfusion was studied in rats with colon ascendens stent peritonitis (CASP)-induced sepsis or after endotoxin [lipopolysaccharide (LPS)] challenge. The following antibiotics were included: daptomycin; erythromycin; imipenem; linezolid; tigecycline; tobramycin; and vancomycin. The number of rolling and adherent leukocytes in intestinal submucosal venules and the functional capillary density (FCD) in three layers of the intestinal wall were assessed using intravital microscopy. CASP-induced sepsis reduces the intestinal FCD by 30-50%. Single administration of daptomycin, tigecycline or linezolid increased the intestinal FCD. CASP sepsis increased the number of rolling leukocytes by 4.5-fold, which was reduced by erythromycin but increased by vancomycin. The number of adherent leukocytes increased 3-fold in rats with CASP sepsis. It was reduced following administration of daptomycin, tigecycline (in V1 and V3 venules), erythromycin and linezolid (in V1 venules). However, following tobramycin and vancomycin, leukocyte adhesion was further enhanced. Administration of tigecycline and linezolid reduced the LPS-induced increase in the number of adherent leukocytes by 50%. However, imipenem did not affect leukocyte adherence. In conclusion, this work highlights the beneficial impact of the antibiotics daptomycin, tigecycline, erythromycin and linezolid in that they improve intestinal capillary perfusion and/or reduce leukocyte recruitment, whilst the antibiotics imipenem, tobramycin and vancomycin do not exert these properties. PMID:23622880

  10. The acute immunological response to blood transfusion is influenced by polymicrobial sepsis.

    PubMed

    Nacionales, Dina C; Cuenca, Alex G; Ungaro, Ricardo; Gentile, Lori F; Joiner, Dallas; Satoh, Minoru; Lomas-Neira, Joanne; Ayala, Alfred; Bihorac, Azra; Delano, Matthew J; Ang, Darwin N; Efron, Philip A

    2012-12-01

    Blood transfusion is a well-established risk factor for adverse outcomes during sepsis. The specific mechanisms responsible for this effect remain elusive, and few studies have investigated this phenomenon in a model that reflects not only the clinical circumstances in which blood is transfused, but also how packed red blood cells (PRBCs) are created and stored. Using a cecal ligation and puncture model of polymicrobial sepsis as well as creating murine allogeneic and stored PRBCs in a manner that replicates the clinical process, we have demonstrated that transfusion of PRBCs induces numerous effects on leukocyte subpopulations. In polymicrobial sepsis, these responses are profoundly dissimilar to the proinflammatory effects of PRBC transfusion observed in the healthy mouse. Transfused septic mice, as opposed to mice receiving crystalloid resuscitation, had a significant loss of blood, spleen, and bone marrow lymphocytes, especially those with an activated phenotype. Myeloid cells behaved similarly, although they were able to produce more reactive oxygen species. Overall, transfusion in the septic mouse may contribute to the persistent immune dysfunction known to be associated with this process, rather than simply promote proinflammatory or anti-inflammatory effects on the host. Thus, it is possible that blood transfusion contributes to the multiple known effects of sepsis on leukocyte populations that have been shown to result in increased morbidity and mortality. PMID:23143057

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

    PubMed

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

    2015-04-01

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

  12. Non-Necrotizing Streptococcal Cellulitis as a Cause of Acute, Atraumatic Compartment Syndrome of the Foot: A Case Report.

    PubMed

    Toney, James; Donovan, Stephanie; Adelman, Vanessa; Adelman, Ronald

    2016-01-01

    Acute compartment syndrome is widely accepted as a surgical emergency. Most cases of acute compartment syndrome occur after high-energy trauma, especially crush injuries. We present a unique case of acute, atraumatic compartment syndrome of the foot associated with infectious cellulitis. A 53-year-old male, with a medical history significant for human immunodeficiency virus, presented to the emergency department secondary to an insidious onset of intense foot pain, swelling, and an inability to bear weight on the affected extremity. He had no history of recent trauma. He was admitted to the hospital because of a suspected infection and subsequently was given intravenous antibiotics. During the admission, he developed a severe infection, and blood cultures demonstrated growth of group A streptococcus. No abscess or hematoma was identified on magnetic resonance imaging or during exploratory surgery. The findings from intraoperative cultures were negative. Despite proper medical care for his infection, the lower extremity pain worsened; therefore, compartmental pressures were obtained at the bedside. Multiple compartment pressures were measured and were >40 mm Hg. Compartment syndrome was diagnosed, and the patient was taken to the operating room for emergent fasciotomies. Surgical release of the medial, lateral, interosseous, and adductor compartments revealed copious amounts of serosanguinous drainage. Again, no definitive hematoma or purulence was identified. The patient's symptoms resolved after the fasciotomies, and he healed uneventfully. Our case highlights the need to consider acute compartment syndrome in the differential diagnosis for pain out of proportion to the clinical situation, even when a traditional etiology is absent. PMID:25981442

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. Important issues in the design and reporting of clinical trials in severe sepsis and acute lung injury.

    PubMed

    Dellinger, R Phillip; Vincent, Jean-Louis; Marshall, John; Reinhart, Konrad

    2008-12-01

    Severe sepsis and acute lung injury are challenging diagnoses as they relate to designing and reporting of clinical trials. The limited success in bringing forward new therapies in these areas is likely proof of that premise. The ability to use preclinical and phase I and II trial data to predict which patients and which dosing regimens are more likely to benefit is perhaps the greatest challenge. Animal models continue to be refined in attempts to more accurately reproduce human sepsis and acute lung injury. Oncology research should serve as a model for optimizing the integration of pharmacodynamics and pharmacogenetics into trial design. The European Organization for Research and Treatment of Cancer provides a valuable template for nonfunded multicenter clinical trial success. The marked heterogeneity of the patient population and small signal (tested therapy)-to-noise (comorbidities) ratio makes identification of treatment effect difficult. Dedicated investigators still enroll ineligible patients who are included in intent to treat analysis. High enrolling centers create less problems in an adequate test of a new therapy. Much has been learned from negative trials as to value of post hoc subgroup and interim analyses. Debate continues on fair and appropriate end point of trials. Extrapolation of adult positive trial results to children is problematic. Conflict of interest issues which rested dormantly for years are now at the forefront of discussion, and journal editorial board responsibility in this area is being recognized. Protocols may also help reduce heterogeneity of treatment across centers in clinical trials. This article reviews many of the problems encountered in clinical trial design and reporting and offers a perspective on dealing with them to the betterment of a clinical trial. PMID:19056012

  16. Scavenger Receptor B and CD36 Targeting Improves Sepsis Survival and Acute Outcomes in Mice*

    PubMed Central

    Leelahavanichkul, Asada; Bocharov, Alexander V.; Kurlander, Roger; Baranova, Irina N.; Vishnyakova, Tatyana G.; Souza, Ana C.P.; Hu, Xuzhen; Doi, Kent; Vaisman, Boris; Amar, Marcelo; Sviridov, Denis; Chen, Zhigang; Remaley, Alan T.; Csako, Gyorgy; Patterson, Amy P.; Yuen, Peter S. T.; Star, Robert A; Eggerman, Thomas L.

    2013-01-01

    Class B scavenger receptors, such as SR-BI/II or CD36, bind lipoproteins, but also mediate bacterial recognition and phagocytosis. In evaluating whether blocking receptors can prevent intracellular bacterial proliferation, phagocyte cytotoxicity and proinflammatory signaling in bacterial infection/sepsis, we found that SR-BI/II- or CD36-deficient phagocytes are characterized by a reduced intracellular bacterial survival, a lower cytokine response, and were protected from bacterial cytotoxicity in the presence of antibiotics. Mice deficient in either SR-BI/II or CD36 are protected from antibiotic-treated cecal ligation and puncture (CLP)-induced sepsis, with greatly increased peritoneal granulocytic phagocyte survival (8-fold), a drastic diminution in peritoneal bacteria counts and 50 to 70% reduction in systemic inflammation (serum levels of IL-6, TNF-α and IL-10) and organ damage relative to CLP in wild-type mice. CD36-deficient mice survival after CLP was 58% compared to 17% in control mice. When compensated for mineralocorticoid and glucocorticoid deficiency, SR-BI/II-deficient mice had almost a 50% survival rate vs. 5% in mineralo-/glucocorticoid-treated controls. Targeting SR-B receptors with L-37pA, a peptide that functions as an antagonist of SR-BI/II and CD36 receptors, also increased peritoneal granulocyte counts, reduced peritoneal bacteria and bacterium-induced cytokine secretion. In the CLP mouse sepsis model L-37pA improved survival from 6% to 27%, reduced multiple organ damage, and improved kidney function. These results demonstrate that the reduction of both SR-BI/II- and CD36-dependent bacterial invasion and inflammatory response in the presence of antibiotic treatment results in granulocyte survival, local bacterial containment, and also reduces systemic inflammation, organ damage and improve animal survival during severe infections. PMID:22327076

  17. Zinc regulates the acute phase response and serum amyloid A production in response to sepsis through JAK-STAT3 signaling.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Sequential Actions of SIRT1-RELB-SIRT3 Coordinate Nuclear-Mitochondrial Communication during Immunometabolic Adaptation to Acute Inflammation and Sepsis*

    PubMed Central

    Liu, Tie Fu; Vachharajani, Vidula; Millet, Patrick; Bharadwaj, Manish S.; Molina, Anthony J.; McCall, Charles E.

    2015-01-01

    We reported that NAD+-dependent SIRT1, RELB, and SIRT6 nuclear proteins in monocytes regulate a switch from the glycolysis-dependent acute inflammatory response to fatty acid oxidation-dependent sepsis adaptation. We also found that disrupting SIRT1 activity during adaptation restores immunometabolic homeostasis and rescues septic mice from death. Here, we show that nuclear SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogenesis, which alters bioenergetics during sepsis adaptation. We constructed this concept using TLR4-stimulated THP1 human promonocytes, a model that mimics the initiation and adaptation stages of sepsis. Following increased expression, mitochondrial SIRT3 deacetylase activates the rate-limiting tricarboxylic acid cycle (TCA) isocitrate dehydrogenase 2 and superoxide dismutase 2, concomitant with increases in citrate synthase activity. Mitochondrial oxygen consumption rate increases early and decreases during adaptation, parallel with modifications to membrane depolarization, ATP generation, and production of mitochondrial superoxide and whole cell hydrogen peroxide. Evidence of SIRT1-RELB induction of mitochondrial biogenesis included increases in mitochondrial mass, mitochondrial-to-nuclear DNA ratios, and both nuclear and mitochondrial encoded proteins. We confirmed the SIRT-RELB-SIRT3 adaptation link to mitochondrial bioenergetics in both TLR4-stimulated normal and sepsis-adapted human blood monocytes and mouse splenocytes. We also found that SIRT1 inhibition ex vivo reversed the sepsis-induced changes in bioenergetics. PMID:25404738

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

    PubMed Central

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

    2014-01-01

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

  1. THE ENDOTHELIUM IN SEPSIS.

    PubMed

    Ince, Can; Mayeux, Philip R; Nguyen, Trung; Gomez, Hernando; Kellum, John A; Ospina-Tascn, Gustavo A; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

    2016-03-01

    Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID:26871664

  2. Comparison of Outcomes of Patients With Sepsis With Versus Without Acute Myocardial Infarction and Comparison of Invasive Versus Noninvasive Management of the Patients With Infarction.

    PubMed

    Smilowitz, Nathaniel R; Gupta, Navdeep; Guo, Yu; Bangalore, Sripal

    2016-04-01

    Patients hospitalized with sepsis may be predisposed to acute myocardial infarction (AMI). The incidence, treatment, and outcomes of AMI in sepsis have not been studied. We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients with a diagnosis of sepsis. The incidence of AMI as a nonprimary diagnosis was evaluated. Propensity score matching was used to identify a cohort of patients with secondary AMI and sepsis with similar baseline characteristics who were managed invasively (defined as cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) or conservatively. The primary outcome was in-hospital all-cause mortality. A total of 2,602,854 patients had a diagnosis of sepsis. AMI was diagnosed in 118,183 patients (4.5%), the majority with non-ST elevation AMI (71.4%). In-hospital mortality was higher in patients with AMI and sepsis than those with sepsis alone (35.8% vs 16.8%, p <0.0001; adjusted odds ratio 1.24, 95% CI 1.22 to 1.26). In patients with AMI, 11,899 patients (10.1%) underwent an invasive management strategy, in which 4,668 patients (39.2%) underwent revascularization. PCI was performed in 3,413 patients (73.1%), CABG in 1,165 (25.0%), and both CABG and PCI in 90 patients (1.9%). In a propensity-matched cohort of 23,708 patients with AMI, invasive management was associated with a lower mortality than conservative management (19.0% vs 33.4%, p <0.001; odds ratio 0.47, 95% CI 0.44 to 0.50). In subgroups that underwent revascularization, the odds of mortality were consistently lower than corresponding matched subjects from the conservative group. In conclusion, myocardial infarction not infrequently complicates sepsis and is associated with a significant increase in in-hospital mortality. Patients managed invasively had a lower mortality than those managed conservatively. PMID:26853952

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

    PubMed Central

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

    2001-01-01

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

  4. [Acute intravasal hemolysis in Clostridium perfringens sepsis. Differential diagnosis of hemolytic episodes].

    PubMed

    Strobel, E; Nathrath, M; Peters, J; Abele-Horn, M; Wllenweber, J

    1994-03-18

    A 19-year-old man with acute lymphoblastic leukaemia developed fever, general deterioration and somnolence 3 days after a cycle of cytostatic treatment. He had anaemia (haemoglobin 6.6 g/dl), leukopenia (100/microliters) and thrombocytopenia (7,000/microliters). As an acute septicaemia was suspected he received broad spectrum antibiotic therapy, together with two units of red cell and platelet concentrates. However, his condition worsened rapidly over the next 5 hours (meningism, seizures, fever to 41.1 degrees C, dyspnoea). Another blood count revealed severe haemolysis. Computed tomography of the skull demonstrated multilocular intraparenchymal gas formation. Although the antibiotic treatment was extended the patient died several hours later. Retrospective examination for suspected transfusion mismatch provided no evidence for erythrocyte incompatibility. But there was liberation of T-antigen as sign of a bacterial cause of erythrocyte damage. An anaerobic blood culture grew Clostridium perfringens. This case demonstrates that acute intravascular haemolysis in septicaemia should be considered in the differential diagnosis of transfusion mismatch. PMID:8131716

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

    PubMed Central

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

    2012-01-01

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

  6. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

    PubMed Central

    Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

    2013-01-01

    Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

  7. Longer storage duration of red blood cells is associated with an increased risk of acute lung injury in patients with sepsis

    PubMed Central

    2013-01-01

    Background The storage duration of red blood cells transfused to critically ill patients is associated with increased morbidity and mortality. Whether the association exists between storage duration of red blood cells transfused to patients with sepsis and the risk of developing ALI/ARDS is unknown. We aimed to determine the association of the storage duration of red blood cells transfused to patients with sepsis and risk of developing acute lung injury in the subsequent 96 hours, with comparator trauma and nonsepsis/nontrauma groups. Methods We conducted a retrospective observational study of 96 transfused, critically ill patients with sepsis, 176 transfused, critically ill patients with traumatic injury, and 125 transfused, critically ill nontrauma, nonsepsis patients. The primary outcome was the development of ALI/ARDS up to 96 hours after transfusion. Results In 96 patients with sepsis, 49 (51%) patients developed ALI/ARDS. The median storage duration of transfused blood in the ALI/ARDS group was greater (24.5 days, interquartile range (IQR) 2031) compared with the patients who did not develop ALI/ARDS (21 days, IQR 1527, p = 0.018). Longer median storage duration was independently associated with an increased risk of developing ALI/ARDS in the subsequent 4 days (odds ratio 1.8, p = 0.028). The same association was not seen in the trauma or nonsepsis, nontrauma patients. Conclusions Transfusion of blood with longer median storage duration to patients with sepsis is associated with a higher risk of developing ALI up to 4 days after transfusion. This same association is not seen in other critically ill patient populations. PMID:24059842

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

    PubMed Central

    Olguner, imen Glben; Ergr, Bekir U?ur; Altekin, Emel; Ta?d?en, Ayd?n; Duru, Seden; Girgin, Pelin; Gndz, Kerim; Cilaker M?c?l?, Serap; Gzelda?, Seda; Akku?, Muhammed

    2013-01-01

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

  9. Neuronal antibody biomarkers for Sydenham's chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection.

    PubMed

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

    2015-01-01

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

  10. A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury

    PubMed Central

    Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A.

    2014-01-01

    Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a unifying theory to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI. PMID:24346647

  11. Pathogenesis of Group A Streptococcal Infections

    PubMed Central

    Cunningham, Madeleine W.

    2000-01-01

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

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

    PubMed Central

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

    2014-01-01

    Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short-term survival when compared with 0.9% saline in this experimental animal model of sepsis. PMID:24335444

  13. [Group A streptococcal meningitis].

    PubMed

    Jouhadi, Z; Sadiki, H; Lehlimi, M; Honsali, Z; Najib, J; Zerouali, K; Belabess, H; Mdaghri, N

    2012-12-01

    An increased incidence and severity of invasive group A streptococcus (GAS) infections over the past decade have been reported by several authors, but GAS remains an uncommon cause of bacterial meningitis. The aim of this study was to describe and analyze the clinical and biological data of GAS meningitis by reporting 10 new cases of pediatric GAS meningitis and making a literature review. The mean age of patients, seven girls and three boys, was 3 years. There was a history of preexisting or concomitant community-acquired infection in five patients over 10. The outcome was fatal in two cases. All patients received an initial empirical antimicrobial therapy with a third generation cephalosporin switched in six cases to amoxicillin. The prognosis for this type of streptococcal meningitis is usually good, but death may occur even in children without any identified risk factor for severe infection. PMID:23102429

  14. Pathogenesis of group A streptococcal infections.

    PubMed

    Henningham, Anna; Barnett, Timothy C; Maamary, Peter G; Walker, Mark J

    2012-05-01

    Group A Streptococcus (GAS; Streptococcus pyogenes) is a human pathogen which causes significant morbidity and mortality globally. GAS typically infects the throat and skin of the host, causing mild infections such as pharyngitis and impetigo, in addition to life threatening conditions including necrotizing fasciitis, streptococcal toxic shock syndrome (STSS), and bacteremia. Repeated infection with GAS may result in the non-suppurative sequelae, acute rheumatic fever, and acute glomerulonephritis. GAS remains sensitive to the antibiotic penicillin which can be administered as a means to treat infection or as prophylaxis. However, issues with patient compliance and a growing concern over the possible emergence of resistant GAS strains may limit the usefulness of antibiotics in the future. A vaccine capable of preventing GAS infection may be the only effective way to control and eliminate GAS infection and disease. PMID:22642914

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

    PubMed

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

    2015-10-15

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

  16. Animal models of sepsis and sepsis-induced kidney injury

    PubMed Central

    Doi, Kent; Leelahavanichkul, Asada; Yuen, Peter S.T.; Star, Robert A.

    2009-01-01

    Sepsis is characterized by a severe inflammatory response to infection, and its complications, including acute kidney injury, can be fatal. Animal models that correctly mimic human disease are extremely valuable because they hasten the development of clinically useful therapeutics. Too often, however, animal models do not properly mimic human disease. In this Review, we outline a bedside-to-bench-to-bedside approach that has resulted in improved animal models for the study of sepsis a complex disease for which preventive and therapeutic strategies are unfortunately lacking. We also highlight a few of the promising avenues for therapeutic advances and biomarkers for sepsis and sepsis-induced acute kidney injury. Finally, we review how the study of drug targets and biomarkers are affected by and in turn have influenced these evolving animal models. PMID:19805915

  17. Pediatric sepsis

    PubMed Central

    Randolph, Adrienne G; McCulloh, Russell J

    2014-01-01

    Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the childs age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID:24225404

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

    PubMed Central

    2013-01-01

    Introduction Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (6065 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis. Methods We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis. Results Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P?sepsis. PMID:24330815

  19. Staphylococcal and Streptococcal Superantigen Exotoxins

    PubMed Central

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

    2013-01-01

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

  20. Coagulation abnormalities in sepsis.

    PubMed

    Tsao, Cheng-Ming; Ho, Shung-Tai; Wu, Chin-Chen

    2015-03-01

    Although the pathophysiology of sepsis has been elucidated with the passage of time, sepsis may be regarded as an uncontrolled inflammatory and procoagulant response to infection. The hemostatic changes in sepsis range from subclinical activation of blood coagulation to acute disseminated intravascular coagulation (DIC). DIC is characterized by widespread microvascular thrombosis, which contributes to multiple organ dysfunction/failure, and subsequent consumption of platelets and coagulation factors, eventually causing bleeding manifestations. The diagnosis of DIC can be made using routinely available laboratory tests, scoring algorithms, and thromboelastography. In this cascade of events, the inhibition of coagulation activation and platelet function is conjectured as a useful tool for attenuating inflammatory response and improving outcomes in sepsis. A number of clinical trials of anticoagulants were performed, but none of them have been recognized as a standard therapy because recombinant activated protein C was withdrawn from the market owing to its insufficient efficacy in a randomized controlled trial. However, these subgroup analyses of activated protein C, antithrombin, and thrombomodulin trials show that overt coagulation activation is strongly associated with the best therapeutic effect of the inhibitor. In addition, antiplatelet drugs, including acetylsalicylic acid, P2Y12 inhibitors, and glycoprotein IIb/IIIa antagonists, may reduce organ failure and mortality in the experimental model of sepsis without a concomitant increased bleeding risk, which should be supported by solid clinical data. For a state-of-the-art treatment of sepsis, the efficacy of anticoagulant and antiplatelet agents needs to be proved in further large-scale prospective, interventional, randomized validation trials. PMID:25544351

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

    PubMed Central

    2013-01-01

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

  2. microRNA-23a-5p acts as a potential biomarker for sepsis-induced acute respiratory distress syndrome in early stage.

    PubMed

    Liu, S; Liu, C; Wang, Z; Huang, J; Zeng, Q

    2016-01-01

    Sepsis is a significant cause of morbidity and mortality worldwide. Acute respiratory distress syndrome (ARDS) is the most common and serious complication of sepsis, which presents with rapid and progressive acute onset respiratory failure. The microRNA-23a-5p, as a kind of circulating microRNA (miRNA), is considered to be a candidate biomarker for cardiovascular diseases. However, correlation between ARDS and miR-23a-5p is also elusive. This study aims to investigate the role of miR-23a-5p as the biomarkers for ARDS. In this study, ARDS was induced by intraperitoneally injected with LPS of Sprague-Dawley rats and serum and lung tissues were collected. The NR8383 macrophages were stimulated with LPS. TNF-α, IL-1β, and miR-23a-5p levels in serum, lung tissues and NR8383 were determined using SYBR-based miRNA quantitative real-time polymerase chain reactions (qRT-PCRs). The results indicated that serum miR-23a-5p was increased by 7 fold, 4 fold and 2 fold at 3 h, 6h, and 12h after injection of LPS, respectively. While the miR-23a-5p in NR8383 was elevated by 3.5 fold, 3 fold, 2.5 fold and 5 fold, at 3 h, 6h, 12h and 24h after stimulated with LPS, respectively. In conclusion, the miR-23a-5p might be employed as the potential biomarkers for ARDS in early stage. PMID:26950448

  3. Granulomatous uveitis and reactive arthritis as manifestations of post-streptococcal syndrome.

    PubMed

    Abderrahim, Kais; Chebil, Ahmed; Falfoul, Yosra; Bouladi, Mejda; El Matri, Leila

    2015-10-01

    To report a case of bilateral granulomatous post-streptococcal syndrome uveitis in association with reactive arthritis as manifestation of post-streptococcal syndrome. To our knowledge, this could represent the first reported case in the literature. A 9-year-old girl, with no past ocular history, presented with a 5-day history of bilateral blurred vision, red eyes, photophobia and walking difficulties because of a right ankle pain. Ophthalmic examination disclosed a visual acuity limited to hand motion, mutton-fat keratic precipitates, anterior chamber cells and posterior synechiae in both eyes. Ocular pressure was normal. Physical examination showed a fever (38 °C), inflammatory ankle arthritis and scarlet fever (streptococcal lesion). Anti-streptococcal lysine O titer was 419 μ/ml. The patient was treated with topical steroids, cycloplegics, high-dose oral steroids and preventive course of penicillin with total improvement and no recurrence. Post-streptococcal syndrome should be considered in the etiology of acute bilateral granulomatous uveitis in children, and anti-streptococcal lysine O titer should be considered in serodiagnostic testing. PMID:22986580

  4. 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, bloodbrain-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 Wernickes encephalopathy. Modulation of microglial activation, prevention of bloodbrain-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

  5. Host-pathogen interactions in streptococcal immune sequelae.

    PubMed

    Nitsche-Schmitz, D Patric; Chhatwal, Gursharan S

    2013-01-01

    Otherwise uncomplicated infections with Streptococcus pyogenes can cause two insidious immune sequelae known as post-streptococcal glomerulonephritis (PSGN) and acute rheumatic fever (ARF). These diseases follow with a latency of a few weeks or months after primary infection and are responsible for high mortality and morbidity. PSGN has also been linked to infections with group C streptococci of the species S. equi ssp. zooepidemicus (SESZ). Moreover, there are some indications that infection with group C and G streptococci (GCGS) of the subspecies Streptococcus dysgalactiae ssp. equisimilis (SDSE) leads to ARF. Despite decades of research, the picture of the molecular pathogenesis of streptococcal immune sequelae resembles a jigsaw puzzle. Herein we try to put some of the puzzle bits together that have been collected till date. PMID:23212184

  6. [Group A streptococcal-associated arthritis in children].

    PubMed

    Brackel, Caroline L H; Noordzij, Jeroen G

    2015-01-01

    Group A streptococcal (GAS) infection can cause septic arthritis (SA), acute rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA). Differentiating between these three entities can have important consequences for both therapy and prognosis. SA is diagnosed by means of clinical, biochemical and microbiological parameters. With respect to ARF and PSRA, evidence of a recent GAS infection should be established, in combination with several other major or minor criteria. Currently there is ongoing scientific debate as to whether PSRA and ARF are two different disease entities or belong to the same spectrum. PSRA presents earlier after GAS pharyngitis than ARF, is normally less responsive to NSAIDs, has a longer duration and is often accompanied by skin abnormalities. However, there are also many similarities. In this report we describe three children suffering from GAS-associated arthritis and discuss the symptoms, diagnosis and therapy. PMID:26420146

  7. MITOCHONDRIAL FUNCTION IN SEPSIS.

    PubMed

    Arulkumaran, Nishkantha; Deutschman, Clifford S; Pinsky, Michael R; Zuckerbraun, Brian; Schumacker, Paul T; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

    2016-03-01

    Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long-term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used both as a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID:26871665

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

    PubMed Central

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

    2015-01-01

    Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24 h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p < 0.05, vs septic WT mice), with lower Bcl-2 and higher caspase-3 levels in septic KO mice (p < 0.05). Molecular analysis revealed increased NF-κB-p65 and phosphorylated IκB-α levels along with higher serum levels of TNF-α and IL-6 in septic KO mice compared to septic WT mice (p < 0.01). Furthermore, in vitro islet cultures stimulated with LPS produced higher TNF-α and IL-6 (p < 0.05) from KO mice compared to WT mice. Collectively, these results demonstrate SP-D plays protective roles by inhibiting apoptosis and modulating NF-κB-mediated inflammation in CLP-induced API. PMID:26634656

  9. Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release

    PubMed Central

    Snäll, Johanna; Linnér, Anna; Uhlmann, Julia; Siemens, Nikolai; Ibold, Heike; Janos, Marton; Linder, Adam; Kreikemeyer, Bernd; Herwald, Heiko; Johansson, Linda; Norrby-Teglund, Anna

    2016-01-01

    Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1-protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus. PMID:26887258

  10. Sepsis Questions and Answers

    MedlinePLUS

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

  11. Group A Streptococcal (GAS) Disease

    MedlinePLUS

    ... Core surveillance (ABCs) Group A Strep Calculator CDC Streptococcus Laboratory Sepsis About Group A Strep Recommend on Facebook Tweet Share Compartir Group A Streptococcus (group A strep) are bacteria that can live ...

  12. Malignant group B streptococcal endocarditis associated with saline-induced abortion.

    PubMed

    Jemsek, J G; Gentry, L O; Greenberg, S B

    1979-12-01

    A 20-year-old woman developed acute group B streptococcal endocarditis following saline-induced abortion. In the pre-antibiotic era, most cases of group B streptococcal endocarditis occurred in parturient or postabortal women. Currently, this disease is rarely described in obstetrical patients, and no previous cases following saline-induced abortion have been reported. Purulent pericarditis and a perivalvular abscess were present in our patient and represent only the second instance in which these findings have been documented in this disease. PMID:389576

  13. Saline breast implant fluid collection and reactive arthritis in a patient with streptococcal toxic shock syndrome.

    PubMed

    Kohannim, Omid; Rubin, Zachary; Taylor, Mihaela

    2011-03-01

    Streptococcal toxic shock syndrome is a potentially lethal condition with an increasing incidence over the last 30 years. We present the case of a 55-year-old patient with signs and symptoms of streptococcal toxic shock syndrome. This patient's presentation was unique in that it was followed by an accumulation of fluid at her breast implant in addition to a polyarticular reactive arthritis. We propose that the patient's reactive arthritis is consistent with the diagnosis of post-streptococcal reactive arthritis, a variant of acute rheumatic fever, which similarly to its variant is immunologically driven. We hypothesize that the fluid collection around the patient's breast implant was triggered by her infection and was also immunologically mediated. PMID:21325958

  14. Group G streptococcal lymphadenitis in rats.

    PubMed

    Corning, B F; Murphy, J C; Fox, J G

    1991-12-01

    Group G streptococci which have been isolated from the oral flora of rats are also normal inhabitants of the human skin, oropharynx, gastrointestinal tract, and female genital tract. This group of streptococci can cause a wide variety of clinical diseases in humans, including septicemia, pharyngitis, endocarditis, pneumonia, and meningitis. Ten days after oral gavage with 7,12-dimethylbenz[a]anthracene, 12 of 22 two-month-old, female, outbred, viral-antibody-free rats presented with red ocular and nasal discharges and marked swelling of the cervical region. Various degrees of firm, nonpitting edema in the region of the cervical lymph nodes and salivary glands as well as pale mucous membranes and dehydration were observed. Pure cultures of beta-hemolytic streptococci were obtained from the cervical lymph nodes of three rats that were necropsied. A rapid latex test system identified the isolates to have group G-specific antigen. These streptococcal isolates fermented trehalose and lactose but not sorbitol and inulin and did not hydrolize sodium hippurate or bile esculin. A Voges-Proskauer test was negative for all six isolates. Serologic tests to detect the presence of immunoglobulin G antibody to rat viral pathogens and Mycoplasma pulmonis were negative. Histopathologic changes included acute necrotizing inflammation of the cervical lymph nodes with multiple large colonies of coccoid bacteria at the perimeter of the necrotiz zone. To our knowledge, this is the first report of naturally occurring disease attributed to group G streptococci in rats. PMID:1757539

  15. [Streptococcal rheumatic fever in adults].

    PubMed

    Lemaire, V; Peyrou, D; Ryckewaert, A

    1982-10-01

    Thirty-seven cases of streptococcal rheumatic fever in adults (20 women and 17 men; mean age 33 years) are reported. Only 3 patients had a history of previous rheumatic fever. In 73% of the cases untreated sore throat had occurred 8 to 30 days before the condition developed. Throat swabs taken during the rheumatic attack were positive for Streptococcus haemolyticus in only 5 out of 22 patients. The joints most commonly affected were those of the lower limbs and the symptoms were severe; in 2 out of 3 patients other joints were subsequently involved. Five patients had stable mitral regurgitation of undetermined duration, with systolic murmur. ECG abnormalities were noted in 7 patients, including 5 with prolongation of the PR interval and 2 with moderate elevation of the ST segment; these abnormalities regressed in all cases. No specific skin lesions were observed. The streptococcal infection was associated with a rise in antistreptolysins in 73% of the cases, a rise in antistreptokinases in 80% and a rise in both types of antibodies in 97%. Response to antibiotics and anti-inflammatory drugs was satisfactory in all cases. Cure was achieved within less than one month in 57% of the patients, but the condition lasted three years in 3 patients. PMID:7177815

  16. [Physiopathology of severe sepsis].

    PubMed

    Caille, Vincent; Bossi, Philippe; Grimaldi, David; Vieillard-Baro, Antoine

    2004-02-28

    Regarding the definition. Severe sepsis associates an explosive inflammatory reaction and organ failure. It is secondary to bacterial, fungal or viral infection. It can be at the origin of acute circulatory failure (state of septic shock). Response of the organism to infection. The presence of certain components of the membrane of pathogenic agents induces the release of various mediators in cascade, notably cytokines. Toll-like receptors (10 cloned in humans) intervene in the detection of microbes and in the inherent and subsequently adaptive immune response. Immune paralysis. The release of pro-inflammatory mediators characterizes the initial phase of sepsis. Persistence of the latter provokes acquired immunodepression, related to an anti-inflammatory profile, and hence to a delayed decrease in hypersensitivity, an incapacity to cope with the infection and the onset of nosocomial infections. The role of the mediators. During sepsis, the cytokines are predominantly pro-inflammatory (TNF-alpha and notably IL-1beta) whereas others, produced concomitantly or subsequently, are predominantly anti-inflammatory (IL-10 in particular). In fact, the majority of the cytokines have multiple and intrinsic effects, they mediate immune defense but also pathological manifestations. Many other mediators intervene: coagulation or complement systems, contact system, breakdown products of the phospholipid membrane, arachidonic acid metabolites, free radicals and nitrous oxide. Endocrine and metabolic dysregulations. The concept of relative adrenal insufficiency and peripheral syndrome of resistance to glycocorticosteroids have led to hormone replacement therapy during septic shock. Acute insulin resistance has also been described. The role of the endothelium and coagulation. The endothelium plays a key part in the onset of vascular insufficiency during sepsis due to abnormalities in vasomotricity and thrombomodulation. The anticoagulant regulating system is perturbed; there is a decrease in protein C with inactivation of its active form, which has pro-fibrinolytic properties, and a decrease in antithrombin III. Regarding myocardial dysfunction During septic shock there is often severe left ventricular systolic dysfunction, sometimes also involving the right ventricle, largely under-diagnosed despite its severe prognosis, and associated with reduced or even collapsed heart rate. PMID:15029017

  17. Group B streptococcal septicemia of the newborn

    MedlinePLUS

    ... streptococcal (GBS) septicemia is caused by the bacterium Streptococcus agalactiae , which is commonly called group B strep ... higher during labor Mother who has group B streptococcus in her gastrointestinal, reproductive, or urinary tract Rupture ...

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

    PubMed Central

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

    2014-01-01

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

  19. Rapidly progressive glomerulonephritis complicating acute rheumatic fever.

    PubMed Central

    Akasheh, M. S.; al-Lozi, M.; Affarah, H. B.; Hajjiri, F. K.; al-Jitawi, S.

    1995-01-01

    A case of acute rheumatic fever and glomerulonephritis following streptococcal throat infection is presented. The coincidence of rheumatic fever and post-streptococcal glomerulonephritis is uncommon, but well recognised. This case is of additional interest since the nephritis was crescentic. Images Figure PMID:7479469

  20. Rapidly progressive glomerulonephritis complicating acute rheumatic fever.

    PubMed

    Akasheh, M S; al-Lozi, M; Affarah, H B; Hajjiri, F K; al-Jitawi, S

    1995-09-01

    A case of acute rheumatic fever and glomerulonephritis following streptococcal throat infection is presented. The coincidence of rheumatic fever and post-streptococcal glomerulonephritis is uncommon, but well recognised. This case is of additional interest since the nephritis was crescentic. PMID:7479469

  1. Prevention of perinatal group B streptococcal disease: updated CDC guideline.

    PubMed

    Cagno, Colleen K; Pettit, Jessie M; Weiss, Barry D

    2012-07-01

    Group B streptococcus is the leading cause of early-onset neonatal sepsis in the United States. Universal screening is recommended for pregnant women at 35 to 37 weeks' gestation. The Centers for Disease Control and Prevention recently updated its guideline for the prevention of early-onset neonatal group B streptococcal disease. The new guideline contains six important changes. First, there is a recommendation to consider using sensitive nucleic acid amplification tests, rather than just routine cultures, for detection of group B streptococcus in rectal and vaginal specimens. Second, the colony count required to consider a urine specimen positive is at least 104 colony-forming units per mL. Third, the new guideline presents separate algorithms for management of preterm labor and preterm premature rupture of membranes, rather than a single algorithm for both conditions. Fourth, there are minor changes in the recommended dose of penicillin G for intrapartum chemoprophylaxis. Fifth, the guideline provides new recommendations about antibiotic regimens for women with penicillin allergy. Cefazolin is recommended for women with minor allergies. For those at serious risk of anaphylaxis, clindamycin is recommended if the organism is susceptible [corrected] and vancomycin is recommended if there is clindamycin resistance or if susceptibility is unknown. [corrected]. Finally, the new algorithm for secondary prevention of early-onset group B streptococcal disease in newborns should be applied to all infants, not only those at high risk of infection. The algorithm clarifies the extent of evaluation and duration of observation required for infants in different risk categories. PMID:22962913

  2. Involvement of Streptococcal Mitogenic Exotoxin Z in Streptococcal Toxic Shock Syndrome

    PubMed Central

    Yang, Lily; Thomas, Mark; Woodhouse, Andrew; Martin, Diana; Fraser, John D.; Proft, Thomas

    2005-01-01

    We report a nonfatal case of streptococcal toxic shock syndrome (STSS) caused by a Streptococcus pyogenes emm118 strain encoding a novel variant of streptococcal mitogenic exotoxin Z (SMEZ-34). This variant was responsible for the major mitogenic activity in the cell culture supernatant. Patient sera showed seroconversion toward SMEZ, implying a role for this toxin in STSS. PMID:16000510

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

    PubMed

    Delano, Matthew J; Ward, Peter A

    2016-01-01

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

  4. Adult Zebrafish model of streptococcal infection

    PubMed Central

    Phelps, Hilary A.; Runft, Donna L.

    2009-01-01

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

  5. Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak

    PubMed Central

    Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolom; Rossi, Marcello; Cayl, Jon A

    2014-01-01

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

  6. Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak.

    PubMed

    Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolom; Rossi, Marcello; Cayl, Jon A

    2014-04-01

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

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

    PubMed Central

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

    2009-01-01

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

  8. Properties and Biological Role of Streptococcal Fratricins

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    1991-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Post-streptococcal glomerulonephritis (GN)

    MedlinePLUS

    Acute renal failure Chronic glomerulonephritis Chronic renal disease Congestive heart failure or pulmonary edema End-stage renal disease Hyperkalemia High blood pressure (hypertension) Nephrotic syndrome

  12. Group B Streptococcal Septic Arthritis of the Shoulder and Potential Association with Pelvic Examination and PAP Smear

    PubMed Central

    Daner, William E.; Meeks, Brett D.; Foster, William C.; Boardman, Norman D.

    2016-01-01

    Group B streptococcal (GBS) infection of a native joint in a nonpregnant adult is uncommon. While many women are colonized with this flora, it rarely becomes pathogenic in its adult host. GBS associated joint infections have been reported, most of which have been related to hematogenous seeding from unknown sources. To our knowledge, there are no published case reports of a GBS joint infection in association with a pelvic exam and Papanicolaou (PAP) smear. In this case report, we present a case of GBS sepsis of a native shoulder, possibly resulting from a routine pelvic exam and PAP smear. PMID:26981299

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

    PubMed

    Floret, D

    2001-09-01

    Staphylococcus aureus and Streptococcus pyogenes produce a lot of toxins, some of them responsible for specific diseases. Staphylococcal food poisoning is due to ingestion of enterotoxin containing food. Seven toxins have been isolated so far. Generalized exfoliative syndrome is related to exfoliatin. Young children are particularly affected. The disease consists in a cutaneous exfoliation usually limited with a favourable outcome. The mucus membranes are not involved. The nose or pharynx are the most usual portal of entry. Staphylococcus aureus is not grown from the bullae. Severe extensive forms have been observed particularly in neonates (Ritter's disease). Bullous impetigo is also due to exfoliatin. It consists in the presence of a restricted number of cloudy bullae, from which staphylococcus can be grown. It is a mild disease with a favourable outcome within a few days. Scarlet fever is related to the streptococcal erythrogenic toxins. The classic form of the disease is presently rare. This disease may be related to staphylococcus as a complication of arthritis, osteomyelitis or wound super-infection. Bacteremia is usual. Staphylococcal scarlet fever is not related to exfoliatin as previously believed, but to enterotoxins or TSST-1, so it seems to be an abortive form of toxic shock syndrome. Toxic shock syndrome is defined as a multi organ failure syndrome with a rapid onset, fever, rash followed by desquamation, vomiting and diarrhea, hypotension, conjunctivitis and strawberry tongue. The disease is related to an infection or colonisation with a toxin (TSST-1) producing strain of Staphylococcus aureus. Enterotoxins (mainly C) may be involved. The disease may occur in childhood, sometimes after superinfection of varicella. The mortality is low (5%) and mainly due to ARDS or cardiac problems. Erythrogenic toxins produced by Streptococcus pyogenes are involved in a streptococcal form of toxic shock syndrome with a quite similar presentation. In most cases however, a cutaneous or soft tissue infection is at the origin. Necrotizing fasciitis complicating varicella is a classic cause in children. Bacteremia is often observed. The mortality rate is as high as 60%. The streptococcal strains involved in north america use to produce the toxin erythrogenic A, the european cases seem to be more related to strains secreting the B toxin with a dysregulation of the mechanisms which control the secretion of the toxin. Staphylococcus strains producing the Panton and Valentine leucocidin are responsible for chronic or relapsing furonculosis and above all for a very severe necrotizing pneumonia observed in children and young adults presenting as an acute respiratory distress syndrome with leucopenia, hemoptysis and shock carrying a heavy mortality rate. Besides these specific diseases, staphylococcal and streptococcal toxins may be involved in some syndromes of unknown origin, in which the intervention of superantigens seems very likely. Kawasaki syndrome is among them as strains producing staphylococcal and streptococcal toxins have been grown from patients with Kawasaki syndrome. In the same way, the intervention of toxins is suspected in the determination of sudden infant death syndrome and atopic eczema. PMID:11582925

  14. IMMUNE CELL PHENOTYPE AND FUNCTION IN SEPSIS.

    PubMed

    Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

    2016-03-01

    Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis.The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of nonextracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed.A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes, but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8, and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes, and the cell function. PMID:26529661

  15. Severe sepsis bundles

    PubMed Central

    Khan, Parvez; Divatia, J. V.

    2010-01-01

    Sepsis is a complex syndrome with its wide spectrum of severity, and is one of the most common causes of death in Critical Care Units. The Surviving Sepsis campaign launched in 2004, is aimed at improving diagnosis, management and survival of patients with sepsis. Care bundles are a group of best evidence based interventions which when instituted together, gives maximum outcome benefit. Care Bundles are simple, uniform and have universal practical applicability. Surviving Sepsis campaign guidelines in 2008 incorporated two sepsis care bundles. The Resuscitation bundle includes seven key interventions to be achieved in 6-h while four interventions have to be completed within 24-h in the Management bundle. Compliance with a bundle implies achieving all the specified goals in that bundle. Limitations to care bundles include the quality of the evidence on which they are based, and that the relative contributions of each element of the bundle are not known. Several observational studies support the hypothesis that sepsis care bundles have an important role in improving outcomes from sepsis. Critical Care Units should develop management strategies to ensure compliance with the sepsis bundles in order to decrease hospital mortality due to severe sepsis. PMID:20606903

  16. Neurology of Sepsis.

    PubMed

    Sweis, Rochelle; Ortiz, Jorge; Biller, Jos

    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

  17. Defensins and Sepsis

    PubMed Central

    Xie, Guo-Hao; Chen, Qi-Xing; Cheng, Bao-Li; Fang, Xiang-Ming

    2014-01-01

    Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1? production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis. PMID:25210703

  18. Medical treatment of multiple streptococcal liver abscesses

    SciTech Connect

    Matlow, A.; Vellend, H.

    1983-04-01

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

  19. Group B streptococcal phospholipid causes pulmonary hypertension

    NASA Astrophysics Data System (ADS)

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

    2003-04-01

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

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

    PubMed

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

    2015-08-01

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

  1. Personalized Medicine for Sepsis.

    PubMed

    Pinheiro da Silva, Fabiano; César Machado, Marcel Cerqueira

    2015-11-01

    Sepsis is a complex syndrome triggered by infection and characterized by systemic deregulation of immune and inflammatory pathways. It is a major cause of death worldwide and results in the widespread use of antibiotics and substantial health care costs. In a vicious circle, sepsis treatment promotes the emergence of highly virulent and resistant pathogens and devastating nosocomial infections. Sepsis is a heterogeneous disease affecting many people worldwide. Because individual patients have different inflammatory responses and unique profiles of immune activation against pathogens, the most effective way to advance the treatment of sepsis is probably through a tailored approach. The advent of high-throughput technologies and the remarkable progress in the field of bioinformatics has allowed the subclassification of many pathological conditions. This has potential to provide better understanding of life-threatening infections in people. The study of host factors, however, needs to be integrated with studies on bacterial signaling in both symbiotic and pathogenic bacteria. Sepsis is certainly the sum of multiple host-microbial interactions and the metagenome should be extensively investigated. Personalized medicine is probably the only strategy able to deconstruct and reassemble our knowledge about sepsis, and its use should allow us to understand and manipulate sepsis as a wide, interconnected phenomenon with myriad variables and peculiarities. In this study, the recent advances in this area, the major challenges that remain, and the reasons why the septic patient should be approached as a superorganism are discussed. PMID:26398478

  2. Pharmacological management of sepsis

    SciTech Connect

    Fletcher, J.R.

    1985-01-01

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

  3. Biomarkers of sepsis

    PubMed Central

    2013-01-01

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

  4. Group B streptococcal neonatal parotitis.

    PubMed

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

    2015-01-01

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

  5. Sepsis Pathophysiology and Anesthetic Consideration

    PubMed Central

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

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

  6. Sepsis pathophysiology and anesthetic consideration.

    PubMed

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

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

  7. Vitamin D and sepsis

    PubMed Central

    Kempker, Jordan A.; Han, Jenny E.; Tangpricha, Vin; Ziegler, Thomas R.; Martin, Greg S.

    2012-01-01

    Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions. The importance of vitamin D’s role in skeletal health has long been understood but recent evidence is beginning to highlight its role in the functioning of other physiologic systems of the body. Basic science data reveal its integral role in local immune responses to pathogens and the systemic inflammatory pathways of sepsis. Furthermore, clinical scientists have found associations with respiratory infections, critical illness and sepsis but the causal relationship and its clinical impact have yet to be clearly defined. The article ends with speculations on the connections between racial disparities and seasonal differences in sepsis and vitamin D insufficiency. PMID:22928065

  8. [Sepsis-associated encephalopathy].

    PubMed

    Szatmri, Szilrd; Vgh, Tams; Antek, Csaba; Takcs, Istvn; Sr, Pter; Flesdi, Bla

    2010-08-15

    Sepsis-associated encephalopathy is a common but neglected clinical symptom of systemic inflammatory reaction in the early phase. The clinical spectrum of diffuse cerebral dysfunction induced by systemic sepsis--sepsis-associated encephalopathy according to the new terms--varies from transient, reversible encephalopathy, to severe irreversible brain damage. The aim of the present publication is to summarize the pathophysiology, frequent symptoms and possible treatments of the disease based on international and Hungarian articles on this topic. We want to emphasize the importance of monitoring the patient's mental status due to the fact that consciousness' disturbance of different severity is an early warning sign of sepsis, so it has high clinical significance. PMID:20693145

  9. Biomarkers in sepsis

    PubMed Central

    Singer, Mervyn

    2013-01-01

    Purpose of review This review discusses the current developments in biomarkers for sepsis. Recent findings With quantum leaps in technology, an array of biomarkers will become available within the next decade as point-of-care tools that will likely revolutionize the management of sepsis. These markers will facilitate early and accurate diagnosis, faster recognition of impending organ dysfunction, optimal selection and titration of appropriate therapies, and more reliable prognostication of risk and outcome. These diagnostics will also enable an improved characterization of the biological phenotype underlying sepsis and thus a better appreciation of the condition. Summary The potential for novel biomarkers in sepsis will need to be properly realized with considerable funding, academicindustry collaborations, appropriate investigations and validation in heterogenous populations, but these developments do hold the capacity to transform patient care and outcomes. PMID:23411577

  10. Targeting neutrophils in sepsis.

    PubMed

    Snego, Fabiane; Alves-Filho, Jos Carlos; Cunha, Fernando Queirz

    2014-08-01

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

  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. Streptococcal toxic shock in a horse.

    PubMed

    Dolente, B A; Seco, O M; Lewis, M L

    2000-07-01

    A 14-year-old horse was admitted to the veterinary hospital for treatment of tachycardia and lethargy. Initial diagnoses were ventricular tachycardia and renal dysfunction. During hospitalization other findings included fever, renal failure, hepatic failure, hypotension, and intermittent ventricular arrhythmias. Bacteriologic culture of 2 blood samples collected during febrile crises 7 days apart yielded Streptococcus mitis. These culture results along with other clinical and physical examination findings fulfill the criteria for a diagnosis of streptococcal toxic shock syndrome, previously described for humans and dogs. To our knowledge this is the first reported instance of this disease in a horse. PMID:10909449

  13. The pathogenesis of sepsis.

    PubMed

    Bone, R C

    1991-09-15

    Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response. PMID:1872494

  14. Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.

    PubMed

    Osuchowski, Marcin F; Craciun, Florin; Weixelbaumer, Katrin M; Duffy, Elizabeth R; Remick, Daniel G

    2012-11-01

    The paradigm of systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition implies that hyperinflammation triggers acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributable to sepsis outcomes remain elusive. In the first part of this study, we characterized the systemic dynamics of the chronic inflammation in dying (DIE) and surviving (SUR) mice suffering from cecal ligation and puncture sepsis (days 6-28). In the second part, we combined the current chronic and previous acute/chronic sepsis data to compare the outcome-dependent inflammatory signatures between these two phases. A composite cytokine score (CCS) was calculated to compare global inflammatory responses. Mice were never sacrificed but were sampled daily (20 μl) for blood. In the first part of the study, parameters from chronic DIE mice were clustered into the 72, 48, and 24 h before death time points and compared with SUR of the same post-cecal ligation and puncture day. Cytokine increases were mixed and never preceded chronic deaths earlier than 48 h (3- to 180-fold increase). CCS demonstrated simultaneous and similar upregulation of proinflammatory and anti-inflammatory compartments at 24 h before chronic death (DIE 80- and 50-fold higher versus SUR). In the second part of the study, cytokine ratios across sepsis phases/outcomes indicated steady proinflammatory versus anti-inflammatory balance. CCS showed the inflammatory response in chronic DIE was 5-fold lower than acute DIE mice, but identical to acute SUR. The systemic mixed anti-inflammatory response syndrome-like pattern (concurrent release of proinflammatory and anti-inflammatory cytokines) occurs irrespective of the sepsis phase, response magnitude, and/or outcome. Although different in magnitude, neither acute nor chronic septic mortality is associated with a predominating proinflammatory and/or anti-inflammatory signature in the blood. PMID:23008446

  15. Update in sepsis 2012.

    PubMed

    Russell, James A; Walley, Keith R

    2013-06-15

    Pivotal sepsis clinical trials and preclinical research in 2012 are reviewed. For interventions ranging from synthetic complex starch solutions to recombinant human activated protein C, large multicenter randomized controlled trials generally failed to show benefit and some even demonstrated harm in the intervention group. In smaller innovative clinical trials simple interventions such as external cooling to control fever and biomarker-guided weaning from mechanical ventilation found potential benefit. Biomarkers for sepsis, including multimarker panels, are increasingly showing promise for clinical application. Breakthroughs in basic research in sepsis continue to highlight the complexity of the systemic inflammatory response and its consequences. A series of publications in AJRCCM follow the septic inflammatory response starting from intracellular structures and organelles to mitochondria and the cytoskeleton. Additional publications explore the key leukocyte subsets acting in sepsis, highlighting the underappreciated role of helper T-cell type 2-related pathways. Cellular remnants in the form of microparticles contribute to coagulopathy and further organ dysfunction. As a consequence, we suggest that sepsis may be the paradigm disease or condition requiring personalized care first to discover and validate new therapies and second to increase survival. PMID:23767902

  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 associated with increased concentrations of 2-hydroxybutyrate, 2-hydroxyisovalerate, 2-methylglutarate, creatinine, glucose and lactate. PMID:25661089

  17. Immunoinflammatory Response in Critically Ill Patients: Severe Sepsis and/or Trauma

    PubMed Central

    Popovic, Nada; Djordjevic, Dragan

    2013-01-01

    Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients. PMID:24371374

  18. Streptococcal infection in young pigs. IV. An outbreak of streptococcal meningitis in weaned pigs.

    PubMed Central

    Windsor, R. S.; Elliott, S. D.

    1975-01-01

    Twenty-eight pigs died in an outbreak of streptococcal meningitis in an East Anglian herd. Most were 10-14 weeks old. The outbreak lasted from January to April and was finally controlled by antibiotic therapy. A similar number of losses had occurred in the previous year though no diagnosis had then been made. The causal agent appeared to be a haemolytic streptococcus belonging to group D and provisionally designated Streptococcus suis type 2. It is probably identical with de Moor's group R streptococcus which causes a similar disease in the Netherlands. It is serologically distinct from Streptococcus suis type 1 which causes meningitis in piglets. Type 2 infection in pigs appears to be widespread in England and Wales and to occur in animals up to the age of at least 14 weeks. A comparison is drawn between Str. suis meningitis in pigs and group B streptococcal meningitis in human infants. PMID:807620

  19. Sepsis: an update.

    PubMed

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

    2011-06-01

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

  20. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

    PubMed Central

    Tan, Jason; Smith, Christine H.; Goldman, Ran D.

    2012-01-01

    Abstract Question I have heard about children who have tic disorders that seem to be exacerbated by group A ?-hemolytic streptococcal infection. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms? Answer Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) constitute a condition that includes neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to streptococcal infections. The actual existence of PANDAS as a unique clinical entity is still up for debate, as a temporal association between group A ?-hemolytic streptococcal infections and symptom exacerbations has been difficult to prove thus far. Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy. PMID:22972724

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

    ERIC Educational Resources Information Center

    Markowitz, Milton

    1979-01-01

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

  2. Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation

    PubMed Central

    Nielsen, Maryke J.; Claxton, Sarah; Pizer, Barry; Lane, Steven; Cooke, Richard P.D.; Paulus, Stéphane; Carrol, Enitan D.

    2016-01-01

    Abstract Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant. Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records. A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia. Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure. The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia. PMID:26945409

  3. Sepsis Associated Encephalopathy

    PubMed Central

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

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

  4. 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. PMID:26556425

  5. Nutrition and sepsis.

    PubMed

    Cohen, Jonathan; Chin, w Dat N

    2013-01-01

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

  6. 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

  7. Intra-abdominal sepsis.

    PubMed

    Holliday, R L

    1976-01-01

    Intra-abdominal sepsis remains one of the major challenges to the surgeon. With a proper appreciation of the bacteriology and pathophysiology involved and an awareness of new diagnostic and therapeutic modalities, hopefully, mortality and morbidity rates can be reduced. PMID:1048948

  8. 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

  9. 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

  10. Neuroinflammation in sepsis: sepsis associated delirium.

    PubMed

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

    2015-01-01

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

  11. Incidence and clinical variables associated with streptococcal throat infections: a prospective diagnostic cohort study

    PubMed Central

    Little, Paul; Hobbs, FD Richard; Mant, David; McNulty, Cliodna AM; Mullee, Mark

    2012-01-01

    Background Management of pharyngitis is commonly based on features which are thought to be associated with Lancefield group A beta-haemolytic streptococci (GABHS) but it is debatable which features best predict GABHS. Non-group A strains share major virulence factors with group A, but it is unclear how commonly they present and whether their presentation differs. Aim To assess the incidence and clinical variables associated with streptococcal infections. Design and setting Prospective diagnostic cohort study in UK primary care. Method The presence of pathogenic streptococci from throat swabs was assessed among patients aged ≥5 years presenting with acute sore throat. Results Pathogenic streptococci were found in 204/597 patients (34%, 95% CI = 31 to 38%): 33% (68/204) were non-group A streptococci, mostly C (n = 29), G (n = 18) and B (n = 17); rarely D (n = 3) and Streptococcus pneumoniae (n = 1). Patients presented with similar features whether the streptococci were group A or non-group A. The features best predicting A, C or G beta-haemolytic streptococci were patient’s assessment of severity (odds ratio [OR] for a bad sore throat 3.31, 95% CI = 1.24 to 8.83); doctors’ assessment of severity (severely inflamed tonsils OR 2.28, 95% CI = 1.39 to 3.74); absence of a bad cough (OR 2.73, 95% CI = 1.56 to 4.76), absence of a coryza (OR 1.54, 95% CI = 0.99 to 2.41); and moderately bad or worse muscle aches (OR 2.20, 95% CI = 1.41 to 3.42). Conclusion Non-group A strains commonly cause streptococcal sore throats, and present with similar symptomatic clinical features to group A streptococci. The best features to predict streptococcal sore throat presenting in primary care deserve revisiting. PMID:23211183

  12. Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life.

    PubMed

    Hoy, Wendy E; White, Andrew V; Dowling, Alison; Sharma, Suresh K; Bloomfield, Hilary; Tipiloura, Bernard T; Swanson, Cheryl E; Mathews, John D; McCredie, David A

    2012-05-01

    Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden. PMID:22297679

  13. 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

  14. Glycocalyx in Sepsis Resuscitation.

    PubMed

    Chen, Leon

    2016-01-01

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

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. Beta-haemolytic streptococcal endocarditis: clinical presentation, management and outcomes.

    PubMed

    El Rafei, Abdelghani; DeSimone, Daniel C; DeSimone, Christopher V; Lahr, Brian D; Steckelberg, James M; Sohail, Muhammad R; Wilson, Walter R; Baddour, Larry M

    2016-05-01

    Background Beta-haemolytic streptococcal (BHS) endocarditis is rare, but well-recognised for its high morbidity and mortality. This study sought to further characterise clinical features, management and outcomes of BHS endocarditis. Methods Retrospective review of all adultpatients (≥ 18 years old) with BHS endocarditis treated at the Mayo Clinic from 1 January 2000 to 31 December 2014. Results Forty-nine cases of BHS endocarditis were identified with a mean (± SD) age of 64 (±14.9) years and 65% were males. The infection was community acquired in 92% of the cases, with a median (IQR) time to diagnosis from symptom onset of 6 days (5-10). Associated conditions included the presence of a prosthetic valve (41%), malignancy (33%) and diabetes mellitus (DM) (31%). Median (IQR) vegetation size was 12 mm (9-17 mm). In a univariate analysis patients with DM had larger vegetations, median (IQR) = 17 mm (10.5-26 mm) compared to non-diabetic patients, median (IQR) = 11 mm (8-15 mm) (p = 0.01). Septic brain emboli occurred in 43% of cases. Eighteen patients (37%) underwent early (within 30 days) surgery. All-cause 1 month and 6 month mortality rates were 25% and 31%, respectively. Conclusion BHS endocarditis has an acute onset and is complicated by relatively large vegetations with a high rate of systemic embolisation. DM was the second most common associated medical condition and patients with DM had larger vegetations. Despite medical and surgical advances, mortality due to BHS endocarditis remains high, particularly within 30 days of diagnosis. PMID:26950685

  18. Streptococcal endocarditis in a captive southern white rhinoceros (Ceratotherium simum simum).

    PubMed

    Houszka, Marek; Dzimira, Stanislaw; Krol, Jaroslaw; Kandefer-Gola, Malgorzata; Ciaputa, Rafal; Sobieraj, Leslaw; Podkowik, Magdalena

    2014-09-01

    Postmortem examination of a 43-yr-old male southern white rhinoceros (Ceratotherium simum simum) revealed gross lesions and histopathologic findings consistent with endocarditis. The animal was born in Umfolozi National Park, South Africa, and then it was moved at 2 yr of age to two successive European zoologic collections. For several weeks prior to death, the animal was increasingly recumbent or assuming a dog-sitting position. Postmortem examination revealed cutaneous pressure sores and multiple rough nodular structures on the mitral valve and left ventricular endocardium. Histopathologic examination revealed vegetative endocarditis, myocardial and hepatocellular degeneration, hepatic fibrosis, and chronic nephritis. Bacterial culture from the oral cavity, trachea, lung, skin, and heart isolated beta hemolytic Streptococcus dysgalactiae subsp. equisimilis and Streptococcus ovis. The cause of death was acute cardiopulmonary failure due mainly to endocarditis and moderate myocardial degeneration. Streptococcal infections are not uncommon causes of morbidity and mortality in rhinoceros. This is the first detailed report of streptococcal endocarditis in a rhinoceros. PMID:25314832

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

    PubMed Central

    Kaufman, David; Fairchild, Karen D.

    2004-01-01

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

  20. Therapeutic iron restriction in sepsis.

    PubMed

    Xia, Yanfang; Farah, Nizam; Maxan, Alexander; Zhou, Juan; Lehmann, Christian

    2016-04-01

    Sepsis represents the systemic immune response to an infection. Mortality of sepsis slightly decreased over the past years, but due to the growing incidence, the absolute number of deaths still increases and belongs to the three most frequent causes of death worldwide. To date, there is no specific treatment for sepsis available yet. Iron is essential to both human beings and microbes and of great significance in many physiological and biochemical processes. Since iron is involved in the bacterial proliferation and immune dysregulation, we hypothesize that restricting host iron levels by application of iron chelators attenuates bacterial growth and improves the detrimental dysregulation of the systemic immune response in sepsis. PMID:26968906

  1. Maternal Sepsis and Septic Shock.

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Macerollo, Antonella; Martino, Davide

    2013-01-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham’s chorea (SC)—the prototypical post-streptococcal neuropsychiatric disorder—and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo’s criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo’s criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders. PMID:24106651

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis

    PubMed Central

    Jovanovich, Anna J.; Ginde, Adit A.; Holmen, John; Jablonski, Kristen; Allyn, Rebecca L.; Kendrick, Jessica; Chonchol, Michel

    2014-01-01

    Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.086.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.112.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis. PMID:24918697

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

    PubMed

    Hagiya, Hideharu; Otsuka, Fumio

    2013-01-01

    A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality. PMID:24292762

  7. Maternal and Fetal Death following Group A Streptococcal Meningitis in Mid-Term Pregnancy.

    PubMed

    Vivekanantham, Sayinthen; Mudalige, Nadeesha; Suri, Venothan; Kamaledeen, Abderahman; Law, Penelope

    2014-01-01

    Background. Group A streptococcal (GAS) meningitis is rarely seen in the antenatal period, but it is associated with significant mortality. We present a case of a mid-trimester woman who developed fulminant meningitis following a rapid onset atypical presentation of infection with this organism. Case. A multiparous 23(+5)-week woman presented with a 10-day history of a non-productive cough associated with pyrexia. Within minutes of her admission she collapsed and lost consciousness; sepsis was suspected and cross-specialty care was initiated. She was managed empirically in extremis with broad-spectrum antibiotics and mannitol with 3% hypertonic saline for suspected infection and raised intracranial pressure, respectively. Despite intensivist management, a CT head revealed diffuse oedema with coning of the cerebellar tonsils. Brainstem death was certified within 19 hours of admission and fetal death ensued. Postmortem bacteriology confirmed GAS meningitis. Conclusion. Through raising awareness of this patient and her disease course, we hope that future policy decisions, primary care, and hospital level management will be informed accordingly for treatment of pregnant women with suspected GAS infection. PMID:24883215

  8. The renal microcirculation in sepsis.

    PubMed

    Ergin, Bulent; Kapucu, Aysegul; Demirci-Tansel, Cihan; Ince, Can

    2015-02-01

    Despite identification of several cellular mechanisms being thought to underlie the development of septic acute kidney injury (AKI), the pathophysiology of the occurrence of AKI is still poorly understood. It is clear, however, that instead of a single mechanism being responsible for its aetiology, an orchestra of cellular mechanisms failing is associated with AKI. The integrative physiological compartment where these mechanisms come together and exert their integrative deleterious action is the renal microcirculation (MC). This is why it is opportune to review the response of the renal MC to sepsis and discuss the determinants of its (dys)function and how it contributes to the pathogenesis of renal failure. A main determinant of adequate organ function is the adequate supply and utilization of oxygen at the microcirculatory and cellular level to perform organ function. The highly complex architecture of the renal microvasculature, the need to meet a high energy demand and the fact that the kidney is borderline ischaemic makes the kidney a highly vulnerable organ to hypoxaemic injury. Under normal, steady-state conditions, oxygen (O2) supply to the renal tissues is well regulated; however, under septic conditions the delicate balance of oxygen supply versus demand is disturbed due to renal microvasculature dysfunction. This dysfunction is largely due to the interaction of renal oxygen handling, nitric oxide metabolism and radical formation. Renal tissue oxygenation is highly heterogeneous not only between the cortex and medulla but also within these renal compartments. Integrative evaluation of the different determinants of tissue oxygen in sepsis models has identified the deterioration of microcirculatory oxygenation as a key component in the development AKI. It is becoming clear that resuscitation of the failing kidney needs to integratively correct the homeostasis between oxygen, and reactive oxygen and nitrogen species. Several experimental therapeutic modalities have been found to be effective in restoring microcirculatory oxygenation in parallel to improving renal function following septic AKI. However, these have to be verified in clinical studies. The development of clinical physiological biomarkers of AKI specifically aimed at the MC should form a valuable contribution to monitoring such new therapeutic modalities. PMID:24848133

  9. Early Onset Sepsis.

    PubMed

    Johnson, Kyrsten; Messier, Stephen

    2016-01-01

    Early onset sepsis (EOS) is a worrisome, life-threatening condition in newborns with onset during the first week of life. Evaluation can be challenging due to the dynamic nature of the condition as the infant transitions to life ex-utero. Symptoms/signs can be nonspecific, thus, a high index of suspicion is warranted for subtle changes in condition including poor feeding, respiratory distress, or decreased activity. Common risk factors include chorioamnionitis, maternal fever, group B strep (GBS) colonization and preterm delivery. Despite universal screening and intrapartum antibiotic prophylaxis (IAP), GBS remains the most frequent cause of EOS followed by Escherichia coli (E. coli). While the gold standard for diagnosis remains a positive blood culture, lab evaluation frequently involves complete blood count (CBC) with differential, c-reactive protein (CRP), and evaluation of spinal fluid if the infant is stable. Unfortunately, there is not a lab test that is rapidly diagnostic for sepsis, so treatment should be empirically started until it is clear that the infant is not infected. Treatment often includes ampicillin and gentamicin for coverage of the most frequent pathogens. There is much debate about timing of discontinuation of antibiotics. Frequently, antibiotics can be discontinued after 48 hours in well appearing, asymptomatic infants with negative blood cultures and either normal CBC analysis or normal CRP values. PMID:26882580

  10. Surgical wound sepsis

    PubMed Central

    Cruse, P. J. E.

    1970-01-01

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

  11. Rheumatic Fever and post-group a streptococcal arthritis in children.

    PubMed

    Barash, Judith

    2013-06-01

    There are several diseases associated with group A beta hemolytic streptococcal infection; the two most common are acute rheumatic fever (ARF) and poststreptococcal reactive arthritis (PsRA). Epidemiological and clinical data for both diseases are described, as well as current recommendations for treatment and prevention. There is an ongoing debate as to whether these two are different diseases or are parts of the spectrum of the same disease. There are some reports of carditis developing after PsRA, suggesting that PsRA may be part of the spectrum of ARF. However, since there are substantial clinical, immunological, and genetic differences between PsRA and ARF, we believe PsRA to be a distinct entity. PMID:23568568

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-08-01

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

  14. Sepsis and ARDS: The Dark Side of Histones.

    PubMed

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

    2015-01-01

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

  15. Sepsis and ARDS: The Dark Side of Histones

    PubMed Central

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

    2015-01-01

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

  16. 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.

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

    PubMed Central

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

    2015-01-01

    Background We aimed to examine whether pre-existing impaired estimated glomerular filtration rate (eGFR) and proteinuria were associated with mortality following community-acquired pneumonia or sepsis among people aged ?65 years with diabetes mellitus, without end-stage renal disease. Methods Patients were followed up from onset of first community-acquired pneumonia or sepsis episode in a cohort study using large, linked electronic health databases. Follow-up was for up to 90 days, unlimited by hospital discharge. We used generalized linear models with log link, normal distribution and robust standard errors to calculate risk ratios (RRs) for all-cause 28- and 90-day mortality according to two markers of chronic kidney disease: eGFR and proteinuria. Results All-cause mortality among the 4743 patients with pneumonia was 29.6% after 28 days and 37.4% after 90 days. Among the 1058 patients with sepsis, all-cause 28- and 90-day mortality were 35.6 and 44.2%, respectively. eGFR <30 mL/min/1.73 m2 was a risk marker of higher 28-day mortality for pneumonia (RR 1.27: 95% CI 1.121.43) and sepsis (RR 1.32: 95% CI 1.071.64), adjusted for age, sex, socio-economic status, smoking status and co-morbidities. Neither moderately impaired eGFR nor proteinuria were associated with short-term mortality following either infection. Conclusions People with pre-existing low eGFR but not on dialysis are at higher risk of death following pneumonia and sepsis. This association was not explained by existing co-morbidities. These patients need to be carefully monitored to prevent modifiable causes of death. PMID:25605811

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

    PubMed

    Leonard, H L; Swedo, S E

    2001-06-01

    The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment. PMID:11466169

  19. The management of sepsis.

    PubMed

    Zawistowski, Christine A

    2013-01-01

    Management of sepsis in the pediatric patient is guideline driven. The treatment occurs in two phases, the first hour being the most crucial. Initial treatment consists of timely recognition of shock and interventions aimed at supporting cardiac output and oxygen delivery along with administration of antibiotics. The mainstay of treatment for this phase is fluid resuscitation. For patients in whom this intervention does not reverse the shock medications to support blood pressure should be started and respiratory support may be necessary. Differentiation between warm and cold shock and risk factors for adrenal insufficiency will guide further therapy. Beyond the first hour of treatment patients may require intensive care unit care where invasive monitoring may assist with further treatment options should shock not be reversed in the initial hour of care. PMID:24295610

  20. Sepsis Resuscitation: Consensus and Controversies.

    PubMed

    Montanaro, Nicholas

    2016-01-01

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

  1. Neonatal Sepsis and Neutrophil Insufficiencies

    PubMed Central

    Melvan, John Nicholas; Bagby, Gregory J.; Welsh, David A.; Nelson, Steve; Zhang, Ping

    2011-01-01

    Sepsis has continuously been a leading cause of neonatal morbidity and mortality despite current advances in chemotherapy and patient intensive care facilities. Neonates are at high risk for developing bacterial infections due to quantitative and qualitative insufficiencies of innate immunity, particularly granulocyte lineage development and response to infection. Although antibiotics remain the mainstay of treatment, adjuvant therapies enhancing immune function have shown promise in treating sepsis in neonates. This chapter reviews current strategies for the clinical management of neonatal sepsis and analyzes mechanisms underlying insufficiencies of neutrophil defense in neonates with emphasis on new directions for adjuvant therapy development. PMID:20521927

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

    PubMed Central

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

    2015-01-01

    Background In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. Methods In this retrospective case-control study SAM children aged 059 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. Results The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). Conclusion and Significance We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children. PMID:26440279

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

    PubMed

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

    2014-10-01

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

  4. ENDOPLASMIC RETICULUM STRESS IN SEPSIS.

    PubMed

    Khan, Mohammad Moshahid; Yang, Weng-Lang; Wang, Ping

    2015-10-01

    Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units. Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration, is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle, is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under stress and inflammatory conditions, ER loses homeostasis in its function, which is termed ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once stress is beyond the compensatory capacity of UPR or protracted, apoptosis would be initiated by triggering cell injuries, even cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidence that ER stress participates in the pathogenesis of sepsis. In this review, we summarize current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma-hemorrhage and ischemia/reperfusion injury. We also discuss the potential implications of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis. PMID:26125088

  5. [Protein C and coagulation in sepsis].

    PubMed

    D'Angelo, A; Della Valle, P; Giudici, D; Vigan D'Angelo, S

    2004-05-01

    The last few years have clarified the tight link between inflammation and coagulation. In addition to the identification of new regulatory mechanisms of the coagulation system and of an explosive number of mediators of inflammation, it is now clear that the existence of a positive feed-back between inflammation and coagulation leads to reciprocal activation of both pathways. Plasma levels of acute phase proteins involved in coagulation and fibrinolysis are elevated during inflammation, while natural anticoagulant mechanisms are depressed. Pro-inflammatory cytokines "activate" cell membranes exposed to flowing blood (endothelium, platelets, monocytes, neutrophils) which from physiologically inert or anticoagulant become procoagulant. Increased tissue factor expression results in increased thrombin formation within the microcirculation. Thrombin is central to fibrin deposition but it also plays a key role in cell-mediated mechanisms involving inflammation, cell proliferation and activation of the natural anticoagulant protein C. Depression of natural anticoagulant mechanisms, occurring in severe sepsis, results in uncontrolled thrombin formation, with pro-inflammatory activity prevailing, and the feed-back loop of inflammation and coagulation ultimately leading to multi-organ failure. However, both in the clinical setting and in animal experiments, heparin or direct anticoagulants have shown no effect on survival even if blocking fibrin deposition. Organ failure is only partially due to the thrombotic occlusion of the microcirculation, while other mechanisms of endothelial damage are probably more relevant in the development of ischemia. The endothelium is central to the maintenance of the natural anticoagulant mechanisms (TFPI, antithrombin, protein C). The protein C system, in addition to dumping thrombin formation, specifically modulates inflammation by cell signaling. This system is markedly depressed in severe sepsis. The infusion of activated protein C, or restoring normal levels of protein C within the circulation - depending on the individual bleeding risk are powerful tools to treat the endothelitis responsible for the clinical sequelae of severe sepsis. PMID:15181414

  6. Neonatal Sepsis and Inflammatory Mediators

    PubMed Central

    Reis Machado, Juliana; Soave, Danilo Figueiredo; da Silva, Marcos Vincius; de Menezes, Liliana Borges; Etchebehere, Renata Margarida; Monteiro, Maria Luiza Gonalves dos Reis; Antnia dos Reis, Marlene; Corra, Rosana Rosa Miranda; Celes, Mara Rbia Nunes

    2014-01-01

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

  7. SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome.

    PubMed

    Vachharajani, Vidula T; Liu, Tiefu; Brown, Candice M; Wang, Xianfeng; Buechler, Nancy L; Wells, Jonathan David; Yoza, Barbara K; McCall, Charles E

    2014-11-01

    Mechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase. PMID:25001863

  8. SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome

    PubMed Central

    Vachharajani, Vidula T.; Liu, Tiefu; Brown, Candice M.; Wang, Xianfeng; Buechler, Nancy L.; Wells, Jonathan David; Yoza, Barbara K.; McCall, Charles E.

    2014-01-01

    Mechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase. PMID:25001863

  9. Diagnostic criteria of acute rheumatic fever.

    PubMed

    Burke, Rebecca J; Chang, Christopher

    2014-01-01

    Acute rheumatic fever is an inflammatory sequela of Group A Streptococcal pharyngitis that affects multiple organ systems. The incidence of acute rheumatic fever has been declining even before the use of antibiotics became widespread, however the disease remains a significant cause of morbidity and mortality in children, particularly in developing countries and has been estimated to affect 19 per 100,000 children worldwide. Acute rheumatic fever is a clinical diagnosis, and therefore subject to the judgment of the clinician. Because of the variable presentation, the Jones criteria were first developed in 1944 to aid clinicians in the diagnosis of acute rheumatic fever. The Jones criteria have been modified throughout the years, most recently in 1992 to aid clinicians in the diagnosis of initial attacks of acute rheumatic fever and to minimize overdiagnosis of the disease. Diagnosis of acute rheumatic fever is based on the presence of documented preceding Group A Streptococcal infection, in addition to the presence of two major manifestations or one major and two minor manifestations of the Jones criteria. Without documentation of antecedent Group A Streptococcal infection, the diagnosis is much less likely except in a few rare scenarios. Carditis, polyarthritis and Sydenham's chorea are the most common major manifestations of acute rheumatic fever. However, despite the predominance of these major manifestations of acute rheumatic fever, there can be significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-Streptococcal reactive arthritis. This overlap between disease processes has led to continued investigation of the pathophysiology as well as development of new biomarkers and laboratory studies to aid in the diagnosis of acute rheumatic fever and distinction from other disease processes. PMID:24424191

  10. 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-?, IL-1?) expression was attenuated by NAH pretreatment. While serum inflammatory indices (KC, IL-6, TNF-?, IL-1?) 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

  11. 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. PMID:22986430

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

    PubMed Central

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

    2007-01-01

    Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients. PMID:18058085

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

    PubMed

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

    2015-01-01

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

  14. Antimicrobial Peptides in Human Sepsis

    PubMed Central

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

    2015-01-01

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

  15. Antimicrobial Peptides in Human Sepsis.

    PubMed

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

    2015-01-01

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

  16. Balance between Hyperinflammation and Immunosuppression in Sepsis.

    PubMed

    Yadav, Hemang; Cartin-Ceba, Rodrigo

    2016-02-01

    Sepsis is a major cause of morbidity and mortality among hospitalized patients and the leading cause of death among patients admitted to intensive care units. The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways. These pathways are concurrent, starting early in the course of sepsis. Given the high burden of morbidity and mortality associated with sepsis, there is an increasing interest in immunomodulatory therapies targeted at improving outcomes in sepsis. This review will summarize current understanding about the balance between hyperinflammation and immunosuppression in sepsis and discuss the role of potential therapies to modulate these responses. PMID:26820273

  17. Streptococcal pharyngitis. Comparison of latex agglutination and throat culture.

    PubMed

    White, C B; Harris, R; Weir, M R; Gonzales, I; Bass, J W

    1988-09-01

    Despite its imperfections, the throat culture remains the "gold standard" against which all rapid streptococcal antigen detection tests are compared. Using triple throat swabs, the accuracy of a rapid latex agglutination (LA) test and back up throat culture was determined and compared with a simultaneously obtained additional throat culture in children with suspected streptococcal pharyngitis. Although there was a 95 percent concordancy between throat cultures, the sensitivity of the throat culture was only 87 percent. Despite the LA test's lower sensitivity (78 percent), in this clinical population with a relatively low prevalence of positive throat cultures (19 percent), the predictive value of a negative LA test was only slightly lower than that of the throat culture (94-95 percent vs. 97 percent). Backup throat cultures are commonly recommended for patients with initially negative LA test results, but 10 percent of the patients with group A beta-hemolytic streptococci-positive throat cultures would have been undetected using this approach. PMID:3046808

  18. PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection).

    PubMed

    Lynch, N E; Deiratany, S; Webb, D W; McMenamin, J B

    2006-05-01

    PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection) is a rare condition first described in 1998. It describes the presence of obsessive-compulsive disorder (OCD) or tics with an episodic course, and a temporal relationship to Group A beta haemolytic streptococcal infection (GABHS). Recurrent episodes can be disruptive and upsetting for a child, but the best way to treat the condition has yet to be established. Penicillin prophylaxis has not proved effective, and other therapies are experimental. There is some evidence in the literature to support the role of tonsillectomy in improving the condition. We report a case of a 6-year-old boy who presented with tic and hemi-chorea associated with GABHS throat infection. He had a recurrence of his symptoms associated with a further GABHS infection, but has had no further symptoms following tonsillectomy. This case report lends further evidence to the role of tonsillectomy in the management of PANDAS. PMID:16892924

  19. Rapid streptococcal testing in Vietnamese children with pharyngitis.

    PubMed

    Finger, R; Ho, S H; Ngo, T T; Ritchie, C D; Nguyen, T N

    1999-01-01

    Streptococcal pharyngitis has been a significant public health problem in Vietnam for many years. Accurate diagnosis of the infection, however, has been difficult. We carried out a clinical trial of a rapid streptococcal antigen detection test (Quick-Vue (R) Flex Strep A) on a population of 777 children with pharyngitis seen at the Institute for the Protection of Children's Health (Children's Hospital) in Hanoi, Vietnam. Bacterial culture was performed in parallel with the rapid test on simultaneously obtained throat swab specimens. The rapid test was found to be 89% sensitive and 92% specific (96% in children not on prior antibiotics) compared to culture. The test was also found to be convenient and acceptable to patients and clinicians. A significant benefit of the test is that those children found positive are more likely to be treated with penicillin rather than a broad spectrum antimicrobial, which in turn will reduce the likelihood of resistant infections in the future. PMID:10829824

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

    EPA Science Inventory

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

  1. Molecular markers for the study of streptococcal epidemiology.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    1978-01-01

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

  3. An outbreak of streptococcal sore throat and rheumatic fever in a Royal Air Force training camp; significance of serum antibody to M-associated protein

    PubMed Central

    Widdowson, Jean P.; Maxted, W. R.; Newrick, C. W.; Parkin, D.

    1974-01-01

    A large outbreak of streptococcal sore throat in a Royal Air Force Training Camp resulted in five cases of rheumatic fever among the 16- to 18-year-old apprentices, and one case in a 33-year-old airman. The most prevalent type of group A streptococcus isolated from throat swabs was M-type 5 and there was serological evidence that at least four of the rheumatic fever (R.F.) cases were due to this type. Among the patients with uncomplicated throat infection the anti-streptolysin O (ASO) and anti-deoxyribonuclease B (anti-DNAase B) responses were in general rather low, even where there was evidence of protective antibody against type 5. However, a combination of the results of the ASO and anti-DNAase B tests gave an estimate of the extent of streptococcal infection 15-25% higher than did either test alone. The titres of antibody to M-associated protein (MAP) were ? 60 in all the R.F. patients, and in about 50% of the other patients with ASO titres ? 200. This figure is unusually high compared with data from several other outbreaks of streptococcal infection due to different serotypes and also greatly exceeds comparable figures for cases of sporadic sore throat and acute glomerulonephritis. PMID:4593739

  4. Extracorporeal treatments in sepsis: are there new perspectives?

    PubMed

    Tetta, C; D'Intini, V; Bellomo, R; Bonello, M; Bordoni, V; Ricci, Z; Ronco, C

    2003-11-01

    Sepsis continues to provide a major challenge to clinicians. Despite vast advancements achieved in the understanding of its pathways and mechanisms, the incidence of sepsis is increasing and the mortality and morbidity rates remain high, generating a considerable burden to health budgets worldwide. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the non-selective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extra-corporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials which lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. We will also review novel information related to other blood purification techniques using largo pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance. PMID:14640234

  5. Improving the Odds of Surviving Sepsis

    MedlinePLUS

    ... detect sepsis early in very low birthweight infants. Credit: Stock image. By the time a person develops ... an anti-inflammatory therapy for people with sepsis. Credit: Stock image. The antibiotics that treat infections do ...

  6. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2012-01-01

    Patients suffering from dental infections and concurrently using immunosuppressive medication are at increased risk of developing systemic streptococcal infections. Tocilizumab is a novel therapeutic agent targeting interleukin-6. We describe a case of streptococcal lung abscesses from a dental focus after use of tocilizumab for treatment of Takayasu arteritis. PMID:23101463

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of nave T-cells but no enduring cell-autonomous defects in T-cell function.

    PubMed

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

    2014-01-01

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

  14. [Acute postinfectious glomerulonephritis].

    PubMed

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

    2012-07-01

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

  15. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis.

    PubMed

    Cheng, Shih-Chin; Scicluna, Brendon P; Arts, Rob J W; Gresnigt, Mark S; Lachmandas, Ekta; Giamarellos-Bourboulis, Evangelos J; Kox, Matthijs; Manjeri, Ganesh R; Wagenaars, Jori A L; Cremer, Olaf L; Leentjens, Jenneke; van der Meer, Anne J; van de Veerdonk, Frank L; Bonten, Marc J; Schultz, Marcus J; Willems, Peter H G M; Pickkers, Peter; Joosten, Leo A B; van der Poll, Tom; Netea, Mihai G

    2016-04-01

    The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis. PMID:26950237

  16. [Neonatal sepsis: new preventive strategies].

    PubMed

    Stronati, M; Bollani, L; Maragliano, R; Ruffinazzi, G; Manzoni, P; Borghesi, A

    2013-02-01

    More than one million neonatal deaths every year in the world are attributable to infection. In nurseries, infections occur with a reported incidence of 0.3-3%; in Neonatal Intensive Care Units (NICUs) the reported incidence is 7-24.5%, and up to 40% in newborns with birth weight less than 1000 g or gestational age at birth <28 weeks. Sepsis is the most severe and frequent infection, accounting for 45-55% of all infections. Several practices have been demonstrated to be effective in reducing the incidence of infection in NICUs, including hand hygiene practices, correct management of central venous catheters (CVC), accurate diagnostic strategies and correct use of antimicrobial drugs. Despite the reduction in the incidence of infection after implementation of these practices, nosocomial infections are still a relevant problem, with high mortality and morbidity rates in hospitalized newborns, especially preterm newborns. Searching for new strategies to further reduce the incidence of nosocomial sepsis in NICUs is a priority of clinical research. New and promising strategies for the prevention of nosocomial infection in NICU include: lactoferrin administration, early identification of infants at risk of infection by means of specific markers (e.g. mannose binding lectin), heparin use for the prevention of CVC-related infections, judicious use of antibiotics, and prevention of fungal sepsis with antifungal agents. On the contrary, recent studies demonstrated that the use of specific immunoglobulins directed against different staphylococcal antigens is not effective in preventing neonatal sepsis. PMID:23422580

  17. Sepsis and Septic Shock: Lingering Questions.

    PubMed

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

    2016-01-01

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

  18. Model of Polymicrobial Peritonitis That Induces the Proinflammatory and Immunosuppressive Phases of Sepsis ?

    PubMed Central

    Barrera, Gabriela; Landoni, Vernica; Martire-Greco, Daiana; Chiarella, Paula; Meiss, Roberto; Gmez, Sonia A.; Alves-Rosa, Fernanda; Rearte, Barbara; Isturiz, Martn; Palermo, Marina S.; Fernndez, Gabriela C.

    2011-01-01

    Severe sepsis is associated with early release of inflammatory mediators that contribute to the morbidity and mortality observed during the first stages of this syndrome. Although sepsis is a deadly, acute disease, high mortality rates have been observed in patients displaying evidence of sepsis-induced immune deactivation. Although the contribution of experimental models to the knowledge of pathophysiological and therapeutic aspects of human sepsis is undeniable, most of the current studies using animal models have focused on the acute, proinflammatory phase. We developed a murine model that reproduces the early acute phases but also the long-term consequences of human sepsis. We induced polymicrobial acute peritonitis (AP) by establishing a surgical connection between the cecum and the peritoneum, allowing the exit of intestinal bacteria. Using this model, we observed an acute phase with high mortality, leukopenia, increased interleukin-6 levels, bacteremia, and neutrophil activation. A peak of leukocytosis on day 9 or 10 revealed the persistence of the infection within the lung and liver, with inflammatory hepatic damage being shown by histological examination. Long-term (20 days) derangements in both innate and adaptive immune responses were found, as demonstrated by impaired systemic tumor necrosis factor alpha production in response to an inflammatory stimulus; a decreased primary humoral immune response and T cell proliferation, associated with an increased number of myeloid suppressor cells (Gr-1+ CD11b+) in the spleen; and a low clearance capacity. This model provides a good approach to attempt novel therapeutic interventions directed to augmenting host immunity during late sepsis. PMID:21173307

  19. Antihypertensive agents acting on the reninangiotensin system and the risk of sepsis

    PubMed Central

    Dial, Sandra; Nessim, Sharon J; Kezouh, Abbas; Benisty, Jacques; Suissa, Samy

    2014-01-01

    Aims In response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients. Methods We performed a nested casecontrol study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs. Results From the cohort of 550?436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10?000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of ?-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.831.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.421.93). Users of ARBs, ?-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure. Conclusions Hypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk. PMID:24803383

  20. New approaches to the study of sepsis

    PubMed Central

    Ward, Peter A

    2012-01-01

    Models of sepsis have been instructive in understanding the sequence of events in animals and, to an extent, in humans with sepsis. Events developing early in sepsis suggest that a hyperinflammatory state exists, accompanied by a buildup of oxidants in tissues reflective of a redox imbalance. Development of immunosuppression and degraded innate and adaptive immune responses are well-established complications of sepsis. In addition, there is robust activation of the complement system, which contributes to the harmful effects of sepsis. These events appear to be associated with development of multiorgan failure. The relevance of animal models of sepsis to human sepsis and the failure of human clinical trials are discussed, together with suggestions as to how clinical trial design might be improved. PMID:23208733

  1. ISSag1 in streptococcal strains of human and animal origin.

    PubMed

    Franken, Carmen; Brandt, Claudia; Brker, Gerd; Spellerberg, Barbara

    2004-10-01

    The chromosomal region of Streptococcus agalactiae harboring the C5a peptidase and the lmb genes displays the structure of a composite transposon. Its presence in a streptococcal strain is associated with the origin of this strain from a human host. In S. agalactiae it is flanked by two copies of the insertion element ISSag2, and the nucleotide sequence for a third IS element (ISSag1) can be found in this region. Based on amino acid sequence similarity of the deduced transposase ISSag1 belongs to the IS3 family. It is 1251 bp long and flanked by 37 bp imperfect inverted repeats. Horizontal gene transfer among different bacterial species is facilitated by mobile genetic elements. To investigate if ISSag1 homologues are also present in other streptococcal species, various species of pyogenic streptococci from animal and human origin were analyzed by Southern blot hybridization and PCR. Among the different streptococcal species, multiple copies of an ISSag1 homologue could only be detected in S. dysgalactiae subsp. dysgalactiae strains of animal origin. All of the S. agalactiae strains harbored only a single copy, that was always found in strains with the scpB-lmb composite transposon. A single copy of an ISSag1 homologue could also be detected in some of the S. pyogenes and S. dysgalactiae subsp. equisimilis strains. Nucleotide sequencing of the IS element in S. dysgalactiae subsp. dysgalactiae strains revealed several different variants. One of the variants showed the features of a regular IS3 element. The other two variants that were observed displayed a 500-bp deletion and a mosaic structure composed of ISSag1 and ISSag2 homologues. This mosaic structure suggests that recombination and horizontal gene transfer events in S. dysgalactiae strains of bovine origin could have played a role in the assembly of the scpB-lmb composite transposon structure. PMID:15532982

  2. Value of Desiccated Swabs for Streptococcal Epidemiology in the Field

    PubMed Central

    Taplin, David; Lansdell, Lyle

    1973-01-01

    Streptococcal surveys in foreign countries or remote areas may be greatly enhanced by the use of calcium alginate swabs desiccated in sterile silica gel. Delays of up to 4 weeks before return to a base laboratory are feasible, and the need for fresh media or laboratory facilities in the field may be eliminated. Comparison of direct plating on crystal violet blood agar versus delayed silica gel preservation during surveys in Uganda, Haiti, Colombia, and Miami, Fla., showed no significant loss of positive cultures from skin lesions and suggests that desiccated swabs increase the recovery of bacitracin-sensitive Streptococcus pyogenes (presumptive group A) from throats. PMID:4346975

  3. Prediction of streptococcal pharyngitis: an option for school nurses?

    PubMed

    Squires, R L; Ellison, G C

    1986-08-01

    In this article the authors address the dilemma confronting school nurses in determining whether or not to counsel parents about seeking medical care for a child with a sore throat. The use of a clinical scorecard in the school setting as an aid in predicting streptococcal pharyngitis is investigated. The authors conclude that the only valid solution to the dilemma is the availability of the throat culture to schools. Using the culture as an additional assessment tool augments those already proven over time--the stethoscope, scoliosis and vision screening, and the otoscope. PMID:3528665

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

    PubMed

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

    1999-01-01

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

  5. Normalization of Activated Partial Thromboplastin Time Correlates with Low Levels of Dabigatran in a Patient with Severe Sepsis.

    PubMed

    Hjland, Rikke Ebenhard; Thorup, Stine Borch; Rasmussen, Bodil Steen

    2015-01-01

    The oral anticoagulant dabigatran etexilate can be a challenge when patients need acute surgery. Sepsis and acute renal failure exacerbate the anticoagulant effect. There is no specific reversal agent for dabigatran etexilate, but it can be removed by hemodialysis. We present a case where a patient treated with dabigatran etexilate was admitted to intensive care unit with severe sepsis and acute renal failure and in need of bilateral lower limp amputation due to ischemia. The patient had severe coagulopathy and was treated with continuous venovenous hemofiltration in attempt to remove dabigatran etexilate before surgery. PMID:26221544

  6. Normalization of Activated Partial Thromboplastin Time Correlates with Low Levels of Dabigatran in a Patient with Severe Sepsis

    PubMed Central

    Hjland, Rikke Ebenhard; Thorup, Stine Borch; Rasmussen, Bodil Steen

    2015-01-01

    The oral anticoagulant dabigatran etexilate can be a challenge when patients need acute surgery. Sepsis and acute renal failure exacerbate the anticoagulant effect. There is no specific reversal agent for dabigatran etexilate, but it can be removed by hemodialysis. We present a case where a patient treated with dabigatran etexilate was admitted to intensive care unit with severe sepsis and acute renal failure and in need of bilateral lower limp amputation due to ischemia. The patient had severe coagulopathy and was treated with continuous venovenous hemofiltration in attempt to remove dabigatran etexilate before surgery. PMID:26221544

  7. Antibodies to basement membrane proteins nidogen and laminin in sera from streptococcal-related diseases and juvenile rheumatoid arthritis patients.

    PubMed Central

    Avila, J L; Rojas, M; Velzquez-Avila, G; Rieber, M

    1987-01-01

    Using the ELISA technique, antibodies against two different basement proteins, laminin and nidogen (ALNA), were determined in 226 children suffering from one of 37 different inflammatory or infectious diseases. These included 80 patients with streptococcal infection and 40 with juvenile rheumatoid arthritis. Forty-eight percent of the streptococcus-infected patients (or 75% of those in the acute phase) and 60% of juvenile rheumatoid arthritis patients had significantly elevated ALNA levels compared with healthy controls. Interestingly 10 adult rheumatoid arthritis patients displayed normal ALNA levels, suggesting a particular immune process occurring in children affected by juvenile rheumatoid arthritis. By means of periodate oxidation and glycosidase treatments we have shown that ALNA positive sera recognized terminal alpha-galactose as the reactive epitope. PMID:2449305

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

    PubMed Central

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

    2016-01-01

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

  9. 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. PMID:26113542

  10. High burden of invasive ?-haemolytic streptococcal infections in Fiji

    PubMed Central

    STEER, A.C.; JENNEY, A.J.W.; OPPEDISANO, F.; BATZLOFF, M.R.; HARTAS, J.; PASSMORE, J.; RUSSELL, F.M.; KADO, J.H.H.; CARAPETIS, J.R.

    2008-01-01

    SUMMARY We undertook a 5-year retrospective study of group A streptococcal (GAS) bacteraemia in Fiji, supplemented by a 9-month detailed retrospective study of ?-haemolytic streptococcal (BHS) infections. The all-age incidence of GAS bacteraemia over 5 years was 116/100 000. Indigenous Fijians were 47 times more likely to present with invasive BHS disease than people of other ethnicities, and 64 times more likely than Indo-Fijians. The case-fatality rate for invasive BHS infections was 28%. emm-typing was performed on 23 isolates: 17 different emm-types were found, and the emm-type profile was different from that found in industrialized nations. These data support the contentions that elevated rates of invasive BHS and GAS infections are widespread in developing countries, and that the profile of invasive organisms in these settings reflects a wide diversity of emm-types and a paucity of types typically found in industrialized countries. PMID:17631691

  11. 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.

  12. 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

  13. Postmortem serum protein growth arrest-specific 6 levels in sepsis-related deaths.

    PubMed

    Palmiere, Cristian; Augsburger, Marc

    2015-09-01

    Growth arrest-specific 6 (Gas6) is widely expressed in leukocytes, platelets, endothelial cells, and monocytes. It regulates various processes including granulocyte adhesion to the endothelium, cell migration, thrombus stabilization, and cytokine release. In humans, increased plasma Gas6 levels have been described in patients with sepsis and septic shock. In this study, Gas6 concentrations were measured in postmortem serum from femoral blood in a series of sepsis-related fatalities and control cases. The aims were twofold: first, to determine whether Gas6 can be reliably determined in postmortem serum; and second, to assess its diagnostic potential in identifying sepsis-related deaths. Two study groups were prospectively formed, a sepsis-related fatalities group (24 cases) and a control group (24 cases) including cases of deep vein thrombosis and fatal pulmonary embolism, cases of systemic inflammatory response syndrome in severe trauma, cases of end-stage renal failure, and cases of hanging (non-septic, non-SIRS, non-end stage renal failure cases). The preliminary results of this study seem to indicate that Gas6 can be effectively measured in postmortem serum. However, Gas6 levels in sepsis-related fatalities do not appear to be clearly distinguishable from concentrations in pulmonary embolism, severe trauma, and end-stage renal failure cases. These findings tend to support previous reports that indicated that Gas6 behaves as an acute phase reactant and can be considered a general marker of inflammation rather than a specific biomarker of sepsis. PMID:26233610

  14. Full activation of CD4+ T cells early during sepsis requires specific antigen.

    PubMed

    Schmoeckel, Katrin; Traffehn, Sarah; Eger, Christin; Ptschke, Christian; Brker, Barbara M

    2015-02-01

    During sepsis, CD4 T cells express activation markers within the first 24 h. In the present study, the mechanisms of T-cell activation and its consequences were addressed in an acute peritonitis model in mice. The response of CD4+ T cells to sepsis induction was compared between OTII mice, characterized by ovalbumin-specific T-cell receptor-transgenic T cells, and C57BL/6 controls (wild type [WT] mice). Because ovalbumin was absent during peritonitis, the OTII CD4+ T cells could not be activated by canonical antigen recognition. In both OTII and WT control mice, CD4+ T effector cells and CD4+ Foxp3+ regulatory T cells (Tregs) expressed the activation marker CD69 early after sepsis onset. However, full activation with upregulation of CD25 and proliferation took place only in the presence of the antigen. Besides this, the fraction of Tregs was lower in OTII than that in WT mice. Sepsis mortality was increased in OTII mice. Our data show that, in sepsis, partial activation of CD4+ T cells is induced by a T-cell receptor-independent pathway, whereas full stimulation and proliferation require a specific antigen. Antigen-dependent T-cell effector functions as well as Treg activity may contribute to sepsis survival. PMID:25243429

  15. Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters

    PubMed Central

    Goldman, John; Cheriyath, Pramil; Nookala, Vinod

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

  17. Differential pathophysiology of bacterial translocation after thermal injury and sepsis.

    PubMed Central

    Jones, W G; Barber, A E; Minei, J P; Fahey, T J; Shires, G T; Shires, G T

    1991-01-01

    Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia. PMID:2064468

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

    PubMed

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

    2009-06-01

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

  19. 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

  20. [Severe infections : causes and management of sepsis].

    PubMed

    Salzberger, B; Hanses, F; Birkenfeld, G; Langgartner, J

    2013-08-01

    The sepsis syndrome has only recently been defined as a clinical syndrome but despite its unspecific definition it has evolved rapidly into an important concept. Although specific therapeutic interventions targeting the inflammatory pathway have not yet been effective in treating sepsis, a better understanding of mechanisms leading to organ dysfunction has led to better management of patients with sepsis. Clinical signs of systemic inflammatory response syndrome (SIRS) or sepsis are hallmarks for the definition of severe infections. Current guidelines are presented for the management of a number of severe infectious syndromes. PMID:23817897

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

    PubMed

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

    2015-05-01

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

  2. Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital.

    PubMed

    Nielsen, Maryke J; Claxton, Sarah; Pizer, Barry; Lane, Steven; Cooke, Richard P D; Paulus, Stéphane; Carrol, Enitan D

    2016-03-01

    Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant.Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records.A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia.Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure.The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia. PMID:26945409

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

    PubMed Central

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

    2006-01-01

    Background It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. Results The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%). Conclusion Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation. PMID:16709255

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

    PubMed Central

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

    2015-01-01

    Objectives Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%). Design Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA. Results The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.3730.17) ng/mL and 1.68 (1.4113.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage. Conclusion An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis. PMID:26361390

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

    PubMed

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

    2001-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. Bacterial skin infections: management of common streptococcal and stapylococcal lesions.

    PubMed

    Witkowski, J A; Parish, L C

    1982-10-01

    Skin infection occurs in any age-group, sex, and race but is particularly common in children. It is usually minor, but may indicate underlying systemic disease or may lead to systemic infection. Streptococci and staphylococci are common causes. Group A beta-hemolytic streptococci account for the majority of streptococcal infections in man. Infection most often involves the lower extremities and produces spreading erythema and necrosis but little purulence. Staphylococcal infections most commonly involve the face, the hair follicles and eccrine sweat ducts being the initial sites. Lesions appear as bullae and pustules with a narrow rim of erythema. Intense cellulitis surrounding the lesions usually points to a virulent, penicillin-resistant strain of Staphylococcus. Treatment of both types of infection consists of cleansing with antibacterial agents, removal of crusts, application of warm compresses, and use of topical or systemic antibiotics, depending on the severity of the infection and the type of pyoderma involved. PMID:7122351

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

    PubMed

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

    1989-03-31

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

  9. Penicillin therapy of spontaneous streptococcal meningitis in pigs.

    PubMed

    McKellar, Q A; Baxter, P; Taylor, D; Bogan, J A

    1987-10-10

    Oral prophylactic medication with either procaine penicillin G or a mixture of chlortetracycline, sulphadimidine and procaine penicillin G reduced the incidence of streptococcal meningitis in a herd of pigs with a high recorded prevalence of the disease, but to a significant extent (P less than 0.01) only in those pigs receiving procaine penicillin G. Subsequent studies showed that after oral administration of procaine penicillin G, benzylpenicillin was detectable in plasma only at very low concentration and similar results were obtained using the potassium salt of penicillin G. However, phenoxymethyl penicillin administered orally provided high plasma concentrations of this drug. A further investigation demonstrated that despite the low plasma concentrations of penicillin after oral administration of the procaine salt, gastrointestinal and urinary concentrations of the drug were relatively high for up to five hours. PMID:3686793

  10. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

    PubMed

    LaRock, Christopher N; Nizet, Victor

    2015-11-01

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

  11. Inflammasome/IL-1β Responses to Streptococcal Pathogens

    PubMed Central

    LaRock, Christopher N.; Nizet, Victor

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

    PubMed

    Claessens, Y-E; Schmidt, J; Batard, E; Grabar, S; Jegou, D; Hausfater, P; Kierzek, G; Gurin, S; Pourriat, J-L; Dhainaut, J-F; Ginsburg, C

    2010-06-01

    Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice. PMID:19747215

  14. 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

  15. Oestrogen sulfotransferase ablation sensitizes mice to sepsis.

    PubMed

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R; Kucera, Heidi R; 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 oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-?B dependent and EST is a NF-?B-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

  16. 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 ...

  17. Clostridium perfringens sepsis following a molar pregnancy.

    PubMed

    Adams, Brandi N; Lekovic, Jovana P; Robinson, Suzzette

    2014-01-01

    Clostridium perfringens sepsis is rare since the legalization of abortion in 1973. This is a 49 year old female who developed clostridial sepsis after suction dilation and curettage for a molar pregnancy. A hysterectomy was performed after prompt recognition, and the patient survived. PMID:24096275

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

    PubMed

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

    2016-02-01

    The objective of this study was to assess the diagnostic accuracy of C-reactive protein (CRP), procalcitonin (PCT), and cellular immune markers levels in sepsis. This was a prospective observational study in adult intensive care unit (ICU) patients, between 2012 and 2014. The 8-color flow cytometric biomarker panel included CD64, CD163, and HLA-DR. Index test results were compared with sepsis, using receiver operating characteristic curve analyses. Multivariate logistic regression assessed the relationship of sets of markers with the probability of sepsis. Of 219 enrolled patients, 120 had sepsis. C-statistic was the highest for CRP (0.86) followed by neutrophil CD64 expression (0.83), procalcitonin (0.82), and Acute Physiology and Chronic Health Evaluation (APACHE) IV (0.72). After adjustment for APACHE IV, the combination of CRP, PCT, and neutrophil CD64 measure remained a significant predictor of sepsis with an excellent AUC (0.90). In a targeted ICU population at increased risk of sepsis, CRP, PCT, and neutrophil CD64 combined improve the diagnostic accuracy of sepsis. PMID:26586579

  19. Identifying severe sepsis via electronic surveillance.

    PubMed

    Brandt, Bristol N; Gartner, Amanda B; Moncure, Michael; Cannon, Chad M; Carlton, Elizabeth; Cleek, Carol; Wittkopp, Chris; Simpson, Steven Q

    2015-01-01

    An electronic sepsis surveillance system (ESSV) was developed to identify severe sepsis and determine its time of onset. ESSV sensitivity and specificity were evaluated during an 11-day prospective pilot and a 30-day retrospective trial. ESSV diagnostic alerts were compared with care team diagnoses and with administrative records, using expert adjudication as the standard for comparison. ESSV was 100% sensitive for detecting severe sepsis but only 62.0% specific. During the pilot, the software identified 477 patients, compared with 18 by adjudication. In the 30-day trial, adjudication identified 164 severe sepsis patients, whereas ESSV detected 996. ESSV was more sensitive but less specific than care team or administrative data. ESSV-identified time of severe sepsis onset was a median of 0.00 hours later than adjudication (interquartile range = 0.05). The system can be a useful tool when implemented appropriately but lacks specificity, largely because of its reliance on discreet data fields. PMID:24970280

  20. Mobilization in Severe Sepsis: An Integrative Review

    PubMed Central

    Govindan, Sushant; Iwashyna, Theodore J.; Odden, Andrew; Flanders, Scott A.; Chopra, Vineet

    2014-01-01

    Severe sepsis is a leading cause of long-term morbidity in the United States. Up to half of severe sepsis is treated in non-intensive care unit (ICU) settings, making it applicable to hospitalist practice. Evidence has demonstrated benefits from physical therapy (PT) in myriad conditions; whether PT may benefit severe sepsis patients either within or outside the ICU is unknown. Therefore, we conduct a review of the literature to understand whether early mobilization improves outcomes in patients with severe sepsis in non-ICU settings. We summarize the pathophysiology of functional decline in severe sepsis, the efficacy of PT in other patient populations, and the potential rationale for PT interventions in patients with severe sepsis. Multiple databases were searched for keywords including length of stay, mortality, costs, mobilization and PT. Two authors (SG and VC) independently determined the eligibility of each study. A secondary review including studies of any infectious pathology with PT interventions or sepsis patients within the ICU was also conducted. Our search did not yield any primary literature regarding the impact of mobilization on severe sepsis outcomes in non-ICU settings. Only one retrospective study showed potential benefit of therapy in sepsis patients in the ICU. Similarly, in non-ICU settings, only one study that included patients with bacterial pneumonia reported outcomes after implementing an intervention consisting of early mobilization. These findings suggest that scant data regarding the efficacy of early mobilization following severe sepsis exists. Since hospitalists often care for this patient population, an opportunity for research in this area exists. PMID:25393649

  1. Exfoliation, cholestasis, and apparent biliary sepsis in a woman with adult-onset diabetes.

    PubMed Central

    Heiman, D. F.; Levine, R. A.; Bia, F. J.

    1985-01-01

    In consultation the authors were requested to evaluate a middle-aged diabetic woman for an apparent episode of biliary sepsis. The patient had been admitted to the dermatology service with a four-day history of rash and pruritus. This was initially thought to represent an allergic reaction to dicloxacillin in someone with a previous history of penicillin hypersensitivity. Persistent right upper quadrant pain, fevers, elevations of serum alkaline phosphatase, and a radionuclide scan which did not demonstrate a functioning gall bladder led to a cholecystectomy for acute cholecystitis and possible biliary sepsis. This diagnosis was not confirmed. Ultimately, this case illustrated the need to review carefully recent changes in any patient's drug regimen. Reactions to commonly prescribed agents may cause syndromes which are difficult to distinguish from episodes of apparent sepsis. Images FIG. 1 PMID:4090534

  2. Sepsis

    MedlinePLUS

    ... prevent infection. Also, make sure people who are sick don't get close to your baby. Children ... head decreased amount of urine any type of behavior or appearance that concerns you If your older ...

  3. Sepsis

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    ... newborns and infants. Bacteria such as group B streptococcus (GBS) , Escherichia coli , Listeria monocytogenes , Neisseria meningitidis , Streptococcus pneumoniae , Haemophilus influenzae type b, and Salmonella are ...

  4. Sepsis

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes

    PubMed Central

    2012-01-01

    Introduction Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol. Methods Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test. Results ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients. Conclusions During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS. PMID:22512779

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

    PubMed Central

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

    2013-01-01

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

  9. Protective effect of rhBNP on intestinal injury in the canine models of sepsis.

    PubMed

    Yang, Huaisong; Song, Zhi; Jin, Hongxu; Cui, Yan; Hou, Mingxiao; Gao, Yan

    2014-04-01

    Sepsis is the leading cause of death in the intensive care units worldwide. Proinflammatory cytokines such as TNF (tumor necrosis factor)-? and IL (interleukin)-6 mediate the pathogenesis of septic shock characterized by hemodynamic instability and end-stage multi-organ functional failure. Brain natriuretic peptide (BNP) has been used as a diagnostic and prognostic biomarker in the cardiovascular disorders. Most recently, plasma level of BNP has also been used to predict outcomes of critical illnesses including sepsis. We have recently reported that human recombinant BNP (rhBNP) could protect lungs from acute proinflammatory injury in response to LPS-injection. In the current study, using LPS (lipopolysaccharide)-induced canine sepsis models, we further investigated the effect of rhBNP on intestinal injury and its potential mechanisms. We have found that rhBNP (5?g or 10?g/kg weight) could significantly reduce intestinal tissue damage in response to LPS-injection in the dog sepsis models through down-regulating proinflammatory cytokines TNF-? and IL-6 (5-10 fold decrease compared to LPS-injection only group) by a mechanism of suppressing I?B phosphorylation and NF-?B expression. These findings suggest that BNP protect intestinal tissues from endotoxin-induced hyper-inflammatory injury and thus, may be used as therapeutic agents for sepsis. PMID:24508538

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

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. 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

  13. A prospective treatment for sepsis.

    PubMed

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

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

  14. Management of neonatal sepsis in term newborns

    PubMed Central

    Du Pont-Thibodeau, Genevive; Joyal, Jean-Sbastien

    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

  15. Sequential events in the pathogenesis of streptococcal cell wall-induced arthritis and their modulation by bis(5-amidino-2-benzimidazolyl)methane (BABIM).

    PubMed Central

    Geratz, J. D.; Tidwell, R. R.; Schwab, J. H.; Anderle, S. K.; Pryzwansky, K. B.

    1990-01-01

    This report builds on the authors' earlier discovery of bis(5-amidino-2-benzimidazolyl)methane (BABIM) as a strong suppressive agent for streptococcal cell wall fragment-induced arthritis in the Lewis rat. As a synthetic inhibitor of trypsinlike proteases, BABIM opens up a new route to the control of inflammatory joint disease. To gain a deeper insight into the function of the compound, the authors have now studied its influence on the sequential development of the joint changes and the associated lesions in spleen and liver. Bis(5-amidino-2-benzimidazolyl)methane is shown to block acute synovitis, to retard and reduce granuloma formation in spleen and liver, to decrease neutrophilic leukocytosis, and to diminish hemopoietic hyperplasia in the bone, and thus also to mitigate the distinctive osteoclastic and chondroclastic events. The compound does not interfere with the splenic immune response, the temporary rise in hepatocytic mitotic activity, or the organ deposition of streptococcal cell walls. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 9 PMID:2327474

  16. Cytotoxic and viral neutralizing antibodies crossreact with streptococcal M protein, enteroviruses, and human cardiac myosin.

    PubMed Central

    Cunningham, M W; Antone, S M; Gulizia, J M; McManus, B M; Fischetti, V A; Gauntt, C J

    1992-01-01

    The development of autoimmunity in certain instances is related to infectious agents. In this report, cytotoxic monoclonal antibodies (mAbs) that recognize epitopes on both enteroviruses and the bacterium Streptococcus pyogenes are described. Murine anti-streptococcal mAbs that were crossreactive with streptococcal M protein, human cardiac myosin, and other alpha-helical coiled-coil molecules were found to neutralize coxsackieviruses B3 and B4 or poliovirus type 1. The viral-neutralizing anti-streptococcal mAbs were also cytotoxic for heart and fibroblast cell lines and reacted with viral capsid proteins on a Western immunoblot. Alignment of amino acid sequences shared between streptococcal M protein, coxsackie-virus B3 capsid protein VP1, and myosin revealed 40% identity in a 14- to 15-amino acid overlap. Synthetic peptides containing these sequences blocked mAb reactivity with streptococcal M protein. The data show that antibodies against alpha-helical structures of bacterial and viral antigens can lead to cytotoxic reactions and may be one mechanism to explain the origin of autoimmune heart disease. Images PMID:1311095

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

    PubMed Central

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

    2014-01-01

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

  18. Pathophysiological aspects of sepsis: an overview.

    PubMed

    Yao, Yong-Ming; Luan, Ying-Yi; Zhang, Qing-Hong; Sheng, Zhi-Yong

    2015-01-01

    Sepsis is defined as severe systemic inflammation in response to invading pathogens, or an uncontrolled hyperinflammatory response, as mediated by the release of various proinflammatory mediators. Although some patients may die rapidly from septic shock accompanied by an overwhelming systemic inflammatory response syndrome (SIRS) triggered by a highly virulent pathogen, most patients survive the initial phase of sepsis, showing multiple organ damage days or weeks later. These patients often demonstrate signs of immune suppression accompanied by enhanced inflammation. Sepsis is a result of a complex process; there is interaction of various pathways, such as inflammation, immunity, coagulation, as well as the neuroendocrine system. This treatise is an attempt to provide a summary of several key regulatory mechanisms and to present the currently recognized molecular pathways that are involved in the pathogenesis of sepsis. PMID:25319775

  19. Intracompartmental Sepsis With Burn: A Case Report.

    PubMed

    Chou, Chieh; Lee, Su-Shin; Wang, Hui-Min; Hsieh, Tung-Ying; Lee, Hsiao-Chen; Chang, Chih-Hau; Lai, Chung-Sheng; Chang, Kao-Ping; Lin, Sin-Daw; Huang, Shu-Hung

    2016-03-01

    Intracompartmental sepsis (IS) is a rare complication in patients with burns. Intracompartmental sepsis presents in patients with inadequate perfusion of intracompartmental tissues and subsequent ischemic necrosis and infection. Contributing factors include high-volume resuscitation, delayed escharotomies, and previous bacteremia. We describe a case of massive burns from a gas explosion and the subsequent development of IS in our intensive care burn unit. The patient presented with a 75% total body surface area burn on admission, with 39% superficial, deep partial-thickness and 26% full-thickness burns. Intracompartmental sepsis was diagnosed 45 days after admission. Anterior compartment muscles, including the tibialis anterior, extensor hallucis longus, and extensor digitorum longus, were necrotic with relatively fair nerve and vascular structures. Intracompartmental sepsis is an overwhelming, infectious complication that appears late and can occur easily in patients with major burns. Early diagnosis and management are a must for improving outcomes. PMID:26808770

  20. Is hypertriglyceridemia a prognostic factor in sepsis?

    PubMed Central

    Cetinkaya, Ali; Erden, Abdulsamet; Avci, Deniz; Karagoz, Hatice; Karahan, Samet; Basak, Mustafa; Bulut, Kadir; Gencer, Vedat; Mutlu, Hasan

    2014-01-01

    Introduction Sepsis and septic shock are important causes of mortality in intensive care unit patients, hence early diagnosis and therapy are important in management of their treatment. The available information on sepsis patients is not enough to recommend or to discard the routine evaluation of triglyceride (TG) levels at the onset of sepsis. The aim of this study was to investigate the association of hypertriglyceridemia and clinical outcome (or mortality) in patients with severe sepsis. Materials and methods Between January 1 and December 31, 2011, a total of 84 patients with sepsis from the intensive internal care unit at the Kayseri Training and Research Hospital, Kayseri, Turkey, were investigated retrospectively. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine/European Society of Intensive Care Medicine consensus conference definitions. For each patient, survival was recorded at the end of the last day of hospitalization as dead or alive. The TG values were taken retrospectively from the records, which were performed routinely for each patient with sepsis at the time of diagnosis. TG >150 mg/dL was considered as hypertriglyceridemia. Results The percentages of male and female patients were 44% and 56%, respectively. The mean age of patients was 71.4911.071 years. The percentage of patients with TG values more than 150 mg/dL was 81% (25/31) in the non-survivor group and 19% (6/31) in the survivor group. There was a significant difference regarding TG values between groups (P=0.039). Discussion It was observed in this study that patients in the intensive care unit with sepsis had high TG levels. We also observed that the TG level >150 mg/dL at 0 hour (onset of sepsis) was a significant predictive marker of sepsis mortality rate. The contribution of hypertriglyceridemia to mortality might be modest compared to increase in severity of illness, but, nevertheless, these simple measurements represent a potential therapeutic target in sepsis. PMID:24600230

  1. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

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

  2. A new role for statins in sepsis.

    PubMed

    Rachoin, Jean-Sebastien; Cerceo, Elizabeth; Dellinger, R Phillip

    2013-01-01

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

  3. Clinical Characteristics of Community-Acquired Viridans Streptococcal Pneumonia

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  5. [Obsessive-compulsive disorder in children induced by streptococcal infection].

    PubMed

    Kochman, F; Hantouche, E G; Karila, L; Bayart, D; Bailly, D

    2001-11-24

    FROM OBSESSIVE-COMPULSIVE DISORDER TO PANDAS: Obsessive-compulsive disorder (OCD) represents a potentially severe and handicapping disorder that affects several hundreds of thousands of children in France. OCD has, for many years, been considered as a neurosis resulting from mental conflicts. It is currently seen as a neurobiological disorder, the etiological substratum of which is more organic than mental. Recently a sub-type of OCD was isolated in children following infection by Group A b-hemolytic streptococci. This sub-type has been described as Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS). A NEW PHYSIOPATHOLOGICAL APPROACH: The putative dysimmune relationship between bacterial infection and neurotic disorder has led to the development of an original etiopathogenic model that may lead to new therapeutic strategies. The clinical case report of an adolescent presenting with trichotillomania associated with recurrent pharyngitis is a good illustration of this. PUBLISHED DATA: Data published in medical literature over the last 10 years indicates a 10% prevalence in the young suffering from OCD, i.e. 0.1 to 0.3% of the young population. PMID:11769071

  6. Invasive Group A Streptococcal Disease: Risk Factors for Adults

    PubMed Central

    Levine, Orin S.; Schwartz, Benjamin; Harrison, Lee H.; Farley, Monica M.; McGeer, Allison; Schuchat, Anne

    2003-01-01

    We conducted a case-control study to identify risk factors for invasive group A streptococcal (GAS) infections, which can be fatal. Case-patients were identified when Streptoccus pyogenes was isolated from a normally sterile site and control subjects (two or more) were identified and matched to case-patients by using sequential-digit telephone dialing. All participants were noninstitutionalized surveillance area residents, >18 years of age. Conditional logistic regression identified the risk factors for invasive GAS infection: in adults 18 to 44 years of age, exposure to one or more children with sore throats (relative risk [RR]=4.93, p=0.02), HIV infection (RR =15.01, p=0.04), and history of injecting drug use (RR=14.71, p=0.003); in adults >45 years of age, number of persons in the home (RR=2.68, p=0.004), diabetes (RR= 2.27, p=0.03), cardiac disease (RR=3.24, p=0.006), cancer (RR= 3.54, p=0.006), and corticosteroid use (RR=5.18, p=0.03). Thus, host and environmental factors increased the risk for invasive GAS disease. PMID:12967496

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

    2014-01-01

    Introduction Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis. Methods Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (?65years) and adult (1864 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (68 weeks) and aged (2022 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured. Results The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P?sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P?sepsis (P?sepsis. PMID:24962182

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

    PubMed Central

    2013-01-01

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

  10. Activation of the alternate complement pathway by peptidoglycan from streptococcal cell wall.

    PubMed

    Greenblatt, J; Boackle, R J; Schwab, J H

    1978-01-01

    Activation of the alternate complement pathway in human serum by several bacterial components was compared. Peptidoglycan from group A streptococcal cell walls was the most active material, on a weight basis, followed by cell walls, protoplast membranes, and whole cells. The group-specific carbohydrate was inactive. Treatment of peptidoglycan with low concentrations of lysozyme or short periods of sonic treatment enhanced complement activation. High concentrations of lysozyme or extended sonic treatment of peptidoglycan destroyed or greatly reduced the capacity to activate complement. Lysozyme treatment of group A streptococcal cell walls or lipopolysaccharide had no measurable effect. Activation of the alternate complement pathway by group D streptococcal cell walls was destroyed by lysozyme. Activity of peptidoglycan was not inhibited by N-acetyl glucosamine, N-acetyl muramic acid, or D-alanine-D-alanine. Conversion of C3 and factored B by peptidoglycan was shown to occur by immunoelectrophoresis and crossed immunoelectrophoresis. PMID:415005

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

    PubMed Central

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

    1976-01-01

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

  12. Sepsis: the need for tolerance not complacency.

    PubMed

    Velho, Tiago R; Santos, Isa; Pvoa, Pedro; Moita, Luis Ferreira

    2016-01-01

    Sepsis is a life-threatening condition that arises as a systemic inflammatory response syndrome to an infection. Its uncontrolled progression can in frequent cases lead to multiple organ failure, which is still associated with high mortality rates. Modern antibiotics made clear that the infection is only an initiating, and not always necessary, event of this syndrome as many patients with sepsis die despite effective eradication of the inciting pathogen. This observation critically contributed to a paradigm shift that focused the pathogenesis of sepsis on the host and not on the pathogen. However, therapeutic strategies based on the inhibition of proinflammatory critical mediators of sepsis or immunostimulation have so far failed to improve sepsis outcome and, therefore, this condition urgently needs transformative therapeutic ideas and strategies. Here we argue that the induction of tolerance, a defence strategy that minimises the impact of an infection on organ function without directly affecting the pathogen burden, is perhaps the missing but essential element to add to the current components of sepsis care and treatment. PMID:26900874

  13. 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

  14. Target blood pressure in sepsis: between a rock and a hard place.

    PubMed

    Beloncle, Franois; Lerolle, Nicolas; Radermacher, Peter; Asfar, Pierre

    2013-01-01

    The optimal target blood pressure in septic shock is still unknown. Therefore, in a long-term, resuscitated porcine model of fecal peritonitis-induced septic shock, Corra and colleagues tested whether different titrations of mean arterial pressure (50 to 60 and 75 to 85 mm Hg) would produce different effects on sepsis-related organ dysfunction. The higher blood pressure window was associated with increased needs for fluid resuscitation and norepinephrine support. However, titrating the lower blood pressure range coincided with an increased incidence of acute kidney injury. In contrast, neither the inflammatory response nor tissue mitochondrial activity showed any difference. This research paper in a clinically relevant model elegantly demonstrates that any standard resuscitation strategy may be a double-edged sword with respect to various therapeutic endpoints. Furthermore, it adds an important piece to the puzzle of the complex pathophysiology of sepsis-related acute kidney injury. PMID:23534963

  15. Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism.

    PubMed

    Chousterman, Benjamin G; Boissonnas, Alexandre; Poupel, Lucie; Baudesson de Chanville, Camille; Adam, Julien; Tabibzadeh, Nahid; Licata, Fabrice; Lukaszewicz, Anne-Claire; Lombs, Amlie; Deterre, Philippe; Payen, Didier; Combadire, Christophe

    2016-03-01

    Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C(high) monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis. PMID:26160897

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

    SciTech Connect

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

    2009-09-15

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

  17. Reactivity with rabbit immunoglobulin G of cold agglutinins isolated from group C streptococcal antisera.

    PubMed Central

    Colling, R G; Brown, J C

    1981-01-01

    Cold agglutinin antibodies were isolated from group C streptococcal antisera by thermal elution from rabbit erythrocytes. These antibodies reacted with bovine submaxillary mucin, fetuin, immunoglobulin G, and the Fc fragment of immunoglobulin G in hemolytic inhibition assays. Further, in radioimmunoassay these antibodies reacted with the major glycopeptide fragment of rabbit immunoglobulin G. Affinity-purified group carbohydrate-specific antibodies reacted weakly with glycopeptide. These data suggest that certain populations of antibody in group C streptococcal antisera may participate in tissue reactivity via interaction with cell surface glycoproteins, including immunoglobulin G. PMID:6174452

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

    PubMed

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

    2015-11-01

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

  19. Factors which affect mortality in neonatal sepsis

    PubMed Central

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

    2015-01-01

    Aim: Neonatal sepsis is an important cause of mortality and morbidity in newborns. The causative agents may be different in different units and may change in time. It was aimed to examine the microbiological agents leading to sepsis, clinical features and antibiotic resistances in babies with sepsis hospitalized in our unit in a two-year period. Material and Methods: The clinical features, microbiological and laboratory results, antibiotic resistance patterns and mortality rates of the newborns with sepsis followed up in our unit between 2010 and 2011 were examined in the patient record system. Results: 351 babies diagnosed with sepsis among 3219 patients hospitalized in the neonatal intensive care unit were included in the study. The mean gestational age was found to be 30.14.1 weeks, the mean birth weight was found to be 1417.4759.1 g and the mean hospitalization time was found to be 43.634.4 days. Blood cultures were found to be positive in 167 (47.6%) patients, urine cultures were found to be positive in 6 (7.1%) patients and cerebrospinal fluid cultures were found to be positive in 34 (9.6%) cases. Candida grew in 5 patients (2 patients with early-onset sepsis and 3 patients with late-onset sepsis). The most common cause of sepsis was found to be staphylococci (coagulase negative staphylococcus was found in 65 patients (51%) and Staphylococcus aureus was found in 38 patients (39%). 49.6% (n=63) of the gram positive bacteriae and 60% (n=21) of the gram negative bacteriae were resistant to antibiotics. Six (7.1%) of the patients who were infected with these bacteriae were lost. In total 24 babies were lost because of sepsis. The bacteriae which caused to mortality with the highest rate included E. coli, coagulase negative staphylocicci, S. aureus and Klebsiella. Low birth weight, mechanical ventilation and parenteral nutrition were found to be significant risk factors in terms of mortality. Conclusions: Staphylococci were found to be the most common agents in neonatal sepsis. Low birth weight, mechanical ventilation and parenteral nutrition are significant risk factors in terms of mortality. PMID:26568693

  20. Development, Implementation and Impact of an Automated Early Warning and Response System for Sepsis

    PubMed Central

    Umscheid, Craig A.; Betesh, Joel; VanZandbergen, Christine; Hanish, Asaf; Tait, Gordon; Mikkelsen, Mark E.; French, Benjamin; Fuchs, Barry D.

    2015-01-01

    Background Early recognition and timely intervention significantly reduce sepsis-related mortality. Objective Describe the development, implementation and impact of an Early Warning and Response System (EWRS) for Sepsis. Design After tool derivation and validation, a pre/post study with multivariable adjustment measured impact. Setting Urban academic healthcare system Patients Adult non-ICU patients admitted to acute inpatient units from: 10/0110/31/2011 for tool derivation, 06/0607/05/2012 for tool validation, and 06/0609/04/2012 and 06/0609/04/2013 for the pre/post analysis. Intervention An EWRS in our electronic health record monitored laboratory values and vital signs in real time. If a patient had >= 4 predefined abnormalities at any one time, the provider, nurse, and rapid response coordinator were notified and performed an immediate bedside patient evaluation. Measurements Screen positive rates, test characteristics, predictive values and likelihood ratios; system utilization; and resulting changes in processes and outcomes. Results The tools screen positive, sensitivity, specificity, and positive and negative predictive values and likelihood ratios for our composite of intensive care unit (ICU) transfer, rapid response team call or death in the derivation cohort was 6%, 16%, 97%, 26%, 94%, 5.3 and 0.9, respectively. Validation values were similar. The EWRS resulted in a statistically significant increase in early sepsis care, ICU transfer, and sepsis documentation, and decreased sepsis mortality and increased discharge to home, although neither of these latter two findings reached statistical significance. Conclusions An automated prediction tool identified at risk patients and prompted a bedside evaluation resulting in more timely sepsis care, improved documentation, and a suggestion of reduced mortality. PMID:25263548

  1. Role of mitochondrial oxidants in an in vitro model of sepsis-induced renal injury.

    PubMed

    Pathak, Elina; MacMillan-Crow, Lee Ann; Mayeux, Philip R

    2012-01-01

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

  2. A retrospective cohort study of perioperative prognostic factors associated with intra-abdominal sepsis

    PubMed Central

    Arun Kumar, R. V.; Channabasappa, Shivakumar M.

    2016-01-01

    Context: Intra-abdominal sepsis following laparotomy for acute abdomen remains still a challenging condition. The understanding of various perioperative risk factors by anesthesiologists are crucial in optimum management these patients. Aims: The objective of this study is to assess the perioperative risk factors, which predicts the outcome of treatment. Settings and Design: This retrospective observational study of 603 patients who underwent Laparotomies between March 2012 and March 2015 at our University Medical College. Of 603 patients, 52 consecutive patients with intra-abdomen sepsis who underwent surgical procedures and admitted in Intensive Care Unit (ICU) were selected and analyzed for prognostic risk factors in relation to severity of the disease. Subjects and Methods: 52 consecutive patients who developed intra-abdominal sepsis following laparotomy was allocated one of two groups; Group Sepsis, patients with peritonitis without systemic hypotension (mean arterial pressure [MAP] >60 mm of Hg); and Group septic shock, patients with peritonitis with systemic hypotension (mean arterial pressure [MAP] <60 mm of Hg) and patients were analyzed for prognostic risk factors Statistical Analysis Used: Categorical variables were analyzed by using Fisher's exact (two-tail) test and continuous variable were analyzed by using Mann–Whitney (two-tail) U-test. Results: Out of 603 patients who underwent laparotomy 52 patients developed an intra-abdominal septic complication. Of these 52 cases studied 28 patients developed septic shock and required a longer duration of admission in ICU and more inotropic support. Preoperative albumin and hematocrit level were significantly low in septic shock patients as compared to the patients with sepsis without systemic hypotension. PaCO2: FiO2 was also significantly low in these patients. Conclusions: Preoperative low hematocrit, low albumin level, and delay in laparotomy more than 72 h were also associated with adverse outcome in the patients with intra-abdominal sepsis. Clinicians should maintain equipoise on this topic pending prospective randomized clinical trials. PMID:26957690

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

    PubMed Central

    Pathak, Elina; MacMillan-Crow, Lee Ann

    2012-01-01

    Oxidative stress has been implicated to play a major role in multiorgan dysfunction during sepsis. To study the mechanism of oxidant generation in acute kidney injury (AKI) during sepsis, we developed an in vitro model of sepsis using primary cultures of mouse cortical tubular epithelial cells exposed to serum (2.510%) collected from mice at 4 h after induction of sepsis by cecal ligation and puncture (CLP) or Sham (no sepsis). CLP serum produced a concentration-dependent increase in nitric oxide (NO) (nitrate + nitrite) release at 6 h and cytotoxicity (lactate dehydrogenase release) at 18 h compared with Sham serum treatment. Before cytotoxicity there was a decrease in mitochondrial membrane potential, which was followed by increased superoxide and peroxynitrite levels compared with Sham serum. The role of oxidants was evaluated by using the superoxide dismutase mimetic and peroxynitrite scavenger manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin tetratosylate hydroxide (MnTmPyP). MnTmPyP (10100 ?M) produced a concentration-dependent preservation of ATP and protection against cytotoxicity. MnTmPyP blocked mitochondrial superoxide and peroxynitrite generation produced by CLP serum but had no effect on NO levels. Although MnTmPyP did not block the initial CLP serum-induced fall in mitochondrial membrane potential, it allowed mitochondrial membrane potential to recover. Data from this in vitro model suggest a time-dependent generation of mitochondrial oxidants, mitochondrial dysfunction, and renal tubular epithelial cell injury and support the therapeutic potential of manganese porphyrin compounds in preventing sepsis-induced AKI. PMID:22011433

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-03-01

    Takotsubo cardiomyopathy consists of a transient dysfunction of the left ventricle. It is characterised by an impaired left ventricular segmentary contractility, without significant coronary lesions in the coronary angiography. It usually occurs after an episode of physical or emotional stress. We present the case of a 70 year-old woman, who, in the postoperative period of an ankle osteosynthesis, developed a Takotsubo cardiomyopathy in the context of a sepsis caused by Staphylococcus aureus. She presented with acute lung oedema and a clinical picture of low cardiac output. The echocardiogram showed left ventricular medioapical akinesia. Coronary angiography was normal. She was treated with supportive measures with good progress. At 33 days from onset she was able to be discharged from hospital to home with normal systolic function on echocardiography. PMID:23664218

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Arzanlou, Mohsen

    2016-04-01

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

  8. Paraoxonase 1 Activity and Survival in Sepsis Patients

    PubMed Central

    ?nal, Volkan; Yamanel, Levent; Ta?k?n, Grhan; Tapan, Serkan; Cmert, Bilgin

    2015-01-01

    Background: Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High density lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous studies suggested a possible role of decreased PON1 activity or HDL levels in sepsis patients. Aims: The present study was designed to test a hypothesis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. Study Design: Observational study. Methods: Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 activity and cytokine assays (TNF-? and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28th day for any cause intra-hospital mortality. Data were statistically analyzed for effects of study parameters on patients survival. Results: In total, 85 patients with sepsis were included in the study. The mean age was 65.217.9 years and 48 were male; at the end of the 28-day follow-up period, 46 survived. TNF-? (86.910.5 vs 118.616.4) and IL-6 levels (906.782.7 vs 1323.154.3) were significantly higher in non-survivors, while PON1 activity (140.742.3 vs 66.746.6) and HDL-cholesterol levels (43.68.1 vs 34.58.9) were significantly higher in survivors (p<0.001 for all). TNF-? (r=?0.763) and IL-6 levels (r=?0.947) showed strong negative correlations, PON1 activity (r=0.644) and HDL-cholesterol levels (r=0.477) showed positive correlations with patient survival (p<0.001 for all). Survival estimates significantly favored TNF-? (Log Rank 59.5, p<0.001) and IL-6 levels (Log Rank 53.2, p<0.001) according to PON1 activity (Log Rank 5.4, p<0.03) and HDL-cholesterol levels (Log Rank 8.3, p<0.005). Regression analyses for relative contributions of parameters to survival showed that higher IL-6 levels (t: ?16.489, p<0.001) were the most significant negative factor for survival, and TNF-? levels (t: ?4.417, p<0.001), whereas PON1 activity had a positive effect (t:3.210, p<0.003). Conclusion: The present study showed that although low PON1 activity and HDL-cholesterol levels were related to mortality, higher levels were not found to be as predictive as cytokine levels for survival. PMID:26167343

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2013-01-01

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

  11. Improving Outcomes in Patients With Sepsis.

    PubMed

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

    2016-01-01

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

  12. Right heart ischemia in cases of sepsis.

    PubMed

    Fracasso, T; Jentgens, L; Pfeiffer, H; Sauerland, C; Mangin, P; Schmeling, A

    2016-02-01

    Data from the literature suggest that cases of sepsis complicated by right ventricular (RV) dysfunction have poorer prognosis. In these cases progressive hypoperfusion associated to increasing, injury-related, pulmonary vascular resistance account for RV ischemia. In the present analysis, we wanted to evaluate whether prevalent RV cardiac ischemic damage could be detected in a series of fatal sepsis cases. We retrospectively investigated 20 cases of sepsis that underwent forensic autopsy (study group-11?, 9?, mean age 57 years) and compared them to a group of 20 cases of hanging (hanging group-4 ?, 16 ?, mean age 44 years) as well as to a group of 20 cases of myocardial infarction (MI group-9 ?, 11 ?, mean age 65 years), as examples of cardiac damage due to global hypoxia during agony and ischemic damage, respectively. We performed immunohistochemistry with the antibodies anti-fibronectin and C5b-9. The reactions were semiquantitively classified and the groups were compared. In 30% of the cases of sepsis prevalent RV ischemic damage could be detected with the antibody anti-fibronectin. This expression was significantly different from that observed in cases of MI (p=0.028) and hanging (p<0.001). Our study showed that, in cases of fatal sepsis, prevalent RV ischemic damage occurred in a substantial minority of cases. PMID:26773220

  13. PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections--an uncommon, but important indication for tonsillectomy.

    PubMed

    Heubi, Christine; Shott, Sally R

    2003-08-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, also know as "PANDAS," is well described in the neurologic and psychiatric literature. PANDAS is associated with obsessive compulsive disorders (OCD) and tic disorders. The streptococcal infections may trigger an autoimmune reaction that exacerbates these conditions. Recurrent streptococcal tonsillitis is one of the recurrent infections associated with PANDAS. This paper reviews the case reports of two brothers, one with OCD and the other with a tic disorder, both of whom improved significantly after undergoing adenotonsillectomy for treatment of their recurrent tonsillitis. A review of the pathophysiology and current understanding of PANDAS is presented. PMID:12880661

  14. Vigilant keratinocytes trigger pathogen-associated molecular pattern signaling in response to streptococcal M1 protein.

    PubMed

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

    2015-12-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    PubMed Central

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

    1992-01-01

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

  17. Severe invasive streptococcal infection by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.

    PubMed

    Watanabe, Shinya; Takemoto, Norihiko; Ogura, Kohei; Miyoshi-Akiyama, Tohru

    2016-01-01

    Streptococcus pyogenes, a group A Streptococcus (GAS), has been recognized as the causative pathogen in patients with severe invasive streptococcal infection with or without necrotizing fasciitis. In recent epidemiological studies, Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been isolated from severe invasive streptococcal infection. Complete genome sequence showed that SDSE is the closest bacterial species to GAS, with approximately 70% of genome coverage. SDSE, however, lacks several key virulence factors present in GAS, such as SPE-B, the hyaluronan synthesis operon and active superantigen against human immune cells. A key event in the ability of GAS to cause severe invasive streptococcal infection was shown to be the acquisition of novel genetic traits such as phages. Strikingly, however, during severe invasive infection, GAS destroys its own covRS two-component system, which negatively regulates many virulence factor genes, resulting in a hyper-virulent phenotype. In contrast, this phenomenon has not been observed in SDSE. The present review describes the epidemiology of severe invasive streptococcal infection and the detailed pathogenic mechanisms of GAS and SDSE, emphasizing findings from their genome sequences and analyses of gene expression. PMID:26762200

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

    PubMed Central

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

    2016-01-01

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

  19. [Acute rheumatic fever, Sydenham's chorea and psychopathology].

    PubMed

    Gimzal, Aylan; Topuo?lu, Volkan; Yazgan, M Yanki

    2002-01-01

    Acute rheumatic fever (ARF) is an autoimmune disorder that is triggered by group A beta-hemolytic streptococcal infections. ARF consists of several combinations of carditis, polyarthritis and Sydenham's chorea, and rarely seen erythema marginatum and subcutaneous nodules. Sydenham's chorea is seen in about 20% of patients with ARF. As a late symptom of ARF, Sydenham's chorea usually occurs 3 months or longer after the streptococcal infection. Sydenham's chorea is a neuropsychiatric disorder that may present with emotional lability, anxiety, obsessive compulsive symptoms, attention deficit and hyperactivity symptoms or tics. Obsessive-compulsive symptoms occur in 70% of patients with Sydenham's chorea. The role of the autoimmune mechanisms and the dysfunction of the basal ganglia have been demonstrated in Sydenham's chorea. Antibodies against group A beta-hemolytic streptococcus cross-react with basal ganglia. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) shares the same mechanism with Sydenham's chorea, but PANDAS has not been shown to require penicillin prophylaxis. Thus it is important to distinguish between them. Sydenham's chorea is associated with adulthood OCD, Tourette syndrome and schizophrenia. These features make Sydenham's chorea an explanatory model for obsessive-compulsive disorder (OCD) and related disorders. This poststreptococcal disorder provides a treatment opportunity with new therapies like antibiotic therapy, plasma exchange and intravenous immunoglobulin therapy for psychiatric disorders. In this paper we summarize the phenomenological and treatment studies of OCD, attention deficit and hyperactivity disorder (ADHD), and tic disorders in subjects with ARF, with or without Sydenham's chorea. PMID:12794666

  20. Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room

    PubMed Central

    Kauppi, Anna M.; Edin, Alicia; Ziegler, Ingrid; Mölling, Paula; Sjöstedt, Anders; Gylfe, Åsa; Strålin, Kristoffer; Johansson, Anders

    2016-01-01

    A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69–0.99) and a specificity 0.84 (95% CI 0.58–0.94) with an AUC of 0.93 (95% CI 0.89–1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85–1.00) and specificity of 0.95 (95% CI 0.74–0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics. PMID:26800189

  1. Group B streptococcal meningitis in a previously healthy man.

    PubMed

    Li, Lucy Qian; Cheema, Sanjay; Goel, Nupur

    2016-01-01

    Group B Streptococcus (GBS) is an infrequent cause of meningitis in adults, usually affecting elderly patients and those with serious underlying disease. It is more commonly recognised as one of the leading aetiological agents of neonatal sepsis following maternally derived infection during pregnancy. We report a case of a previously healthy 26-year-old man who presented with fevers, confusion and headache. Lumbar puncture results were consistent with bacterial meningitis, and blood cultures grew GBS. To the best of our knowledge, our patient represents one of the few reported cases of GBS meningitis in a previously healthy young man. Interestingly, our patient had a significant family history of central nervous system infection including a son with herpes simplex virus encephalitis, a sister with meningococcal meningitis and a great-uncle with meningitis of unknown cause. We discuss genetic factors that may predispose certain people to develop meningitis with normally harmless microorganisms such as GBS. PMID:26759446

  2. Anticoagulant modulation of inflammation in severe sepsis.

    PubMed

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

    2015-05-01

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

  3. 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

  4. Sepsis guidelines: Suggestions to improve adherence.

    PubMed

    Kissoon, Niranjan

    2015-06-01

    The context in which a sepsis guideline is to be used is important and to a large extent determines whether it will be implemented successfully. Factors such as lack of time and resources, lack of reimbursement and organizational constraints may also preclude adoption of guidelines. Thus, sepsis guidelines have been adapted to suit the resources in both resource rich and poor regions of the world. However, even when resources are present, physicians' may not follow guidelines due a myriad of reasons including a lack of agreement with the sepsis guideline or with guidelines in general, as well as lack of motivation and expectations of the desired outcomes. A holistic approach is necessary to address all issues that may be impediments to guideline adoption and adherence. This approach would include a rigorous transparent method to craft the guideline, which includes both clinicians and policy makers and addresses cultural and resource issues. PMID:25917797

  5. 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

  6. Clinical review: The liver in sepsis

    PubMed Central

    2012-01-01

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

  7. Is There NO Treatment For Severe Sepsis?

    PubMed

    As, Bredan; A, Cauwels

    2008-01-01

    Sepsis is a systemic inflammatory response syndrome in the presence of suspected or proven infection, and it may progress to or encompass organ failure (severe sepsis) and hypotension (septic shock). Clinicians possess an arsenal of supportive measures to combat severe sepsis and septic shock, and some success, albeit controversial, has been achieved by using low doses of corticosteroids or recombinant human activated protein C. However, a truly effective mediator-directed specific treatment has not been developed yet. Treatment with low doses of corticosteroids or with recombinant human activated protein C remains controversial and its success very limited. Attempts to treat shock by blocking LPS, TNF or IL-1 were unsuccessful, as were attempts to use interferon-gamma or granulocyte colony stimulating factor. Inhibiting nitric oxide synthases held promise but met with considerable difficulties. Scavenging excess nitric oxide or targeting molecules downstream of inducible nitric oxide synthase, such as soluble guanylate cyclase or potassium channels, might offer other alternatives. PMID:21499479

  8. Molecular mechanisms in the pathogenesis of sepsis.

    PubMed

    Pop-Began, V; Păunescu, V; Grigorean, V; Pop-Began, D; Popescu, C

    2014-01-01

    Innate immune system is a universal form of host defense against infections. The recognition of the innate immunity is based on a limited number of encoded receptors that have evolved to recognize microbial metabolism products. The recognition of these molecular structures allows the immune system to distinguish its own infectious components from non-communicable structures. The immune suppression is a hallmark of sepsis. The complement system is activated in the early stages of sepsis, generating large amounts of anaphylatoxin C5a. Complement and TLRs (toll-like receptors) family are two major upstream sensors and effectors systems of innate immunity. It was found that TLR4 and complement system are involved in the initiation of the inflammatory response in sepsis. Clinical studies in which TLR4 was blocked have not shown beneficial effects. TLRs, that are a subfamily of PRRs (pattern recognition receptors), have emerged as the crucial receptors for the recognition of DAMPs (Damage-associated molecular pattern molecules). Recently, a special form of non-coding genetic material called microRNA has been highlighted in the complex cascade of sepsis. The individual role of every microRNA and the exact role of microRNA network are under investigation. Currently, studies are performed in order to find micro RNA to be used as biomarkers of sepsis. Researches are performed to determine microRNA, small fragments of non-coding RNA, in order to distinguish between patients with sepsis and healthy patients, and if the plasma levels of microRNA correlate with the severity of the disease. Recent researches report that the regulation of gene expression through microRNA plays a very important role in the following cellular processes, for example: apoptosis, the differentiation process, and the cell cycle. PMID:25870671

  9. Current concept of abdominal sepsis: WSES position paper

    PubMed Central

    2014-01-01

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

  10. Fluid Resuscitation in Sepsis: Reexamining the Paradigm

    PubMed Central

    Tirupakuzhi Vijayaraghavan, Bharath Kumar; Cove, Matthew Edward

    2014-01-01

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

  11. Fatal Yersinia enterocolitica sepsis after blood transfusion.

    PubMed

    Wright, D C; Selss, I F; Vinton, K J; Pierce, R N

    1985-11-01

    A patient with fatal Yersinia enterocolitica sepsis was seen recently in our intensive care unit. The patient had received two units of packed red blood cells during a surgical procedure. Cultures of the donor blood yielded Y enterocolitica, and a whole-organism enzyme-linked immunosorbent assay of the donors' sera suggested a recent infection with Y enterocolitica in an asymptomatic donor. Though rare, Y enterocolitica, which can grow at the cold temperatures of refrigerated blood, should be considered as a possible source of sepsis following blood transfusion. PMID:3840356

  12. Hepatosplanchnic circulation in cirrhosis and sepsis

    PubMed Central

    Prin, Meghan; Bakker, Jan; Wagener, Gebhard

    2015-01-01

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

  13. 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

  14. Intra-abdominal sepsis after hepatic resection.

    PubMed Central

    Pace, R F; Blenkharn, J I; Edwards, W J; Orloff, M; Blumgart, L H; Benjamin, I S

    1989-01-01

    One hundred and thirty hepatic resections performed over an 8-year period were reviewed for evidence of postoperative intra-abdominal sepsis. Of 126 patients who survived for more than 24 hours after operation, 36 developed culture positive intra-abdominal collections (28.6%). Significant independent variables associated with the development of intra-abdominal sepsis were diagnoses of trauma or cholangiocarcinoma, and the need for reoperation to control hemorrhage during the postoperative period. Before 1984, infected fluid collections were treated predominantly by operative drainage, but this has largely been replaced by percutaneous methods, which have proven effective in most cases. Eighteen (50%) of the infections were caused by a mixed bacterial culture, with Streptococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus and Escherichia coli being the most common isolates. Six patients with clinical signs of sepsis had a sterile fluid collection drained with complete relief of symptoms. This review suggests that intra-abdominal sepsis is a frequent complication after hepatic resection, and can often be managed successfully by nonoperative percutaneous drainage. PMID:2493775

  15. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePLUS

    ... first an infection (such as pneumonia or a urinary tract infection) and then a powerful and harmful response by ... University of Pittsburgh School of Medicine. In the case of severe sepsis, that ... and costly approaches. The study helped to clarify that a lot of the ...

  16. [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

  17. Leclercia adecarboxylata Sepsis and Cerebral Herniation.

    PubMed

    Sethi, Karen; Barker, Eric M; Metlay, Leon A; Caserta, Mary T; Daugherty, Louis Eugene

    2014-03-01

    Leclercia adecarboxylata, a gram-negative bacillus of the Enterobacteriaceae family, is rarely identified as a pathogen in humans. We describe a fatal case of L adecarboxylata sepsis in a child. This is the first reported pediatric death associated with infection due to L adecarboxylata. PMID:26624912

  18. Several Cytokines and Protein C Levels with the Apache II Scoring System for Evaluation of Patients with Sepsis

    PubMed Central

    Kartal, Elif Doyuk; Karka, Emine; Glba?, Zafer; Alpat, Sayg?n Nayman; Erben, Nurettin; olak, Ertu?rul

    2012-01-01

    Objective: We investigated whether determination IL-6, IL-8, IL-1beta and TNF-alpha at baseline, total protein C (PC) levels at time of admission and 48 hours after initiation could complement the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system to identify patients with sepsis, severe sepsis or septic shock for clinical outcome. Material and Methods: The study was carried out prospectively. 60 consecutive patients with sepsis, severe sepsis or septic shock were included. Blood samples were obtained at baseline and 48 hours after initiation. Cytokines and PC levels in plasma were measured with an enzyme-linked immunoabsorbent assay (ELISA). APACHE II score was calculated on admission. Results: Baseline IL-6 levels and PC levels 48 hours after initiation were predictive of increased mortality (p=0.016, p=0.044 respectively). Baseline IL-6, IL-8 and TNF-alpha baseline levels correlate with the severity of physiologic insult, as determined by the APACHE II score. However, our multiple logistic regression analysis of these did not reveal any predictive value in combination with the APACHE II score. Conclusion: Determination of baseline IL-6 and PC 48 hours after initiation were of predictive value for prognostic evaluation of septic patients, but did not significantly increase predictive power of the APACHE scoring system to identify patients with sepsis for fatal clinical outcome. PMID:25206990

  19. The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.

    PubMed

    Michels, Monique; Vieira, Andriele S; Vuolo, Francieli; Zapelini, Hugo Galvane; Mendonça, Bruna; Mina, Francielle; Dominguini, Diogo; Steckert, Amanda; Schuck, Patrícia Fernanda; Quevedo, João; Petronilho, Fabrícia; Dal-Pizzol, Felipe

    2015-01-01

    Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 μg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors. PMID:25019583

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

    PubMed Central

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

    2016-01-01

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

  1. Objective Sepsis Surveillance Using Electronic Clinical Data.

    PubMed

    Rhee, Chanu; Kadri, Sameer; Huang, Susan S; Murphy, Michael V; Li, Lingling; Platt, Richard; Klompas, Michael

    2016-02-01

    OBJECTIVE To compare the accuracy of surveillance of severe sepsis using electronic health record clinical data vs claims and to compare incidence and mortality trends using both methods. DESIGN We created an electronic health record-based surveillance definition for severe sepsis using clinical indicators of infection (blood culture and antibiotic orders) and concurrent organ dysfunction (vasopressors, mechanical ventilation, and/or abnormal laboratory values). We reviewed 1,000 randomly selected medical charts to characterize the definition's accuracy and stability over time compared with a claims-based definition requiring infection and organ dysfunction codes. We compared incidence and mortality trends from 2003-2012 using both methods. SETTING Two US academic hospitals. PATIENTS Adult inpatients. RESULTS The electronic health record-based clinical surveillance definition had stable and high sensitivity over time (77% in 2003-2009 vs 80% in 2012, P=.58) whereas the sensitivity of claims increased (52% in 2003-2009 vs 67% in 2012, P=.02). Positive predictive values for claims and clinical surveillance definitions were comparable (55% vs 53%, P=.65) and stable over time. From 2003 to 2012, severe sepsis incidence imputed from claims rose by 72% (95% CI, 57%-88%) and absolute mortality declined by 5.4% (95% CI, 4.6%-6.7%). In contrast, incidence using the clinical surveillance definition increased by 7.7% (95% CI, -1.1% to 17%) and mortality declined by 1.7% (95% CI, 1.1%-2.3%). CONCLUSIONS Sepsis surveillance using clinical data is more sensitive and more stable over time compared with claims and can be done electronically. This may enable more reliable estimates of sepsis burden and trends. Infect. Control Hosp. Epidemiol. 2016;37(2):163-171. PMID:26526737

  2. Abdominal sepsis managed by leaving abdomen open.

    PubMed

    Duff, J H; Moffat, J

    1981-10-01

    Intra-abdominal sepsis and necrotizing infection of the abdominal wall are usually fatal unless adequate drainage and wide debridement are possible. To follow these principles, we managed 18 seriously ill patients with abdominal sepsis by leaving the abdomen completely open. All except two of the patients had severe intra-abdominal sepsis. Eight patients had full-thickness wound infections and intra-abdominal infections refractory to the usual surgical drainage techniques. Two had necrotizing wound infections only. In 12 an upper abdominal incision was managed open, and in six the open incision was lower. As part of the initiating illness, there were eight small bowel and six colon fistulas. They were managed by colostomy in five patients and ileostomy in two. More than one organism was cultured in all patients and 12 of 18 had a positive blood culture. Respiratory failure made mechanical ventilation necessary in 13 patients for an average of 44 days. Previous adhesions, usually present, or an intact greater omentum, were necessary to prevent bowel evisceration, but three patients required paralysis and mechanical ventilation until adhesions became strong enough to prevent evisceration. There were seven deaths (39%), six caused by continuing sepsis and one from hemorrhage. In those surviving, granulation tissue grew over omentum or bowel loops to eventually seal the abdominal cavity. The late management was split-skin grafting in five and secondary closure in two. Four healed by second intention. We conclude that leaving the abdomen completely open facilitates the widest possible drainage, uncompromising debridement of the abdominal wall, and is compatible with good recovery. The ultimate result in survivors is acceptable. This technique is preferable to closing an abdominal wall of questionable viability in the face of intraperitoneal sepsis. PMID:6456563

  3. Objective Sepsis Surveillance Using Electronic Clinical Data

    PubMed Central

    Rhee, Chanu; Kadri, Sameer; Huang, Susan S.; Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael

    2016-01-01

    OBJECTIVE To compare the accuracy of surveillance of severe sepsis using electronic health record clinical data vs claims and to compare incidence and mortality trends using both methods. DESIGN We created an electronic health recordbased surveillance definition for severe sepsis using clinical indicators of infection (blood culture and antibiotic orders) and concurrent organ dysfunction (vasopressors, mechanical ventilation, and/or abnormal laboratory values). We reviewed 1,000 randomly selected medical charts to characterize the definitions accuracy and stability over time compared with a claims-based definition requiring infection and organ dysfunction codes. We compared incidence and mortality trends from 20032012 using both methods. SETTING Two US academic hospitals. PATIENTS Adult inpatients. RESULTS The electronic health recordbased clinical surveillance definition had stable and high sensitivity over time (77% in 20032009 vs 80% in 2012, P=.58) whereas the sensitivity of claims increased (52% in 20032009 vs 67% in 2012, P=.02). Positive predictive values for claims and clinical surveillance definitions were comparable (55% vs 53%, P=.65) and stable over time. From 2003 to 2012, severe sepsis incidence imputed from claims rose by 72% (95% CI, 57%88%) and absolute mortality declined by 5.4% (95% CI, 4.6%6.7%). In contrast, incidence using the clinical surveillance definition increased by 7.7% (95% CI, ?1.1% to 17%) and mortality declined by 1.7% (95% CI, 1.1%2.3%). CONCLUSIONS Sepsis surveillance using clinical data is more sensitive and more stable over time compared with claims and can be done electronically. This may enable more reliable estimates of sepsis burden and trends. PMID:26526737

  4. 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. PMID:24698888

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

    PubMed

    Jeddi, Ramzi; Achour, Mriem; Amor, Ramzi Ben; Aissaoui, Lamia; Boutera, Walid; Kacem, Karima; Lakhal, Raihane Ben; Abid, Hla Ben; BelHadjAli, Zaher; Turki, Amel; Meddeb, Balkis

    2010-02-01

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

  6. Hypothyroidism abolishes the hyperdynamic phase and increases susceptibility to sepsis.

    PubMed

    Moley, J F; Ohkawa, M; Chaudry, I H; Clemens, M G; Baue, A E

    1984-03-01

    To evaluate the role of thyroid hormones in sepsis, 250-400 g rats were surgically thyroidectomized and 2-6 weeks later sepsis was produced by cecal ligation and puncture (CLP). In normal rats, total body O2 consumption (VO2) increased by 12.8% (P less than 0.05) in early sepsis (6 hr after CLP) and decreased slightly in late sepsis (16 hr after CLP). In hypothyroid (HT) rats, VO2 was depressed by 19.8% (P less than 0.05) in early sepsis and further decreased to 46.7% (P less than 0.001) of preoperative levels in late sepsis. Hepatic blood flow increased in early sepsis in normal rats but was unchanged in HT rats. The normal hyperglycemic response to early sepsis was also absent in HT rats. The respiratory control ratio (RCR) of isolated mitochondria with succinate was not increased in HT rats in early sepsis. In late sepsis, hypothyroid animals showed further decreases in VO2 and mitochondrial RCR, and, in contrast to normal rats, showed no change in blood glucose levels. Survival (5 days) following late sepsis in normal, HT, and HT rats given daily ip injections of thyroxine (30 micrograms/kg) were 65.2% (15/23), 30% (6/20) (P less than 0.025), and 77.1% (14/18), respectively. Thus, absence of thyroid hormone abolishes the hyperdynamic phase of sepsis and significantly increases mortality in sepsis, and thyroxine replacement following thyroidectomy prevents the increased mortality from sepsis. PMID:6700215

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

    Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection. PMID:25629609

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

    PubMed

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

    2015-11-01

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

  10. 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

  11. 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

  12. Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

    PubMed

    Pavone, P; Rapisarda, V; Serra, A; Nicita, F; Spalice, A; Parano, E; Rizzo, R; Maiolino, L; Di Mauro, P; Vitaliti, G; Coco, A; Falsaperla, A; Trifiletti, R R; Cocuzza, S

    2014-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS. PMID:25280028

  13. Lemierre's syndrome: two cases of postanginal sepsis.

    PubMed

    Lustig, L R; Cusick, B C; Cheung, S W; Lee, K C

    1995-06-01

    Lemierre's disease consists of suppurative thrombophlebitis of the IJV in the presence of oropharyngeal infection and can be complicated by septic pulmonary emboli. If a patient has an oropharyngeal or deep neck infection and neck pain suspicious for IJV thrombosis, a CT or MRI is warranted to establish the diagnosis. Blood cultures should be obtained to establish the responsible organism. In most cases F. necrophorum, an anaerobic bacterium, is responsible for the sepsis. Once the diagnosis of Lemierre's disease is made, long-term, high-dose intravenous antibiotics with beta-lactamase anaerobic activity should be initiated. In cases with persistent sepsis and emboli despite appropriate medical management, ligation or excision of the IJV should be performed. Finally, if there is clinical or radiologic evidence of retrograde cavernous sinus thrombosis, the use of anticoagulants should be considered. PMID:7777368

  14. Emergency department antimicrobial considerations in severe sepsis.

    PubMed

    Green, Robert S; Gorman, Sean K

    2014-11-01

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

  15. 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

  16. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gmez, Alonso; Murray, Patrick; Gmez, 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

  17. Management of perianal sepsis in immunosuppressed patients.

    PubMed

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

    2001-05-01

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

  18. Designing a Pediatric Severe Sepsis Screening Tool

    PubMed Central

    Sepanski, Robert J.; Godambe, Sandip A.; Mangum, Christopher D.; Bovat, Christine S.; Zaritsky, Arno L.; Shah, Samir H.

    2014-01-01

    We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). Gold standard SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2?months. The tools identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tools predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3?years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an early or late indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tools positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower. PMID:24982852

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

    PubMed

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

    2013-05-01

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

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

    PubMed

    Maslove, David M; Wong, Hector R

    2014-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Weeks, C R; Ferretti, J J

    1984-01-01

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

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

    PubMed Central

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

    2015-01-01

    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. PMID:24754535

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

    PubMed Central

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

    2012-01-01

    Background The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. Objective This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. Methods Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. Results Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.8450.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. Conclusions Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care. Trial Registration ClinicalTrials.gov NCT01568853 PMID:23091606

  5. Autophagy and Skeletal Muscles in Sepsis

    PubMed Central

    Mofarrahi, Mahroo; Sigala, Ioanna; Guo, Yeting; Godin, Richard; Davis, Elaine C.; Petrof, Basil; Sandri, Marco

    2012-01-01

    Background Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles. Methodology/Principal Findings Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca++ retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific I?B? superrepresor. Conclusion/Significance We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis and increased autophagy compared with the ventilatory muscles and that autophagy in skeletal muscles during sepsis is regulated in part through the NF?B transcription factor. PMID:23056618

  6. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium

    PubMed Central

    2012-01-01

    Introduction Sepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis. Methods Cerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was measured daily during the first 4 days of sepsis. Diagnosis of a SAD was performed using the confusion assessment method for ICU (CAM-ICU) and, furthermore the predominant brain electrical activity in electroencephalogram (EEG) both at day 4 after reduction of sedation to RASS >-2. Results 30 critically ill adult patients with severe sepsis or septic shock (APACHE II 32 6) were included. AR was impaired at day 1 in 60%, day 2 in 59%, day 3 in 41% and day 4 in 46% of patients; SAD detected by CAM-ICU was present in 76 % of patients. Impaired AR at day 1 was associated with the incidence of SAD at day 4 (p = 0.035). Conclusions AR is impaired in the great majority of patients with severe sepsis during the first two days. Impaired AR is associated with SAD, suggesting that dysfunction of AR is one of the trigger mechanisms contributing to the development of SAD. Trial registration clinicalTrials.gov ID NCT01029080 PMID:23036135

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    1993-01-01

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

  9. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

    PubMed Central

    Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

    2012-01-01

    Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Saraceni, Christine; Schwed-Lustgarten, Daniel

    2013-12-01

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

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

    PubMed Central

    Takeuchi, Muneyuki; Tachibana, Kazuya

    2015-01-01

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

  13. Public Awareness of Sepsis Is Low in Sweden.

    PubMed

    Mellhammar, Lisa; Christensson, Bertil; Linder, Adam

    2015-12-01

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

  14. Hemodynamic optimization of sepsis-induced tissue hypoperfusion

    PubMed Central

    2006-01-01

    Sepsis is associated with cardiovascular changes that may lead to development of tissue hypoperfusion. Early recognition of sepsis and tissue hypoperfusion is critical to implement appropriate hemodynamic support and prevent irreversible organ damage. End points for resuscitation need to be defined and invasive hemodynamic monitoring is usually required. Targets for hemodynamic optimization should include intravascular volume, blood pressure, and cardiac output. Therapeutic interventions aimed at optimizing hemodynamics in patients with sepsis include aggressive fluid resuscitation, the use of vasopressor agents, inotropic agents and in selected cases transfusions of blood products. This review will cover the most important aspects of hemodynamic optimization for treatment of sepsis induced tissue-hypoperfusion. PMID:17164014

  15. 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

  16. Public Awareness of Sepsis Is Low in Sweden

    PubMed Central

    Mellhammar, Lisa; Christensson, Bertil; Linder, Adam

    2015-01-01

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

  17. 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

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

    PubMed Central

    Prescott, Hallie C.; Chang, Virginia W.; OBrien, James M.; Langa, Kenneth M.; Iwashyna, Theodore

    2014-01-01

    Objectives While critical care physicians view obesity as an independent poor prognostic marker, growing evidence suggests that obesity is, instead, associated with improved mortality following ICU admission. However, this prior empirical work may be biased by preferential admission of obese patients to ICUs, and little is known about other patient-centered outcomes following critical illness. We sought to determine whether one-year mortality, health care utilization, and functional outcomes following a severe sepsis hospitalization differ by BMI. Design Observational cohort study. Patients We analyzed 1,404 severe sepsis hospitalizations (19992005) among Medicare beneficiaries enrolled in the nationally representative Health & Retirement Study, of which 597 (42.5%) were normal weight, 473 (33.7%) were overweight, and 334 (23.8%) were obese or severely obese, as assessed at their survey prior to acute illness. Underweight patients were excluded a priori. Interventions None. Measurements and Main Results Using Medicare claims, we identified severe sepsis hospitalizations and measured inpatient health care facility use and calculated total and itemized Medicare spending in the year following hospital discharge. Using the National Death Index, we determined mortality. We ascertained pre- and post-morbid functional status from survey data. Patients with greater BMIs experienced higher 1-year mortality compared to non-obese patients, and there was a dose response relationship such that obese (OR=0.59, 95%CI 0.39, 0.88) and severely obese patients (OR=0.46, 95%CI 0.26, 0.80) had the lowest mortality. Total days in a health care facility and Medicare expenditures were greater for obese patients (p<0.01 for both comparisons), but average daily utilization (p=0.44) and Medicare spending were similar (p=0.65) among normal, overweight and obese survivors. Total function limitations following severe sepsis did not differ by BMI category (p=0.64). Conclusions Obesity is associated with improved mortality among severe sepsis patients. Due to longer survival, obese sepsis survivors use more health care and result in higher Medicare spending in the year following hospitalization. Median daily health care utilization was similar across BMI categories. PMID:24717466

  19. Redox regulation of mitophagy in the lung during murine S. aureus sepsis

    PubMed Central

    Chang, Alan L.; Ulrich, Allison; Suliman, Hagir B.; Piantadosi, Claude A.

    2014-01-01

    Background Oxidative mitochondrial damage is closely linked to inflammation and to cell death, but low levels of reactive oxygen and nitrogen species serve as signals that involve mitochondrial repair and resolution of inflammation. More specifically, cytoprotection relies on the elimination of damaged mitochondria by selective autophagy (mitophagy) during mitochondrial quality control. Objective To identify and localize mitophagy in mouse lung as a potentially up-regulatable redox response to S. aureus sepsis. Methods Anesthetized C57BL/6 and B6.129X1-Nfe2l2tm1Ywk/J (Nrf2−/−) mice had fibrin clots loaded with S. aureus (1×107 CFU) implanted abdominally. At the time of implantation, mice were given Vancomycin (6mg/kg) and fluid resuscitation. Mouse lungs were harvested at 0, 6, 24, and 48 hours for bronchoalveolar lavage (BAL), Western blot analysis and qRT-PCR. To localize mitochondria with autophagy protein LC3, we used lung immunofluorescence staining in LC3-GFP transgenic mice. Results In C57BL/6 mice, sepsis-induced pulmonary inflammation was detected by significant increases in mRNA for the inflammatory markers IL-1β and TNF-α at 6h and 24h respectively hours. BAL cell count and protein increased. Sepsis suppressed lung Beclin-1 protein, but not mRNA, suggesting activation of canonical autophagy. Notably sepsis also increased the LC3-II autophagosome marker, as well as the lung’s non-canonical autophagy pathway as evidenced by loss of p62, a redox-regulated scaffolding protein of the autophagosome. In LC3-GFP mice lungs, immunofluorescence staining showed co-localization of LC3-II to mitochondria, mainly in Type 2 epithelium and alveolar macrophages. In contrast, marked accumulation of p62, as well as attenuation of LC3-II in Nrf2 KO mice supported an overall decrease in autophagic turnover. Conclusions The down-regulation of canonical autophagy during sepsis may contribute to lung inflammation while the switch to non-canonical autophagy selectively removes damaged mitochondria and accompanies tissue repair and cell survival. Furthermore, mitophagy in the alveolar region appears to depend on activation of Nrf2. Thus, efforts to promote mitophagy may be a useful therapeutic adjunct for acute lung injury in sepsis. PMID:25450328

  20. Redox regulation of mitophagy in the lung during murine Staphylococcus aureus sepsis.

    PubMed

    Chang, Alan L; Ulrich, Allison; Suliman, Hagir B; Piantadosi, Claude A

    2015-01-01

    Oxidative mitochondrial damage is closely linked to inflammation and cell death, but low levels of reactive oxygen and nitrogen species serve as signals that involve mitochondrial repair and resolution of inflammation. More specifically, cytoprotection relies on the elimination of damaged mitochondria by selective autophagy (mitophagy) during mitochondrial quality control. This aim of this study was to identify and localize mitophagy in the mouse lung as a potentially upregulatable redox response to Staphylococcus aureus sepsis. Fibrin clots loaded with S. aureus (110(7) CFU) were implanted abdominally into anesthetized C57BL/6 and B6.129X1-Nfe2l2tm1Ywk/J (Nrf2(-/-)) mice. At the time of implantation, mice were given vancomycin (6mg/kg) and fluid resuscitation. Mouse lungs were harvested at 0, 6, 24, and 48h for bronchoalveolar lavage (BAL), Western blot analysis, and qRT-PCR. To localize mitochondria with autophagy protein LC3, we used lung immunofluorescence staining in LC3-GFP transgenic mice. In C57BL/6 mice, sepsis-induced pulmonary inflammation was detected by significant increases in mRNA for the inflammatory markers IL-1? and TNF-? at 6 and 24h, respectively. BAL cell count and protein also increased. Sepsis suppressed lung Beclin-1 protein, but not mRNA, suggesting activation of canonical autophagy. Notably sepsis also increased the LC3-II autophagosome marker, as well as the lung?s noncanonical autophagy pathway as evidenced by loss of p62, a redox-regulated scaffolding protein of the autophagosome. In LC3-GFP mouse lungs, immunofluorescence staining showed colocalization of LC3-II to mitochondria, mainly in type 2 epithelium and alveolar macrophages. In contrast, marked accumulation of p62, as well as attenuation of LC3-II in Nrf2-knockout mice supported an overall decrease in autophagic turnover. The downregulation of canonical autophagy during sepsis may contribute to lung inflammation, whereas the switch to noncanonical autophagy selectively removes damaged mitochondria and accompanies tissue repair and cell survival. Furthermore, mitophagy in the alveolar region appears to depend on activation of Nrf2. Thus, efforts to promote mitophagy may be a useful therapeutic adjunct for acute lung injury in sepsis. PMID:25450328

  1. Regulation of IL-17 Family Members by Adrenal Hormones During Experimental Sepsis in Mice

    PubMed Central

    Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D.; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

    2014-01-01

    Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. PMID:23499051

  2. Milk Fat Globule-EGF Factor VIII in Sepsis and Ischemia-Reperfusion Injury

    PubMed Central

    Matsuda, Akihisa; Jacob, Asha; Wu, Rongqian; Zhou, Mian; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

    2011-01-01

    Sepsis and ischemia-reperfusion (I/R) injury are among the leading causes of death in critically ill patients at the surgical intensive care unit setting. Both conditions are marked by the excessive inflammatory response which leads to a lethal disease complex such as acute lung injury, systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Despite the advances in the understanding of the pathophysiology of those conditions, very little progress has been made toward therapeutic interventions. One of the key aspects of these conditions is the accumulation of apoptotic cells that have the potential to release toxic and proinflammatory contents due to secondary necrosis without appropriate clearance by phagocytes. Along with the prevention of apoptosis, that is reported to be beneficial in sepsis and I/R injury, thwarting the development of secondary necrosis through the active removal of apoptotic cells via phagocytosis may offer a novel therapy. Milk fat globule-EGF factor VIII (MFG-E8), which is mainly produced by macrophages and dendritic cells, is an opsonin for apoptotic cells and acts as a bridging protein between apoptotic cells and phagocytes. Recently, we have shown that MFG-E8 expression is decreased in experimental sepsis and I/R injury models. Exogenous administration of MFG-E8 attenuated the inflammatory response as well as tissue injury and mortality through the promotion of phagocytosis of apoptotic cells. In this review, we describe novel information available about the involvement of MFG-E8 in the pathophysiology of sepsis and I/R injury, and the therapeutic potential of exogenous MFG-E8 treatment for those conditions. PMID:20882259

  3. Efficacy of traditional Chinese medicine on sepsis: a systematic review and Meta-Analysis

    PubMed Central

    Liang, Xiao; Zhou, Miao; Ge, Xin-Yu; Li, Cheng-Bao; Fang, Shang-Ping; Tang, Ling; Shao, Dong-Hua; Xu, Guo

    2015-01-01

    Background: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. Methods: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. Results: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU-stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = -0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-? [SMD = -0.61; 95% CI: -0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. Conclusion: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion. PMID:26884914

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

    PubMed

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

    2015-01-01

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

  5. 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

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

    PubMed Central

    Houston, C W; Ferretti, J J

    1981-01-01

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

  7. [Pathophysiological basis of surgery-linked sepsis].

    PubMed

    Vollmar, B

    2011-03-01

    Infection or injury, including surgical procedures, induces an inflammatory response of the host organism. This immune response must be finely tuned and precisely regulated, because deficiencies or excesses of the inflammatory response cause morbidity and shorten the lifespan. Activated receptors of the innate immune system (pattern recognition receptors, PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) including injured tissue-associated intracellular proteins (alarmins), lead to an exaggerated immune response. This is characterized by a complex interplay of cytokines, chemokines, complement and coagulation factors as well as inflammatory and immune regulatory cells. There is increasing recognition that the major pathophysiologic event in sepsis is the progression from the initial hyperinflammatory state to an immunosuppressive state in which the host is unable to eradicate invading pathogens and particularly prone to develop secondary nosocomial infections and organ damage. Surgical trauma-associated immune dysfunction per se predisposes the host to surgery-related sepsis. Immune suppression is mediated by massive apoptosis-induced depletion of lymphocytes and dendritic cells, decreased expression of the cell surface antigen complex HLA-DR and increased expression of negative costimulatory molecules. Besides increased numbers of regulatory T cells there is a shift from a phenotype of inflammatory Th1 cells to an antiinflammatory phenotype of Th2 cells characterized by the production of interleukin-10. Key mediators of sepsis are HMGB1, MIF and complement factor C5a. With the identification of central pathomechanistic events, e.g. amplification of the coagulation, complement and inflammation cascades, immune dysbalance and neuroimmunomodulation via the cholinergic anti-inflammatory reflex, the opportunity now exists to apply these insights to the development of new and novel therapeutics aimed at modulating rather than inhibiting the systemic host response to infection. PMID:21249327

  8. Consistency and pathophysiological characterization of a rat polymicrobial sepsis model via the improved cecal ligation and puncture surgery.

    PubMed

    Liu, Xin; Wang, Ning; Wei, Guo; Fan, Shijun; Lu, Yongling; Zhu, Yuanfeng; Chen, Qian; Huang, Min; Zhou, Hong; Zheng, Jiang

    2016-03-01

    Sepsis is the leading cause of death for critical ill patients and an essential focus in immunopharmacological research. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study. However, this animal model is easily affected by variability problems and dramatically affects pharmacological evaluation of anti-sepsis therapies, which requires standardized procedures and stable outcomes. Herein, the traditional syringe needle based puncture method was used as the major unstable factor for CLP models. Syringe needles created varied mortality in parallel experimental groups of CLP rats; they were inconsistent for severity control as mortality in CLP rats was not correlated with change in punctures, ligation lengths, or needle sizes. Moreover, the use of drainage tubes or strips, which was supposed to strengthen drainage stability, also failed to improve consistency of traditional syringe needles. To solve the consistency problem, an improved design of CLP surgery by puncture with newly-developed three-edged needles was described herein. In contrast to traditional syringe needles, these three-edged needles ensured more stable outcomes in repetitive groups. Furthermore, increased severity was found to be consistent with the enlarged needle size, as shown by the elevated mortality, increased proinflammatory cytokines, abnormal coagulation, worsen acidosis and more severe acute lung injury. In conclusion, application of the newly-developed three-edged needles provides a simple and feasible method to improve stability when conducting CLP surgery, which is significant for pharmacological studies on sepsis. PMID:26802602

  9. MFHAS1 Is Associated with Sepsis and Stimulates TLR2/NF-κB Signaling Pathway Following Negative Regulation

    PubMed Central

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

    2015-01-01

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

  10. [The scientific, organizational and methodological bases for the epidemiological surveillance of streptococcal group A infection in a large city].

    PubMed

    Filatov, N N; Bruko, N I; Shakhanina, I L; Lytkina, I N; Serzhenko, S V; Kogan, K M; Zolotareva, G D; Dobrovol'skaia, Z M

    1998-01-01

    These investigations have made it possible to establish the extent and scale of the spread of streptococcal infection (group A) and its socioeconomic importance in Moscow, a great mega-police of the world. The deterioration of the epidemiological situation in recent years, accompanied by an increase in morbidity and mortality caused by streptococcal infection, has been demonstrated. The program and conceptual foundations of epidemiological surveillance on this infection in Moscow are presented. The aspects of epidemiological surveillance (informational and analytical, diagnostic, administrative) have been indicated and described. The order and direction of their realization have been determined. PMID:9532684

  11. Insurance type and sepsis-associated hospitalizations and sepsis-associated mortality among US adults: A retrospective cohort study

    PubMed Central

    2011-01-01

    Introduction Socio-demographic and clinical factors associated with increased sepsis risk, including older age, non-white race and specific co-morbidities, are more common among patients with Medicare or Medicaid or no health insurance. We hypothesized that patients with Medicare and/or Medicaid or without health insurance have a higher risk of sepsis-associated hospitalization or sepsis-associated death than those with private health insurance. Methods We performed a retrospective cohort study of records from the 2003 Nationwide Inpatient Sample. We stratified the study cohort by Medicare age-qualification (18 to 64 and 65+ years old). We examined the association between insurance category and sepsis diagnosis and death among admissions involving sepsis. We used validated diagnostic codes to determine the presence of sepsis, co-morbidities and organ dysfunction and to provide risk-adjustment. Results Among patients 18 to 64 years old, those with Medicaid (adjusted odds ratio (AOR) 1.50), Medicare (AOR 1.96), Medicaid + Medicare (AOR 2.22) and the uninsured (AOR 1.18) had significantly higher risk-adjusted odds of a sepsis-associated admission than those with private insurance (all P < 0.0001). Those with Medicaid (AOR 1.17, P < 0.001) and those without insurance (AOR 1.45, P < 0.001) also had significantly higher adjusted odds of sepsis-associated hospital mortality than those with private insurance. Among those 65+ years old, those with Medicaid (AOR 1.43), Medicare alone (AOR 1.13) or Medicaid + Medicare (AOR 1.62) had significantly higher risk-adjusted odds of sepsis-associated admission than those with private insurance and Medicare (all P < 0.0001). Among sepsis patients 65+, uninsured patients had significantly higher risk-adjusted odds (AOR 1.45, P = 0.0048) and those with Medicare alone had significantly lower risk-adjusted odds (AOR 0.92, P = 0.0072) of hospital mortality than those with private insurance and Medicare. Lack of health insurance remained associated with sepsis-associated mortality after stratification of hospitals into quartiles based on rates of sepsis-associated admissions or mortality in both age strata. Conclusions Risks of sepsis-associated hospitalization and sepsis-associated death vary by insurance. These increased risks were not fully explained by the available socio-demographic factors, co-morbidities or hospital rates of sepsis-related admissions or deaths. PMID:21605427

  12. Myocardial Dysfunction in Sepsis: A Large, Unsolved Puzzle

    PubMed Central

    Fernandes Jr., Constantino Jose; de Assuncao, Murillo Santucci Cesar

    2012-01-01

    Sepsis has high incidence and mortality rates around the world. The role of cardiac depression in myocardial dysfunction during sepsis remains to be elucidated. This review attempts to summarize our understanding of the anatomical, histopathological, and pathophysiological mechanisms behind cardiac dysfunction. Biomarkers to detect cardiac depression have been used to recognize developing problems, but the actual impact of these tools remains unclear. PMID:22482045

  13. B cells enhance early innate immune responses during bacterial sepsis.

    PubMed

    Kelly-Scumpia, Kindra M; Scumpia, Philip O; Weinstein, Jason S; Delano, Matthew J; Cuenca, Alex G; Nacionales, Dina C; Wynn, James L; Lee, Pui Y; Kumagai, Yutaro; Efron, Philip A; Akira, Shizuo; Wasserfall, Clive; Atkinson, Mark A; Moldawer, Lyle L

    2011-08-01

    Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1(-/-) mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell-deficient or anti-CD20 B cell-depleted mice, but not ?/? T cell-deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell-deficient mice with serum from wild-type (WT) mice and repletion of Rag1(-/-) mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-?/? receptor [IFNAR]), and repleting Rag1(-/-) mice with WT, but not IFNAR(-/-), B cells improves IFN-I-dependent and -independent early cytokine responses. Repleting B cell-deficient mice with the IFN-I-dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I-activated B cells in protective early innate immune responses during bacterial sepsis. PMID:21746813

  14. 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

  15. Disruption of tight junctions during polymicrobial sepsis in vivo.

    PubMed

    Li, Qiurong; Zhang, Qiang; Wang, Chenyang; Liu, Xiaoxiang; Li, Ning; Li, Jieshou

    2009-06-01

    The disruption of intestinal epithelial tight junctions may result in barrier function dysfunction during polymicrobial sepsis. The pathophysiology of sepsis involves breakdown of barrier integrity, which correlates with adverse outcome during sepsis. However, the mechanisms underlying loss of barrier function in sepsis remain unknown. In the present study in mice, tight junction (TJ) structure was analysed by transmission electron microscopy; intestinal permeability was assessed using molecular tracer measurement; and the distribution of TJ proteins was investigated by immunofluorescence microscopy. The membrane microdomains of TJs were isolated using discontinuous sucrose density gradients and the expression of TJ proteins in these was determined by western blot. Immunofluorescence microscopy revealed that claudins 1, 3, 4, 5, and 8 were present predominantly in the microvillous surface of epithelial cells and along the lateral membranes of the cells; in sepsis, however, labelling of these proteins was present diffusely within cells and was no longer focused at the lateral cell boundaries. Moreover, the expression of claudin-2 was markedly up-regulated in sepsis. Using western blot analysis, we found that occludin and claudins were displaced from raft fractions to non-raft fractions in membrane microdomains of TJs in sepsis. In addition, the disruption of TJ structure was accompanied by increased intestinal permeability. Our results demonstrate for the first time that redistribution of TJ proteins in TJ membrane microdomains and redistribution of claudins in epithelial cells of the colon lead to alteration of TJ architecture and TJ barrier dysfunction during the development of polymicrobial sepsis. PMID:19235836

  16. Prognosis of AKI in malignant diseases with and without sepsis

    PubMed Central

    2013-01-01

    Background AKI significantly worsens prognosis of hospitalized patients. This is particularly the case in patients with sepsis. The risk for aquiring sepsis is significantly increased in malignant diseases. Aim of the present retrospective study was to analyze outcomes of tumor patients with sepsis and AKI. Methods One-thousand and seventeen patients, treated at the ICU of the Department of Nephrology and Rheumatology of the University Hospital Göttingen from 2009 to 2011 were retrospectively analyzed for mortality, sepsis, AKI, need for renal replacement therapy (dialysis) and malignancies. Results AKI occurred significantly more frequent in septic than in non-septic patients and in tumor as oposed to non-tumor patients. Mortaliy rates were higher in the respective latter groups. Mortality increased even further if patients suffered from a malignant disease with sepsis and AKI. Mortality rates peaked if dialysis treatment became mandatory. In non-solid tumors 100% of the patients died if they suffered drom sepsis and AKI. This was not the case in solid malignancies (mortality rate 56%). Conclusions We conclude that prognosis of tumor patients with AKI and sepsis is very poor. Mortality increases to almost 70% if diaylsis therapy is initiated. Non-solid tumors are associated with a 100% mortality if sepsis and AKI conincide. PMID:24168374

  17. Clinical use of plasma chitotriosidase in severe sepsis.

    PubMed

    Chiarla, Carlo; Giovannini, Ivo; Antuzzi, Daniela; Piras, Andrea; Ardito, Francesco; Giuliante, Felice

    2016-02-01

    Plasma chitotriosidase activity (ChT) was previously proposed to quantify severity of sepsis. In a complex surgical case, with prolonged sepsis and consistently high ChT, we found that the least increased values occurred in stages of extreme illness, with profound hypocholesterolemia. ChT needs better characterization before becoming a reliable biomarker of septic evolution. PMID:26550788

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

    PubMed

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

    2016-01-01

    Background.  The importance of bacteria other than group A streptococci (GAS) in different clinical presentations of cellulitis is unclear, commonly leading to treatment with broad-spectrum antibiotics. The aim of this study was to describe the etiological and clinical spectrum of cellulitis and identify clinical features predicting streptococcal etiology. Methods.  We prospectively enrolled 216 patients hospitalized with cellulitis. Clinical details were registered. Bacterial culture was performed from blood, cutaneous or subcutaneous tissue, and/or swabs from skin lesions. Paired serum samples were analyzed for anti-streptolysin O and anti-deoxyribonuclease B antibodies. Results.  Serology or blood or tissue culture confirmed β-hemolytic streptococcal (BHS) etiology in 72% (146 of 203) of cases. An additional 13% (27 of 203) of cases had probable BHS infection, indicated by penicillin response or BHS cultured from skin swabs. β-hemolytic streptococcal etiology was predominant in all clinical subgroups, including patients without sharply demarcated erythema. β-hemolytic group C or G streptococci (GCS/GGS) were more commonly isolated than GAS (36 vs 22 cases). This predominance was found in the lower extremity infections. Group C or G streptococci in swabs were associated with seropositivity just as often as GAS. Staphylococcus aureus was cultured from swabs as a single pathogen in 24 cases, 14 (64%) of which had confirmed BHS etiology. Individual BHS-associated clinical characteristics increased the likelihood of confirmed BHS disease only slightly; positive likelihood ratios did not exceed 2.1. Conclusions.  β-hemolytic streptococci were the dominating cause of cellulitis in all clinical subgroups and among cases with S aureus in cutaneous swabs. Group C or G streptococci were more frequently detected than GAS. No single clinical feature substantially increased the probability of confirmed BHS etiology. PMID:26734653

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

    PubMed Central

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

    2016-01-01

    Background. The importance of bacteria other than group A streptococci (GAS) in different clinical presentations of cellulitis is unclear, commonly leading to treatment with broad-spectrum antibiotics. The aim of this study was to describe the etiological and clinical spectrum of cellulitis and identify clinical features predicting streptococcal etiology. Methods. We prospectively enrolled 216 patients hospitalized with cellulitis. Clinical details were registered. Bacterial culture was performed from blood, cutaneous or subcutaneous tissue, and/or swabs from skin lesions. Paired serum samples were analyzed for anti-streptolysin O and anti-deoxyribonuclease B antibodies. Results. Serology or blood or tissue culture confirmed β-hemolytic streptococcal (BHS) etiology in 72% (146 of 203) of cases. An additional 13% (27 of 203) of cases had probable BHS infection, indicated by penicillin response or BHS cultured from skin swabs. β-hemolytic streptococcal etiology was predominant in all clinical subgroups, including patients without sharply demarcated erythema. β-hemolytic group C or G streptococci (GCS/GGS) were more commonly isolated than GAS (36 vs 22 cases). This predominance was found in the lower extremity infections. Group C or G streptococci in swabs were associated with seropositivity just as often as GAS. Staphylococcus aureus was cultured from swabs as a single pathogen in 24 cases, 14 (64%) of which had confirmed BHS etiology. Individual BHS-associated clinical characteristics increased the likelihood of confirmed BHS disease only slightly; positive likelihood ratios did not exceed 2.1. Conclusions. β-hemolytic streptococci were the dominating cause of cellulitis in all clinical subgroups and among cases with S aureus in cutaneous swabs. Group C or G streptococci were more frequently detected than GAS. No single clinical feature substantially increased the probability of confirmed BHS etiology. PMID:26734653

  20. 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

  1. Coagulation dysfunction in sepsis and multiple organ system failure.

    PubMed

    Nimah, Marianne; Brilli, Richard J

    2003-07-01

    In patients diagnosed with sepsis, severe sepsis or septic shock, cytokine-mediated endothelial injury, and TF activation initiate a cascade of events that culminate in the development of coagulation dysfunction characterized as procoagulant and antifibrinolytic. This abnormal state predisposes the patient to develop microvascular thrombosis, tissue ischemia, and organ hypoperfusion. Multiple organ dysfunction syndrome may be a product of this pertubation in coagulation regulation. Treatments aimed at correcting this coagulation dysfunction have met with mixed success. Current data suggest that AT III replacement therapy has limited efficacy in adults with severe sepsis. In contrast, adult patients diagnosed with severe sepsis and organ failure and treated with aPC (drotrecogin alfa activate) have a significantly reduced risk of death when compared with placebo-treated patients. A phase III trial examining the efficacy of protein C replacement therapy in pediatric patients with severe sepsis and organ failure is underway. PMID:12848314

  2. Improving the management and care of people with sepsis.

    PubMed

    Fitzpatrick, David; McKenna, Michael; Rooney, Kevin; Beckett, Dan; Pringle, Norma

    2014-04-01

    Many hospitals struggle to implement the full sepsis care bundle, but research suggests that many patients with sepsis are transported to hospital by ambulance. In 2011, the Scottish Ambulance Service introduced a pre-hospital sepsis screening tool (PSST) to expedite sepsis identification and care delivery. However, ambulance clinicians have reported varying degrees of interest and enthusiasm from hospital staff during handover. Therefore, an online survey was set up to investigate medical and nursing staff perceptions and experiences of the introduction of a PSST. This article discusses the results, which show that participants perceive the PSST reduces time to treatment, improves continuity of care, benefits patients and is accurately applied by ambulance clinicians, but which also highlight problems with communication. The delivery of in-hospital and pre-hospital sepsis care is challenging, but simple measures such as improving and standardising communication and alert systems between ambulance services and receiving hospitals could improve the clinical effects of a PSST. PMID:24689480

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

    PubMed Central

    2010-01-01

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

  4. 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 hosts 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

  5. Therapeutic potential of HMGB1-targeting agents in sepsis

    PubMed Central

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

    2008-01-01

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

  6. 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

  7. Staphylococcal and streptococcal colonization of the newborn infant: effect of antiseptic cord care.

    PubMed

    Speck, W T; Driscoll, J M; Polin, R A; O'Neill, J; Rosenkranz, H S

    1977-09-01

    A randomized controlled study was undertaken to compare the effectiveness of three umbilical cord treatment regimens in controlling neonatal bacterial colonization. The three regimens studied included castile soap, triple dye, and silver sulfadiazine. The triple dye and silver sulfadiazine application inhibited bacterial colonization. Staphylococcal colonization was inhibited by both treatment regimens but most effectively by triple dye. Group B streptococcal colonization was inhibited most effectively by silver sulfadiazine while triple dye application to the umbilicus promoted colonization with this microorganism. Silver sulfadiazine was more effective in controlling colonization with Gram-negative microorganisms. PMID:331941

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

    PubMed

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

    2015-01-01

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

  9. Lactoferrin for prevention of neonatal sepsis

    PubMed Central

    Turin, Christie G.; Zea-Vera, Alonso; Pezo, Alonso; Cruz, Karen; Zegarra, Jaime; Bellomo, Sicilia; Cam, Luis; Llanos, Raul; Castañeda, Anne; Tucto, Lourdes; Ochoa, Theresa J.

    2015-01-01

    Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF´s role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide. PMID:24935001

  10. 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

  11. 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.

  12. The Economic and Humanistic Burden of Severe Sepsis.

    PubMed

    Tiru, Bogdan; DiNino, Ernest K; Orenstein, Abigail; Mailloux, Patrick T; Pesaturo, Adam; Gupta, Abhinav; McGee, William T

    2015-09-01

    Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases "severe sepsis" and "septic shock" and the MeSH terms "epidemiology", "statistics", "mortality", "economics", and "quality of life". Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use. PMID:25935211

  13. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS. PMID:25466727

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

    PubMed Central

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

    2013-01-01

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

  15. Pyrogenicity and Cytokine-Inducing Properties of Streptococcus pyogenes Superantigens: Comparative Study of Streptococcal Mitogenic Exotoxin Z and Pyrogenic Exotoxin A

    PubMed Central

    Müller-Alouf, Heide; Proft, Thomas; Zollner, Thomas M.; Gerlach, Dieter; Champagne, Eric; Desreumaux, Pierre; Fitting, Catherine; Geoffroy-Fauvet, Christiane; Alouf, Joseph E.; Cavaillon, Jean-Marc

    2001-01-01

    Streptococcal mitogenic exotoxin Z (SMEZ), a superantigen derived from Streptococcus pyogenes, provoked expansion of human lymphocytes expressing the Vβ 2, 4, 7 and 8 motifs of T-cell receptor. SMEZ was pyrogenic in rabbits and stimulated the expression of the T-cell activation markers CD69 and cutaneous lymphocyte-associated antigen. A variety of cytokines was released by human mononuclear leukocytes stimulated with SMEZ, which was 10-fold more active than streptococcal pyrogenic exotoxin A. Th2-derived cytokines were elicited only by superantigens and not by streptococcal cells. PMID:11349089

  16. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve.

    PubMed

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  17. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

    PubMed Central

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T.; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

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

    PubMed Central

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

    2014-01-01

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

  19. High burden of invasive group A streptococcal disease in the Northern Territory of Australia.

    PubMed

    Boyd, R; Patel, M; Currie, B J; Holt, D C; Harris, T; Krause, V

    2016-04-01

    Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response. PMID:26364646

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    1990-12-31

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

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

    PubMed Central

    Helm, Caitlin E.; Blackwood, R. Alexander

    2015-01-01

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

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

    EPA Science Inventory

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    PubMed

    Frre, Julie; Bidet, Philippe; Tapiro, Bruce; Rallu, Fabien; Minodier, Philippe; Bonacorsi, Stephane; Bingen, Edouard; Ovetchkine, Philippe

    2016-01-01

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

  7. Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections

    PubMed Central

    Kovacevic, Miro; Grant, Paul

    2015-01-01

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

  8. Challenges in the diagnosis and management of neonatal sepsis

    PubMed Central

    Zea-Vera, Alonso

    2015-01-01

    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. PMID:25604489

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

    PubMed Central

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

    2015-01-01

    In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis? PMID:26579527

  10. Activated Complement Factors as Disease Markers for Sepsis

    PubMed Central

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

    2015-01-01

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

  11. Serum Calprotectin: A Potential Biomarker for Neonatal Sepsis

    PubMed Central

    Decembrino, Lidia; De Amici, Mara; Pozzi, Margherita; De Silvestri, Annalisa; Stronati, Mauro

    2015-01-01

    Introduction. The correct diagnosis of neonatal sepsis is a relevant problem because sepsis is one of the most important causes of neonatal morbidity, mortality, and prolonged hospital stay. Calprotectin is an antimicrobial, calcium and zinc binding heterocomplex protein that could be used as a nonspecific marker for activation of granulocytes and mononuclear phagocytes. Calprotectin has been proposed for the diagnosis of inflammatory conditions. Our aim is to study serum calprotectin as a biomarker for neonatal sepsis diagnosis. Methods. 41 (20 females, 21 males) infants who underwent blood culture due to suspected sepsis were enrolled in the study. Serum calprotectin was measured by a commercial ELISA assay (Calprest, Eurospital, Trieste, Italy). Statistical analysis was performed using the statistical software package Stata 13.1 (Stata Corporation, College Station, Texas, USA). Results. 8 neonates (19.51%) showed sepsis with positive culture and 33 (80.49%) showed suspected sepsis. The optimal cut-off for calprotectin is 2.2??g/mL with a sensitivity of 62.5% and a specificity of 69.7%. Conclusions. Calprotectin may be considered a promising early, sensitive, specific marker of sepsis thanks to the importance of calprotectin in defense mechanisms and physiological functions of the immune system. PMID:26380313

  12. 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 2050%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients. Methods: This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNF?) levels and patients were followed up for clinical outcome. Results: There were 54% males and 46% females, with no significant difference of age or comorbids between genders. Respiratory tract infection was the commonest source of sepsis, and was more common in females (60%) compared to males (39%) (p=0.034). Males had a higher mortality (p=0.048, RR 1.73) and plasma IL-6 level(p=0.040) compared to females. Mean IL-6 plasma level was significantly (p<0.01) higher in patients who died vs. who recovered. Conclusion: Our study shows that males with sepsis have a 70% greater mortality rate, and mortality is associated with a higher IL-6 plasma level. PMID:26649014

  13. Low Socioeconomic Status Is Associated with Prolonged Times to Assessment and Treatment, Sepsis and Infectious Death in Pediatric Fever in El Salvador

    PubMed Central

    Gavidia, Ronald; Fuentes, Soad L.; Vasquez, Roberto; Bonilla, Miguel; Ethier, Marie-Chantal; Diorio, Caroline; Caniza, Miguela; Howard, Scott C.; Sung, Lillian

    2012-01-01

    Background Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. Method This prospective cohort study included children aged 016 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. Findings Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.020.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.03.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P?=?0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.098.63; P?=?0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.031.81; P?=?0.031) and in families with an annual household income sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families and staying at a nearby guest house during periods of neutropenia may decrease sepsis and infectious mortality. PMID:22928008

  14. Non-sporing anaerobes in hospital sepsis.

    PubMed

    Chakraborti, C K; Chatterjee, B D; Sanyal, S N; Banerjee, M

    1991-07-01

    In comparison to normal controls, the non-sporing anaerobes were often isolated from orodental sepsis (42% to 44.4%), chronic suppurative otitis media (40%), septic abortion (40.3%), uterocervical wound (45.4%), vaginitis (50%) and cancer cervix (50%). This was true (40%) in perforating ulcers of foot in leprosy. These organisms were less frequently noted in abdominal (11%) and episiotomy (22.8%) wounds and leucorrhoea (33.3%). The role of non-sporing anaerobes was also suggested by the high percentage ratio of number of isolates to number of cases and by its primary isolation in moderate to heavy number. Barring the cases of cancer cervix, the aerobic bacteria were the most common (78.8% to 100%) in all other conditions. PMID:1940415

  15. 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. PMID:26063312

  16. Rahnella aquatilis Sepsis in a Premature Newborn

    PubMed Central

    Kuzdan, Canan; Soysal, Ahmet; zdemir, Hlya; Co?kun, ?enay; Akman, ?pek; Bilgen, Hlya; zek, Eren; Bak?r, Mustafa

    2015-01-01

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

  17. 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.

  18. Management and Treatment Guidelines for Sepsis in Pediatric Patients

    PubMed Central

    El-wiher, Nidal; Cornell, Timothy T.; Kissoon, Nranjany; Shanley, Thomas P.

    2012-01-01

    Sepsis remains one of the leading causes of morbidity and mortality in children despite improved understanding of the pathophysiology leading to better clinical management and survival. Recent studies have identified several areas that must be addressed by the clinician in order to continue to impact the morbidity and mortality associated with sepsis. In this review, we discuss the evidence in several of these areas including initial resuscitation, pathogen eradication, maintenance of oxygen delivery, and directed modifiers of the inflammatory response. Our overall goal is to provide the bedside clinician with an updated systematic approach to treat sepsis in children. PMID:23125881

  19. 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. PMID:25016494

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

    PubMed

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

    2015-09-01

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

  1. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Mihaljevic, Susan E; Howard, Valerie M

    2016-01-01

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

  4. 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 24hours 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 7.8mg/dl, 1616ng/ml and 0.3ng/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 2ng/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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. [Epigenetic regulation in sepsis : current state of knowledge].

    PubMed

    Weiterer, S; Uhle, F; Siegler, B H; Lichtenstern, C; Bartkuhn, M; Weigand, M A

    2015-01-01

    Sepsis is known to be a severe systemic immune reaction based on an infection of various origins. The initial immune response is accompanied by excess activation of immune cells and release of proinflammatory cytokines. Simultaneously initiated compensatory mechanisms lead to high levels of anti-inflammatory mediators to counterbalance the generalized inflammatory reaction; however, the compensatory immunoreaction itself equally overreacts and results in a prolonged sepsis-induced immunosuppression. The underlying mechanisms for these exaggerated immune responses and the resulting global immunosuppression that increase the risk for secondary infection are still unknown. Recent findings indicate that epigenetic mechanisms change basic properties of important immune cells by mechanisms leading to changes in gene expression. Dynamic exchanges of histone modifications result in a variation of transcription and seem to play a key role in cell function of macrophages and other immune cells. This article provides a current overview of epigenetic sepsis research and the sepsis-induced effects on the immune system. PMID:25471356

  7. HDL in sepsis risk factor and therapeutic approach

    PubMed Central

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

    2015-01-01

    High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 4070% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis. PMID:26557091

  8. Immunotherapy in Neonatal Sepsis: Advances in Treatment and Prophylaxis

    PubMed Central

    Cohen-Wolkowiez, Michael; Benjamin, Daniel K.; Capparelli, Edmund

    2012-01-01

    Purpose of review Systemic infections in premature and term infants cause significant morbidity and mortality in spite of appropriate antimicrobial therapy. Consequently, immunotherapy has emerged as a potential adjuvant therapeutic modality to reduce the incidence and mortality associated with neonatal sepsis. Recent findings The most recent findings during the review period include systematic reviews of previously published trials evaluating the use of intravenous immunoglobulin and colony stimulating factors in neonatal sepsis. In addition, the most recent trials describing the use of anti-staphylococcal antibodies, probiotics, glutamine supplementation, recombinant human protein C, and lactoferrin in the prevention and treatment of neonatal sepsis have been reviewed. Summary Immunotherapy used as an adjuvant for the prevention and treatment of neonatal sepsis holds promise. Clinical trials specifically designed towards the neonatal population and appropriately powered to detect treatment differences are necessary prior to universal recommendation of these therapies in the nursery. PMID:19276977

  9. Continuous hemodiafiltration with a cytokine-adsorbing hemofilter for sepsis.

    PubMed

    Hirasawa, Hiroyuki; Oda, Shigeto; Nakamura, Masataka; Watanabe, Eizo; Shiga, Hidetoshi; Matsuda, Kenichi

    2012-01-01

    Since the introduction of the new pathophysiological concept of pathogen-associated molecular patterns (PAMPS) and alarmins, endotoxin has been recognized as only one of the PAMPS. It is widely accepted that hypercytokinemia plays a pivotal role in the pathophysiology of sepsis. Many kinds of blood purification modalities have been proposed as a therapeutic tool against sepsis, including high-volume continuous hemofiltration whose efficacy has recently been questioned. We report that continuous hemodiafiltration (CHDF) with a cytokine-adsorbing hemofilter (CAH), such as polymethyl methacrylate hemofilter and AN69ST hemofilter (CAH-CHDF), can remove many kinds of cytokines and has been very effective in the treatment of severe sepsis and septic shock. Based on the understanding of the recent pathophysiology, we suggest that CAH-CHDF is an alternate therapy to direct hemoperfusion with endotoxin-adsorbing column in the treatment of sepsis. PMID:23095416

  10. Why we need a new definition of sepsis

    PubMed Central

    Lanspa, Michael J.

    2015-01-01

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

  11. Why we need a new definition of sepsis.

    PubMed

    Beesley, Sarah J; Lanspa, Michael J

    2015-11-01

    On April 23, 2015, Kaukonen and colleagues published an article in the New England Journal of Medicine entitled "Systemic inflammatory response syndrome criteria in defining severe sepsis", which investigated the sensitivity and validity of using SIRS criteria to define intensive care unit (ICU) patients with severe sepsis. This study used admission data of over 100,000 patients in order to investigate patients with severe sepsis who either met or didn't meet SIRS criteria. The investigators found that in-hospital mortality increased linearly with the number of SIRS criteria met; raising concern that SIRS criterion is not sensitive enough. This study of SIRS criteria raises important questions about the recognition and diagnosis of severe sepsis. PMID:26697456

  12. Clinical Decision Support for Early Recognition of Sepsis.

    PubMed

    Amland, Robert C; Hahn-Cover, Kristin E

    2016-03-01

    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

  13. 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

  14. 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

  15. Early diagnosis of sepsis using serum hemoglobin subunit Beta.

    PubMed

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

    2015-02-01

    The development of new sepsis-specific biomarkers is mandatory to improve the detection and monitoring of the disease. Hemoglobin is the main oxygen and carbon dioxide carrier in cells of the erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. Hemoglobin subunit beta (HB?) is a component of a larger protein called hemoglobin. The aim of this study was to evaluate blood levels of HB? in septic patients. A prospective study of 82 patients with sepsis was conducted. Furthermore, C57BL/6 mice were subjected to cecal ligation and puncture (CLP) surgery. Alternatively, human umbilical vein endothelial cells (HUVECs) or C57BL/6 mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to mice). The data showed that LPS induced upregulation of the synthesis and secretion of HB? in LPS-treated HUVECs and in LPS-injected and CLP mice. In patients admitted to the intensive care unit with sepsis, circulating levels of HB? were significantly high (sepsis, 64.93-114.76 ng/ml, n?=?30; severe sepsis, 157.37-268.69 ng/ml, n?=?22; septic shock, 309.98-427.03 ng/ml, n?=?30) when compared to the levels of control donors (9.76-12.28 ng/ml, n?=?21). Patients with septic shock had higher HB? levels when compared to patients with severe sepsis. Furthermore, the HB? levels in septic patients were higher than those in healthy volunteers. These results suggest that in septic patients, HB? blood level is related to the severity of sepsis and may represent a novel endothelial cell dysfunction marker. Moreover, HB? can be used as a biomarker to determine the severity of sepsis. PMID:25338941

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

    PubMed

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

    2014-01-01

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

  17. Sepsis and Septic Shock in the Equine Neonate.

    PubMed

    Fielding, Christopher Langdon; Magdesian, Kiragos Gary

    2015-12-01

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

  18. 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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. Possible interventional therapies in severe sepsis or septic shock.

    PubMed

    Wu, Chin-Chen

    2012-06-01

    For many years, basic research with relatively straightforward pathophysiologic approaches has driven clinical trials using molecules that supposedly interfere positively with inflammatory processes. However, most of these trials have failed to demonstrate any outcome benefit. Indeed, we need to revisit current paradigms and to think about the possibility that outcome may be predetermined in severe sepsis or septic shock. In addition, an early diagnosis of sepsis prior to the onset of clinical decline is also of particular interest to health practitioners because this information increases the possibilities for early and specific treatment of this life threatening condition. Indeed, the time to initiate therapy is thought to be crucial and the major determent factor in surviving sepsis. Despite substantial progress in sepsis therapy, the gap between the discovery of new effective medical molecules and their implementation in the daily clinical practice of the intensive care unit remains a major hurdle. Fortunately, ongoing research continues to provide new information on the management of sepsis, in particular, severe sepsis or septic shock. High quality and effective management tools are necessary to bring evidence-based therapy to the bedside. On this basis, new therapies could be tested to reduce mortality rates with respect to recently published studies. PMID:22769862

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

    PubMed

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

    2015-12-01

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

  3. Improving time to antibiotics and implementing the Sepsis 6

    PubMed Central

    McGregor, Calum

    2014-01-01

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

  4. 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

  5. Circulating MicroRNAs as Biomarkers for Sepsis.

    PubMed

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

    2016-01-01

    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. PMID:26761003

  6. Circulating MicroRNAs as Biomarkers for Sepsis

    PubMed Central

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

    2016-01-01

    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. PMID:26761003

  7. Spontaneous Neutrophil Migration Patterns during Sepsis after Major Burns

    PubMed Central

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

    2014-01-01

    Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before th