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1

Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets.  

PubMed

We investigated whether group B streptococcal (STREP) infusion impairs the cerebral blood flow (CBF) response to acute hypercarbia in piglets, and whether STREP-induced prostanoids or hemodynamic alterations could account for this impairment. Piglets, 2-3 wk old, were anesthetized, paralyzed, and mechanically ventilated (50% O2; partial pressure of arterial CO2 (PaCO2) approximately 40 torr). CBF was assessed by internal carotid artery blood flow (ICBF). Group 1 (n = 5) received a continuous infusion of STREP for 4 h (2.0-8.0 x 10(7) org/kg-min). Group 2 (n = 5) was pretreated with indomethacin (5 mg/kg), then received the identical STREP infusion. Group 3 (n = 6) did not receive STREP, but cardiac output (CO) and systemic blood pressure (BP) were reduced to levels equal to that of group 1 by incremental inflation of a left atrial balloon (LAB) catheter. Cerebral vascular reactivity to acute hypercarbia (PaCO2 approximately 70 torr for 7.5 min) was assessed at baseline and after each hour of STREP infusion or LAB inflation. We found that 4 h of STREP infusion caused CO to fall significantly (634 +/- 121 to 324 +/- 172 mL/min, group 1; 600 +/- 68 to 291 +/- 80 mL/min, group 2) and BP to fall significantly (104 +/- 20 to 57 +/- 4 mm Hg, group 1; 91 +/- 11 to 53 +/- 16 mm Hg, group 2) By design, in group 3 LAB inflation caused CO (573 +/- 181 to 375 +/- 159 mL/min) and BP (104 +/- 14 to 60 +/- 9 mm Hg) to fall to values not significantly different from septic groups 1 and 2. At 4 h, unilateral ICBF decreased significantly during STREP infusion in group 1 (32.0 +/- 10.8 to 21.0 +/- 7.3 mL/min) and group 2 (22.9 +/- 9.9 to 13.1 +/- 4.3 mL/min), but not in nonseptic group 3 (23.1 +/- 7.4 to 19.6 +/- 6.3 mL/min). At baseline, hypercarbia induced an increase in ICBF (% delta ICBF = 68.7 +/- 13.0% in group 1, 62.2 +/- 15.6% in group 2, and 87.7 +/- 34.0% in group 3). After 4 h of STREP, this response was completely ablated as ICBF fell during hypercarbia by -7.8 +/- 23.2% (group 1). Indomethacin did not protect cerebral vascular reactivity after 4 h of STREP infusion, as % delta ICBF fell during hypercarbia by -10.9 +/- 17.7% (group 2). In contrast, despite equivalent reductions in CO and BP after 4 h of LAB inflation in nonseptic group 3, ICBF rose during hypercarbia by 61.8 +/- 23.2%, not significantly different from baseline, but significantly different from the decrease in % delta ICBF in groups 1 and 2. We conclude that STREP infusion reduces ICBF and cerebral vascular reactivity to acute hypercarbia in piglets. This phenomenon is not accounted for by STREP-induced reduction in CO or BP, and is not mediated by prostanoids. PMID:8825386

Rudinsky, B F; Lozon, M; Bell, A; Hipps, R; Meadow, W L

1996-01-01

2

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

E-print Network

% of all cases of sepsis [1]. Group B strep- tococci (GBS; Streptococcus agalactiae ) are a major etiologicGroup B Streptococcal b-Hemolysin Induces Mortality and Liver Injury in Experimental Sepsis Axel-type (wt) group B streptococci (GBS) serotype III strain (COH1) and its isogenic nonhemolytic (NH

Nizet, Victor

3

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

PubMed

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

Reglinski, Mark; Sriskandan, Shiranee

2014-01-01

4

Sudden unexpected neonatal death due to late onset group B streptococcal sepsis--a case report.  

PubMed

We report a case of sudden unexpected death due to late onset neonatal group B streptococcal sepsis. A male neonate weighing 2731g was born at 35week gestational age, and discharged at the age of 4days after the birth. At 6days after the discharge (10days after the birth), because of consciousness loss and hypothermia, the neonate was conveyed to an emergency hospital, eventually followed by his death. Forensic autopsy revealed neither severe trauma nor cardiac anomaly. Both lungs were edematous. Histopathologically, a lot of bacterial clusters were found in the lungs and intracerebral vessels. Cerebrospinal fluid contained a lot of leukocytes. Streptococcus agalactiae was detected in the specimens from the feces and the blood. Collectively, we diagnosed that the cause of the neonate's death was late onset group B streptococcal sepsis. In autopsy cases of neonates, careful macroscopic and microscopic observations and bacteriological/virological examination should be performed. PMID:23541873

Kawaguchi, Takashi; Hama, Mizuki; Abe, Makoto; Suenaga, Tomohiro; Ishida, Yuko; Nosaka, Mizuho; Kuninaka, Yumi; Kawaguchi, Mariko; Yoshikawa, Norishige; Kimura, Akihiko; Kondo, Toshikazu

2013-09-01

5

Synchronous recurrence of group B streptococcal late-onset sepsis in twins.  

PubMed

Group B Streptococcus (GBS) remains the leading cause of neonatal sepsis and meningitis in industrialized countries. Whereas the use of intrapartum antibiotic prophylaxis has led to a significant decline in early-onset sepsis, the incidence of late-onset sepsis has remained unchanged. Whether late-onset sepsis usually originates from established mucocutaneous GBS colonization of the infant or whether it results from an acute exogenous GBS infection remains controversial. Here we report on twins who both twice developed GBS sepsis in a strikingly parallel fashion, with both instances originating from a single hypervirulent GBS clone. Factored together, the presentation as cervical soft tissue infection in both cases, the synchronicity of the episodes, and the detection of GBS DNA in breast milk all strongly suggest an enteral mode of transmission with a short incubation period. PMID:24709927

Elling, Roland; Hufnagel, Markus; de Zoysa, Aruni; Lander, Fabian; Zumstein, Katharina; Krueger, Marcus; Henneke, Philipp

2014-05-01

6

Mortality in sepsis versus non-sepsis induced acute lung injury  

Microsoft Academic Search

Introduction  Sepsis-induced acute lung injury (ALI) has been reported to have a higher case fatality rate than other causes of ALI. However,\\u000a differences in the severity of illness in septic vs. non-septic ALI patients might explain this finding.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  520 patients enrolled in the Improving Care of ALI Patients Study (ICAP) were prospectively characterized as having sepsis\\u000a or non sepsis-induced ALI. Biologically

Jonathan E Sevransky; Gregory S Martin; Carl Shanholtz; Pedro A Mendez-Tellez; Peter Pronovost; Roy Brower; Dale M Needham

2009-01-01

7

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

PubMed

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

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

2015-04-01

8

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

PubMed Central

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

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

2015-01-01

9

Evidence of streptococcal origin of acute non-necrotising cellulitis: a serological study.  

PubMed

Bacteriological diagnosis is rarely achieved in acute cellulitis. Beta-haemolytic streptococci and Staphylococcus aureus are considered the main pathogens. The role of the latter is, however, unclear in cases of non-suppurative cellulitis. We conducted a serological study to investigate the bacterial aetiology of acute non-necrotising cellulitis. Anti-streptolysin O (ASO), anti-deoxyribonuclease B (ADN) and anti-staphylolysin (ASTA) titres were measured from acute and convalescent phase sera of 77 patients hospitalised because of acute bacterial non-necrotising cellulitis and from the serum samples of 89 control subjects matched for age and sex. Antibiotic treatment decisions were also reviewed. Streptococcal serology was positive in 53 (69 %) of the 77 cases. Furthermore, ten cases without serological evidence of streptococcal infection were successfully treated with penicillin. Positive ASO and ADN titres were detected in ten (11 %) and three (3 %) of the 89 controls, respectively, and ASTA was elevated in three patients and 11 controls. Our findings suggest that acute non-necrotising cellulitis without pus formation is mostly of streptococcal origin and that penicillin can be used as the first-line therapy for most patients. PMID:25403372

Karppelin, M; Siljander, T; Haapala, A-M; Aittoniemi, J; Huttunen, R; Kere, J; Vuopio, J; Syrjänen, J

2015-04-01

10

Chronic kidney disease worsens sepsis and sepsis-induced acute kidney injury by releasing High Mobility Group Box Protein1  

Microsoft Academic Search

We have shown that folate-induced kidney dysfunction and interstitial fibrosis predisposes mice to sepsis mortality. Agents that increase survival in normal septic mice were ineffective in a two-stage kidney disease model. Here we used the 5\\/6 nephrectomy mouse model of progressive chronic kidney disease (CKD) to study how CKD affects acute kidney injury (AKI) induced by sepsis. We induced sepsis

Asada Leelahavanichkul; Yuning Huang; Xuzhen Hu; Hua Zhou; Takayuki Tsuji; Richard Chen; Jeffrey B Kopp; Jürgen Schnermann; Peter S T Yuen; Robert A Star

2011-01-01

11

[Sepsis, acute renal failure and multiple organ dysfunction syndrome].  

PubMed

The so-called systemic inflammatory response syndrome (SIRS ) represents the cellular inflammatory and neuroendocrine systemic reaction in response to many adverse events. epsis is defined as IR induced by bacterial, mycotic or viral toxins. The circulating toxins deriving from the bacterial wall can activate the septic cascade that induces many systemic reactions involving the activation of the cellular immunity, complement and coagulation system. The endothelial cell is the target of the systemic phlogistic reaction; its stimulation is followed by the production of many vasoactive paracrine and systemic agents. In this context, local and systemic cytokine production plays a major role in inducing the septic cascade, which although meant to be a phlogistic defense reaction, can often become an uncontrolled and dangerous inflammatory reaction. The sepsis-derived lesions can involve many organs and apparatus leading to the picture of sepsis syndrome. Sepsis syndrome often induces severe pulmonary lesions with a picture of acute respiratory distress syndrome (ARDS ). The combination of acute renal failure and sepsis is associated with a high mortality rate, namely in patients with a nitric oxide-induced systemic reduction in peripheral vascular resistances and septic shock. The toxinemia can also induce myocardial damage with a reduction in cardiac performance. Therefore, septic patients who have a combination of pulmonary, cardio-vascular, renal and cerebral lesions present with the picture of multiple organ dysfunction syndrome, that can increase mor-tality to > 0%. PMID:17068725

Graziani, G; Buskermolen, M; Oldani, S; Brambilla, G

2006-01-01

12

[Acute-phase reactants in sepsis].  

PubMed

In 71 patients with fever and bacteremia without complications, a prospective study of acute-phase reactants is done. Raises in haptoglobin, ceruloplasmin, alpha-1-antitrypsin, protein C, beta-2-microglobulin, IgA and ferritin serum levels, together with leucocytosis and GSR, were very significant when diagnosis was done. Fibronectin, sideremia and transferrin were lowered. After 3 and 6 days of treatment haptoglobins, alpha-1-antitrypsin, protein C, ferritin, leucocytosis and GSR are lowered, while immunoglobulins, sideremia, transferrin and fibronectin raised, the latter until normalization. Fibronectin as well as changes in iron metabolism were very reliable parameters of inflammation and favorable evolution. PMID:1488535

Díaz, J; Arribas, J M; Vallina, E; Maradona, J A; Hevia, C; Blanco, F

1992-12-01

13

Risk Factors for Early-onset Group B Streptococcal Sepsis: Estimation of Odds Ratios by Critical Literature Review  

Microsoft Academic Search

ABSTRACT. Objective. To identify and to establish the prevalence of ORs for factors associated with in- creased risk for early-onset group B streptococcal (EOGBS) infection in neonates. Study Design. Literature review and reanalysis of published data. Results. Risk factors for EOGBS infection include group B streptococcal (GBS)-positive vaginal culture at delivery (OR: 204), GBS-positive rectovaginal culture at 28 (OR: 9.64)

William E. Benitz; Jeffrey B. Gould; Maurice L. Druzin

14

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

PubMed Central

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

Hoton, Delphine; Castanares-Zapatero, Diego

2015-01-01

15

Sepsis  

PubMed Central

Sepsis represents a major challenge in medicine. It begins as a systemic response to infection that can affect virtually any organ system, including the central and peripheral nervous systems. Akin to management of stroke, early recognition and treatment of sepsis are just as crucial to a successful outcome. Sepsis can precipitate myasthenic crisis and lead to encephalopathy and critical illness neuropathy. Stroke and traumatic brain injury can predispose a patient to develop sepsis, whereas Guillain-Barré syndrome is similarly not uncommon following infection. This review article will first describe the essential principles of sepsis recognition, pathophysiology, and management and will then briefly cover the neurologic aspects associated with sepsis. Vigilant awareness of the clinical features of sepsis and timeliness of intervention can help clinicians prevent progression of this disease to a multisystem organ failure, which can be difficult to reverse even after the original source of infection is under control. PMID:23983879

Karnatovskaia, Lioudmila V.; Festic, Emir

2012-01-01

16

Recurrent Acute Nonrheumatic Streptococcal Myocarditis Mimicking STEMI in a Young Adult.  

PubMed

Myocarditis consists of an inflammation of the cardiac muscle, definitively diagnosed by endomyocardial biopsy. The causal agents are primarily infectious: in developed countries, viruses appear to be the main cause, whereas in developing countries rheumatic carditis, Chagas disease, and HIV are frequent causes. Furthermore, myocarditis can be indirectly induced by an infectious agent and occurs following a latency period during which antibodies are created. Typically, myocarditis observed in rheumatic fever related to group A streptococcal (GAS) infection occurs after 2- to 3-week period of latency. In other instances, myocarditis can occur within few days following a streptococcal infection; thus, it does not fit the criteria for rheumatic fever. Myocarditis classically presents as acute heart failure, and can also be manifested by tachyarrhythmia or chest pain. Likewise, GAS-related myocarditis reportedly mimics myocardial infarction (MI) with typical chest pain, electrocardiograph changes, and troponin elevation. Here we describe a case of recurrent myocarditis, 5 years apart, with clinical presentation imitating an acute MI in an otherwise healthy 37-year-old man. Both episodes occurred 3 days after GAS pharyngitis and resolved quickly following medical treatment. PMID:24963417

Chikly, Amanda; Durst, Ronen; Lotan, Chaim; Chen, Shmuel

2014-01-01

17

Sepsis  

Microsoft Academic Search

Sepsis is an often deadly systemic inflammatory response to infection that occurs frequently among older patients due to multiple\\u000a risk factors, including immunosenescence, comorbid illness, institutionalization, and instrumentation.\\u000a \\u000a Nonspecific or atypical symptoms are common among older patients with sepsis, and clinicians must have a high index of suspicion\\u000a for sepsis when patients present with such symptoms.\\u000a \\u000a \\u000a \\u000a The diagnostic approach to

Timothy D. Girard

18

Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome  

PubMed Central

BACKGROUND In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure–free days to day 14. RESULTS The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. PMID:24835849

2014-01-01

19

Effect of Resident Physician Education Regarding Selective Chemoprophylaxis for the Prevention of Early Onset Group B Streptococcal Sepsis: An Outcome Study  

E-print Network

Objective: The aim of this study was to evaluate the effect of a voluntary protocol for selective intrapartum chemoprophylaxis on the incidence of early onset group B streptococcal sepsis (GBS EOS). Methods: Cases ofGBS EOS were defined as a positive GBS culture from a normally sterile fluid obtained during the first 7 days of life. All cases of GBS EOS at an urban, university-affiliated community hospital were reviewed during 2 time periods. The 2-year period before instituting a resident education program to promote selective chemoprophylaxis (1988-89) was retrospectively reviewed; the 2-year period after the education program was introduced (1990-91) was prospectively recorded. The outcome measure was the incidence of GBS EOS. Results: The rate ofGBS EOS was 7/14,335 deliveries (0.05%) before and 9/13,999 (0.064%) after the introduction of the education program (observed difference between proportions 0.016%, 95% confidence interval [CI] for the difference between the proportions-0.071 % to 0.04%, P not significant [NS]). The rate ofGBS EOS in preterm infants was 5/1,331 (0.376%) before and 3/1,297 (0.23%) afterward (observed difference between proportions 0.14%, 95 % CI-0.28 % to 0.56%, P

Jeffrey S. Greenspoon; Doron J. D. Rosen; Anita P. Sumen

20

High prevalence of streptococcal or Epstein-Barr virus infections in children with acute non-septic monoarthritis.  

PubMed

To investigate associations between infections and acute monoarthritis, we performed a prospective study on 32 children consecutively hospitalized and 32 age-matched controls. Among 26 (81%) children having infections, the most frequent agents were Group A ?-hemolytic Streptococcus (GAS: 53%) and Epstein-Barr virus (EBV: 37.5%). Among controls, only 5 (16%) were infected with GAS and 2 (6%) with EBV (P<0.005). The most frequently involved joints were hip in 15 children and ankle in 10 children. Our study showed that acute monoarthritis in children may be frequently associated with streptococcal or EBV infections. PMID:24531174

Di Loreto, Simona; Fabiano, Cecilia; Nigro, Giovanni

2014-01-01

21

Knockdown of Burton's tyrosine kinase confers potent protection against sepsis-induced acute lung injury.  

PubMed

Sepsis is a common and critical complication in surgical patients that often leads to multiple organ failure syndrome (MOFS), including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite intensive supportive care and treatment modalities, the mortality of these patients remains high. In this study, we investigated the role of Burton's tyrosine kinase (BTK), a member of the Btk/Tec family of cytoplasmic tyrosine kinases, in the pathogenesis of sepsis, and evaluated the protective effect of in vivo Btk RNA interference in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. After intratracheal injection of Btk siRNA, the mice were then subjected to CLP to induce sepsis. The results demonstrated that this approach conferred potent protection against sepsis-induced ALI, as evidenced by a significant reduction in pathological scores, epithelial cell apoptosis, pulmonary edema, vascular permeability, and the expression of inflammatory cytokines and neutrophil infiltration in the lung tissues of septic mice. In addition, RNA interference of Btk significantly suppressed p-38 and iNOS signaling pathways in transduced alveolar macrophages in vitro. These results identify a novel role for BTK in lethal sepsis and provide a potential new therapeutic approach to sepsis and ALI. PMID:24906236

Zhou, Panyu; Ma, Bing; Xu, Shuogui; Zhang, Shijie; Tang, Hongtai; Zhu, Shihui; Xiao, Shichu; Ben, Daofeng; Xia, Zhaofan

2014-11-01

22

Preventing group B streptococcal infections in newborns.  

PubMed

Despite advances in intrapartum antibiotic prophylaxis (IAP), group B streptococcal infection continues to be a predominant cause of early-onset disease in neonates. About 2% of neonates exposed to group B Streptococcus develop clinical manifestations including sepsis, pneumonia, and meningitis. Screening in late pregnancy reduces the incidence of early-onset sepsis by more than 80%. Clinicians must be able to identify the risk factors and clinical manifestations of group B streptococcal infection and to understand management and prevention guidelines. PMID:25675327

Porta, Kelly; Rizzolo, Denise

2015-03-01

23

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

PubMed

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

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

2012-02-01

24

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

PubMed Central

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

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

2011-01-01

25

Antimicrobial dosing in critically ill patients with sepsis-induced acute kidney injury  

PubMed Central

Severe sepsis often leads to multiple organ dysfunction syndromes (MODS) with acute kidney injury (AKI). AKI affects approximately, 35% of Intensive Care Unit patients, and most of these are due to sepsis. Mortality rate of sepsis-induced AKI is high. Inappropriate use of antimicrobials may be responsible for higher therapeutic failure, mortality rates, costs and toxicity as well as the emergence of resistance. Antimicrobial treatment is particularly difficult due to altered pharmacokinetic profile, dynamic changes in patient's clinical status and, in many cases, need for renal replacement therapy. This article aims to describe the appropriate antimicrobial dosing and reviews the factors contributing to the difficulties in establishing precise guidelines for antimicrobial dosing in sepsis-induced AKI patients. Search strategy: Text material was collected by systematic search in PubMed, Google (1978–2013) for original articles. PMID:25722552

Kumar, Anish; Singh, Narinder Pal

2015-01-01

26

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

Microsoft Academic Search

BACKGROUND: Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. METHODS: We studied nineteen

Rubens Feferbaum; Cláudio Leone; Arnaldo AF Siqueira; Vitor E Valenti; Paulo R Gallo; Alberto OA Reis; Ary C Lopes; Viviane G Nascimento; Adriana G de Oliveira; Tatiana Dias de Carvalho; Rubens Wajnsztejn; Claudia de Castro Selestrin; Luiz Carlos de Abreu

2010-01-01

27

Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats  

Microsoft Academic Search

Rationale: Our study has shown that plasma levels of ghrelin, a stomach-derived peptide, are significantly reduced in sepsis, and that ghrelin administration improves organ blood flow via a nuclear factor (NF)-kB-dependent pathway. However, it remains unknown whether ghrelin has any protective effects on severesepsis-induced acute lung injury (ALI) and, if so, whether inhibition of NF-kB plays any role in it.

Rongqian Wu; Weifeng Dong; Mian Zhou; Fangming Zhang; Corrado P. Marini; S. Ravikumar; Ping Wang

2007-01-01

28

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

PubMed Central

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

2014-01-01

29

Capnocytophaga canimorsus sepsis presenting as an acute abdomen in an asplenic patient.  

PubMed

Acute abdominal symptoms are frequently caused by surgical intra-abdominal problems. However, the differential diagnosis also includes several internal diseases. Overwhelming infections may present with acute abdominal signs, particularly in the immunocompromised host. Asplenic patients are highly susceptible to infections with encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Severe infections due to Capnocytophaga canimorsus (DF2), are also common in this group. C. canimorsus is a Gram-negative rod, present as a commensal organism in cat and dog saliva. We describe the atypical presentation of a fatal C. canimorsus-sepsis in a 46-year-old man, who underwent traumatic splenectomy two decades earlier. PMID:11705640

Deprés-Brummer, P; Buijs, J; van Engelenburg, K C; Oosten, H R

2001-11-01

30

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

PubMed

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

Lee, Icksoo; Hüttemann, Maik

2014-09-01

31

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

PubMed Central

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

2014-01-01

32

Time-Dependent Alterations of VEGF and Its Signaling Molecules in Acute Lung Injury in a Rat Model of Sepsis  

Microsoft Academic Search

Molecular mechanisms of sepsis-associated acute lung injury (ALI) are poorly defined. Since vascular endothelial growth factor\\u000a (VEGF) is a potent vascular permeability and mitogenic factor, it might contribute to the development of ALI in sepsis. Thus,\\u000a using lipopolysaccharide (LPS)-induced (15 mg\\/kg, intraperitoneal) endotoxemic rat model, we studied the timeline (1, 3, 6,\\u000a and 10 h) of pulmonary VEGF expression and its signaling

Subrina Jesmin; Sohel Zaedi; A. M. Shahidul Islam; S. Nusrat Sultana; Yoshio Iwashima; Takeshi Wada; Naoto Yamaguchi; Michiaki Hiroe; Satoshi Gando

33

Neonatal sepsis: an old problem with new insights.  

PubMed

Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW<1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter ? inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount. PMID:24185532

Shah, Birju A; Padbury, James F

2014-01-01

34

Gene expression profiles analysis identifies key genes for acute lung injury in patients with sepsis.  

PubMed

BackgroundTo identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI¿+¿sepsis compared with patients with sepsis alone were performed with bioinformatic tools.MethodsGSE10474 was downloaded from Gene Expression Omnibus, including a collective of 13 whole blood samples with ALI¿+¿sepsis and 21 whole blood samples with sepsis alone. After pre-treatment with robust multichip averaging (RMA) method, differential analysis was conducted using simpleaffy package based upon t-test and fold change. Hierarchical clustering was also performed using function hclust from package stats. Beisides, functional enrichment analysis was conducted using iGepros. Moreover, the gene regulatory network was constructed with information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and then visualized by Cytoscape.ResultsA total of 128 differentially expressed genes (DEGs) were identified, including 47 up- and 81 down-regulated genes. The significantly enriched functions included negative regulation of cell proliferation, regulation of response to stimulus and cellular component morphogenesis. A total of 27 DEGs were significantly enriched in 16 KEGG pathways, such as protein digestion and absorption, fatty acid metabolism, amoebiasis, etc. Furthermore, the regulatory network of these 27 DEGs was constructed, which involved several key genes, including protein tyrosine kinase 2 (PTK2), v-src avian sarcoma (SRC) and Caveolin 2 (CAV2).ConclusionPTK2, SRC and CAV2 may be potential markers for diagnosis and treatment of ALI.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_176. PMID:25257390

Guo, Zhiqiang; Zhao, Chuncheng; Wang, Zheng

2014-09-26

35

Role of surfactant proteins A and D in sepsis-induced acute kidney injury.  

PubMed

Sepsis is a major cause of acute kidney injury (AKI) with high rates of morbidity and mortality. Surfactant proteins A and D (SP-A, SP-D) play a critical role in host defense and regulate inflammation during infection. Recent studies indicate SP-A and SP-D are expressed in the kidney. The current study examines the role of SP-A and SP-D in the pathogenesis of sepsis-induced AKI. Wild-type (WT) and SP-A/SP-D double-knockout (KO) C57BL/6 mice were treated by cecal ligation and puncture (CLP) or sham surgery. Histological, cellular, and molecular indices of kidney injury were investigated in septic mice 6 and 24 h after CLP. Twenty-four hours after CLP, kidney injury was more severe, renal function was decreased, and blood creatinine and blood urea nitrogen were higher in septic SP-A/SP-D KO mice (P < 0.05, versus septic WT mice). Kidney edema and vascular permeability were increased in septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Apoptotic cells increased significantly (P < 0.01) in the kidney of septic SP-A/SP-D KO mice compared with septic WT mice. Molecular analysis revealed levels of Bcl-2 (an inhibitor of apoptosis) were lower and levels of caspase 3 (a biomarker of apoptosis) were higher in the kidney of septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Furthermore, levels of nuclear factor ?B and phosphorylated I?B-? increased significantly in the kidney of septic SP-A/SP-D KO mice compared with septic WT mice, suggesting SP-A/SP-D KO mice have a more pronounced inflammatory response to sepsis. We conclude SP-A and SP-D attenuate kidney injury by modulating inflammation and apoptosis in sepsis-induced AKI. PMID:25255378

Liu, Jiao; Abdel-Razek, Osama; Liu, Zhiyong; Hu, Fengqi; Zhou, Qingshan; Cooney, Robert N; Wang, Guirong

2015-01-01

36

The fatty acid composition of maternal diet affects lung prostaglandin E2 levels and survival from group B streptococcal sepsis in neonatal rat pups.  

PubMed

Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators. The effects of maternal dietary fatty acid composition upon lung prostaglandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups. Beginning on d 2 of gestation and throughout lactation, pregnant dams were fed a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered to dams of the same diet group to minimize litter effects; litters were then culled to 10 pups per dam. On postnatal d 7, pups were either injected with 1 x 10(7.5) GBS organisms or were killed for determination of lung tissue levels of PGE2 and lung and erythrocyte fatty acid composition. Arachidonic acid and PGE2 levels were significantly higher in the lungs of pups in the corn oil group compared with the fish oil group. Forty-nine percent of pups in the corn oil group survived the GBS challenge compared with 79% of pups in the fish oil group (P = 0.0005). These data suggest that the fatty acid composition of pre- and/or postnatal diet affects the neonatal response to immune challenge, which may be due in part to effects upon the synthesis of pro-inflammatory mediators. PMID:9311955

Rayon, J I; Carver, J D; Wyble, L E; Wiener, D; Dickey, S S; Benford, V J; Chen, L T; Lim, D V

1997-10-01

37

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

PubMed Central

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

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

38

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

PubMed

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

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; Zönnchen, Tina; Rahbari, Nuh N; Schölch, Sebastian; Klotzsche-von Ameln, Anne; Chavakis, Triantafyllos; Weitz, Jürgen; Hofer, Stefan; Weigand, Markus A; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K

2015-03-13

39

Development of Oxidative Stress in the Peritubular Capillary Microenvironment Mediates Sepsis-Induced Renal Microcirculatory Failure and Acute Kidney Injury  

PubMed Central

Acute kidney injury is a frequent and serious complication of sepsis. To better understand the development of sepsis-induced acute kidney injury, we performed the first time-dependent studies to document changes in renal hemodynamics and oxidant generation in the peritubular microenvironment using the murine cecal ligation and puncture (CLP) model of sepsis. CLP caused an increase in renal capillary permeability at 2 hours, followed by decreases in mean arterial pressure, renal blood flow (RBF), and renal capillary perfusion at 4 hours, which were sustained through 18 hours. The decline in hemodynamic parameters was associated with hypoxia and oxidant generation in the peritubular microenvironment and a decrease in glomerular filtration rate. The role of oxidants was assessed using the superoxide dismutase mimetic/peroxynitrite scavenger MnTMPyP [Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin]. At 10 mg/kg administered 6 hours after CLP, MnTMPyP did not alter blood pressure, but blocked superoxide and peroxynitrite generation, reversed the decline in RBF, capillary perfusion, and glomerular filtration rate, preserved tubular architecture, and increased 48-hour survival. However, MnTMPyP administered at CLP did not prevent capillary permeability or the decrease in RBF and capillary perfusion, which suggests that these early events are not mediated by oxidants. These data demonstrate that renal hemodynamic changes occur early after sepsis and that targeting the later oxidant generation can break the cycle of injury and enable the microcirculation and renal function to recover. PMID:22119717

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

2012-01-01

40

Role of C3, C5 and Anaphylatoxin Receptors in Acute Lung Injury and in Sepsis  

PubMed Central

The complement system plays a major role in innate immune defenses against infectious agents, but exaggerated activation of complement can lead to severe tissue injury. Systemic (intravascular) activation of complement can, via C5a, lead to neutrophil (PMN) activation, sequestration and adhesion to the pulmonary capillary endothelium, resulting in damage and necrosis of vascular endothelial cells and acute lung injury (ALI). Intrapulmonary (intraalveolar) activation of complement can cause ALI that is complement and PMN-dependent, resulting in a cytokine/chemokine storm that leads to intense ALI. Surprisingly, C3?/? mice develop the full intensity of ALI in a C5a-dependent manner due to the action of thrombin that generates C5a directly from C5. There is conflicting evidence on the role of the second C5a receptor, C5L2 in development of ALI. There is accumulating evidence that C5a may suppress inflammatory responses or divert them from Th1 to Th2 responses, impacting the innate immune system. Finally, in experimental polymicrobial sepsis, there is evidence that many of the adverse outcomes can be linked to the roles of C5a and engagement of its two receptors, C5aR and C5L2. These observations underscore the diversity of effects of C5a in a variety of inflammatory settings. PMID:21948367

Bosmann, Markus

2012-01-01

41

Growth Arrest-Specific Protein 6 (Gas6) Attenuates Neutrophil Migration and Acute Lung Injury in Sepsis  

PubMed Central

Sepsis is an acute inflammatory condition that can result in multiple organ failure and acute lung injury (ALI). Growth arrest-specific protein 6 (Gas6) is a broad regulator of the innate immune response involved with the NF-?B signaling pathway. We hypothesized that Gas6 could have a protective role in attenuating the severity of ALI 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 AST, ALT and LDH as well as proinflammatory cytokines IL-6 and IL-17, compared to the vehicle group (P<0.05). The parenchyma of the lungs damaged by CLP was attenuated by rmGas6 treatment. Lung mRNA levels of TNF-?, IL-1?, IL-6, IL-17 and MIP-2 were decreased by 60%, 86%, 82%, 93% and 82%, respectively, with rmGas6 treatment as determined by real time RT-PCR (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

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

2013-01-01

42

Anti-Inflammatory Mechanisms of Apolipoprotein A-I Mimetic Peptide in Acute Respiratory Distress Syndrome Secondary to Sepsis  

PubMed Central

Acute respiratory distress syndrome (ARDS) due to sepsis has a high mortality rate with limited treatment options. High density lipoprotein (HDL) exerts innate protective effects in systemic inflammation. However, its role in ARDS has not been well studied. Peptides such as L-4F mimic the secondary structural features and functions of apolipoprotein (apo)A-I, the major protein component of HDL. We set out to measure changes in HDL in sepsis-mediated ARDS patients, and to study the potential of L-4F to prevent sepsis-mediated ARDS in a rodent model of lipopolysaccharide (LPS)-mediated acute lung injury, and a combination of primary human leukocytes and human ARDS serum. We also analyzed serum from non-lung disease intubated patients (controls) and sepsis-mediated ARDS patients. Compared to controls, ARDS demonstrates increased serum endotoxin and IL-6 levels, and decreased HDL, apoA-I and activity of anti-oxidant HDL-associated paraoxanase-1. L-4F inhibits the activation of isolated human leukocytes and neutrophils by ARDS serum and LPS in vitro. Further, L-4F decreased endotoxin activity and preserved anti-oxidant properties of HDL both in vitro and in vivo. In a rat model of severe endotoxemia, L-4F significantly decreased mortality and reduces lung and liver injury, even when administered 1 hour post LPS. Our study suggests the protective role of the apoA-I mimetic peptide L-4F in ARDS and gram-negative endotoxemia and warrant further clinical evaluation. The main protective mechanisms of L-4F are due to direct inhibition of endotoxin activity and preservation of HDL anti-oxidant activity. PMID:23691230

Sharifov, Oleg F.; Xu, Xin; Gaggar, Amit; Grizzle, William E.; Mishra, Vinod K.; Honavar, Jaideep; Litovsky, Silvio H.; Palgunachari, Mayakonda N.; White, C. Roger; Anantharamaiah, G. M.; Gupta, Himanshu

2013-01-01

43

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

PubMed

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

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

2015-05-01

44

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

PubMed

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

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

2013-02-01

45

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

PubMed

Acute kidney injury (AKI) dramatically increases sepsis mortality, but AKI diagnosis is delayed when based on serum creatinine (SCr) changes, due in part, to decreased creatinine production. During experimental sepsis, we compared serum cystatin C (sCysC), SCr, and blood urea nitrogen (BUN) to inulin glomerular filtration rate (iGFR) before or 3-18 h after cecal ligation and puncture (CLP)-induced sepsis in CD-1 mice. sCysC had a faster increase and reached peak levels more rapidly than SCr in both sepsis and bilateral nephrectomy (BiNx) models. sCysC was a better surrogate of iGFR than SCr during sepsis. Combining sCysC with SCr values into a composite biomarker improved correlation with iGFR better than any biomarker alone or any other combination. We determined the renal contribution to sCysC handling with BiNx. sCysC and SCr were lower post-BiNx/CLP than post-BiNx alone, despite increased inflammatory and nonrenal organ damage biomarkers. Sepsis decreased CysC production in nephrectomized mice without changing body weight or CysC space. Sepsis decreased sCysC production and increased nonrenal clearance, similar to effects of sepsis on SCr. sCysC, SCr, and BUN were measured 6 h postsepsis to link AKI with mortality. Mice with above-median sCysC, BUN, or SCr values 6 h postsepsis died earlier than mice with below-median values, corresponding to a substantial AKI association with sepsis mortality in this model. sCysC performs similarly to SCr in classifying mice at risk for early mortality. We conclude that sCysC detects AKI early and better reflects iGFR in CLP-induced sepsis. This study shows that renal biomarkers need to be evaluated in specific contexts. PMID:25143457

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

2014-10-15

46

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

PubMed

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?sepsis group was lower compared with the ghrelin group (2.27?±?0.37) (p?sepsis group at 20 h. Ghrelin group pathological scores were lower than in the sepsis group (p?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

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

2015-04-01

47

Inhibition of Interleukin22 Attenuates Bacterial Load and Organ Failure during Acute Polymicrobial Sepsis  

Microsoft Academic Search

Interleukin-22 (IL-22) is a recently discovered proinflammatory cytokine, structurally related to IL-10. Since IL-22 is induced by lipopolysaccharide in vivo, we studied the role of IL-22 in a model of polymicrobial peritonitis. Quantitative real-time reverse transcription-PCR analysis showed marked induction of IL-22 and IL-22 receptor in spleen and kidney during the course of sepsis. The biological activity of IL-22 is

Georg F. Weber; Sylvia Schlautkotter; Simone Kaiser-Moore; Felicitas Altmayr; Bernhard Holzmann; Heike Weighardt

2007-01-01

48

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

PubMed

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

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

2014-01-01

49

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

PubMed Central

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

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

2012-01-01

50

Aggressive Periodontitis with Streptococcal Gingivitis: A Case Report  

PubMed Central

Acute streptococcal gingivitis is an acute inflammation of the oral mucosa and also may be seen with the other oral diseases as aggressive periodontitis that is characterized by a considerable attachment loss over a relatively short period of time. Streptococcal infections of gingiva are seen rarely; also the origin of this gingival inflammation is occasionally different from that of routine plaque-associated gingivitis. The clinical features and treatment methods of these diseases are already reported in previous literatures. This case report describes a patient who presented with severe gingival inflammation and attachment loss that was diagnosed as an acute streptococcal infection associated with aggressive periodontitis. In this study a supportive treatment option was demonstrated based on these data and antacid treatment as adjunctive to the recommended treatment modalities was used for streptococcal gingivitis. PMID:19212476

Kara, Cankat; Demir, Turgut; Tezel, Adnan; Zihni, Meltem

2007-01-01

51

[Streptococcal tonsillopharyngitis: clinical vs. microbiological diagnosis].  

PubMed

This study aimed to evaluate the role of clinical diagnosis vs. rapid antigen detection tests (RADT) in identifying streptococcal vs. non-streptococcal cases of acute pharyngitis (AP) with respect to a scoring schedule. The Breese scoring system, modified by eliminating the count of peripheral WBC, was used in the study. At enrolment, cases of AP observed by office-based pediatricians were judged on a clinical basis as possibly of streptococcal or of non-streptococcal origin and a clinical score recorded. At the end of the visit and following completion of the clinical score to document the presence/absence of a group A beta haemolytic streptococcus (GABHS), a confirmatory RADT was performed. In RADT negative cases a standard throat swab and culture were performed. In all, 629 children presenting with AP were enrolled in the study. A correct clinical diagnosis was predicted on the basis of the clinical observation in 74.2% of cases (with a sensitivity of 81.1% and specificity of 70.5%). In cases judged as "streptococcal", a mean score of 27.6 was recorded both in those patients with a positive or negative RADT/throat swab for GABHS. By contrast, among cases considered of non-streptococcal aetiology, negative RADT/culture had a mean score of 24.3 compared to a mean score of 25 in those with a positive RADT/culture. Intragroup score differences were not significant, while intergroup differences were highly significant. Optimization of AP treatment requires careful identification of streptococcal cases, avoiding unnecessary antibiotic treatment which would contribute to enhancing antibiotic resistance and increase medical treatment costs. We document that clinical observation alone, although performed by skilled pediatricians, will misdiagnose a sizeable percentage of cases. As indicated by this study, scores may suffer from a subjective interpretative bias in grading the severity of signs and symptoms. PMID:21753249

Boccazzi, A; Garotta, M; Pontari, S; Agostoni, C V

2011-06-01

52

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

PubMed

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

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

2008-12-01

53

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

PubMed Central

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

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

2014-01-01

54

Sequential actions of SIRT1-RELB-SIRT3 coordinate nuclear-mitochondrial communication during immunometabolic adaptation to acute inflammation and sepsis.  

PubMed

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

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

2015-01-01

55

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

PubMed Central

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

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

56

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

PubMed Central

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

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

2015-01-01

57

Gut Origin Sepsis, Macrophage Function, and Oxygen Extraction Associated with Acute Pancreatitis in the Rat  

Microsoft Academic Search

. It has been suggested that the gut plays a role in the development of bacterial complications, which are important\\u000a contributors to morbidity and mortality in patients with acute pancreatitis. The present study evaluated the enteric bacterial\\u000a translocation, bacterial homeostasis, and reticuloendothelial system function in experimental acute pancreatitis induced by\\u000a intraductal injection of 5% sodium taurodeoxycholate in the rat. The

Xiangdong Wang; Roland Andersson; Vasile Soltesz; Per Leveau; Ingemar Ihse

1996-01-01

58

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

PubMed

Respiratory burst function of neutrophils is thought to play a pivotal role in the development of pathologies such as indirect (extra-pulmonary) acute lung injury (iALI), as well as sepsis. The current study was conducted to determine the effect of an HIV transactivator of transcription (TAT)-fusion protein containing a soluble N-ethylmaleimide-sensitive factor attachment protein receptor domain from synaptosome-associated protein-23 (SNAP-23) on the shock/sepsis- and sepsis-enhanced neutrophil burst capacity using the clinical relevant two-hit iALI mouse model and the classical cecal ligation and puncture (CLP) septic model. TAT-SNAP-23 significantly decreased the blood neutrophil respiratory burst in vitro, and also in vivo in CLP and hemorrhaged mice. We found that the neutrophil influx to the lung tissue, as measured by myeloperoxidase levels and neutrophil-specific esterase(+) cells, was also decreased in the TAT-SNAP-23-treated group. Consistent with this, treatment of TAT-SNAP-23 significantly reduced the disruption of lung tissue architecture and protein concentration of bronchoalveolar lavage fluid in iALI mice compared with vehicle-treated iALI mice. In addition, although TAT-SNAP-23 did not alter the extent of local cytokine/chemokine expression, the in vitro migration capacity of neutrophils was blunted from septic and hemorrhagic mice. These data support our hypothesis that TAT-SNAP-23 reduces neutrophil dysfunction in iALI and sepsis by inhibiting neutrophil respiratory burst. PMID:24391146

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

2015-01-01

59

Renal Vascular Resistance in Sepsis  

Microsoft Academic Search

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

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

2006-01-01

60

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

PubMed Central

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

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

2013-01-01

61

Streptococcal Infections: Not A or B  

MedlinePLUS

... A or B Health Issues Listen Streptococcal Infections: Not A or B Article Body While many streptococcal ... Group A or B, other streptococcal infections do not fall into either category. In infants and children, ...

62

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

PubMed Central

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

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

2014-01-01

63

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

PubMed

We report an 18-year-old ice skater with acute lymphoblast leukemia. She developed Staphylococcus epidermidis bacteremia, severe sepsis, septic shock, and ARDS following chemotherapy-induced severe bone marrow failure. She was successfully treated with extraordinary life support measures, which included extracorporeal membrane oxygenation, double lumen lung ventilation for management of hemoptysis, and lung assist membrane ventilation. After 57 days of ICU treatment and a year of rehabilitation, the patient has fully regained her functional status, is now finishing high school, and is ice skating again. PMID:22369998

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

2012-07-01

64

Neuropsychiatric movement disorders following streptococcal infection.  

PubMed

The aim of this study was to describe post-streptococcal movement disorders that form part of the acute rheumatic fever complex. The clinical records of patients diagnosed with Sydenham's chorea were analyzed retrospectively to investigate epidemiology, the significance of socioeconomic deprivation, clinical manifestations, treatments, outcomes, long-term morbidity, and disease evolution. Forty-two patients (21 males, 21 females) were diagnosed with Sydenham's chorea. The median presentation age was 9 years 8 months (range 3y 5mo to 13y 2mo). Nineteen patients were of indigenous African ancestry; 23 were of mixed ancestry. All patients lived in poverty and had poor access to medical care. Twelve of the total group had disabling symptoms for longer than 2 years; six of these patients developed paediatric autoimmune neuropsychiatric disorder associated with Streptococcus (Paediatric autoimmune neuropsychiatric disorder associated with Streptococcus [PANDAS]), five Tourette syndrome (TS), and one learning difficulties. Poor outcome was significantly more prevalent in patients of mixed ancestry, in those with a positive family history, previous behavioural problems, or a failure to complete 10 days of penicillin and 'bed-rest'/hospitalization. Sydenham's chorea is one manifestation of post-streptococcal neuropsychiatric movement disorders. This study demonstrates that patients can present with one diagnosis and evolve other neuropsychiatric conditions such as TS and PANDAS. In the South African context, it is important to delineate neuropsychiatric movement disorders associated with streptococcal infections. The potential genetic susceptibility should be explored. PMID:16225742

Walker, K G; Lawrenson, J; Wilmshurst, J M

2005-11-01

65

The Role of Whole Blood Impedance Aggregometry and Its Utilisation in the Diagnosis and Prognosis of Patients with Systemic Inflammatory Response Syndrome and Sepsis in Acute Critical Illness  

PubMed Central

Objective To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). Methods We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. Results 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p?=?0.001, Collagen 102.6±33.0 vs 79.1±38.8; p?=?0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p?=?0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Conclusions Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant. PMID:25269018

Davies, Gareth R.; Mills, Gavin M.; Lawrence, Matthew; Battle, Ceri; Morris, Keith; Hawkins, Karl; Williams, Phylip Rhodri; Davidson, Simon; Thomas, Dafydd; Evans, Phillip Adrian

2014-01-01

66

Invasive Group B Streptococcal  

E-print Network

was recovered in 80% of meningitis cases. Group B Streptococcus (GBS) is the leading cause of in- fectious illness among newborns. Invasive infections in neonates can result in pneumonia, sepsis, or meningitis

Paris-Sud XI, Université de

67

Pediatric sepsis  

PubMed Central

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 child’s 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

Randolph, Adrienne G; McCulloh, Russell J

2014-01-01

68

Neonatal sepsis  

MedlinePLUS

... coli ( E.coli ), Listeria , and some strains of streptococcus. The herpes virus can also cause a severe ... infant's risk of early-onset sepsis: Group B streptococcus infection during pregnancy Preterm delivery Water breaking (rupture ...

69

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

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

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

70

Understanding brain dysfunction in sepsis  

PubMed Central

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

2013-01-01

71

Pathogenesis of Group A Streptococcal Infections  

PubMed Central

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

Cunningham, Madeleine W.

2000-01-01

72

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

PubMed Central

Background Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients. Methods/Design This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 ?g.kg-1.min-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom. Discussion This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action. Trial registration Current controlled trials ISRCTN12776039 (19 September 2013) PMID:24894386

2014-01-01

73

Reactivity of Rheumatic Fever and Scarlet Fever Patients' Sera with Group A Streptococcal M Protein, Cardiac Myosin, and Cardiac Tropomyosin: a Retrospective Study  

Microsoft Academic Search

While a definitive link between group A streptococcal (GAS) pharyngitis and the pathogenesis of acute rheumatic fever (ARF) is still largely undetermined, early studies have pointed to serological cross-reactions between streptococcal antigens and cardiac tissue as a possible connection (3, 6, 24-28, 46, 48, 49). M protein, the primary virulence factor for GAS (32), has received the most scrutiny in

KEVIN F. JONES; STEPHEN S. WHITEHEAD; MADELEINE W. CUNNINGHAM; V. A. Fischetti

2000-01-01

74

Streptococcal infections of skin and PANDAS.  

PubMed

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

Carelli, Rosanna; Pallanti, Stefano

2014-01-01

75

STUDIES ON STREPTOCOCCAL FIBRINOLYSIS  

PubMed Central

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

1947-01-01

76

Staphylococcal and Streptococcal Superantigen Exotoxins  

PubMed Central

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

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

2013-01-01

77

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

PubMed

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 ?/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

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

2012-09-18

78

Properdin Levels in Human Sepsis  

PubMed Central

Properdin is a normal serum protein that increases the production of complement activation products by binding C3b integral to convertase complexes and amplifying their activity at the site of activation. Thereby, it not only can aid in the resolution of infection but also contribute to tissue damage. In human sepsis, circulating complement C3 concentrations are decreased, though C3 is described as a positive acute phase reactant. However, properdin levels in human sepsis have not been reported. In this study, serum from 81 critically ill patients (predominately abdominal and respiratory sepsis) were analyzed for properdin levels at defined points of their stay in the intensive care unit (ICU) and compared with 61 age and sex-matched healthy volunteers. Properdin concentrations were significantly decreased in patients with sepsis on admission to ICU, but increased after clinical recovery to exceed levels observed in healthy volunteers. Properdin concentrations at ICU admission were decreased in non-survivors of sepsis compared to survivors, but this did not correlate with APACHE II score. However, pathologically low properdin levels (<7 ?g/ml) were related to increased duration of treatment. PMID:25699043

Stover, Cordula M.; McDonald, John; Byrne, Simon; Lambert, David G.; Thompson, Jonathan P.

2015-01-01

79

Host-pathogen interactions in streptococcal immune sequelae.  

PubMed

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

Nitsche-Schmitz, D Patric; Chhatwal, Gursharan S

2013-01-01

80

Targeting sepsis as a performance improvement metric: role of the nurse.  

PubMed

Sepsis is the body's systemic response to infection that can be complicated by acute organ dysfunction and is associated with high mortality rates and adverse outcomes for acute and critically ill patients. The 2012 Surviving Sepsis Campaign guidelines advocated for implementation of evidence-based practice care for sepsis, with a focus on quality improvement. Nurses are directly involved in identification and management of sepsis. Implementing performance improvement strategies aimed at early recognition and targeted treatment can further improve sepsis care and patient outcomes. This article presents an overview of the process of implementing performance improvement initiatives for sepsis care, highlighting the significant contribution of nursing care. PMID:24752031

Kleinpell, Ruth; Schorr, Christa A

2014-01-01

81

Real-Time Polymerase Chain Reaction for the Rapid Detection of Group B Streptococcal Colonization in Neonates  

Microsoft Academic Search

BACKGROUND.Group B streptococcal (GBS) infection remains a leading cause of neonatal sepsis. Currently, the management guidelines of neonates born to women with unknown GBS status at delivery are unclear. In this cohort, who undergo at least a 48-hour observation, a rapid method of detection of GBS colonization would allow targeted evaluation and treatment, as well as prevent delayed discharge. OBJECTIVE.The

Girija Natarajan; Yvette R. Johnson; Fan Zhang; Kang Mei Chen; Maria J. Worsham

2010-01-01

82

Current treatment of severe sepsis  

Microsoft Academic Search

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

Ismail Cinel; R. Phillip Dellinger

2006-01-01

83

Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea  

Microsoft Academic Search

Recent evidence suggests that the pathogenesis of Sydenham's chorea following group A streptococcal infection is due to antibodies which develop due to the infection and infiltrate the brain and basal ganglia. Antibodies present in acute chorea react with the surface of neuronal cells and signal the induction of calcium calmodulin dependent protein kinase II with elevation of tyrosine hydroxylase and

Christine A. Kirvan; Susan E. Swedo; David Kurahara; Madeleine W. Cunningham

2006-01-01

84

JAMA Patient Page: Sepsis  

MedlinePLUS

... blood flow) to 1 or more organs Septic shock 4. : sepsis with persisting arterial hypotension or hypoperfusion ... severe sepsis, and more than 60% for septic shock. Those who recover may have some permanent organ ...

85

The immunopathogenesis of sepsis  

Microsoft Academic Search

Sepsis is a condition that results from a harmful or damaging host response to infection. Many of the components of the innate immune response that are normally concerned with host defences against infection can, under some circumstances, cause cell and tissue damage and hence multiple organ failure, the clinical hallmark of sepsis. Because of the high mortality of sepsis in

Jonathan Cohen

2002-01-01

86

Bacteriæmia and Oral Sepsis  

PubMed Central

Transient streptococcal bacteriæmias are a frequent sequel to dental extractions especially when the mouth is the seat of severe chronic gum infection. Bacteria may also gain admission to the blood-stream in such cases irrespective of operative procedures and probably as the result, in many instances, of minor degrees of gum injury such as is produced by biting on a loose tooth. Acute apical infections do not appear to be especially associated with blood infection of this kind, the focus of infection here apparently being effectively “walled off” by the associated inflammatory reaction. Of the two factors, infection and trauma, involved in the production of these post-operative bacteriæmias, infection appears to be the more important since, when it is marked, very slight degrees of gum injury are sufficient to produce blood-stream invasion. In the complete absence, however, of the type of trauma induced by the “rocking” of a tooth during its removal, extraction may be accomplished without producing a heavy bacterial shower in the blood. Usually these transient bacteriæmias produce no permanent ill-effect, but there is some evidence that, occurring in subjects with abnormal heart valves, they may lead to subacute infective endocarditis. Thirteen cases are reported where the valvular infection appeared to result from a post-operative dental bacteriæmia. Prevention of such bacteriæmias may be achieved by the reduction or elimination of infection and trauma. Complete elimination of the gum infection is difficult although preliminary treatment of the gum margin by some measure such as cauterization may lessen it and lead to a reduction of the post-operative bacterial shower. Similarly, by manipulating an infected tooth as little as possible during its extraction the incidence or degree of blood infection may be decreased. PMID:19991911

Elliott, S. D.

1939-01-01

87

Biomarkers of Sepsis  

PubMed Central

Sepsis remains a leading cause of death in critically ill patients, despite efforts to improve patient outcome. Thus far, no magic drugs exist for severe sepsis and septic shock. Instead, early diagnosis and prompt initial management such as early goal-directed therapy are key to improve sepsis outcome. For early detection of sepsis, biological markers (biomarkers) can help clinicians to distinguish infection from host response to inflammation. Ideally, biomarkers can be used for risk stratification, diagnosis, monitoring of treatment responses, and outcome prediction. More than 170 biomarkers have been identified as useful for evaluating sepsis, including C-reactive protein, procalcitonin, various cytokines, and cell surface markers. Recently, studies have reported on the usefulness of biomarker-guided antibiotic stewardships. However, the other side of these numerous biomarkers is that no novel single laboratory marker can diagnose, predict, and track the treatment of sepsis. The purpose of this review is to summarize several key biomarkers from recent sepsis studies. PMID:24693464

Cho, Sung-Yeon

2014-01-01

88

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

PubMed Central

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

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

2014-01-01

89

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

PubMed Central

Doripenem is a novel wide-spectrum antibiotic, and a derivate of carbapenems. It is an ideal antibiotic for treatment of serious nosocomial infections and severe sepsis for its exceptionally high efficiency and broad antibacterial spectrum of action. Doripenem is eliminated mainly by the kidneys. In cases of acute kidney injury, dosing of doripenem depends on creatinine clearance and requires adjustments. Doripenem is eliminated during hemodialysis because its molecular weight is 300–400 Da. The aim of this study was to establish the impact of continuous renal replacement therapy (CRRT) slow low-efficiency dialysis (SLED) on doripenem serum concentrations in a population of intensive-therapy patients with life-threatening infections and severe sepsis. Ten patients were enrolled in this observational study. Twelve blood samples were collected during the first administration of doripenem in a 1-hour continuous infusion while CRRT SLED was provided. Fluid chromatography was used for measurement of the concentration of doripenem in serum. In all collected samples, concentration of doripenem was above the minimum inhibition concentration of this antibiotic. Based on these results, we can draw the conclusion that doripenem concentration is above the minimum inhibition concentration throughout all of CRRT. The dosing pattern proposed by the manufacturer can be used in patients receiving CRRT SLED without necessary modifications. PMID:25364230

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

2014-01-01

90

Sepsis biomarkers: a review  

PubMed Central

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

2010-01-01

91

Group B streptococcal septicemia of the newborn  

MedlinePLUS

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

92

Pharmacotherapy of sepsis.  

PubMed

Treatment of sepsis involves prompt recognition and treatment to optimize outcome. Several medication considerations are pertinent to patients with sepsis, severe sepsis, and septic shock. Medications play a crucial role in providing resuscitation, hemodynamic support, resolution of infection, and reduction of complications of the disease. Over the past 20 years, significant focus has been devoted to the pharmacologic treatment of septic shock, resulting in significant advances and controversies. Ongoing research will continue to focus on this disease process and will continue to shape treatment in the future. The use of medication therapies directed at treatment of sepsis will be reviewed in this article. PMID:25741953

Pavlik, David J; Simpson, Robert W; Horn, Edward T; King, Lauren; Finoli, Lauren

2015-01-01

93

Identifying sepsis too late.  

PubMed

Sepsis campaign awareness and adherence to the SSC bundles remain a challenge for many healthcare providers causing wide-ranging results, but hospitals are consistently reporting reduced sepsis-related mortality associated with adherence to the SSC guidelines. This case study is likely very similar to many of the other hundreds of thousands of people who died of sepsis in 2010. Would following the SSC guidelines have made a difference for this patient? It’s difficult to know for sure, but this case illustrates the importance of remaining in formed about the latest research and guidelines in healthcare. Visit www.surviving sepsis.org to learn more about the guidelines for treating sepsis. PMID:24430381

Miller, April

2014-02-01

94

Rapid diagnosis of sepsis  

PubMed Central

Fast and appropriate therapy is the cornerstone in the therapy of sepsis. However, the discrimination of sepsis from non-infectious causes of inflammation may be difficult. Biomarkers have been suggested to aid physicians in this decision. There is currently no biochemical technique available which alone allows a rapid and reliable discrimination between sepsis and non-infectious inflammation. Procalcitonin (PCT) is currently the most investigated biomarker for this purpose. C-reactive protein and interleukin 6 perform inferior to PCT in most studies and their value in diagnosing sepsis is not defined. All biomarkers including PCT are also released after various non-infectious inflammatory impacts. This shortcoming needs to be taken into account when biomarkers are used to aid the physician in the diagnosis of sepsis. Polymerase chain reaction (PCR) based pathogen detection may improve time to adequate therapy but cannot rule out the presence of infection when negative. PMID:24335467

Bloos, Frank; Reinhart, Konrad

2014-01-01

95

Normal ranges of streptococcal antibody titers are similar whether streptococci are endemic to the setting or not.  

PubMed

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

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

2009-02-01

96

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

PubMed Central

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

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

1991-01-01

97

Pharmacological management of sepsis  

SciTech Connect

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.

Fletcher, J.R.

1985-01-01

98

Biomarkers of sepsis  

PubMed Central

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

2013-01-01

99

The older adult experiencing sepsis.  

PubMed

Sepsis is a potentially fatal response to infection affecting patients across the life span. Sepsis can progress from systemic inflammatory response to severe sepsis and septic shock if not recognized promptly and managed effectively. Risk factors for sepsis include age, gender, the presence of invasive devices (eg, urinary catheters), and chronic medical conditions (eg, chronic obstructive pulmonary disease). Sepsis awareness is essential and includes identification of population-focused risk factors, recognition of clinical signs and symptoms, and timely implementation of interventions. The purpose of this article was to examine sepsis in older adults, including prevalence, atypical presentation of the condition, and considerations for sepsis management in the elderly population. PMID:25741958

Englert, Nadine C; Ross, Carl

2015-01-01

100

The Microcirculation in Sepsis  

PubMed Central

Summary Sepsis is a leading cause of mortality in critically ill patients. The pathophysiology of sepsis involves a highly complex and integrated response, including the activation of various cell types, inflammatory mediators, and the haemostatic system. Recent evidence suggests an emerging role of the microcirculation in sepsis, necessitating a shift in our locus away Irom the macrohaemodynamics to ill icrohaemodynanmics in a septic patient. This review article provides a brief overview of the microcirculation, its assessment techniques, and specific therapies to resuscitate the microhaemodynamics. PMID:20640135

Tyagi, Asha; Sethi, Ashok Kumar; Girotra, Gautam; Mohta, Medha

2009-01-01

101

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

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

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

102

Immunological studies of post-streptococcal sequelae: serological studies with an extracellular protein associated with nephritogenic streptococci.  

PubMed Central

Using the Ouchterlony double diffusion and the crossed-immunoelectrophoresis techniques the reactivity to a purified extracellular product of nephritogenic group A streptococci (NASP) was examined with both acute and convalescent sera obtained from patients with documented post-streptococcal glomerulonephritis and patients with documented acute rheumatic fever. The streptococcal antigen utilized in these studies was first purified on SDS gels and then eluted from the gel, resulting in a single protein band on SDS electrophoresis. Double diffusion studies revealed that only nephritis patients reacted to this extracellular product associated with nephritogenic strains, whereas rheumatic fever sera produced no line of precipitation. An assay of serial bleedings from nephritis patients suggested that the antibody reactive to the NASP was in higher titre in the acute phase of the disease and decreased with convalescence. In confirmation of these findings, crossed-immunoelectrophoresis experiments were conducted with a battery of sera from acute nephritic and non-nephritic patients against the NASP antigen. A striking increase was detected in the reactivity of nephritis patients (96%) compared to non-nephritis sera (15-20%). Comparison between acute and convalescent sera using this technique confirmed the finding of decreasing antibody titre with resolution of disease. These findings of a specific humoral response in patients with acute post-streptococcal nephritis to the NASP of nephritogenic strains further implicates an aetiological function to this protein. Images Fig. 6 Fig. 7 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6413107

Ohkuni, H; Friedman, J; van de Rijn, I; Fischetti, V A; Poon-King, T; Zabriskie, J B

1983-01-01

103

Biomarkers in sepsis  

PubMed Central

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, academic–industry collaborations, appropriate investigations and validation in heterogenous populations, but these developments do hold the capacity to transform patient care and outcomes. PMID:23411577

Singer, Mervyn

2013-01-01

104

Sepsis Response Team  

Microsoft Academic Search

\\u000a The transition from sepsis to severe life-threatening disease frequently develops well before admission to an intensive care\\u000a unit (ICU), often in the pre-hospital setting, the emergency department (ED), general medical-surgical floors, operating room\\u000a or the outpatient clinic setting. One would hope that as soon as possible after the sepsis syndrome occurs, treatment with\\u000a resuscitation fluids, restoration of adequate oxygen delivery

Emanuel P. Rivers; David Amponsah; Victor Coba

105

Pathophysiology of Sepsis  

PubMed Central

Sepsis remains a critical problem with significant morbidity and mortality even in the modern era of critical care management. Multiple derangements exist in sepsis involving several different organs and systems, although controversies exist over their individual contribution to the disease process. Septic patients have substantial, life-threatening alterations in their coagulation system, and currently, there is an approved therapy with a component of the coagulation system (activated protein C) to treat patients with severe sepsis. Previously, it was believed that sepsis merely represented an exaggerated, hyperinflammatory response with patients dying from inflammation-induced organ injury. More recent data indicate that substantial heterogeneity exists in septic patients’ inflammatory response, with some appearing immuno-stimulated, whereas others appear suppressed. Cellular changes continue the theme of heterogeneity. Some cells work too well such as neutrophils that remain activated for an extended time. Other cellular changes become accelerated in a detrimental fashion including lymphocyte apoptosis. Metabolic changes are clearly present, requiring close and individualized monitoring. At this point in time, the literature richly illustrates that no single mediator/system/pathway/pathogen drives the pathophysiology of sepsis. This review will briefly discuss many of the important alterations that account for the pathophysiology of sepsis. PMID:17456750

Remick, Daniel G.

2007-01-01

106

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

107

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

PubMed Central

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

Popovic, Nada; Djordjevic, Dragan

2013-01-01

108

Humanized In Vivo Model for Streptococcal Impetigo  

Microsoft Academic Search

An in vivo model for group A streptococcal (GAS) impetigo was developed, whereby human neonatal foreskin engrafted onto SCID mice was superficially damaged and bacteria were topically applied. Severe infection, indicated by a purulent exudate, could be induced with as few as 1,000 CFU of a virulent strain. Early findings (48 h) showed a loss of stratum corneum and adherence

DOMINICK A. SCARAMUZZINO; JENNIFER M. MCNIFF; DEBRA E. BESSEN

2000-01-01

109

Streptococcal genomes provide food for thought  

Microsoft Academic Search

sepsis (blood infection), pneumonia, otitis media and meningitis; Streptococcus pyogenes, or group A Streptococcus, the agent of pharyn- gitis (strep throat), impetigo and rheumatic fever; and Streptococcus agalactiae, or group B Streptococcus, which infects neonates and results in bacterial sepsis, pneumonia or meningitis. S. thermophilus is also related to Streptococcus mutans, a cause of tooth decay. The genome sequence of

Hervé Tettelin; Bob Crimi

2004-01-01

110

Sepsis in vulnerable populations.  

PubMed

Despite the acquisition of a large body of evidence, there are many unanswered questions about sepsis. The definition of this disease is plagued by the lack of a simple pathophysiological description linking cause to effect and the activation of host immune responses that hinders disease progression at the same time producing multiorgan dysfunction. A plethora of inconsistent clinical features has served to obfuscate rather than illuminate. The Surviving Sepsis Guidelines (SSG) are a major advance because it comprehensively interrogates all aspects of care for the critically ill. For vulnerable populations living in low- and middle-income countries, this guideline is ineffectual because of the lack of region-specific data, differences in etiology of sepsis and burden of disease, limited human capacity and infrastructure, as well as socioeconomic realities. Appropriate care must be guided by common sense guidelines that are sensitive to local realities and adapted as relevant data are acquired. PMID:25667179

Bhagwanjee, Satish; Ugarte, Sebastian

2014-09-01

111

Biomarkers for Sepsis  

PubMed Central

Bloodstream infections are a major concern because of high levels of antibiotic consumption and of the increasing prevalence of antimicrobial resistance. Bacteraemia is identified in a small percentage of patients with signs and symptoms of sepsis. Biomarkers are widely used in clinical practice and they are useful for monitoring the infectious process. Procalcitonin (PCT) and C-reactive protein (CRP) have been most widely used, but even these have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. PCT has been used to guide empirical antibacterial therapy in patients with respiratory infections and help to determine if antibacterial therapy can be stopped. New biomarkers such as those in this review will discuss the major types of biomarkers of bloodstream infections/sepsis, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin. PMID:24800240

Henriquez-Camacho, Cesar; Losa, Juan

2014-01-01

112

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

PubMed Central

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

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

2009-01-01

113

Organ dysfunction during sepsis  

Microsoft Academic Search

Background  Multiple organ dysfunction syndrome is the commonest reason for sepsis-associated mortality.\\u000a \\u000a \\u000a \\u000a Discussion  In the 40 years since it was first described understanding of its pathophysiology has improved, and novel methodologies for\\u000a monitoring and severity of illness scoring have emerged. These, together with the development of systematic strategies for\\u000a managing organ dysfunction in sepsis, and potentially effective new therapeutic interventions, should assist in

Suveer Singh; Timothy W. Evans

2006-01-01

114

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

PubMed Central

Background Streptococcus salivarius K12 is an oral probiotic strain releasing two lantibiotics (salivaricin A2 and salivaricin B) that antagonize the growth of S. pyogenes, the most important bacterial cause of pharyngeal infections in humans also affected by episodes of acute otitis media. S. salivarius K12 successfully colonizes the oral cavity, and is endowed with an excellent safety profile. We tested its preventive role in reducing the incidence of both streptococcal and viral pharyngitis and/or tonsillitis in children. Materials and methods We enrolled 61 children with a diagnosis of recurrent oral streptococcal disorders. Thirty-one of them were enrolled to be treated daily for 90 days with a slow-release tablet for oral use, containing no less than 1 billion colony-forming units/tablet of S. salivarius K12 (Bactoblis®), and the remaining 30 served as the untreated control group. During treatment, they were all examined for streptococcal infection. Twenty children (ten per group) were also assessed in terms of viral infection. Secondary end points in both groups were the number of days under antibiotic and antipyretic therapy and the number of days off school (children) and off work (parents). Results The 30 children who completed the 90-day trial with Bactoblis® showed a significant reduction in their episodes of streptococcal pharyngeal infection (>90%), as calculated by comparing the infection rates of the previous year. No difference was observed in the control group. The treated group showed a significant decrease in the incidence (80%) of oral viral infections. Again, there was no difference in the control group. With regard to secondary end points, the number of days under antibiotic treatment of the treated and control groups were 30 and 900 respectively, days under antipyretic treatment 16 and 228, days of absence from school 16 and 228, and days of absence from work 16 and 228. The product was well tolerated by the subjects, with no side effects, and only one individual reported bad product palatability and dropped out. Conclusion Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal disease resulted in a considerable reduction of episodes of both streptococcal and viral infections and reduced the number of days under antibiotic and/or antipyretic therapy and days of absence from school or work. PMID:24600248

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

2014-01-01

115

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

PubMed Central

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

2014-01-01

116

Dentigerous cyst of mandible presenting as sepsis.  

PubMed

Dentigerous cysts are odontogenic cysts that develop by accumulation of fluid between reduced enamel epithelium and a crown of an unerupted tooth. Dentigerous cysts typically are slow growing and incidental findings on radiographic images [1]. These cysts are usually small but when they become large, they will cause a pathologic fracture. Occasionally, they can become painful when infected, which will cause swelling and erythema [1]. We present a rare case of a dentigerous cyst that presented as sepsis. Dentigerous cysts are the most common type of noninflammatory odontogenic cyst [2]. The atypical acute presentation and extent of this patient's soft tissue manifestations resulting in tracheal midline shift and sepsis make this a rare case for presentation. PMID:24985943

Anderson, Dustin W; Evans, David

2014-12-01

117

Revisiting caspases in sepsis  

PubMed Central

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

Aziz, M; Jacob, A; Wang, P

2014-01-01

118

Severe sepsis and septic shock  

PubMed Central

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

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

2014-01-01

119

Medical treatment of multiple streptococcal liver abscesses  

SciTech Connect

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.

Matlow, A.; Vellend, H.

1983-04-01

120

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

PubMed Central

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

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

2014-01-01

121

Group B streptococcal phospholipid causes pulmonary hypertension  

NASA Astrophysics Data System (ADS)

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.

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

2003-04-01

122

Group a streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen  

PubMed Central

Heart-reactive antibody (HRA) appears in the sera of experimental animals inoculated with group A streptococci as well as patients with acute rheumatic fever. Adsorption of either serum with group A streptococcal membranes will remove the HRA. Blocking experiments between these two types of HRAs have demonstrated that the antibodies are directed towards different antigenic determinants on either the same or different molecules. To isolate and purify the antigen from the group A streptococcus cross-reactive with sarcolemmal sheaths of cardiac myofibers, it became necessary to purify the HRA from rheumatic fever patients’ sera. Isolated gamma globulin containing all of the HRA was adsorbed onto human sarcolemmal sheaths. The specific HRA was released by using potassium iodide. Over 99 percent of the purified HRA was shown to bind the sarcolemmal sheath whereas less than 1 percent of the antibody would bind nonspecifically to other material. Preparations of group A streptococcal membrane will bind HRA purified from the sera of acute rheumatic patients at levels of 97 percent or greater. The cross-reactive antigen solubilized by nonionic detergent was purified 120-fold by column chromatography. On sodium dodecyl sulfate polyacrylamide electrophoresis, the antigen was demonstrated to be composed of four polypeptides with mol wt of 32,000, 28,000, 26,000, and 22,000 daltons, respectively. Only proteolytic enzymes could destroy the antigenic determinant whereas glycosidases and lipases had no effect. The purified antigen blocked the binding of purified HRA to normal human heart sections. PMID:327018

Van De Rijn, I; Sabriskie, JB; McCarty, M

1977-01-01

123

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

PubMed Central

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

2012-01-01

124

Are similar inflammatory factors involved in strenuous exercise and sepsis?  

Microsoft Academic Search

An increasing body of data suggest that strenuous exercise triggers an inflammatory response having some similarity with those occurring in sepsis. Indices of this inflammatory response to exercise (IRE) especially include leukocytosis, release of inflammatory mediators and acute phase reactants, tissue damage, priming of various white blood cell lines, production of free radicals; activation of complement, coagulation and fibrinolytic cascades.

G. Camus; G. Deby-Dupont; J. Duchateau; C. Deby; J. Pincemail; M. Lamy

1994-01-01

125

Sepsis-induced Cardiomyopathy  

PubMed Central

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

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

2011-01-01

126

Hematopoietic Stem-Progenitor Cells Restore Immunoreactivity and Improve Survival in Late Sepsis  

PubMed Central

Sepsis progresses from an early/acute hyperinflammatory to a late/chronic hypoinflammatory phase with immunosuppression. As a result of this phenotypic switch, mortality in late sepsis from persistent primary infection or opportunistic new infection often exceeds that in acute sepsis. Emerging data support that persistence of the hypoinflammatory (hyporesponsive) effector immune cells during late sepsis might involve alterations in myeloid differentiation/maturation that generate circulating repressor macrophages that do not readily clear active infection. Here, we used a cecal ligation and puncture (CLP) murine model of prolonged sepsis to show that adoptive transfer of CD34+ hematopoietic stem-progenitor cells after CLP improves long-term survival by 65%. CD34+ cell transfer corrected the immunosuppression of late sepsis by (i) producing significantly higher levels of proinflammatory mediators upon ex vivo stimulation with the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide, (ii) enhancing phagocytic activity of peritoneal macrophages, and (iii) clearing bacterial peritonitis. Improved immunity by CD34+ cell transfer decreased inflammatory peritoneal exudate of surviving late-sepsis mice. Cell tracking experiments showed that the transferred CD34+ cells first appeared in the bone marrow and then homed to the spleen and peritoneum. Because CD34+ cells did not affect the early-phase hyperinflammatory response, it is likely that the newly incorporated pluripotent CD34+ cells differentiated into competent immune cells in blood and tissue, thereby reversing or replacing the hyporesponsive endotoxin-tolerant cells that occur and persist after the initiation of early sepsis. PMID:22144495

Brudecki, Laura; Ferguson, Donald A.; Yin, Deling; Lesage, Gene D.; McCall, Charles E.

2012-01-01

127

The renal microcirculation in sepsis.  

PubMed

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

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

2015-02-01

128

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

PubMed

Angiopoietin-2 (Ang-2) is an important mediator in sepsis. We have previously shown that endotoxemia levels are related to the underlying infection and affect septic patients' outcome. Based on this background we now investigated if circulating Ang-2 (cAng-2) and monocyte Ang-2 expression in septic patients are associated with the underlying infection and organ failure. We measured cAng-2 in 288 septic patients (121 with sepsis, 167 with severe sepsis/septic shock) at less than 24h post study inclusion (day 1) and on days 3 and 7. Peripheral blood mononuclear cells (PBMCs) were additionally isolated; Ang-2 gene expression was estimated by means of real-time PCR. Levels of cAng-2 were higher under severe sepsis and septic shock, as compared to uncomplicated sepsis; PBMC Ang-2 copies were higher in severe sepsis. On day 1, cAng-2 and Ang-2 gene copies were greater under severe sepsis/septic shock in sufferers from all types of infections with the exception of community-acquired pneumonia and ventilator-associated pneumonia. cAng-2 increased proportionally to the number of failing organs, and was higher under metabolic acidosis and acute coagulopathy as compared to no failing organ. On day 1, copies of Ang-2 were higher in survivors, whereas cAng-2 was higher in non-survivors. In a large cohort of septic patients, cAng-2 kinetics appears associated with the underlying infection and organ failure type. PMID:25748839

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

2015-05-01

129

Glycocalyx and sepsis-induced alterations in vascular permeability.  

PubMed

Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients. PMID:25777848

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

2015-12-01

130

Streptococcal Infections, Rheumatic Fever and School Health Services.  

ERIC Educational Resources Information Center

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)

Markowitz, Milton

1979-01-01

131

Group B Streptococcal ??Hemolysin Induces Mortality and Liver Injury in Experimental Sepsis  

Microsoft Academic Search

New Zealand White rabbits were challenged with the wild-type (wt) group B streptococci (GBS) serotype III strain (COH1) and its isogenic nonhemolytic (NH) and hyperhemolytic (HH) mutants. Mortality differed significantly between rabbits infected with the HH mutant IN40 (67%), compared with rabbits infected with the wt COH1 strain (27%) and the NH strains COH1-20 and COH1:cyl EDcat (13% and 0%,

Axel Ring; Jürgen Pohl; Victor Nizet; Wolfgang Stremmel

2002-01-01

132

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

Microsoft Academic Search

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

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

133

Solution: Rapid Rescuers and Sepsis Survivors  

Microsoft Academic Search

Phone: 202.877.8046 IDENTIFICATION: Nearly 600 patients die every day due to severe sepsis. Forty percent of all ICU expenditures are related to the care of patients with severe sepsis. Our rapid response statistics show 38% of calls are for patient who screen positive for severe sepsis. Our goal was to identify potential severe sepsis patients utilizing our proactive rapid response

Patricia McCabe

2009-01-01

134

Puerperal Group A Streptococcal Infections: A Case Series and Discussion  

PubMed Central

Puerperal group A streptococcal infections, a major postpartum killer during the late 19th and early 20th centuries, have become (fortunately) rare. We describe a cluster of 4 serious peripartum group A streptococcal infections occurring within the past five years at a single medical center. These cases were not epidemiologically linked and serve to illustrate the continuing risk of these potentially fulminant infections. PMID:23710192

Busowski, Mary T.; Lee, Melissa; Busowski, John D.; Akhter, Kauser; Wallace, Mark R.

2013-01-01

135

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

PubMed Central

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

1989-01-01

136

Neonatal Sepsis and Neutrophil Insufficiencies  

PubMed Central

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

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

2011-01-01

137

Serum sepsis, not sickness.  

PubMed

Rarely taught in medical schools, clinical reasoning is the ability to discern the important from the unimportant and to arrive at accurate and efficient clinical conclusions. Identifying errors in reasoning is difficult; however, undetected clinical reasoning errors can have exponential consequences. As quality and patient safety come into focus, identifying and preventing clinical reasoning errors have become imperative. The authors present a case of a man sent for admission from a subspecialty clinic diagnosed with infliximab-induced serum sickness. Not countering the expert's diagnosis, initial workup failed to diagnose joint abscess and sepsis. Heuristics are mental shortcuts used to make decision making more efficient but can lead to error. The anchoring heuristic, premature closure, confirmation bias and the blind obedience heuristic are examples. Introspective surveillance and interactive hypothesis testing defend against heuristics. The authors conclude by discussing 4 types of hypersensitivity reactions, serum sickness in particular, and the chimeric nature of infliximab. PMID:21273840

Guidry, Michelle M; Drennan, Robert H; Weise, Jeff; Hamm, L Lee

2011-02-01

138

[Streptococcal myositis in children: four case histories].  

PubMed

We report about four children, who suffered from myositis caused by beta-hemolytic group A streptococci (GAS). The cases were observed during the last 12 months, and differed much in severity. Soft tissue infections caused by GAS are reported with increasing frequency from the USA, Australia and Europe. They occur in hitherto healthy children and young adults, mostly without a predisposing trauma. In children, a preceding varicella infection is often found. Some patients develop a streptococcal toxic shock syndrome with a letality of 20-50%. The bacteria, which can be isolated from normally sterile body sites, are morphologically inconspicuous, and are mostly of the serological type M1 or M3. PMID:7982716

Schemken-Birk, E M; Thomas, P; Terzija-Wessel, U; Stevens, D L; Wirsing von König, C H

1994-10-01

139

Effects of selective ß1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis.  

PubMed

IntroductionActivation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective ß1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.MethodsHyperdynamic sepsis was induced by infusion of live E. Coli for 24 hours in 9 conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective ß1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/Kg/h) from 8 to 24 hours of sepsis.ResultsHyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused a sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor-¿ (TNF-¿), interleukin-6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-¿ or IL-6.ConclusionsIn sepsis, selective ß1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect. PMID:25413250

Calzavacca, Paolo; Lankadeva, Yugeesh R; Bailey, Simon R; Bailey, Michael; Bellomo, Rinaldo; May, Clive N

2014-11-21

140

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

PubMed

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

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

141

Neonatal Sepsis and Inflammatory Mediators  

PubMed Central

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

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

2014-01-01

142

Increased Resistin Levels in Intra-abdominal Sepsis  

PubMed Central

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

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

2014-01-01

143

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

PubMed Central

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

Macerollo, Antonella; Martino, Davide

2013-01-01

144

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

PubMed

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

Macerollo, Antonella; Martino, Davide

2013-01-01

145

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

PubMed Central

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

Martin, Greg S

2012-01-01

146

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

PubMed Central

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

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

2012-01-01

147

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

PubMed

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

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

2013-07-01

148

Sepsis severity predicts outcome in community-acquired pneumococcal pneumonia.  

PubMed

Easily performed prognostic rules are helpful for guiding the intensity of monitoring and treatment of patients. The aim of the present study was to compare the predictive value of the sepsis score and the Confusion, Respiratory rate (> or =30 breaths.min(-1)), Blood pressure (systolic value <90 mmHg or diastolic value < or =60 mmHg) and age > or =65 yrs (CRB-65) score in 105 patients with community-acquired pneumococcal pneumonia. In addition, the influence of timing of the antimicrobial treatment on outcome was investigated. The sepsis and the CRB-65 scores were used to allocate patients to subgroups with low, intermediate and high risk. Comparable, highly predictive values for mortality were found for both scores (sepsis score versus CRB-65): 1) low-risk group, 0 versus 0%; 2) intermediate-risk group, 0 versus 8.6%; 3) high-risk group, 30.6 versus 40%, with an area under the curve of 0.867 versus 0.845. Patients with ambulatory antibiotic pre-treatment had less severe disease with a lower acute physiology score, lower white blood cell count and a faster decline of C-reactive protein levels. No pre-treated patient died. In summary, both scores performed equally well in predicting mortality. The prediction of survival in the intermediate-risk group might be more accurate with the sepsis score. Pre-hospital antibiotic treatment was associated with less severe disease. PMID:17537775

Schaaf, B; Kruse, J; Rupp, J; Reinert, R R; Droemann, D; Zabel, P; Ewig, S; Dalhoff, K

2007-09-01

149

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

PubMed Central

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

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

2013-01-01

150

Case of intraperitoneal sepsis secondary to rupture of the appendix on the background of pseudomyxoma peritonei  

PubMed Central

Introduction Pseudomyxoma peritonei (PMP) is characterised by gelatinous ascites and pools of mucin associated with neoplastic mucinous epithelium within the peritoneal cavity. It can rarely present as acute intraperitoneal sepsis, requiring urgent medical attention. Presentation of case A 59-year old male was referred to our centre in February 2014 following a diagnostic laparotomy, which showed jelly-like material with occasional epithelial cells. He was listed for peritonectomy in a month's time at our centre. Three weeks later, he was admitted urgently to our hospital due to generalised abdominal pain and watery diarrhoea. Examination at admission was unremarkable. On the following day, he became haemodynamically unstable and was suspected to have intraperitoneal sepsis due to infected PMP. At emergency laparotomy, we found gross intraperitoneal sepsis and did extensive debulking of tumour, appendectomy and extensive division of adhesions. Another laparotomy was done 24 h later for washout. He was discharged three weeks after. Discussion Although we have done 780 peritonectomy procedures, this was the first patient with this presentation of widerspread intraperitoneal sepsis. Continuous mucous production of appendiceal adenoma can lead to appendiceal rupture. The appendix may decompress by perforation and then reseal. However, one episode of appendiceal rupture can cause bacterial contamination of PMP, leading to sepsis. Conclusion Intraperitoneal sepsis secondary to appendiceal rupture is rare. Hence surgeons may face an emergency of intraperitoneal sepsis during waiting period of planned CRS or as a primary presentation. With combined therapy of CRS and PIC, the prognosis of mucinous appendiceal adenoma is excellent. PMID:25685336

Huang, Y.; Alzahrani, N.A.; Liauw, W.; Morris, D.L.

2014-01-01

151

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

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

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

152

Synergistic inhibition of Streptococcal biofilm by ribose and xylitol.  

PubMed

Streptococcus mutans and Streptococcus sobrinus are the major causative agents of human dental caries. Therefore, the removal or inhibition of these streptococcal biofilms is essential for dental caries prevention. In the present study, we evaluated the effects of ribose treatment alone or in combination with xylitol on streptococcal biofilm formation for both species. Furthermore, we examined the expression of genes responsible for dextran-dependent aggregation (DDAG). In addition, we investigated whether ribose affects the biofilm formation of xylitol-insensitive streptococci, which results from long-term exposure to xylitol. The viability of streptococci biofilms formed in a 24-well polystyrene plate was quantified by fluorescent staining with the LIVE/DEAD bacterial viability and counting kit, which was followed by fluorescence activated cell sorting analysis. The effects of ribose and/or xylitol on the mRNA expression of DDAG-responsible genes, gbpC and dblB, was evaluated by RT-qPCR. Our data showed that ribose and other pentose molecules significantly inhibited streptococcal biofilm formation and the expression of DDAG-responsible genes. In addition, co-treatment with ribose and xylitol decreased streptococcal biofilm formation to a further extent than ribose or xylitol treatment alone in both streptococcal species. Furthermore, ribose attenuated the increase of xylitol-insensitive streptococcal biofilm, which results in the reduced difference of biofilm formation between S. mutans that are sensitive and insensitive to xylitol. These data suggest that pentose may be used as an additive for teeth-protective materials or in sweets. Furthermore, ribose co-treatment with xylitol might help to increase the anti-cariogenic efficacy of xylitol. PMID:25463908

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

2015-02-01

153

Peripheral photoplethysmography variability analysis of sepsis patients  

Microsoft Academic Search

Sepsis is associated with impairment in autonomic regulatory function. This work investigates the application of heart rate\\u000a and photoplethysmogram (PPG) waveform variability analysis in differentiating two categories of sepsis, namely systemic inflammatory\\u000a response syndrome (SIRS) and severe sepsis. Electrocardiogram-derived heart period (RRi) and PPG waveforms, measured from\\u000a fingertips (Fin-PPG) and earlobes (Ear-PPG), of Emergency Department sepsis patients (n = 28) with different

Paul M. MiddletonCollin; Collin H. H. Tang; Gregory S. H. Chan; Sarah Bishop; Andrey V. Savkin; Nigel H. Lovell

2011-01-01

154

Crisis management during anaesthesia: sepsis  

PubMed Central

Background: Anaesthesia with concurrent sepsis is risky, and involves consideration of possible organ dysfunctions—respiratory, cardiovascular, renal, and haematological—as well as ensuring that appropriate antibiotics are given after taking the necessary microbiological specimens. Because prompt attention needs to be paid to so many body systems, the place for a structured approach during anaesthesia for a septic patient was assessed. Objectives: To examine the role of a previously described core algorithm "COVER ABCD–A SWIFT CHECK", supplemented by a specific sub-algorithm for sepsis, in the management of sepsis occurring in association with anaesthesia. Methods: The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. Results: Sepsis was identified as the primary problem in 13 of the first 4000 reports (<1%) to AIMS. The incidents reported generally occurred in sick patients; 70% were ASA status III or worse. The COVER ABCD algorithm provided a diagnosis and corrective manoeuvre in only 15% (2/13) of reported incidents, and the sepsis sub-algorithm provided adequate therapeutic strategies in a further 38% (5/13) of the incidents. Eight cases required the use of additional sub-algorithms for desaturation (30%), cardiac arrest (15%), hypotension (8%), and aspiration (8%). Conclusion: Sepsis involves a serious physiological stress upon multiple organ systems. The use of a structured approach involving a core algorithm and additional sub-algorithms as required provides a series of checklists that can successfully deal with the complex multiple and interrelating problems that these patients present. PMID:15933296

Myburgh, J; Chapman, M; Szekely, S; Osborne, G

2005-01-01

155

Invasive group A streptococcal disease: Management and chemoprophylaxis  

PubMed Central

Given the potentially devastating consequences of severe invasive group A streptococcal disease, attention has been directed toward the role of chemoprophylaxis and the optimization of management strategies. In response to this issue, Canadian guidelines were previously developed. However, the uptake of these recommendations is variable across Canada. The present document summarizes key components of the recommendations for use by Canadian physicians. The importance of penicillin in the treatment of group A streptococcal disease is reaffirmed, and the role of clindamycin is discussed. In addition, in situations in which chemoprophylaxis may be considered, the preferred agents are summarized. PMID:21886647

Allen, UD; Moore, DL

2010-01-01

156

Invasive group A streptococcal disease: Management and chemoprophylaxis  

PubMed Central

Given the potentially devastating consequences of severe invasive group A streptococcal disease, attention has been directed toward the role of chemoprophylaxis and the optimization of management strategies. In response to this issue, Canadian guidelines were previously developed. However, the uptake of these recommendations is variable across Canada. The present document summarizes key components of the recommendations for use by Canadian physicians. The importance of penicillin in the treatment of group A streptococcal disease is reaffirmed, and the role of clindamycin is discussed. In addition, in situations in which chemoprophylaxis may be considered, the preferred agents are summarized. PMID:21532795

Allen, UD; Moore, DL

2010-01-01

157

Septic Acute Kidney Injury: New Concepts  

Microsoft Academic Search

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

Rinaldo Bellomo; Li Wan; Christoph Langenberg; Clive May

2008-01-01

158

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

PubMed

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

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

159

Sepsis progression and outcome: a dynamical model  

Microsoft Academic Search

BACKGROUND: Sepsis (bloodstream infection) is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis

Sergey M Zuev; Stephen F Kingsmore; Damian DG Gessler

2006-01-01

160

Sepsis in obese pregnant women.  

PubMed

Animal, epidemiological and limited human studies have reported that obesity increases susceptibility to both bacterial and viral infections. Obesity has now reached worldwide epidemic proportions with a recent study estimating that there are currently 2.1 billion obese adults in the world. The rates of sepsis in both the non-pregnant and pregnant population are also increasing. Obesity is an independent risk factor for both infection and sepsis in pregnancy. This review article addresses the epidemiology, immunological factors, infection sites, investigation, management, specific intrapartum care and postnatal care of the obese pregnant woman with infection. PMID:25467427

Orr, Katrine; Chien, Patrick

2015-04-01

161

The role of Nox2-derived ROS in the development of cognitive impairment after sepsis  

PubMed Central

Background Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. Methods Sepsis was induced in WT and gp91phox knockout mice (gp91phox-/-) by cecal ligation and puncture (CLP) to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene expression and neuroinflammation in the hippocampus at six hours, twenty-four hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with the inhibitory avoidance test and the Morris water maze in control and apocynin-treated WT mice. Results Acute oxidative damage to the hippocampus was identified by increased 4-HNE expression in parallel with an increase in Nox2 gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin completely inhibited hippocampal oxidative stress in septic animals. Pharmacologic inhibition or the absence of Nox2 in gp91phox-/- mice prevented glial cell activation, one of the central mechanisms associated with SAE. Finally, treatment with apocynin and inhibition of hippocampal oxidative stress in the acute phase of sepsis prevented the development of long-term cognitive impairment. Conclusions Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE. PMID:24571599

2014-01-01

162

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

PubMed

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

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

2014-10-01

163

Structure of a streptococcal adhesion carbohydrate receptor  

SciTech Connect

Interactions between complementary protein and carbohydrate structures on different genera of human oral bacteria have been implicated in the formation of dental plaque. The carbohydrate receptor on Streptococcus sanguis H1 that is specific for the adhesion on Capnocytophaga ochracea ATCC 33596 has been isolated from the streptococcal cell wall, purified, and structurally characterized. The hexasaccharide repeating unit of the polysaccharide was purified by reverse-phase, amino-bonded silica, and gel permeation high performance liquid chromatography. Earlier studies established that the repeating unit was a hexasaccharide composed of rhamnose, galactose, and glucose in the ration of 2:3:1, respectively. In the present study, determination of absolute configuration by gas chromatography of the trimethylsilyl (+)-2-butyl glycosides revealed that the rhamnose residues were of the L configuration while the hexoses were all D. 252Californium plasma desorption mass spectrometry of the native, the acetylated and the reduced and acetylated hexasaccharide determined that the molecular mass of the native hexasaccharide was 959, and that the 2 rhamnose residues were linked to each other at the nonreducing terminus of the linear molecule. Methylation analysis revealed the positions of the glycosidic linkages in the hexasaccharide and showed that a galactose residue was present at the reducing end. The structural characterization of the hexasaccharide was completed by one and two dimensional 1H and 13C NMR spectroscopy. Complete 1H and 13C assignments for each glycosyl residue were established by two-dimensional (1H,1H) correlation spectroscopy, homonuclear Hartmann-Hahn, and (13C,1H) correlation experiments. The configurations of the glycosidic linkages were inferred from the chemical shifts and coupling constants of the anomeric 1H and 13C resonances.

Cassels, F.J.; Fales, H.M.; London, J.; Carlson, R.W.; van Halbeek, H. (National Institute of Dental Research, Bethesda, MD (USA))

1990-08-25

164

New approaches to the study of sepsis  

PubMed Central

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

Ward, Peter A

2012-01-01

165

Streptococcal Meningitis Resulting from Contact with an Infected Horse  

PubMed Central

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

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

2001-01-01

166

Superantigen profiles of emm and emm-like typeable and nontypeable pharyngeal streptococcal isolates of South India  

PubMed Central

Background The major virulence factors determining the pathogenicity of streptococcal strains include M protein encoded by emm and emm-like (emmL) genes and superantigens. In this study, the distribution of emm, emmL and superantigen genes was analyzed among the streptococcal strains isolated from the patients of acute pharyngitis. Methods The streptococcal strains were isolated from the throat swabs of 1040 patients of acute pharyngitis. The emm and emmL genes were PCR amplified from each strain and sequenced to determine the emm types. The dot-blot hybridization was performed to confirm the pathogens as true emm nontypeable strains. The presence of eleven currently known superantigens was determined in all the strains by multiplex PCR. Results Totally, 124 beta-hemolytic streptococcal strains were isolated and they were classified as group A streptococcus (GAS) [15.3% (19/124)], group C streptococcus (GCS) [59.7% (74/124)] and group G streptococcus (GGS) [25.0% (31/124)]. Among 124 strains, only 35 strains were emm typeable and the remaining 89 strains were emm nontypeable. All GAS isolates were typeable, whereas most of the GCS and GGS strains were nontypeable. These nontypeable strains belong to S. anginosus [75.3% (67/89)] and S. dysgalactiae subsp. equisimilis [24.7% (22/89)]. The emm and emmL types identified in this study include emm12.0 (28.6%), stG643.0 (28.6%), stC46.0 (17.0%), emm30.11 (8.5%), emm3.0 (2.9%), emm48.0 (5.7%), st3343.0 (2.9%), emm107.0 (2.9%) and stS104.2 (2.9%). Various superantigen profiles were observed in typeable as well as nontypeable strains. Conclusions Multiplex PCR analysis revealed the presence of superantigens in all the typeable strains irrespective of their emm types. However, the presence of superantigen genes in emm and emmL nontypeable strains has not been previously reported. In this study, presence of at least one or a combination of superantigen coding genes was identified in all the emm and emmL nontypeable strains. Thus, the superantigens may inevitably play an important role in the pathogenesis of these nontypeable strains in the absence of the primary virulence factor, M protein. PMID:22296671

2012-01-01

167

Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection.  

PubMed

The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain. PMID:24892819

Cunningham, Madeleine W

2014-01-01

168

Plasma potassium response to acute respiratory alkalosis  

Microsoft Academic Search

Plasma potassium response to acute respiratory alkalosis. Acute respiratory alkalosis (hyperventilation) occurs in clinical settings associated with electrolyte-induced complications such as cardiac arrhythmias (such as myocardial infarction, sepsis, hypoxemia, cocaine abuse). To evaluate the direction, magnitude and mechanisms of plasma potassium changes, acute respiratory alkalosis was induced by voluntary hyperventilation for 20 (18 and 36 liter\\/min) and 35 minutes (18

Reto Krapf; Pia Caduff; Philippe Wagdi; Max Stäubli; Henry N Hulter

1995-01-01

169

Scientific and Clinical Challenges in Sepsis  

PubMed Central

Advances in intensive care and antibiotics have prevented the spread of some infections, though sepsis mortality rates remain high. With failure of over thirty clinical trials, sepsis remains a scientific and clinical challenge in modern medicine. Sepsis is defined by the clinical signs of a systemic inflammatory response to infection. “Severe sepsis” is when these symptoms are associated with multiple organ dysfunction. These definitions of sepsis may be too broad and common to heterogeneous groups of patients who do not necessarily have the same disorder. This consideration has become especially evident in the clinical trials that have failed to obtain consistent results in similar studies of patients diagnosed with severe sepsis. In these trials, patients with infections caused by different microorganisms, and affecting different organs, have been combined under the general diagnosis of severe sepsis. The situation is analogous to attempting a clinical trial based on the general definition of cancer, combining all patients with tumor independent of the type of malignancy. In this consideration, it would not be very surprising that activated protein C, the only treatment in sepsis approved by the Food and Drug Administration, is projected for use in only a small subset of patients with severe sepsis. This article reviews novel inflammatory molecular aspects and the experimental anti-inflammatory strategies for sepsis, as they may represent particular pathological processes in specific subsets of patients. PMID:19519432

Ulloa, Luis; Brunner, Michael; Ramos, Laura; Deitch, Edwin A.

2011-01-01

170

Full Activation of CD4+ T Cells Early During Sepsis Requires Specific Antigen  

PubMed Central

ABSTRACT 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

Schmoeckel, Katrin; Traffehn, Sarah; Eger, Christin; Pötschke, Christian; Bröker, Barbara M.

2015-01-01

171

[Neonatal Streptococcus group B sepsis: problems of early diagnosis, therapy and prevention].  

PubMed

38 cases of neonatal group B streptococcal (GBS) sepsis (31 with early onset and 7 with late onset) were observed during the years 1976-1982. Early onset disease showed the following clinical characteristics: 1. frequent lack of risk factors for infection in obstetric history, 2. very early onset of symptoms of respiratory distress, 3. rapid development of shock after only minor or missing clinical signs of infection, and 4. unspecific findings on chest radiography. Neutropenia or marked leukocyte left shift as well as the presence of gram-positive cocci in gastric or tracheal aspirate proved to be useful diagnostic clues. The latex agglutination test for the detection of GBS-antigen in urine yielded in our hands many false positive results and unspecific reactions. Given the big difficulties of early diagnosis of early onset GBS-sepsis, the relatively liberal use of antibiotics in newborns with respiratory distress is probably unavoidable. Hereby prior culturing of blood and early termination of antibiotic therapy with negative cultures (of blood, CSF, tracheal aspirate) seems essential to us. The clinical significance of newer therapeutic (granulocyte transfusions, exchange transfusions, immunoglobulins) and prophylactic (intra-partum antibiotics, vaccination) modalities is according to the current literature still not clear in many respects. PMID:6399717

Kind, C; Gnehm, H; Seger, R; Duc, G

1984-12-01

172

Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters  

PubMed Central

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

Goldman, John; Cheriyath, Pramil; Nookala, Vinod

2014-01-01

173

Surviving sepsis in the critical care environment.  

PubMed

The management of sepsis and septic shock in the intensive care environment is a complex task requiring the cooperation of a multidisciplinary team. The Surviving Sepsis Campaign provides systematic guidelines for the recognition, early intervention, and supportive management of sepsis. Critical care nurses are instrumental in ensuring that these guidelines and other sources of evidence-based practice are used for patients with severe sepsis or septic shock. This article discusses the pathophysiologic processes in severe sepsis and septic shock and discusses the appropriate interventions as recommended by the Surviving Sepsis Campaign. Recommended early treatments are reviewed along with interventions related to hemodynamics, perfusion, and supportive care in the critical care environment. PMID:25741954

Benedict, Lara

2015-01-01

174

Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis  

PubMed Central

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

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

2014-01-01

175

Myocardial Dysfunction in Sepsis and Septic Shock  

Microsoft Academic Search

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

Anand Kumar; Aseem Kumar; Joseph E. Parrillo

176

Surviving sepsis: going beyond the guidelines  

Microsoft Academic Search

The Surviving Sepsis Campaign is a global effort to improve the care of patients with severe sepsis and septic shock. The\\u000a first Surviving Sepsis Campaign Guidelines were published in 2004 with an updated version published in 2008. These guidelines\\u000a have been endorsed by many professional organizations throughout the world and come regarded as the standard of care for the\\u000a management

Paul E Marik

2011-01-01

177

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock  

Microsoft Academic Search

Objective: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase aware- ness and improve outcome in severe sepsis. Design: The process included a modified Delphi

R. Phillip Dellinger; Jean M. Carlet; Henry Masur; Herwig Gerlach; Thierry Calandra; Jonathan Cohen; Juan Gea-Banacloche; Didier Keh; John C. Marshall; Margaret M. Parker; Graham Ramsay; Janice L. Zimmerman; Jean-Louis Vincent; Mitchell M. Levy

2004-01-01

178

Intrauterine Group A Streptococcal Infections are Exacerbated by Prostaglandin E2  

PubMed Central

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

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

2013-01-01

179

[Acute rheumatic fever: a report].  

PubMed

Acute rheumatic fever (ARF) is still an important disease of the pediatric and adult age. The increased number of cases described in the literature in the last 10 years brought us to evaluate the ARF cases diagnosed in a Pediatric Teaching Hospital in the period 1988-1997. Most of the children with ARF presented with joint involvement even if patients with cardiac disease or chorea minor were numerous. About 50% of our patients with ARF did not refer a history of a febrile tonsillopharyngitis in the 15-60 days before the presentation of ARF. The remaining patients have had a preceding pharyngitis not adequately treated. In none of the subjects a throat swab positive for group A beta hemolytic streptococci was available. These results confirm the importance of the correct diagnosis and treatment of streptococcal pharyngitis but suggest that ARF can develop without any outstanding clinical evidence of streptococcal infection. PMID:12845313

Boccazzi, A; Bellosta, C; Tonelli, P

1997-12-01

180

Presepsin as a powerful monitoring tool for the prognosis and treatment of sepsis: a multicenter prospective study.  

PubMed

Presepsin is a protein whose levels increase specifically in the blood of patients with sepsis. It is proposed as a diagnostic and prognostic marker for assessing the degree of sepsis severity. The present multicenter prospective study compared the clinical utility of presepsin with other conventional sepsis biomarkers including procalcitonin, interleukin-6, and C-reactive protein for evaluating the severity of sepsis during follow-up. Patients with sepsis (n = 103) admitted to the emergency room or intensive care unit were enrolled in this study and classified into 3 diagnostic groups: sepsis, severe sepsis, and septic shock. Blood samples were obtained from each patient on admission and after 1, 3, 5, and 7 days. The patients were further divided into the favorable and unfavorable prognosis groups on the basis of several indicators of sepsis severity (i.e., Sequential Organ Failure Assessment score, and Acute Physiology and Chronic Health Evaluation II score). The patients in the favorable prognosis group exhibited significant decreases in all biomarker levels on days 3 and 7 after admission. In the unfavorable prognosis group, only presepsin levels did not decrease significantly during follow-up. The period of antibiotics treatment in the unfavorable prognosis group was significantly longer than those in the favorable prognosis group (P < 0.05). The unfavorable prognosis group had significantly higher 28-day mortality than the favorable prognosis group (P < 0.05). Therefore, the results suggest that presepsin levels correlated with the severity of sepsis during follow-up in comparison with other conventional sepsis biomarkers. PMID:24462421

Endo, Shigeatsu; Suzuki, Yasushi; Takahashi, Gaku; Shozushima, Tatsuyori; Ishikura, Hiroyasu; Murai, Akira; Nishida, Takeshi; Irie, Yuhei; Miura, Masanao; Iguchi, Hironobu; Fukui, Yasuo; Tanaka, Kimiaki; Nojima, Tsuyoshi; Okamura, Yoshikazu

2014-01-01

181

Clinical acute lung injury and acute respiratory distress syndrome  

Microsoft Academic Search

Opinion statement  This article provides a description of the clinical disorders associated with the development of acute noncardiogenic pulmonary\\u000a edema, better known as clinical acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). Much has been learned\\u000a about the mechanisms by which the lung is injured in patients with sepsis, pneumonia, aspiration of gastric contents, and\\u000a following major trauma.

Michael A. Matthay; Tokujiro Uchida; Xiaohui Fang

2002-01-01

182

Purification and properties of streptococcal nicotinamide adenine dinucleotide glycohydrolase.  

PubMed

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

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

1975-05-01

183

Increasing incidence of streptococcal impetigo in atopic dermatitis  

Microsoft Academic Search

Streptococcal impetigo associated with atopic dermatitis has dramatically increased from 1989 to 1994 in outpatients visiting our hospital, totalling 174 cases. The most frequent causative agents were group A streptococci (Streptococcus pyogenes, 70.7%) followed by group G (19.5%) and group B (9.8%). Streptococcus was isolated singly in 28.2% of cases and in concomitant with Staphylococcus aureus (S. aureus) in 71.8%.

Jun Adachi; Kaoru Endo; Takayuki Fukuzumi; Nobuko Tanigawa; Toshiyuki Aoki

1998-01-01

184

Group A Streptococcal Meningitis in the Antibiotic Era  

Microsoft Academic Search

A case of group A streptococcal meningitis is reported and the 51 cases reported in the literature since 1966 reviewed. A\\u000a total of 24 men and 24 women were included in the study; the mean age (±SD) was 20.9±25.5 years. Fifty-eight percent of the\\u000a patients had comorbid conditions, 80% had a distant focus of infection, and 65.8% had blood cultures

M. A. Baraldés; P. Domingo; A. Mauri; J. Monmany; M. Castellanos; R. Pericas; G. Vázquez

1999-01-01

185

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...

186

Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A.  

PubMed

There is concern that group A streptococci, which have caused less serious infections in developed countries in recent decades, may be acquiring greater virulence. We describe 20 patients from the Rocky Mountain region who had group A streptococcal infections from 1986 to 1988 that were remarkable for the severity of local tissue destruction and life-threatening systemic toxicity. Among the 20 patients (median age, 36), necrotizing fasciitis with or without myositis was the most common soft-tissue infection (55 percent). Nineteen patients (95 percent) had shock, 16 (80 percent) had renal impairment, and 11 (55 percent) had acute respiratory distress syndrome. The mortality rate was 30 percent. All patients but 1 had positive tissue cultures for Streptococcus pyogenes; 12 had positive blood cultures. Most of the patients had no underlying disease; 2 used intravenous drugs. Strains of group A beta-hemolytic streptococci isolated from 10 patients were not of a single M or T type; however, 8 of the 10 strains produced pyrogenic exotoxin A (scarlet fever toxin A, a classic erythrogenic toxin), which has rarely been observed in recent years. From our study of this cluster of severe streptococcal infections with a toxic shock-like syndrome, we conclude that in our region, more virulent group A streptococci have reappeared that produce the pyrogenic toxin A associated with scarlet fever. PMID:2659990

Stevens, D L; Tanner, M H; Winship, J; Swarts, R; Ries, K M; Schlievert, P M; Kaplan, E

1989-07-01

187

Detection ofGroupB Streptococcal Antigen inEarly-Onset andLate-Onset GroupB Streptococcal Disease withthe Wellcogen Strep B LatexAgglutination Test  

Microsoft Academic Search

TheWellcogen Strep B latex agglutination test (Wellcome Diagnostics, Dart- ford, England) wasevaluated asamethodofdetecting groupB streptococcal antigen inurine, cerebrospinal fluid, andserumfromneonates withearly-onset (c7daysofage)andlate-onset group Bstreptococcal disease. Urine wasthebest source ofantigen, whichwasdetected in100%ofsixneonates withearly-onset groupB streptococcal disease whohadurine available inthefirst 12hofillness andin88%of17groupB streptococcus-infected neonates withurine available in thefirst 48hofillness. Antigen wasnotdetected inanysamples frompatients without groupB streptococcal disease except intheurine ofonepatient with Proteus

DONNA M. SUGGS; Chlapel Hill

1982-01-01

188

Significance of apoptotic cell death in systemic complications with severe acute pancreatitis  

Microsoft Academic Search

In severe acute pancreatitis, multiple organ failure in the early stage after onset, and sepsis in the late stage, due to infection of pancreatic or peripancreatic devitalized tissue, contribute to its high mortality. In analogy with sepsis, evidence has accumulated of the significance of apoptotic cell death in the systemic manifestations associated with acute pancreatitis. Since we identified apoptosis-inducing activity

Yoshifumi Takeyama

2005-01-01

189

Heterogeneity of group A streptococcal pyrogenic exotoxin type B.  

PubMed Central

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

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

1978-01-01

190

Molecular markers for the study of streptococcal epidemiology.  

PubMed

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

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

2013-01-01

191

Detection of group B streptococcal bacteremia in simulated intrapartum antimicrobial prophylaxis  

Microsoft Academic Search

The diagnostic value of negative blood cultures from neonates whose mothers receive intrapartum antimicrobial prophylaxis for prevention of perinatal group B streptococcal disease is uncertain. We investigated whether blood culture medium containing resin designed to adsorb antibiotic improved group B streptococcal detection following simulated intrapartum antimicrobial prophylaxis. Group B streptococcus (Streptococcus agalactiae) was preincubated with varying antibiotic concentrations before inoculation

Katherine K. Hsu; Stephen I. Pelton; Daniel S. Shapiro

2003-01-01

192

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

ERIC Educational Resources Information Center

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…

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

2008-01-01

193

Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis  

Microsoft Academic Search

Streptococcal pyrogenic exotoxin B is an extracellular cysteine protease. Only nephritis-associated strains of group A streptococci secrete this protease and this may be involved in the pathogenesis of post-streptococcal glomerulonephritis. Mice were actively immunized with a recombinant protease inactive exotoxin B mutant or passively immunized with exotoxin B antibody. Characteristics of glomerulonephritis were measured using histology, immunoglobulin deposition, complement activation,

Y-H Luo; C-F Kuo; K-J Huang; J-J Wu; H-Y Lei; M T Lin; W-J Chuang; C-C Liu; C-F Lin; Y-S Lin

2007-01-01

194

Novel strategies for the treatment of sepsis  

Microsoft Academic Search

The history of therapeutic interventions in clinical trials for sepsis has been referred to as the “graveyard for pharmaceutical companies.” That is now set to change, as research provides hope for new approaches that will be therapeutically effective in humans with sepsis.

Niels C. Riedemann; Ren-Feng Guo; Peter A. Ward

2003-01-01

195

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 ...

196

Metabolic response to injury and sepsis: changes in protein metabolism.  

PubMed

The metabolic response to trauma and sepsis involves an increased loss of body proteins. Specific sites of changes of protein and amino acid metabolism have been identified. In skeletal muscle, the rate of proteolysis is accelerated greatly. The rate of protein synthesis also may be increased but not enough to match the increase in degradation. Intramuscular glutamine concentration is decreased because of increased efflux and possibly decreased de novo synthesis. In the liver, the rate of synthesis of selected proteins (i.e., albumin, transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased, whereas acute phase protein synthesis is accelerated. Tissues characterized by rapidly replicating cells, such as enterocytes, immune cells, granulation tissue, and keratinocytes, exhibit early alterations in the case of decreased protein synthesis capacity. In these tissues, glutamine use is accelerated. Increased stress hormone (cortisol and glucagon) and cytokine secretion, as well as intracellular glutamine depletion, are potential mediators of altered protein metabolism in trauma and sepsis. However, the relative importance of these factors has not been clarified. Therapy of acute protein catabolism may include the use of biosynthetic human growth hormone, possibly in combination with insulin-like growth factor-1, and the administration of metabolites at pharmacologic doses. We recently studied the effects of carnitine and alanyl-glutamine administration in severely traumatized patients. We found that both carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without affecting selected indices of protein metabolism in the skeletal muscle. PMID:9290110

Biolo, G; Toigo, G; Ciocchi, B; Situlin, R; Iscra, F; Gullo, A; Guarnieri, G

1997-09-01

197

Mobilization in severe sepsis: an integrative review.  

PubMed

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 conducted a review of the literature to understand whether early mobilization improves outcomes in patients with severe sepsis in non-ICU settings. We summarized 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 (S.G. and V.C.) 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 1 retrospective study showed potential benefit of therapy in sepsis patients in the ICU. Similarly, in non-ICU settings, only 1 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 exist. Because hospitalists often care for this patient population, an opportunity for research in this area exists. PMID:25393649

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

2015-01-01

198

Dynamic Changes in Amino Acid Concentration Profiles in Patients with Sepsis  

PubMed Central

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

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

199

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

PubMed

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

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

2015-01-01

200

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

PubMed Central

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

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

2015-01-01

201

Psychosis following acute Sydenham’s chorea  

Microsoft Academic Search

Sydenham’s chorea (SC) is characterized by motor, mainly choreic involuntary movements, and psychiatric symptoms, including\\u000a anxiety, depression, obsessive–compulsive and attention-deficit\\/hyperactivity disorders. Symptoms of SC may be considered\\u000a as the result of basal ganglia dysfunction determined by autoimmune mechanisms elicited by streptococcal infection. We report\\u000a on a case of a 13-year-old boy with brief psychotic episode following acute SC. His hallucinations

Antônio Lúcio Teixeira; Débora Palma Maia; Francisco Cardoso

2007-01-01

202

Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis  

PubMed Central

Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

2014-01-01

203

Clinical application of urine antigen detection in early onset group B streptococcal disease  

Microsoft Academic Search

The aim of this study was to test the sensitivity and specificity of antigen detection for group B streptococcus (GBS) from the urine of neonates with early onset GBS sepsis. GBS sepsis was defined as early (< 48 hours) signs of sepsis in a neonate colonised with GBS. Neonates of 26 weeks' gestation or more, considered at risk for sepsis,

E D McIntosh; H E Jeffery

1992-01-01

204

Sepsis  

MedlinePLUS

... more organs fail. In the worst cases, blood pressure drops and the heart weakens, leading to septic shock. ... infection, sustain the vital organs, and prevent a drop in blood pressure. Many patients receive oxygen and intravenous fluids. Other ...

205

Sepsis  

MedlinePLUS

... updated August 2014 Share Print E-mail House Image Highlight Header Highlight Body Related Links Up to top This page last reviewed on August 18, 2014 Social Media Links Bookmark & Share Free Subscriptions Twitter Facebook YouTube ...

206

Sepsis  

MedlinePLUS

... 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 ...

207

The changing immune system in sepsis  

PubMed Central

Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity. PMID:24067565

Boomer, Jonathan S; Green, Jonathan M; Hotchkiss, Richard S

2014-01-01

208

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

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

Ang, Yuchen; Meier, Rudolf

2010-01-01

209

Management of neonatal sepsis in term newborns  

PubMed Central

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

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

2014-01-01

210

A Clinical Evaluation of Primary Angioplasty and Stenting in Acute Myocardial Infarction  

Microsoft Academic Search

In 1949 the fibrinolytic effect of streptococcal fibrinolysin (streptokinase) was described for the\\u000atreatment of fibrous, pUl1llent or sanguineous pleural exudations. The effect of this lytic agent\\u000ain patients with acute myocardial infarction was described by Fletcher in 1958. In the late\\u000anineteensevcnties the pathofysiologic mechanism underlying acute myocardial infarction was\\u000arecognised. In the majority of patients with acute myocardial

Hof van't A. W. J

1998-01-01

211

Are IL6, IL10 and PCT plasma concentrations reliable for outcome prediction in severe sepsis? A comparison with APACHE III and SAPS II  

Microsoft Academic Search

Objective:Prospective examination whether changes in interleukin (IL)-6, IL-10 or procalcitonin (PCT) concentrations correlate with poor outcome in patients with severe sepsis in comparison with APACHE III or SAPS II. Methods:33 patients who fulfilled the criteria for severe sepsis have been included in the study. Blood samples were collected for cytokine and PCT determinations. The Acute Physiology, Age and Chronic Health

C. Wunder; O. Eichelbrönner; N. Roewer

2004-01-01

212

Pediatric case of crescentic post-streptococcal glomerulonephritis with myeloperoxidase anti-neutrophil cytoplasmic antibody.  

PubMed

Post-streptococcal glomerulonephritis (PSGN) generally has a good renal prognosis, and immunosuppressive therapies are not needed. However, a few patients present with severe acute kidney injury and extensive crescent formations. The etiology of such patients is not well known, and involvement of anti-neutrophil cytoplasmic antibodies is rarely reported. A 9-year-old girl with rapidly progressive nephritic syndrome was diagnosed with PSGN. A biopsy showed diffuse crescentic glomerulonephritis with immunoglobulin G and C3 deposits; moreover, humps were observed on electron microscopy. After she was administered methylprednisolone pulse therapy and intravenous cyclophosphamide, followed by prednisolone and azathioprine therapy, her urinary abnormalities improved and renal function normalized. However, the myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) titers gradually increased. We speculated that PSGN may be augmented by increased MPO-ANCA levels. Therefore, the patient is currently being treated with losartan, enalapril, azathioprine, and prednisolone. Although the MPO-ANCA titer remains high, urinary findings show mild proteinuria and her renal function has been norma for 18 months since onset. A progressive clinical course and severe histological findings may indicate the involvement of ANCA in deterioration of condition in patients with PSGN. Furthermore, in such cases immunosuppressive therapies should be considered even in pediatric PSGN. PMID:25161112

Kanai, Hiroaki; Sawanobori, Emi; Koizumi, Keiichi; Ohashi, Ryuji; Higashida, Kosuke

2015-04-01

213

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

PubMed Central

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

2014-01-01

214

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

PubMed

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

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

2014-04-01

215

Ensemble models of neutrophil trafficking in severe sepsis.  

PubMed

A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture)-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population) that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental studies to advance understanding of the complex biological response to severe infection, a problem of growing magnitude in humans. PMID:22412365

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

2012-01-01

216

Global fibrinolytic capacity in neonatal sepsis.  

PubMed

In this study, we studied global fibrinolytic capacity (GFC) in newborn infants with sepsis. Sixty-one newborn infants, admitted to neonatal intensive care unit at Yuzuncu Yil University Hospital were enrolled in this study. White blood cell count, immature (I) / mature (M) neutrophil ratios, prothrombin time, and d-dimer levels were significantly higher in patient group than those of control group (P < .05). We found GFC to be significantly lower in the patient group compared to the control group (P < .05). The GFC value was negatively correlated to the Tollner scores but this correlation was not statistically significant (r = -.267, P = .095). Our findings showed that GFC decreases in severe neonatal sepsis; therefore, we suggest that GFC may be used for prognosis or in the early prediction of severe sepsis rather than the diagnosis of neonatal sepsis. PMID:21078608

Peker, Erdal; Akbayram, Sinan; Geylani, Hadi; Dogan, Murat; Kirimi, Ercan

2011-01-01

217

Severe sepsis: take care, take part.  

PubMed

Severe sepsis is defined as organ dysfunction in the setting of systemic inflammatory response due to infection. With changes in population age, comorbidity and the delivery of medical care, severe sepsis is increasingly common, and can present in every area of the hospital. The major obstacles to improved outcomes in severe sepsis are deficiencies in healthcare staffing and education, haphazard recognition and response to early clinical deterioration and deviation from optimal management as defined by international guidelines. Major treatment errors were identified in 30% of patients with bacteraemia in one recent investigation. Against this, substantial reductions in mortality can be achieved by improving recognition, urgent care and resuscitation. With a view to improving survival in sepsis, collaborative efforts are required to measure outcomes, implement guidelines and secure adequate funding for ongoing practice improvement, education and research. PMID:21265960

Huggan, P J

2011-01-01

218

[Severe human parechovirus-3 sepsis in a 6-week-old infant].  

PubMed

Febrile infants under 3 months of age are often treated with broad-spectrum intravenous antibiotics while awaiting culture results, to prevent mother-to-child bacterial infections. Human parechoviruses (HPeV) have recently been described as etiologic agents of meningitis and severe sepsis in neonates and young infants. They are rarely investigated and are therefore probably underestimated. They cause acute clinical symptoms that can incorrectly suggest a bacterial infection. In the present case, a 6-week-old infant infected with HPeV developed severe sepsis, complicated by hepatic cytolysis, meningitis, acute renal failure, and mild hemophagocytic lymphohistiocytosis. HPeV type 3 was found by routine specific RT-PCR in cerebrospinal fluid, stools, and plasma. The outcome was spontaneously favorable after 4 days. Early diagnosis of the HPeV infection by routine specific RT-PCR reduces unnecessary antibiotic use and extended hospitalization in febrile young infants. PMID:24630623

Ollier, V; Farfour, E; Charara, O; Marque Juillet, S; Mirand, A; Chalouhi, C; Foucaud, P

2014-04-01

219

Genetic Polymorphisms and Sepsis in Premature Neonates  

PubMed Central

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

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

2014-01-01

220

Is hypertriglyceridemia a prognostic factor in sepsis?  

PubMed Central

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 71.49±11.071 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

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

2014-01-01

221

Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge.  

PubMed

Patients surviving the acute stages of sepsis develop compromised T cell immunity and increased susceptibility to infection. Little is known about the decreased CD4 T cell function after sepsis. We tracked the loss and recovery of endogenous Ag-specific CD4 T cell populations after cecal ligation and puncture-induced sepsis and analyzed the CD4 T cell response to heterologous infection during or after recovery. We observed that the sepsis-induced early loss of CD4 T cells was followed by thymic-independent numerical recovery in the total CD4 T cell compartment. Despite this numerical recovery, we detected alterations in the composition of naive CD4 T cell precursor pools, with sustained quantitative reductions in some populations. Mice that had experienced sepsis and were then challenged with epitope-bearing, heterologous pathogens demonstrated significantly reduced priming of recovery-impaired Ag-specific CD4 T cell responses, with regard to both magnitude of expansion and functional capacity on a per-cell basis, which also correlated with intrinsic changes in V? clonotype heterogeneity. Our results demonstrate that the recovery of CD4 T cells from sepsis-induced lymphopenia is accompanied by alterations to the composition and function of the Ag-specific CD4 T cell repertoire. PMID:25595784

Cabrera-Perez, Javier; Condotta, Stephanie A; James, Britnie R; Kashem, Sakeen W; Brincks, Erik L; Rai, Deepa; Kucaba, Tamara A; Badovinac, Vladimir P; Griffith, Thomas S

2015-02-15

222

Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis  

PubMed Central

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

Spearman, Paul W.; Stoll, Barbara J.

2015-01-01

223

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

Microsoft Academic Search

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

Blake Bulloch; Amin Kabani; Milton Tenenbein

2003-01-01

224

[Fatal course of B-streptococcal infection in early infancy].  

PubMed

We report on a fatal case of "late onset" -sepsis by B-streptococcus in a seven weeks olk suckling. B-Streptococcus is considered to be a typical strain of early stage neonatal sepsis that is connected with foudroyant progress and high letality. As in our case the outcome is decisively determined by early diagnosis and timely beginning therapy for the strain can still be controlled effectively. Misjodging early symptoms of the infection may lead to fateful progression even after the neonatal period. PMID:1495264

Weigt, G; Kläber, H G

1992-06-01

225

Blood purification in sepsis: a new paradigm.  

PubMed

Sepsis is one of the main causes of death in critically ill patients. The pathophysiology of sepsis is complex and not completely understood. The proinflammatory and anti-inflammatory response leads to cell and organ dysfunction and, in many cases, death. Thus, the goal of the intervention is to restore the homeostasis of circulating mediators rather than to inhibit selectively the proinflammatory or anti-inflammatory mediators. Blood purification has been reported to remove a wide array of inflammatory mediators. The effects are broad-spectrum and auto-regulating. Blood purification has also been demonstrated to restore immune function through improving antigen-presenting capability, adjusting leukocyte recruitment, oxidative burst and phagocytosis, and improving leukocyte responsiveness. A great deal of work has to be done in order to find and optimize the best extracorporeal blood purification therapy for sepsis. New devices specifically target the pathophysiological mechanisms involved in these conditions. High-volume hemofiltration, hemoadsorption, coupled plasma filtration adsorption, and high cutoff membrane are now being tested in septic patients. Preliminary data indicate the feasibility of these modified techniques in sepsis. Their impact on patient prognosis, however, still needs proof by large randomized clinical trials. Finally, the emerging paradigm of sepsis-induced immune suppression provides additional rationale for the development of extracorporeal blood purification therapy for sepsis. PMID:20427984

Peng, Zhiyong; Singbartl, Kai; Simon, Peter; Rimmelé, Thomas; Bishop, Jeffery; Clermont, Gilles; Kellum, John A

2010-01-01

226

Physician-led sepsis quality improvement team.  

PubMed

Over the last decade, hospitalizations for sepsis have more than doubled and the incidence of postsurgical sepsis tripled between 1997 and 2006. This upward trend is expected to continue for several reasons, including population-specific characteristics (eg, age, chronic disease status) and health care-specific characteristics (eg, lack of understanding of sepsis, medical treatments that leave patients susceptible). Highly effective, focused, quality improvement teams need to be established in order to successfully manage this condition. Quality improvement, and specifically quality improvement in health care, has evolved substantially over the past few decades. This evolution has been pushed by government initiatives and private accrediting bodies that have exposed concerns regarding quality of care. Hospitals have responded with not only corrective actions but also actions that improve quality despite a lack of noted deficiencies (ie, taking quality from "good" to "better"). Key components of a successful quality improvement program have been identified, as have components of successful quality improvement teams. By applying these components to a physician-led sepsis quality improvement team, hospitals can successfully decrease sepsis mortality and increase compliance with the application of sepsis best practice in the emergency department, intensive care unit, or non-intensive care unit nursing units. PMID:25741960

Hampe, Holly M

2015-01-01

227

Sepsis and Organ(s) Dysfunction — Key Points, Reflections, and Perspectives  

Microsoft Academic Search

Sepsis is one of the main problems in medicine due to its complexity from pathophysiology, clinical, and therapeutic standpoints.\\u000a Although several definitions have been proposed for this syndrome, it can in general be assumed that it represents the clinical\\u000a manifestation of a system response of the body to infection or to an inflammatory-associated acute disease [1,2]. Despite advances in medical

A. Gullo; F. Iscra; F. Rubulotta

228

Levels of soluble Fc?RIII correlate with disease severity in sepsis  

PubMed Central

Neutrophil activation is thought to play a crucial role in the pathogenesis of sepsis. During activation, neutrophils adhere to and migrate through the endothelium. Therefore, the amount of circulating neutrophils does not adequately reflect the total amount of neutrophils that are involved in the pathophysiologic process of this condition. In this study we test the hypothesis that the severity of sepsis is associated with the total body mass of neutrophils as reflected in the plasma concentration of soluble Fc? receptor type III (sFc?RIII). Nineteen patients with sepsis (12 male, seven female, median age of 69 years, range 29–87 years) were included in this study. Ten healthy volunteers served as controls. Plasma sFc?RIII concentrations were measured by ELISA. Other parameters that were studied were leucocyte count, plasma concentrations of lactoferrin and soluble l-selectin, and surface expression of CD11b and CD66b on circulating neutrophils. Disease activity was measured using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Soluble Fc?RIII levels were elevated in sepsis patients whereas soluble l-selectin levels were moderately decreased compared with healthy controls. Markers of cell activation were significantly increased in sepsis patients. Soluble Fc?RIII correlated with disease severity as measured by the APACHE score (P < 0.05, r = 0.53), whereas the other parameters did not correlate with the APACHE score. In conclusion, this study demonstrates that soluble Fc?RIII is a useful marker for disease severity in patients with sepsis. PMID:9822280

Muller Kobold, A C; Zijlstra, J G; Koene, H R; DE Haas, M; Kallenberg, C G M; Cohen Tervaert, J W

1998-01-01

229

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

PubMed Central

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

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

230

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

PubMed Central

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

Pathak, Elina; MacMillan-Crow, Lee Ann

2012-01-01

231

Rolipram improves renal perfusion and function during sepsis in the mouse.  

PubMed

Microcirculatory dysfunction is correlated with increased mortality among septic patients and is believed to be a major contributor to the development of acute kidney injury (AKI). Rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, has been shown to reduce microvascular permeability and in the kidney, increase renal blood flow (RBF). This led us to investigate its potential to improve the renal microcirculation and preserve renal function during sepsis using a murine cecal ligation and puncture (CLP) model to induce sepsis. Rolipram, tested at doses of 0.3-10 mg/kg i.p., acutely restored capillary perfusion in a bell-shaped dose-response effect with 1 mg/kg being the lowest most efficacious dose. This dose also acutely increased RBF despite transiently decreasing mean arterial pressure. Rolipram also reduced renal microvascular permeability. It is noteworthy that delayed treatment with rolipram at 6 hours after CLP restored the renal microcirculation, reduced blood urea nitrogen and serum creatinine, and increased glomerular filtration rate at 18 hours. However, delayed treatment with rolipram did not reduce serum nitrate/nitrite levels, a marker of nitric oxide production, nor reactive nitrogen species generation in renal tubules. These data show that restoring the microcirculation with rolipram, even with delayed treatment, is enough to improve renal function during sepsis despite the generation of oxidants and suggest that PDE4 inhibitors should be evaluated further for their ability to treat septic-induced AKI. PMID:24018639

Holthoff, Joseph H; Wang, Zhen; Patil, Naeem K; Gokden, Neriman; Mayeux, Philip R

2013-11-01

232

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

PubMed Central

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

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

2012-01-01

233

Proteome Analysis of Skin Distinguishes Acute Guttate from Chronic Plaque Psoriasis  

Microsoft Academic Search

Psoriasis is a disease with considerable heterogeneity in clinical presentation. This is the first study using two-dimensional gel electrophoresis to compare global protein expression patterns in lesional and non-lesional skin from subjects with acute guttate psoriasis associated with streptococcal throat infection and chronic plaque psoriasis. Samples from experimentally induced contact eczema and normal skin from healthy controls were also included.

Lina M. Carlen; Fabio Sánchez; Ann-Charlotte Bergman; Susanne Becker; Daniel Hirschberg; Bo Franzén; Jonathan Coffey; Hans Jörnvall; Gert Auer; Ayodele A. Alaiya; Mona Ståhle

2005-01-01

234

[Epidemiology of invasive group A streptococcal infections in developed countries : the Canadian experience with necrotizing fasciitis].  

PubMed

In industrialized countries, group A streptococcal infections were a source of concern, mainly due to the occurrence of rheumatic fever and its cardiac complications. At present, the incidence of rheumatic fever is decreasing in these countries, giving way to an increasing occurrence of invasive streptococcal group A infections with high level of morbidity and mortality. Streptococcal necrotizing fasciitis, a specific entity, emerged these last decades, often in association with chickenpox. The introduction of the varicella vaccine in the province of Quebec routine immunization program, was followed by a significant decrease in the number of necrotizing fasciitis or other skin and soft-tissues infections in our pediatric population. However, in our experience at the CHU Sainte-Justine, this immunization program has not been helpful to reduce the overall incidence of invasive group A streptococcal infections. Conversely, an increase in the number of pleuro-pulmonary and osteo-articular infections was observed. PMID:25456684

Ovetchkine, Ph; Bidet, Ph; Minodier, Ph; Frère, J; Bingen, E

2014-11-01

235

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

PubMed Central

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

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

1983-01-01

236

Group G Beta-Hemolytic Streptococcal Bacteremia Characterized by 16S Ribosomal RNA Gene Sequencing  

Microsoft Academic Search

Little is known about the relative importance of the four species of Lancefield group G beta-hemolytic streptococci in causing bacteremia and the factors that determine the outcome for patients with group G beta-hemolytic streptococcal bacteremia. From 1997 to 2000, 75 group G beta-hemolytic streptococcal strains were isolated from the blood cultures of 66 patients. Sequencing of the 16S rRNA genes

PATRICK C. Y. WOO; AMI M. Y. FUNG; SUSANNA K. P. LAU; SAMSON S. Y. WONG; KWOK-YUNG YUEN

2001-01-01

237

Cross-Reactions of Reagents from Streptococcal Grouping Kits with Streptococcus porcinus  

Microsoft Academic Search

Streptococcus porcinus is usually associated with swine. Because we have received several isolates from human sources that had cross-reacted with commercial group B streptococcal reagents, we examined several com- mercial kits to determine the extent of this cross-reaction. Fifteen reference and 15 clinical strains of S. porcinus were tested for cross-reactions with group B streptococcal reagents from 12 different commercial

TERRY THOMPSON; RICHARD FACKLAM

1997-01-01

238

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS): a Controversial Diagnosis  

Microsoft Academic Search

Despite more than a decade of studying pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection\\u000a (PANDAS), it is still not possible to confirm its existence and whether it is a poststreptococcal autoimmune disorder. Many\\u000a controversies remain: the diagnostic criteria have not been validated, evidence of autoimmunity remains inconclusive, evidence\\u000a of a genetic predisposition is weak, and streptococcal infections are common

Sheila Knupp Feitosa de Oliveira; Christina Feitosa Pelajo

2010-01-01

239

Clostridium perfringens Sepsis and Fetal Demise after Genetic Amniocentesis  

PubMed Central

Clostridium perfringens is a rare cause of intrauterine infection. There have been five case reports concerning infection associated with invasive procedures. We report a woman who underwent a genetic amniocentesis due to her history of chronic granulomatous disease. She presented to the hospital ?38 hours after the amniocentesis complaining of fever and chills. Due to acute decompensation, she underwent an emergent dilatation and evacuation. During her stay, blood cultures came back positive for C. perfringens. Gradual improvement with intensive monitoring led to hospital discharge 4 days after the procedure. Uterine infection due to C. perfringens leading to maternal sepsis is associated with a high morbidity and mortality rate. Our patient was able to survive without a hysterectomy due to the rapid administration of antibiotics and surgical intervention while being evaluated. PMID:23705080

Hendrix, Nancy W.; Mackeen, A. Dhanya; Weiner, Stuart

2011-01-01

240

Duration of empirical antibiotic therapy for infants suspected of early-onset sepsis  

PubMed Central

Purpose of review Clinicians’ adherence to AAP and CDC Guidelines to prevent Group B Streptococcal (GBS) early onset sepsis (EOS) have reduced GBS EOS. While evidence-based testing and empirical antibiotic initiation is likely saving lives, clinicians have less compelling data to guide duration of empirically initiated antibiotics when cultures remain sterile and clinical signs resolve quickly. Our purpose is to review current opinions and evidence influencing clinicians’ choices for duration of empirically initiated antibiotics in newborns with sterile cultures. Recent findings Retrospective cohort studies indicate potential for harm with longer duration of empirical antibiotics for EOS when cultures are sterile. Cohort studies indicate timing of widely used tests used to estimate EOS risk affects their predictive value, and tests acquired 24 – 48 hours postnatally may provide reassurance for safe discontinuation. Summary Every day clinicians caring for thousands of neonates in the US stop antibiotics which were started empirically to treat EOS on the first postnatal day. Evidence is lacking to support a universal approach to decisions on duration of empirical antibiotics when cultures remain sterile. Reviewing predictive value relative to timing of laboratory testing can help clinicians develop locally appropriate antimicrobial duration decision-making guidelines. PMID:23407181

Cotten, C. Michael; Smith, P Brian

2013-01-01

241

Brazilian Sepsis Epidemiological Study (BASES study)  

PubMed Central

Introduction Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome Methods This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used. Results For the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract. Conclusion Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate. PMID:15312226

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

2004-01-01

242

Protective effect of erythropoietin against myocardial injury in rats with sepsis and its underlying mechanisms  

PubMed Central

The aim of this study was to investigate the protective effect of erythropoietin (EPO) against acute myocardial injury and its underlying mechanisms. Mice (n=146) were randomly divided in a double-blind manner into four groups, sham, Rocephin, EPO and sepsis, and mortality was observed on the seventh day after cecal ligation and puncture. In addition, a total of 252 rats were randomly divided into three groups, sham, EPO and sepsis, and indicators of cardiac function, inflammatory mediators and serum creatine kinase levels were assessed. Mitochondrial membrane potential, cell apoptosis and nuclear factor ?-light-chain-enhancer of activated B cells (NF-?B) p65 expression levels were detected using flow cytometry. Following intervention with EPO, the mortality rate in mice with sepsis was significantly reduced and the cardiac function of septic rats was significantly improved. In addition, the levels of inflammatory mediators, serum creatine kinase and apoptosis and the myocardial mitochondrial membrane potential and expression of NF-?B p65 in cardiac tissue were all improved following EPO treatment, and the differences between the results for the sepsis and EPO groups were statistically significant (P<0.05). These findings suggest that EPO reduces the myocardial inflammatory response in septic rats, attenuates the reduction in mitochondrial membrane potential and inhibits myocardial cell apoptosis by reducing NF-?B p65 expression, and therefore exerts a protective effect in the myocardium. PMID:25572660

ZHANG, XINLIANG; DONG, SHIMIN; QIN, YANJUN; BIAN, XIAOHUA

2015-01-01

243

Elevated Cardiac Troponin I in Sepsis and Septic Shock: No Evidence for Thrombus Associated Myocardial Necrosis  

PubMed Central

Background Elevated cardiac troponin I (cTnI) is frequently observed in patients with severe sepsis and septic shock. However, the mechanisms underlying cTnI release in these patients are still unknown. To date no data regarding coagulation disturbances as a possible mechanism for cTnI release during sepsis are available. Methodology/Principal Findings Consecutive patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock without evidence of an acute coronary syndrome were analyzed. Coagulation parameters (clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), ?-angle) were assessed in native whole blood samples, and using specific activators to evaluate the extrinsic and intrinsic as well as the fibrin component of the coagulation pathway with the use of rotational thrombelastometry (ROTEM). Thirty-eight patients were included and 22 (58%) were cTnI-positive. Baseline characteristics between TnI-positive and -negative patients were similar. The CT, CFT, MCF and the ?-angle were similar between the groups with trends towards shorter CT in the extrinsic and fibrin activation. Conclusions/Significance We found no differences in coagulation parameters analyzed with rotational thrombelastometry between cTnI-positive and -negative patients with SIRS, severe sepsis, and septic shock. These findings suggest that pathophysiological mechanisms other than thrombus-associated myocardial damage might play a major role, including reversible myocardial membrane leakage and/or cytokine mediated apoptosis in these patients. PMID:20140242

Altmann, David R.; Korte, Wolfgang; Maeder, Micha T.; Fehr, Thomas; Haager, Philipp; Rickli, Hans; Kleger, Gian-Reto; Rodriguez, Regulo; Ammann, Peter

2010-01-01

244

Modeling Testing and Discharge Decisions for Pneumonia and Sepsis Patients  

E-print Network

Modeling Testing and Discharge Decisions for Pneumonia and Sepsis Patients Jennifer E. Kreke-acquired pneumonia (CAP), and at some point during their treatment, develop sepsis. This paper assumes that diagnosis

Schaefer, Andrew

245

Deposition of circulating streptococcal lipoteichoic acid in mouse tissues.  

PubMed

The tissue binding properties of streptococcal lipoteichoic acid (LTA) were studied using normal and passively immunized BALB/c mice. After intraperitoneal injection in non-immunized mice, 3H-LTA concentrations in blood, heart, kidney and liver were highest between 24 and 30 h post-injection. LTA deposits in heart remained high for the next 24 h, whereas other tissue levels decreased. Constant amounts of 3H-LTA were detected in urine throughout the 48 h period. In passively immunized mice, the amount of tissue deposition of 3H-LTA was inversely proportional to the ratio of antibodies to LTA. Autoradiography revealed focal deposits of 3H-LTA in heart, kidney and liver. These observations indicate that LTA, released by streptococci growing at remote body sites, can be carried by the blood to internal organs where it can accumulate and participate in pathogenesis. PMID:1453925

Hyzy, J; Sciotti, V; Albini, B; Stinson, M

1992-08-01

246

Host innate immune responses to sepsis  

PubMed Central

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

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

2014-01-01

247

[Postoperative sepsis: diagnosis, special features, management].  

PubMed

A high level of suspicion is necessary to detect postoperative sepsis in good time. It may be difficult to differentiate sepsis from normal SIRS in the postoperative setting. Early signs and symptoms include delirium and respiratory compromise. These should trigger the search for a septic focus aggressively with special attention to the original site of surgery. Key recommendations include early goal-directed resuscitation of the septic patient, administration of broad-spectrum antibiotic therapy within 1 hour of diagnosis, and source control with attention to the balance of risks and benefits of the chosen method. In cases of severe abdominal sepsis the concept of relaparotomy on-demand has become most popular. PMID:20549587

Utzolino, S; Hopt, U T; Kaffarnik, M

2010-06-01

248

Role of immunoglobulins in neonatal sepsis  

PubMed Central

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

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

2015-01-01

249

Neonatal sepsis caused by Shewanella algae: A case report.  

PubMed

Sepsis remains a leading cause of mortality among neonates, especially in developing countries. Most cases of neonatal sepsis are attributed to Escherichia coli and other members of the Enterobacteriaceae family. Shewanella algae (S. algae) is a gram-negative saprophytic bacillus, commonly associated with the marine environment, which has been isolated from humans. Early onset neonatal sepsis caused by S. algae is uncommon. We report a case of S. algae blood stream infection in a newborn with early onset neonatal sepsis. PMID:25810789

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

2015-01-01

250

Current concept of abdominal sepsis: WSES position paper  

PubMed Central

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

2014-01-01

251

Severe sepsis and septic shock in pregnancy.  

PubMed

Pregnancies complicated by severe sepsis and septic shock are associated with increased rates of preterm labor, fetal infection, and preterm delivery. Sepsis onset in pregnancy can be insidious, and patients may appear deceptively well before rapidly deteriorating with the development of septic shock, multiple organ dysfunction syndrome, or death. The outcome and survivability in severe sepsis and septic shock in pregnancy are improved with early detection, prompt recognition of the source of infection, and targeted therapy. This improvement can be achieved by formulating a stepwise approach that consists of early provision of time-sensitive interventions such as: aggressive hydration (20 mL/kg of normal saline over the first hour), initiation of appropriate empiric intravenous antibiotics (gentamicin, clindamycin, and penicillin) within 1 hour of diagnosis, central hemodynamic monitoring, and the involvement of infectious disease specialists and critical care specialists familiar with the physiologic changes in pregnancy. Thorough physical examination and imaging techniques or empiric exploratory laparotomy are suggested to identify the septic source. Even with appropriate antibiotic therapy, patients may continue to deteriorate unless septic foci (ie, abscess, necrotic tissue) are surgically excised. The decision for delivery in the setting of antepartum severe sepsis or septic shock can be challenging but must be based on gestational age, maternal status, and fetal status. The natural inclination is to proceed with emergent delivery for a concerning fetal status, but it is imperative to stabilize the mother first, because in doing so the fetal status will likewise improve. Aggressive [corrected] treatment of sepsis can be expected to reduce the progression to severe sepsis and septic shock and prevention strategies can include preoperative skin preparations and prophylactic antibiotic therapy as well as appropriate immunizations. PMID:22914482

Barton, John R; Sibai, Baha M

2012-09-01

252

Molecular mechanisms in the pathogenesis of sepsis  

PubMed Central

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.

Pop-Began, V; P?unescu, V; Grigorean, V; Pop-Began, D; Popescu, C

2014-01-01

253

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

Microsoft Academic Search

Objective  To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign\\u000a guidelines for management of severe sepsis and septic shock,” published in 2004.\\u000a \\u000a \\u000a \\u000a Design  Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and\\u000a key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process\\u000a was

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

2008-01-01

254

Hepatosplanchnic circulation in cirrhosis and sepsis  

PubMed Central

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

Prin, Meghan; Bakker, Jan; Wagener, Gebhard

2015-01-01

255

Sepsis and septic shock: a review.  

PubMed

Sepsis and septic shock are a continuum of disease resulting from a complex host response to infection. They are major health issues in the United States, causing significant financial burden to the health care system in addition to multisystem morbidity and high rates of mortality. In recent decades, landmark trials in sepsis management have demonstrated improved mortality. Although the value of protocol-driven care is currently under question, it is clear that early recognition, prompt resuscitation, and timely use of antibiotics are of utmost importance. PMID:25741952

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

2015-01-01

256

Fluid Resuscitation in Sepsis: Reexamining the Paradigm  

PubMed Central

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

Tirupakuzhi Vijayaraghavan, Bharath Kumar; Cove, Matthew Edward

2014-01-01

257

Prevention of Early-onset Neonatal Group B Streptococcal Disease  

PubMed Central

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

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

2013-01-01

258

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

PubMed

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

Akinosoglou, Karolina; Alexopoulos, Dimitrios

2014-02-01

259

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

PubMed Central

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

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

1990-01-01

260

Injurious mechanical ventilation causes kidney apoptosis and dysfunction during sepsis but not after intra-tracheal acid instillation: an experimental study  

PubMed Central

Background Intratracheal aspiration and sepsis are leading causes of acute lung injury that frequently necessitate mechanical ventilation (MV), which may aggravate lung injury thereby potentially increasing the risk of acute kidney injury (AKI). We compared the effects of ventilation strategies and underlying conditions on the development of AKI. Methods Spraque Dawley rats were challenged by intratracheal acid instillation or 24 h of abdominal sepsis, followed by MV with a low tidal volume (LVT) and 5 cm H2O positive end-expiratory pressure (PEEP) or a high tidal volume (HVT) and no PEEP, which is known to cause more lung injury after acid instillation than in sepsis. Rats were ventilated for 4 hrs and kidney function and plasma mediator levels were measured. Kidney injury was assessed by microscopy; apoptosis was quantified by TUNEL staining. Results During sepsis, but not after acid instillation, MV with HVT caused more renal apoptosis than MV with LVT. Increased plasma active plasminogen activator inhibitor-1 correlated to kidney apoptosis in the cortex and medulla. Increased apoptosis after HVT ventilation during sepsis was associated with a 40% decrease in creatinine clearance. Conclusions AKI is more likely to develop after MV induced lung injury during an indirect (as in sepsis) than after a direct (as after intra-tracheal instillation) insult to the lungs, since it induces kidney apoptosis during sepsis but not after acid instillation, opposite to the lung injury it caused. Our findings thus suggest using protective ventilatory strategies in human sepsis, even in the absence of overt lung injury, to protect the kidney. PMID:25073618

2014-01-01

261

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis  

PubMed Central

Introduction Severe sepsis is characterised by intravascular or extravascular infection with microbial agents, systemic inflammation and microcirculatory dysfunction, leading to tissue damage, organ failure and death. The growth factor angiopoietin (Ang-1) has therapeutic potential but recombinant Ang-1 tends to aggregate and has a short half-life in vivo. This study aimed to investigate the acute effects of the more stable Ang-1 variant matrilin-1-angiopoietin-1 (MAT.Ang-1) on the function of the microcirculation in an experimental model of sepsis, and whether any protection by MAT-Ang-1 was associated with modulation of inflammatory cytokines, angiogenic factors or the endothelial nitric oxide synthase (eNOS)-Akt and vascular endothelial (VE)-cadherin pathways. Methods Aluminium window chambers were implanted into the dorsal skinfold of male C3H/HeN mice (7 to 10 weeks old) to expose the striated muscle microcirculation. Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg at 0 and 19 hours). MAT.Ang-1 was administered intravenously 20 hours after the onset of sepsis. Microcirculatory function was evaluated by intravital microscopy and Doppler fluximetry. Results Endotoxemia resulted in macromolecular leak, which was ameliorated by MAT.Ang-1 post-treatment. LPS induced a dramatic reduction in tissue perfusion, which was improved by MAT.Ang-1. Proteome profiler array analysis of skeletal muscle also demonstrated increased inflammatory and reduced angiogenic factors during endotoxemia. MAT.Ang-1 post-treatment reduced the level of IL-1? but did not significantly induce the expression of angiogenic factors. MAT.Ang-1 alone did not induce leak or increase angiogenic factors but did reduce vascular endothelial growth factor expression in controls. Conclusion Administration of MAT.Ang-1 after the onset of sepsis protects the microcirculation from endotoxemia-induced vascular dysfunction through reducing inflammation but without pro-angiogenic actions, thus representing a novel, potential pharmacotherapeutic agent for the treatment of sepsis. PMID:23036162

2012-01-01

262

Severe sepsis: Low expression of the renin-angiotensin system is associated with poor prognosis  

PubMed Central

Severe sepsis has a high fatality rate, but no clinical indices for prognosis have been established. In recent years, the renin-angiotensin system (RAS) has received considerable attention. However, clinical data on RAS are inconsistent. Therefore, the aim of the present study was to assess the significance of RAS in the prognosis of sepsis. Blood samples were collected from patients, who met the diagnostic criteria of severe sepsis, on day 1 (D1) and 3 (D3). For each sample, the levels of angiotensin II (AngII), angiotensin-converting enzyme (ACE) and additional indices were measured. Patients were monitored for 28 days. On the D1 of inclusion, the average Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22.2 and the Sepsis-related Organ Failure Assessment (SOFA) score was 6.1. Logistic regression analysis revealed that mortality-associated variables included the APACHE II score on D1, the SOFA score on D1, high lactic acid levels on D3 and low AngII and ACE levels on D1 and D3. AngII levels (<86.1 ng/ml) on D1 had a sensitivity of 88.2% and specificity of 77.3% for predicting mortality. ACE levels (<39.2 ng/ml) on D1 had a sensitivity of 88.2% and specificity of 72.7% for predicting mortality. These two indices were better than the APACHE II and SOFA scores. Therefore, low expression levels of AngII and ACE are valuable in predicting the mortality of patients with severe sepsis. PMID:24940436

ZHANG, WEI; CHEN, XIAOWEI; HUANG, LING; LU, NING; ZHOU, LEI; WU, GUOJIE; CHEN, YUGUO

2014-01-01

263

[An inquiry into the relevant issues about burn sepsis].  

PubMed

Since the definition of sepsis was proposed in Chest by American College of Chest Physicians and Society of Critical Care Medicine in 1992, researches on burn sepsis have focused on the regulation of immune-inflammation response resulting in minimizing tissue injury resulted from excessive inflammatory response. Treatment of sepsis should focus on effect of early circulation oxygenation support in preventing and treating multiple organ dysfunction. The hypothesis of producing a hibernation-like state which might prevent multiple organ dysfunction in patients with sepsis provides us a new therapeutic strategy in protecting organs in the early stage of sepsis in future. PMID:24684982

Zhang, Qin; Liao, Zhenjiang

2014-02-01

264

New concepts in the pathophysiology of oxygen metabolism during sepsis.  

PubMed

Sepsis is an intriguing pathological condition associated with many complex metabolic and physiological alterations. In this review a novel hypothesis in the pathophysiology of oxygen metabolism during sepsis is explored. It is proposed that the hypermetabolic response to sepsis results from enhanced reactive oxygen generation by phagocytes. Reactive oxygen detoxification by host enzyme systems subsequently leads to alterations in oxidative metabolism. The similarities between the metabolic consequences of reactive oxygen metabolism and the metabolic changes observed during sepsis are outlined. A unified concept is presented to help explain the pathophysiological changes in oxygen metabolism during sepsis. PMID:7648095

Vlessis, A A; Goldman, R K; Trunkey, D D

1995-07-01

265

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis.  

PubMed

Multipotent mesenchymal stem (stromal) cells (MSCs) have shown promising therapeutic effects in preclinical models of both acute respiratory distress syndrome (ARDS) and sepsis. Although initial research focused on the ability of MSCs to engraft at sites of tissue injury, increasing evidence suggests that MSCs have their therapeutic effects through mechanisms unrelated to long-term incorporation into host tissue. One of the most compelling of these pathways is the ability of MSCs to interact with injured tissue through the release of soluble bioactive factors. This Review provides an overview of the general properties of MSCs, and then outlines ways in which the paracrine effects of MSCs might reduce lung injury and enhance lung repair in ARDS and sepsis. Finally, we summarise ongoing challenges in MSC research and identify areas in which the discipline might progress in the coming years. PMID:25465643

Walter, James; Ware, Lorraine B; Matthay, Michael A

2014-12-01

266

Postsplenectomy sepsis: Historical background and current concepts  

Microsoft Academic Search

Although most common in infancy and early childhood, susceptibility to postsplenectomy infection is not limited by age or underlying pathological condition. Postsplenectomy sepsis is a fulminant, rapid process which often begins with vague symptoms. Death may follow in hours unless appropriate fluid resuscitation and antibiotic therapy is promptly instituted. Experimental evidence suggests that spienectomy results in a loss of both

Karen W. West; Jay L. Grosfeld

1985-01-01

267

Recurrent Sepsis Due To Bacillus Licheniformis  

PubMed Central

Bacillus licheniformis is recognized as a human pathogen causing infections, mainly in immunocompromised patients. We present a case of sepsis in an immunocompetent patient, caused by B. licheniformis. This case is of particular interest because the patient had no history of any immune deficiency and the disease did not respond to antibiotic treatment. PMID:22529634

Haydushka, Irina A; Markova, Nadya; Kirina, Vesselina; Atanassova, Maria

2012-01-01

268

Sepsis due to asymptomatic Candida prostatitis.  

PubMed

A case of a asymptomatic prostatitis due to Candida Albicans that caused a sepsis is presented. Up today in literature only 3 cases of Candida infections of the prostate gland without general illness were described. In this case the transurethral electro-resection of prostate was the adequate treatment. PMID:16372510

Mahlknecht, Alois; Pecorari, Valentina; Richter, Astrid

2005-06-01

269

[Innate immunity, Toll receptor and sepsis].  

PubMed

The innate immune response is the first line of defense against infection. Toll-like receptors (TLRs) recognize bacterial lipopolysaccharide and other pathogen-associated molecular patterns (PAMPs). Intracellular signals initiated by interaction between Toll receptors and specific PAMPs results in inflammatory response. Sepsis and septic shock are the result of an exaggerated inflammatory systemic response induced by innate immune dysregulation. PMID:14617415

Carrillo-Esper, Raúl

2003-01-01

270

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

PubMed

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

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

2010-02-01

271

Plasma-amino acid profiles in sepsis and stress.  

PubMed Central

Sepsis has been associated with specific plasma amino acid patterns. Sixty-five patients were prospectively investigated as to whether these patterns are indeed sepsis specific, or specific for metabolic stress without concomitant sepsis, or associated with the presence of organ failure. Virtually all aminoacid levels were decreased by 10-30% (p less than 0.05), whereas cystine and phenylalanine were significantly elevated. These changes were more pronounced in severe sepsis. Organ failure was not associated with significantly altered amino acid profiles. No differences were found between sepsis and stress without signs of sepsis. In addition, imminent death was not associated with aberrant amino acid profiles. We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles, but that such changes are aspecific and therefore poor indicators of disease severity. PMID:2910215

Vente, J P; von Meyenfeldt, M F; van Eijk, H M; van Berlo, C L; Gouma, D J; van der Linden, C J; Soeters, P B

1989-01-01

272

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

PubMed Central

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

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

1992-01-01

273

Mental and physical disability after sepsis.  

PubMed

Sepsis remains a major cause of admissions to Intensive Care Units (ICU) and has a high mortality rates and significant morbidity in survivors. There are physical, cognitive and psychological sequelae from severe sepsis that have a negative effect on the patients' health related quality of life in the longer term and a social care and humanitarian impact. Although muscle mass loss during the septic period happens very quickly, recovery takes a considerable time and requires the patient to commit to exercising and eating well to rebuild. Where cognitive impairment has resulted from the septic illness the patients' ability to look after themselves may be affected and this has financial and family implications for future care. Patients may also develop psychological problems such as anxiety, depression or post traumatic stress disorder (PTSD), which can have a profound effect on their everyday functioning and the possibility of returning to work. As yet there are no published studies of rehabilitation with patients surviving severe sepsis, although there is one in progress at the moment. The use of techniques such as ICU diaries to help patients to understand their illness and deal with delusional memories they may have from their ICU stay has been shown to aid psychological recovery in general ICU patients, a percentage of whom will have suffered from sepsis. The use of a self-guided manualised 6 week rehabilitation program, the ICU Recovery Manual, has been shown to accelerate physical recovery in general ICU patients. Considerable amounts of money are spent treating patients with severe sepsis in ICU and not completing the job of returning them to as close as possible to their normal functioning does not make financial sense. PMID:23857443

Jones, C; Griffiths, R D

2013-11-01

274

Automated electronic medical record sepsis detection in the emergency department  

PubMed Central

Background. While often first treated in the emergency department (ED), identification of sepsis is difficult. Electronic medical record (EMR) clinical decision tools offer a novel strategy for identifying patients with sepsis. The objective of this study was to test the accuracy of an EMR-based, automated sepsis identification system. Methods. We tested an EMR-based sepsis identification tool at a major academic, urban ED with 64,000 annual visits. The EMR system collected vital sign and laboratory test information on all ED patients, triggering a “sepsis alert” for those with ?2 SIRS (systemic inflammatory response syndrome) criteria (fever, tachycardia, tachypnea, leukocytosis) plus ?1 major organ dysfunction (SBP ? 90 mm Hg, lactic acid ?2.0 mg/dL). We confirmed the presence of sepsis through manual review of physician, nursing, and laboratory records. We also reviewed a random selection of ED cases that did not trigger a sepsis alert. We evaluated the diagnostic accuracy of the sepsis identification tool. Results. From January 1 through March 31, 2012, there were 795 automated sepsis alerts. We randomly selected 300 cases without a sepsis alert from the same period. The true prevalence of sepsis was 355/795 (44.7%) among alerts and 0/300 (0%) among non-alerts. The positive predictive value of the sepsis alert was 44.7% (95% CI [41.2–48.2%]). Pneumonia and respiratory infections (38%) and urinary tract infection (32.7%) were the most common infections among the 355 patients with true sepsis (true positives). Among false-positive sepsis alerts, the most common medical conditions were gastrointestinal (26.1%), traumatic (25.7%), and cardiovascular (20.0%) conditions. Rates of hospital admission were: true-positive sepsis alert 91.0%, false-positive alert 83.0%, no sepsis alert 5.7%. Conclusions. This ED EMR-based automated sepsis identification system was able to detect cases with sepsis. Automated EMR-based detection may provide a viable strategy for identifying sepsis in the ED. PMID:24765577

Nguyen, Su Q.; Mwakalindile, Edwin; Booth, James S.; Hogan, Vicki; Morgan, Jordan; Prickett, Charles T.; Donnelly, John P.

2014-01-01

275

Mortality from early onset group B streptococcal infection in the United Kingdom  

PubMed Central

AIMS—To assess the assumption that group B streptococcal infection is less common in the United Kingdom than it is in the United States.?METHODS—All stillbirth and neonatal death records in the former Northern Health Region were scrutinised to determine how many babies had died of infection in 1981-96, and what had been the cause.?RESULTS—Fifty one of 630 206 live born babies had died of confirmed group B streptococcal infection after becoming symptomatic within 48 hours of birth (0.8 neonatal deaths per 10 000 live births). There were a further 27 deaths from infection without a confirmed microbiological diagnosis, and 17 stillbirths from confirmed group B streptococcal infection.?CONCLUSIONS—The incidence of death from early onset infection was marginally higher than the officially estimated rate for the United States before widespread prophylaxis was attempted. Strategies for perinatal prevention deserve greater attention in the United Kingdom.?? PMID:10325793

Embleton, N.; Wariyar, U.; Hey, E.

1999-01-01

276

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

PubMed

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

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

2014-09-01

277

[Management of severe invasive group A streptococcal infections].  

PubMed

The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a ?-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention. PMID:25456687

Faye, A; Lorrot, M; Bidet, Ph; Bonacorsi, S; Cohen, R

2014-11-01

278

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

PubMed

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

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

2014-12-01

279

A novel streptococcal integrative conjugative element involved in iron acquisition.  

PubMed

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 (55)Fe 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

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

2008-12-01

280

A novel streptococcal integrative conjugative element involved in iron acquisition  

PubMed Central

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

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

281

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

PubMed Central

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

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

2012-01-01

282

Primary Vibrio vulnificus sepsis in Kentucky.  

PubMed

Vibrio vulnificus is associated with infection acquired during contact with sea water or with seafood, and is seldom suspected by physicians in noncoastal states. The ease of transportation of fresh raw seafood has facilitated this organism's capacity to produce disease in geographic areas in which it was previously unseen. We have reported a case of fatal Vibrio vulnificus sepsis acquired from ingestion of fresh oysters in the inland United States. PMID:2315791

Ali, M B; Raff, M J

1990-03-01

283

Designing a Pediatric Severe Sepsis Screening Tool  

PubMed Central

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 tool’s 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 tool’s 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 tool’s 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

Sepanski, Robert J.; Godambe, Sandip A.; Mangum, Christopher D.; Bovat, Christine S.; Zaritsky, Arno L.; Shah, Samir H.

2014-01-01

284

Epigenetics in sepsis: targeting histone deacetylases.  

PubMed

Severe sepsis and septic shock are lethal complications of infection, characterised by dysregulated inflammatory and immune responses. Our understanding of the pathogenesis of sepsis has improved markedly in recent years, but unfortunately has not been translated into efficient treatment strategies. Epigenetic mechanisms such as covalent modification of histones by acetylation are master regulators of gene expression under physiological and pathological conditions, and strongly impact on inflammatory and host defence responses. Histone acetylation is controlled by histone acetyltransferases and histone deacetylases (HDACs), which affect gene expression also by targeting non-histone transcriptional regulators. Numerous HDAC inhibitors (HDACi) are being tested in clinical trials, primarily for the treatment of cancer. We performed the first comprehensive study of the impact of HDACi on innate immune responses in vitro and in vivo. We showed that HDACi act essentially as negative regulators of the expression of critical immune receptors and antimicrobial pathways in innate immune cells. In agreement, HDACi impaired phagocytosis and killing of bacteria by macrophages, and increased susceptibility to non-severe bacterial and fungal infections. Strikingly, proof-of-principle studies demonstrated that HDACi protect from lethal toxic shock and septic shock. Overall, our observations argue for a close monitoring of the immunological and infection status of patients treated with HDACi, especially immunocompromised cancer patients. They also support the concept of pharmacological inhibitors of HDACs as promising drugs to treat inflammatory diseases, including sepsis. PMID:23664675

Ciarlo, Eleonora; Savva, Athina; Roger, Thierry

2013-06-01

285

Mesenchymal stem cells as a therapeutic tool to treat sepsis.  

PubMed

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

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

2015-03-26

286

Mesenchymal stem cells as a therapeutic tool to treat sepsis  

PubMed Central

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.

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

2015-01-01

287

Betulinic acid attenuates renal oxidative stress and inflammation in experimental model of murine polymicrobial sepsis.  

PubMed

Sepsis is a common cause of acute kidney injury (AKI) and is associated with substantial morbidity and mortality. Objective of the study was to evaluate the effect of betulinic acid, a triterpenoid in sepsis-induced AKI using cecal ligation puncture (CLP) mouse model. Mice subjected to CLP developed histologic AKI at 18h after CLP. There was an increase in renal proinflammatory response (nuclear factor-kappa B expression, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10), matrix metalloproteinase-9, plasma creatinine, renal neutrophil gelatinase-associated lipocalin and oxidant stress response (malondialdehyde, inducible nitric oxide synthase, total nitrite and superoxide); decrease in anti-oxidant levels (superoxide dismutase and catalase) at 18h of CLP. However, BA pretreatment at the doses of 10 and 30mg/kg prevented the CLP-induced kidney damage by restoring the aforementioned inflammatory mediators, oxidant and anti-oxidant imbalance. These evidences suggest that, the protective effects of BA on kidney are associated with defending action against inflammatory and oxidative stress response in CLP mice and BA could be potential therapeutic agent in sepsis-induced AKI. PMID:25585354

Lingaraju, Madhu Cholenahalli; Pathak, Nitya Nand; Begum, Jubeda; Balaganur, Venkanna; Ramachandra, Harish Darasaguppe; Bhat, Rafia Ahmad; Ram, Mahendra; Singh, Vishakha; Kandasamy, Kannan; Kumar, Dhirendra; Kumar, Dinesh; Tandan, Surendra Kumar

2015-04-01

288

Neuronal NF-kappaB influences thermoregulation and survival in a sepsis model.  

PubMed

Gene regulation in sepsis is known to be controlled by the transcription factor NF-kappaB. However, the function of neuronal NF-kappaB in sepsis is not well defined. In a mouse model of sepsis induced by i.p. injection of lipopolysaccharides (LPS), we found an activation of NF-kappaB in the brain as shown by the induction of a transgenic NF-kappaB reporter. Inhibition of neuronal NF-kappaB by cell-specific expression of the NF-kappaB super-repressor IkappaBalpha-SR improved LPS-induced hypothermia and survival but had no effect on body weight or on the humoral response to LPS. In contrast, glial inhibition of NF-kappaB did not influence body temperature and survival. By immunohistochemistry, we detected the active NF-kappaB subunit RelA in neuronal nuclei of the organum vasculosum of the lamina terminalis. Our data reveal an important role of neuronal NF-kappaB in thermoregulation and survival. The upcoming group of NF-kappaB inhibitors may have a place in the treatment of the acute-phase response. PMID:17655939

Jüttler, Eric; Inta, Ioana; Eigler, Verena; Herrmann, Oliver; Maegele, Ira; Maser-Gluth, Christiane; Schwaninger, Markus

2007-09-01

289

Redox regulation of mitophagy in the lung during murine Staphylococcus aureus sepsis.  

PubMed

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 (1×10(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

Chang, Alan L; Ulrich, Allison; Suliman, Hagir B; Piantadosi, Claude A

2015-01-01

290

TRPV1 and SP: key elements for sepsis outcome?  

PubMed Central

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

Bodkin, Jennifer Victoria; Fernandes, Elizabeth Soares

2013-01-01

291

Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia  

PubMed Central

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P < 0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients. PMID:24895569

Takele, Yegnasew; Woldeyohannes, Desalegn; Tiruneh, Moges; Mohammed, Rezika; Lynen, Lutgarde; van Griensven, Johan

2014-01-01

292

Group a streptococcal diseases and their global burden.  

PubMed

Group A streptococcus (GAS) or Streptococcus pyogenes has been recognised as an important human pathogen since early days of modern microbiology, and it remains among the top ten causes of mortality from an infectious disease. Clinical manifestations attributable to this organism are perhaps the most diverse of any single human pathogen. These encompass invasive GAS infections, with high mortality rates despite effective antimicrobials, toxin-mediated diseases including scarlet fever and streptococcal toxic shock syndrome, the autoimmune sequelae of rheumatic fever and glomerulonephritis with potential for long-term disability, and nuisance manifestations of superficial skin and pharyngeal infection, which continue to consume a sizable proportion of healthcare resources. Although an historical perspective indicates major overall reductions in GAS infection rates in the modern era, chiefly as a result of widespread improvements in socioeconomic circumstances, this pathogen remains as a leading infectious cause of global morbidity and mortality. More than 18 million people globally are estimated to suffer from serious GAS disease. This burden disproportionally affects least affluent populations, and is a major cause of illness and death among children and young adults, including pregnant women, in low-resource settings. We review GAS transmission characteristics and prevention strategies, historical and geographical trends and report on the estimated global burden disease attributable to GAS. The lack of systematic reporting makes accurate estimation of rates difficult. This highlights the need to support improved surveillance and epidemiological research in low-resource settings, in order to enable better assessment of national and global disease burdens, target control strategies appropriately and assess the success of control interventions. PMID:23242849

Ralph, Anna P; Carapetis, Jonathan R

2013-01-01

293

Streptococcal pyrogenic exotoxin type A (scarlet fever toxin) is related to Staphylococcus aureus enterotoxin B  

Microsoft Academic Search

The nucleotide sequence of the gene encoding group A streptococcal pyrogenic exotoxin type A (SPE A) was determined by the dideoxy chain termination method. The first 30 residues of the translation product represented a hydrophobic signal peptide. The mature protein was 220 amino acids in length and had a molecular weight of 25,805. It has significant protein sequence homology with

James J. L'Italien; Patrick M. Schlievert

1986-01-01

294

Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis.  

PubMed Central

Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats. Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula. Clarithromycin was marginally superior to clindamycin against small amounts of inocula. Clarithromycin may be considered for endocarditis chemoprophylaxis in human. PMID:8851620

Vermot, D; Entenza, J M; Vouillamoz, J; Glauser, M P; Moreillon, P

1996-01-01

295

Rapid detection of group B streptococcal colonization of the genital tract by a commercial optical immunoassay  

Microsoft Academic Search

The performance of a commercial optical immunoassay (OIA) was compared at two institutions with that of routine agar and broth culture methods for the detection of group B streptococcal (GBS) colonization of the genital tract. The Strep B OIA (Bio Star, USA) was used to test 962 vaginal swabs from pregnant women for the presence of GBS antigen. The prevalence

K. C. Carroll; D. Ballou; M. Varner; H. Chun; R. Traver; J. Salyer

1996-01-01

296

Original article Perimyocarditis following streptococcal group A infection: From clinical cases to  

E-print Network

culture grew hemolytic Strep- tococcus group A. Physical examination revealed a pericardial friction rubOriginal article Perimyocarditis following streptococcal group A infection: From clinical cases Doniger b , Alon Basevitz a , Ron Unger b a Department of Internal Medicine C, Kaplan Medical Center

Unger, Ron

297

PUSTULAR PSORIASIS ELICITED BY STREPTOCOCCAL ANTIGEN AND LOCALIZED TO THE SWEAT PORE  

Microsoft Academic Search

A woman, aged 39 years, presented with a localized, painful, pustular eruption of the neck, scalp, and finger of five years' duration. A diagnosis of pustular psoriasis was made clinically and histologically. It was possible to reproduce the disease by the intradermal injection of killed Group A streptococcal organisms. The induced pustules, as well as those appearing clinically, were intraepidermal

Walter B. Shelley; Margaret Gray Wood; Herman Beerman

1975-01-01

298

Nosocomial streptococcal blood stream infections in the SCOPE program: Species occurrence and antimicrobial resistance  

Microsoft Academic Search

Nosocomial blood stream infections due to streptococci represent an increasingly important problem, particularly among neutropenic cancer patients. This problem is compounded by the emerging resistance to antimicrobial agents commonly used for empiric or prophylactic treatment of hospitalized patients. In this study, we examined the species distribution and antimicrobial susceptibility profile of 295 streptococcal nosocomial blood stream isolates from more than

Michael A. Pfaller; Ronald N. Jones; Steven A. Marshall; Michael B. Edmond; Richard P. Wenzel

1997-01-01

299

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

300

Role of Benzathine Penicillin G in Prophylaxis for Recurrent Streptococcal Cellulitis of the Lower Legs  

Microsoft Academic Search

Cellulitis of the lower leg is an infection caused by streptococci or, less commonly, Staphylococcus aureus and other gram-negative rods. Recurrence of cellulitis is a common problem. In the present study, we evaluated the use of monthly intramuscular injections of benzathine penicillin G to prevent recurrences of cellulitis. A total of 115 patients with definite or presumptive cases of streptococcal

1997-01-01

301

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

PubMed Central

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

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

1992-01-01

302

Cloning, Expression, and Characterization of the Superantigen Streptococcal Pyrogenic Exotoxin G from Streptococcus dysgalactiae  

Microsoft Academic Search

We identified seven novel variants of streptococcal pyrogenic exotoxin G (SPEGG), a superantigen, in Streptococcus dysgalactiae subsp. dysgalactiae or equisimilis isolates from clinical cases of infection in humans and animals. Phylogenetic analysis of the SPEGG variants indicated two clades in the dendrogram: one composed of variants derived from the bacteria isolated from the humans and the other composed of variants

Jizi Zhao; Tomohito Hayashi; Susanna Saarinen; Anastassios C. Papageorgiou; Hidehito Kato; K. Imanishi; T. Kirikae; R. Abe; T. Uchiyama; T. Miyoshi-Akiyama

2007-01-01

303

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

Microsoft Academic Search

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

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

1998-01-01

304

Insurance type and sepsis-associated hospitalizations and sepsis-associated mortality among US adults: A retrospective cohort study  

PubMed Central

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

2011-01-01

305

Procalcitonin—a sepsis parameter in severe burn injuries  

Microsoft Academic Search

Procalcitonin (PCT) levels increase in patients with systemic infections; the highest levels have been found in sepsis. This study tested whether plasma procalcitonin level was related to sepsis, CRP, burn size, inhalation injury or mortality in severely burned patients over the entire clinical course.In 27 patients with 51 (20–91)% TBSA, PCT was measured three times weekly from admission over the

D von Heimburg; W Stieghorst; R Khorram-Sefat; N Pallua

1998-01-01

306

Letale Sepsis nach Splenektomie trotz Reimplantation von Milzgewebe  

Microsoft Academic Search

Summary A fatal case of a postsplenectomy sepsis is presented which occured in a 5-year-old boy 11 month following splenectomy due to trauma and reimplantation of splenic tissue. The patient died 4 h after admission to the hospital. The post mortem revealed an encephalitis and a sepsis although splenic regenerates were found in the omentum pouch. Our report increases the

S. Michalski; P. Blankenhorn; G. Lepsien; F. E. Lüdtke

1991-01-01

307

Severe sepsis and septic shock in the elderly: An overview  

PubMed Central

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

Nasa, Prashant; Juneja, Deven; Singh, Omender

2012-01-01

308

A VLU complicated by severe group a streptococcal infection resulting in necrotising fasciitis and septic shock: a case report.  

PubMed

This case study outlines the management of a patient with a venous leg ulcer whose swabs cultured Staphylococcus aureus and beta-haemolytic streptococcus group A while in hospital with cellulitis, which was treated with antibiotics as per sensitivities. However, the patient presented at the emergency department five weeks later with a diagnosis of invasive group A streptococcal disease resulting in necrotising fasciitis and streptococcal toxic shock syndrome. This paper describes the holistic care and wound management that the patient received. PMID:25289649

Meagher, H; Corkery, M; Concannon, L; Kavanagh, E

2014-10-01

309

Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report  

Microsoft Academic Search

INTRODUCTION: We report a case of optic atrophy, necrotizing anterior scleritis and keratitis presenting in a patient with Streptococcal Toxic Shock Syndrome. CASE PRESENTATION: A 43-year-old woman developed streptococcal toxic shock syndrome secondary to septic arthritis of her right ankle. Streptococcus pyogenes (b-haemolyticus Group A) was isolated from blood cultures and joint aspirate. She was referred for ophthalmology review as

Konstantinos I Papageorgiou; Alexander S Ioannidis; Petros S Andreou; Ajay J Sinha

2008-01-01

310

Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis  

PubMed Central

Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies. PMID:25821827

Yan, Jun; Liang, Hua-ping

2015-01-01

311

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy  

PubMed Central

Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

2014-01-01

312

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy.  

PubMed

Sepsis - which is a severe life-threatening infection with organ dysfunction - initiates a complex interplay of host pro-inflammatory and anti-inflammatory processes. Sepsis can be considered a race to the death between the pathogens and the host immune system, and it is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses provides a novel approach for treating this highly lethal condition. Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of sepsis and in the field of infectious disease. PMID:24232462

Hotchkiss, Richard S; Monneret, Guillaume; Payen, Didier

2013-12-01

313

suPAR as a prognostic biomarker in sepsis  

PubMed Central

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis. PMID:22221662

2012-01-01

314

Targeting HMGB1 in the treatment of sepsis  

PubMed Central

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

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

2013-01-01

315

Managing oncology neutropenia and sepsis in the intensive care unit.  

PubMed

Neutropenic sepsis results as a post-cancer treatment complications and is considered an oncologic emergency. Neutropenic sepsis can result in mortality, especially if it is not identified at an early stage. Septic syndrome is the leading cause of nonrelapse mortality in patients with hematologic malignancies and solid tumors. Therefore, intensive care unit (ICU) nurses must possess a thorough understanding of cancer treatments, hematopoiesis, neutropenia, sepsis, risk factors, and the ability to perform a comprehensive assessment of the oncology patient. Each of these components plays a vital role in the patient's overall management following treatments with chemotherapy, radiation, and stem cell transplantation. The ICU nurse who encompasses this understanding will be able to identify neutropenic sepsis in a timely manner. The early identification of neutropenic sepsis will enable the ICU nurse to expeditiously implement preventive treatment and management to prevent mortality. PMID:25741957

Vioral, Anna N; Wentley, Dawn

2015-01-01

316

Improving the management and care of people with sepsis.  

PubMed

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

Fitzpatrick, David; McKenna, Michael; Rooney, Kevin; Beckett, Dan; Pringle, Norma

2014-04-01

317

Biomarkers in acute lung injury.  

PubMed

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

Mokra, Daniela; Kosutova, Petra

2014-10-22

318

Association between early peak temperature and mortality in neutropenic sepsis.  

PubMed

Fever is often the first sign of neutropenic infection, but its prognostic impact has not been established. We aimed to determine whether early peak temperature is associated with mortality in patients with neutropenic sepsis admitted to intensive care units (ICUs). We used a database of admissions to 157 ICUs in Australia and New Zealand between 2005 and 2013 to seek an association between peak temperature within the first 24 h in ICU and in-hospital mortality in neutropenic and non-neutropenic sepsis. Odds ratios for in-hospital death were calculated for four temperature bands, adjusting for illness severity. Two patient cohorts were identified: neutropenic sepsis (N?=?4027) and non-neutropenic sepsis (N?=?114,040). In-hospital mortality was higher in neutropenic sepsis than non-neutropenic sepsis. In both cohorts, early peak temperature below 36.5 °C was associated with significantly increased mortality compared to normothermia. Among non-neutropenic patients, an early peak temperature of 37.5 °C or higher was associated with reduced mortality compared to normothermia. In contrast, in patients with neutropenic sepsis, fever was not associated with reduced mortality compared to normothermia. Similar findings were seen in a subgroup of the neutropenic sepsis cohort with a documented haematological malignancy. In neutropenic sepsis patients admitted to ICU, a temperature below 36.5 °C is associated with increased mortality compared with normothermia. In contrast to non-neutropenic sepsis, fever was not associated with a significant reduction in mortality in neutropenic patients. Interventional studies are needed to determine whether physical or pharmacological measures to reduce fever influence outcomes during neutropenic infections. PMID:25516454

Weinkove, Robert; Bailey, Michael; Bellomo, Rinaldo; Saxena, Manoj K; Tam, Constantine S; Pilcher, David V; Beasley, Richard; Young, Paul J

2015-05-01

319

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

PubMed

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

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

2014-10-01

320

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis  

Microsoft Academic Search

BACKGROUND: Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat

Katharine A Robertson; Jimmy A Volmink; Bongani M Mayosi

2005-01-01

321

Bai-hu-tang, ancient chinese medicine formula, may provide a new complementary treatment option for sepsis.  

PubMed

Bai-Hu-Tang (BHT) has been broadly applied to treating the early stage of acute infection with systemic inflammation for two thousand years in Chinese medicine. We explore whether BHT is beneficial in treating sepsis and its effects on proinflammatory cytokine, interleukin-6, and anti-inflammatory cytokine interleukin-10, in which both play key roles in the progress of sepsis. Thirty-six male Sprague-Dawley rats were randomized into six groups, with cecal ligation and puncture (CLP) performed in all but the sham-control group. Rats in CLP + BHT-L6 and CLP + BHT-H6 groups, respectively, received a low (0.45?g/kg) and high doses (0.9?g/kg) of BHT, 6?hrs postoperatively. CLP + BHT-L12 and CLP + BHT-H12 groups, respectively, received low and high doses of BHT, 12?hrs postoperatively. Sham-control and sepsis-control groups received distilled water (1?mL) as vehicle, 6 hrs postoperatively. Serial blood samples were drawn before operation, as baseline, and at 4, 8, and 12?hrs postoperatively for IL-6 and IL-10 assay. All rats were monitored for 3 days for survival study. Rats in the CLP + BHT-H6 group had significantly higher survival rate (80%) and significantly lower levels of both IL-6 and IL-10 at 12?hrs postoperatively than those in the sepsis-control group. Results suggested that BHT may be a new complementary treatment option for sepsis. PMID:23762108

Lin, Chien-Jung; Su, Yi-Chang; Lee, Cheng-Hung; Li, Tsai-Chung; Chen, Yun-An; Lin, Sunny Jui-Shan

2013-01-01

322

Bai-Hu-Tang, Ancient Chinese Medicine Formula, May Provide a New Complementary Treatment Option for Sepsis  

PubMed Central

Bai-Hu-Tang (BHT) has been broadly applied to treating the early stage of acute infection with systemic inflammation for two thousand years in Chinese medicine. We explore whether BHT is beneficial in treating sepsis and its effects on proinflammatory cytokine, interleukin-6, and anti-inflammatory cytokine interleukin-10, in which both play key roles in the progress of sepsis. Thirty-six male Sprague-Dawley rats were randomized into six groups, with cecal ligation and puncture (CLP) performed in all but the sham-control group. Rats in CLP + BHT-L6 and CLP + BHT-H6 groups, respectively, received a low (0.45?g/kg) and high doses (0.9?g/kg) of BHT, 6?hrs postoperatively. CLP + BHT-L12 and CLP + BHT-H12 groups, respectively, received low and high doses of BHT, 12?hrs postoperatively. Sham-control and sepsis-control groups received distilled water (1?mL) as vehicle, 6 hrs postoperatively. Serial blood samples were drawn before operation, as baseline, and at 4, 8, and 12?hrs postoperatively for IL-6 and IL-10 assay. All rats were monitored for 3 days for survival study. Rats in the CLP + BHT-H6 group had significantly higher survival rate (80%) and significantly lower levels of both IL-6 and IL-10 at 12?hrs postoperatively than those in the sepsis-control group. Results suggested that BHT may be a new complementary treatment option for sepsis. PMID:23762108

Lin, Chien-Jung; Su, Yi-Chang; Lee, Cheng-Hung; Li, Tsai-Chung; Chen, Yun-An; Lin, Sunny Jui-Shan

2013-01-01

323

Zymomonas mobilis culture protects against sepsis by modulating the inflammatory response, alleviating bacterial burden and suppressing splenocyte apoptosis.  

PubMed

Microorganisms with immunomodulating effects beneficially affect the host organism by improving the microbial equilibrium and balancing the immune system. Zymomonas mobilis is reported to have antagonistic properties against yeast and other pathogenic microorganisms in humans and animals. This study assessed the effects of Z. mobilis UFPEDA 202 (10(9)CFU/mL) cultures on polymicrobial sepsis induced by cecal ligation and puncture (CLP). The survival of animals subjected to lethal sepsis was evaluated after pre-treatment, post-treatment or a combination of both. 6h after the induction of sepsis, neutrophil migration, the number of bacteria, myeloperoxidase, TNF-?, MCP-1, and IL-10 were performed in the peritoneal lavage of animals. Histopathological changes in the spleen of animals were evaluated by light microscopy, and apoptosis of splenocytes was analyzed by transmission electron microscopy. The results showed that the combination of prophylactic and therapeutic treatment with Z. mobilis increased the survival of animals by 50% at 96 h after the induction of sepsis. There was a reduction in the levels of TNF-? and myeloperoxidase (MPO) in lung tissue. There was also a reduction in the number of viable bacteria in peritoneal fluid. However, increases in neutrophil migration and IL-10 levels were observed. The observed levels of MCP-1 remained similar to the control. Histopathology analysis showed a decrease in acute lung injury. The group pre-treated with the Z. mobilis culture demonstrated a marked decrease in the number of apoptotic cells in the spleen (24%). This study demonstrates that Z. mobilis cultures increased the survival of animals with severe sepsis. This survival was mediated by improvement of neutrophil migration, enhanced activity against pathogenic enteric bacteria and reduced lung injury. PMID:23123332

Campos, Ingrid Araújo; Ximenes, Eulália Azevedo; Carvalho Júnior, Carlson Helder R; de Mesquita, Amanda Rafaela C; Silva, José Bruno N F; Maia, Maria Bernadete S; Franco, Eryvelton Souza; Medeiros, Paloma Lys; Peixoto, Christina A; da Silva, Teresinha Gonçalves

2013-01-23

324

Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock  

PubMed Central

Introduction The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Methods Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. Results A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ?1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ?2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR?=?5.9; 95% CI, 1.7–19.6; p?=?0.004), delta SOFA 24 h (OR?=?1.7; 95% CI, 1.2–2.3; p?=?0.001), mechanical ventilation (OR?=?30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR?=?6.8; 95% CI, 2.0–22.6; p?=?0.002), admission from the ward (OR?=?3.4; 95% CI, 1.2–9.7; p?=?0.02) and acute kidney injury stage 3 (OR?=?5.7; 95% CI,1.9–16.6; p?=?0.002). Conclusions Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction. PMID:25369197

de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

2014-01-01

325

The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis  

PubMed Central

Introduction Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis. Methods We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (?35.5°C, 35.6–36.5°C, 36.6–37.5°C, 37.6–38.5°C, 38.6–39.5°C, ?39.6°C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups. Results Patients with Tb of ?36.5°C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5°C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb ?35.5°C when compared with patients with Tb >36.5°C. The 28-day and hospital mortality was significantly higher in patients with Tb ?36.5°C. The difference in mortality rate was especially noticeable when patients with Tb ?35.5°C were compared with patients who had Tb of >36.5°C. Although mortality did not relate to Tb ranges of ?37.6°C as compared to reference range of 36.6–37.5°C, relative risk for 28-day mortality was significantly greater in patients with 35.6–36.5°C and ?35.5°C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (?36.5°C, n?=?160) or absence (>36.5°C, n?=?464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock. Conclusions In patients with severe sepsis, hypothermia (Tb ?36.5°C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock. Trial registration UMIN-CTR ID UMIN000008195 PMID:24220071

2013-01-01

326

Low Socioeconomic Status Is Associated with Prolonged Times to Assessment and Treatment, Sepsis and Infectious Death in Pediatric Fever in El Salvador  

PubMed Central

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 0–16 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] 5.0–20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0–3.0). 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] 1.09–8.63; P?=?0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03–1.81; 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

Gavidia, Ronald; Fuentes, Soad L.; Vasquez, Roberto; Bonilla, Miguel; Ethier, Marie-Chantal; Diorio, Caroline; Caniza, Miguela; Howard, Scott C.; Sung, Lillian

2012-01-01

327

Culture independent and rapid identification of bacterial pathogens in necrotising fasciitis and streptococcal toxic shock syndrome by fluorescence in situ hybridisation.  

PubMed

Fluorescence in situ hybridisation (FISH) targeted to ribosomal RNA is well established for studies in environmental microbiology. Initial applications of this technique in the field of medical microbiology showed that FISH is also a suitable means for the rapid, reliable and cultivation-independent identification of bacterial pathogens. In particular, for infectious diseases that follow a fulminant live-threatening course, such as sepsis or necrotising fasciitis (NF), a fast and reliable detection technique is of great importance. This study describes the development of an rRNA-targeted oligonucleotide set covering more than 95% of the pathogens associated with NF. These probes were tested with a broad collection of target and non-target organisms and found to be highly specific. Subsequently, the FISH approach was applied for the direct detection of bacterial pathogens in clinical samples. Two cases of NF and one case of streptococcal toxic shock syndrome (STSS) were analysed. FISH correctly identified almost all pathogens present in the samples examined within 2-3 h. However, Proteus mirabilis, which was identified in one sample by conventional methods was detected as a rod-shaped bacteria but could not be identified by FISH, since no specific probe was available for this particular organism. In contrast, identification of pathogens in these samples by conventional laboratory methods took 48-72 h. Furthermore, in one patient with pre-sampling antimicrobial therapy bacteria could not be grown from any of the samples. FISH unequivocally revealed the presence of Streptococcus pyogenes in affected tissue samples from this patient. In an experimental setting we demonstrated that FISH readily identifies S. pyogenes cells rendered non-cultivable by antibiotic treatment. PMID:10917153

Trebesius, K; Leitritz, L; Adler, K; Schubert, S; Autenrieth, I B; Heesemann, J

2000-06-01

328

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

PubMed Central

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

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

2015-01-01

329

Antibiotic therapy in severe sepsis in HIV-positive patients.  

PubMed

Severe sepsis has become one of the most frequent causes of hospitalization in intensive care units for patients diagnosed with HIV infection. The difficulty in setting a sepsis diagnosis in HIV-positive patients led to the systematic exclusion of these patients from studies on sepsis, which limited the understanding of its impact on the evolution of the disease. Our study aims to evaluate the etiology of sepsis in immunocompromised HIV-positive patients and the evolution after antibiotic therapy. 30 patients diagnosed with HIV infection and sepsis, admitted to our clinic between January 2008 and April 2012, were followed. Severity of illness, time since diagnosis, CD4 count, antiretroviral treatment, incidence of severe sepsis, and organ dysfunctions were registered. Patients were between 1 and 61 years of age, most of them were classified into stages B2, B3 and C3, requiring hospitalization for a period ranging from 14 to 28 days, with an average of 16.7 days and a median of 18 days, while 8 required monitoring in the intensive care unit. In about 40% of cases, the starting point was an infection of the lower respiratory tract, but also of the upper urinary tract and skin infections. Evolution and mortality in sepsis associated with HIV/AIDS infection depend on the presence of organ failure and are less influenced by the level of immunodepression, complex antibiotic therapy being the cornerstone in controlling patients. PMID:23272515

Dorob??, Carmen-Mihaela; Dorob??, G; Bejan, Codrina; Ghibu, Laura; Ro?u, F; Petrovici, Cristina; Loghin, Isabela; Manciuc, Carmen

2012-01-01

330

Mast Cell Stabilization Improves Survival by Preventing Apoptosis in Sepsis  

PubMed Central

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

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

2011-01-01

331

Challenges in the diagnosis and management of neonatal sepsis.  

PubMed

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

Zea-Vera, Alonso; Ochoa, Theresa J

2015-02-01

332

Sepsis in Canadian children: a national analysis using administrative data  

PubMed Central

Background Severe infection resulting in sepsis is recognized as a leading cause of morbidity and mortality worldwide. The purpose of this study is to use longitudinal, population-based data to report national-level hospital metrics, providing a current assessment of the status of sepsis hospitalizations in Canadian children. Methods We performed an analysis of previously abstracted data from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD). Children aged 0–17 years at the time of hospital admission were identified from a cohort of patients with sepsis or severe sepsis using the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10-CA) and the Canadian Classification of Health Interventions (CCI). Descriptive population-based statistics are reported. Results Hospitalization data for 20,130 children admitted over 5 years were reviewed. The majority of children were young, with neonates (56.3%) and infants under 2 months (18.8%) representing the majority of cases. A decline in age-adjusted hospitalization rates was demonstrated in both overall and non-severe sepsis across the study period; however, no change was demonstrated for severe sepsis. While overall in-hospital crude mortality rates did not change significantly across the study period (range 5.1%–5.4%), a significant decrease was found in children aged 3–23 months and adolescents. Multi-organ failure was reported in more than one-quarter of children with severe sepsis. Odds of mortality increased significantly with number of organs failed. Conclusion Sepsis remains an important cause of morbidity and mortality in Canadian children, posing a significant burden on health care resources. Age continues to be associated with the incidence and severity of illness. Overall hospitalization rates have declined over time, as has mortality in severe sepsis. This report provides baseline metrics for future outcome-based research in Canada targeting prevention strategies and early diagnosis, as well as therapies preventing and managing organ failure. PMID:25525390

Thompson, Graham C; Kissoon, Niranjan

2014-01-01

333

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

PubMed Central

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

Persson, Helena; Vindebro, Reine

2013-01-01

334

Streptococcal L-forms isolated from Drosophila paulistorum semispecies cause sterility in male progeny.  

PubMed Central

The Drosophila paulistorum complex contains six semispecies that do not normally interbreed. In the laboratory, crosses between semispecies produce fertile daughters and sterile sons. Microbial endosymbionts have been observed in all D. paulistorum flies that display this male sterility. Streptococcal L-forms have been isolated from the Andean-Brazilian (Mesitas) and Transitional (Santa Marta) semispecies and cultured in artificial medium. Transfer of these L-forms from their native hosts into reciprocal semispecies resulted in sterile male progeny. When L-forms were inoculated into the semispecies from which they had been isolated, most of the male progeny were fertile. Control streptococcal L-forms did not show this sterility pattern. PMID:6582483

Somerson, N L; Ehrman, L; Kocka, J P; Gottlieb, F J

1984-01-01

335

NOVEL HMGB1-INHIBITING THERAPEUTIC AGENTS FOR EXPERIMENTAL SEPSIS  

PubMed Central

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

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

2010-01-01

336

Pantoea dispersa: an unusual cause of neonatal sepsis.  

PubMed

Neonatal septicemia is the most important cause of neonatal mortality. A wide variety of bacteria both aerobic and anaerobic can cause neonatal sepsis. Genus Pantoea is a member of Enterobacteriaceae family that inhabits plants, soil and water and rarely causes human infections, however, Pantoea dispersa has not been reported as a causative organism for neonatal sepsis. We hereby report two neonates with early onset sepsis caused by Pantoea dispersa. Early detection and appropriate antibiotic therapy can improve overall outcome of this rare infection in neonates. PMID:24120830

Mehar, Veerendra; Yadav, Dinesh; Sanghvi, Jyoti; Gupta, Nidhi; Singh, Kuldeep

2013-01-01

337

Group A Streptococcal Bacteremia Without a Source is Associated With Less Severe Disease in Children.  

PubMed

We analyzed characteristics of 86 Group A streptococcal bacteremia cases at Boston Children's Hospital from 1992 to2012. Twenty-three percent of children had severe disease, using intensive care unit admission (18), disability (7) or death (2) as indicators. Children with bacteremia without a source (30% of cases) were less likely to have severe disease than children with focal infections in adjusted models. PMID:25319760

Gauguet, Stefanie; Ahmed, Asim A; Zhou, Jing; Pfoh, Elizabeth R; Ahnger-Pier, Kathryn K; Harper, Marvin B; Ozonoff, Al; Wessels, Michael R; Lee, Grace M

2015-04-01

338

GROUP B STREPTOCOCCAL DISEASE IN THE ERA OF INTRAPARTUM ANTIBIOTIC PROPHYLAXIS  

Microsoft Academic Search

Background Group B streptococcal infections are a leading cause of neonatal mortality, and they also affect pregnant women and the elderly. Many cases of the disease in newborns can be prevented by the ad- ministration of prophylactic intrapartum antibiotics. In the 1990s, prevention efforts increased. In 1996, consensus guidelines recommended use of either a risk-based or a screening-based approach to

J. S CHRAG; D. P HIL; S ARA Z YWICKI; M ONICA M. F ARLEY; L. R EINGOLD; L EE H. H ARRISON; L EWIS B. L EFKOWITZ; J AMES; L. H ADLER; R ICHARD D ANILA; P AUL; R. C IESLAK

339

Amino Acid Sequence and Physicochemical Similarities between Streptococcal M Protein and Mammalian Tropomyosin  

Microsoft Academic Search

The amino-terminal sequences of two peptides of type 24 streptococcal M protein show similarities with that of rabbit skeletal muscle tropomyosin, having up to 40% identical residues and probabilities of occurring by chance as low as P < 10-5. In addition, a hexapeptide (Glu-Ala-Glu-Lys-Ala-Ala) that is found five times in the M24 protein was shown to be identical to a

Barbara Hosein; Maclyn McCarty; Vincent A. Fischetti

1979-01-01

340

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

Microsoft Academic Search

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

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

1995-01-01

341

Single-Oral-Dose Azithromycin Prophylaxis against Experimental Streptococcal or Staphylococcal Aortic Valve Endocarditis  

Microsoft Academic Search

Azithromycin and ampicillin protected 94 and 72% of animals challenged with Streptococcus oralis, respec- tively (P 5 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant Staphylococcus aureus (MRSA)-challenged animals, respectively (P 5 0.018). Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin. Azithromycin (AZM) differs from other macrolide

ARTEMIS TSITSIKA; ANGELOS PEFANIS; GEORGE S. PERDIKARIS; ISMINI DONTA; PANAYIOTIS KARAYIANNAKOS; HELEN GIAMARELLOU

2000-01-01

342

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

Microsoft Academic Search

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

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

2006-01-01

343

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

Microsoft Academic Search

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

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

2006-01-01

344

Beta-Hemolytic Streptococcal Erythroderma Syndrome: A Clinical and Pathogenic Analysis  

PubMed Central

The syndrome of erythroderma due to beta-hemolytic streptococci is rarely seen and should be distinguished from cellulitis and toxic shock-like syndrome. We describe a novel syndrome of non-group A, beta-hemolytic streptococcal infection truncal erythroderma. The characteristics of this syndrome suggest that local factors were likely operative in the cutaneous manifestations of an exotoxin-associated erythroderma. PMID:21841465

Tyner, Harmony L; Schlievert, M; Baddour

2011-01-01

345

In-111 WBC imaging in musculoskeletal sepsis  

SciTech Connect

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.

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

1984-01-01

346

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.  

PubMed

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

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

347

Induction of contact-dependent CD8+ regulatory T cells through stimulation with staphylococcal and streptococcal superantigens*  

PubMed Central

The bacterial superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes are potent stimulators of polyclonal T-cell proliferation. They are the causes of toxic shock syndrome but also induce CD25+ FOXP3+ regulatory cells in the CD4 compartment. Several studies have recently described different forms of antigen-induced regulatory CD8+ T cells in the context of inflammatory diseases and chronic viral infections. In this paper we show that bacterial superantigens are potent inducers of human regulatory CD8+ T cells. We used four prototypic superantigens of S. aureus (toxic shock syndrome toxin-1 and staphylococcal enterotoxin A) and Str. pyogenes (streptococcal pyrogenic exotoxins A and K/L). At concentrations below 1 ng/ml each toxin triggers concentration-dependent T-cell receptor V?-specific expression of CD25 and FOXP3 on CD8+ T cells. This effect is independent of CD4+ T-cell help but requires antigen-presenting cells for maximum effect. The cells also express the activation/regulatory markers cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumour necrosis factor receptor-related protein and skin homing adhesins CD103 and cutaneous lymphocyte-associated antigen. Superantigen-induced CD25+ FOXP3+ CD8+ T cells were as potent as freshly prepared naturally occurring CD4+ regulatory T cells in suppressing proliferation of CD4+ CD25? T cells in response to anti-CD3 stimulation. Although superantigen-induced CD8+ CD25+ FOXP3+ express interleukin-10 and interferon-? their suppressive function is cell contact dependent. Our findings indicate that regulatory CD8+ T cells may be a feature of acute bacterial infections contributing to immune evasion by the microbe and disease pathogenesis. The presence and magnitude of regulatory CD8+ T-cell responses may represent a novel biomarker in such infections. Superantigen-induced regulatory CD8+ T cells also have therapeutic potential. PMID:22043981

Taylor, Amanda L; Cross, Elizabeth L A; Llewelyn, Martin J

2012-01-01

348

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

PubMed Central

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

2013-01-01

349

Hydrogen sulfide reduces kidney injury due to urinary-derived sepsis by inhibiting NF-?B expression, decreasing TNF-? levels and increasing IL-10 levels  

PubMed Central

The present study aimed to investigate the effect of hydrogen sulfide (H2S) on kidney injury induced by urinary-derived sepsis. Rabbits were randomly divided into control, sham, sepsis, NaHS 2.8 ?mol/kg and NaHS 8.4 ?mol/kg groups, with six rabbits in each group. Upper urinary tract obstruction and acute infection was induced to establish the sepsis model. Blood was collected to carry out a white blood cell (WBC) count, and creatinine (Cr) and blood urea nitrogen (BUN) analysis. Morphological changes were observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression levels of tumor necrosis factor (TNF)-?, interleukin (IL)-10 and nuclear factor ?-light-chain-enhancer of activated B cells (NF-?B). Cystathionine-?-lyase (CSE) activity was measured by the spectrophotometric methylene blue method and the blood H2S concentration was measured by deproteinization. WBC, Cr and BUN levels were significantly elevated in the sepsis group compared with those in the control group (P<0.05). Following treatment with NaHS, the WBC, Cr and BUN levels were significantly decreased in the NaHS groups compared with those in the sepsis group (P<0.05). The pathological features of kidney injury were also alleviated by NaHS. In the sepsis group, the levels of TNF-?, IL-10 and NF-?B were significantly increased compared with those in the control group (P<0.05). In the NaHS groups, the TNF-? and NF-?B levels were significantly reduced whereas the IL-10 level was significantly increased compared with the respective levels in the sepsis group (P<0.05). The H2S concentration was significantly decreased in the sepsis group and this reduction was attenuated in the NaHS groups (P<0.05). Furthermore, the NaHS 8.4 ?mol/kg dose revealed a more potent effect than the NaHS 2.8 ?mol/kg dose. Thus, exogenous H2S reduced kidney injury from urinary-derived sepsis by decreasing the levels of NF-?B and TNF-?, and increasing the level of IL-10. PMID:25009602

CHEN, XIAN; XU, WUJUN; WANG, YI; LUO, HONGMEI; QUAN, SUQIN; ZHOU, JING; YANG, NING; ZHANG, TAO; WU, LEI; LIU, JUN; LONG, XIANGYANG; ZHU, NENG; XIE, HUANG; LUO, ZHIGANG

2014-01-01

350

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection  

Microsoft Academic Search

Streptococcal infections can induce obsessive-compulsive and tic disorders. In children, this syndrome, frequently associated with disturbances in attention, learning and mood, has been designated pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Autoantibodies recognizing central nervous system (CNS) epitopes are found in sera of most PANDAS subjects, but may not be unique to this neuropsychiatric subset. In support of

K Yaddanapudi; M Hornig; R Serge; J De Miranda; A Baghban; G Villar; W I Lipkin

2010-01-01

351

Improving the emergency department management of post-chemotherapy sepsis in haematological malignancy patients.  

PubMed

OBJECTIVE. To review the result of the implementation of treatment protocol for post-chemotherapy sepsis in haematological malignancy patients. DESIGN. Case series with internal comparison. SETTING. Accident and Emergency Department, Queen Elizabeth Hospital, Hong Kong. PATIENTS. Febrile patients presenting to the Accident and Emergency Department with underlying haematological malignancy and receiving chemotherapy within 1 month of Accident and Emergency Department visit between June 2011 and July 2012. Similar cases between June 2010 and May 2011 served as historical referents. MAIN OUTCOME MEASURES. The compliance rate among emergency physicians, the door-to-antibiotic time before and after implementation of the protocol, and the impact of the protocol on Accident and Emergency Department and hospital service. RESULTS. A total of 69 patients were enrolled in the study. Of these, 50 were managed with the treatment protocol while 19 patients were historical referents. Acute myeloid leukaemia was the most commonly encountered malignancy. Overall, 88% of the patients presented with sepsis syndrome. The mean door-to-antibiotic time of those managed with the treatment protocol was 47 minutes versus 300 minutes in the referent group. Overall, 86% of patients in the treatment group met the target door-to-antibiotic time of less than 1 hour. The mean lengths of stay in the emergency department (76 minutes vs 105 minutes) and hospital (11 days vs 15 days) were shorter in those managed with the treatment protocol versus the historical referents. CONCLUSION. Implementation of the protocol can effectively shorten the door-to-antibiotic time to meet the international standard of care in neutropenic sepsis patients. The compliance rate was also high. We proved that effective implementation of the protocol is feasible in a busy emergency department through excellent teamwork between nurses, pharmacists, and emergency physicians. PMID:25306894

Ko, H F; Tsui, S S; Tse, J Wk; Kwong, W Y; Chan, O Y; Wong, G Ck

2015-02-01

352

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

PubMed

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

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

2014-12-01

353

Which Biomarkers Reveal Neonatal Sepsis? Kun Wang1,2  

E-print Network

Which Biomarkers Reveal Neonatal Sepsis? Kun Wang1,2 , Vineet Bhandari3 , Sofya Chepustanova1 with LASSO Logistic Regression. Citation: Wang K, Bhandari V, Chepustanova S, Huber G, O9Hara S, et al. (2013

O'Hern, Corey S.

354

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...

355

Biomarkers for Sepsis: A Review with Special Attention to India  

PubMed Central

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

Nelson, George E.; Gupta, Amita

2014-01-01

356

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

PubMed Central

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

Weeks, C R; Ferretti, J J

1984-01-01

357

Pelvic Sepsis After Extended Hartmann’s?Procedure  

Microsoft Academic Search

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

Anders Tøttrup; Lise Frost

2005-01-01

358

Functional roles for C5a receptors in sepsis  

Microsoft Academic Search

The function of the C5a receptors, C5ar (encoded by C5ar) and C5l2 (encoded by Gpr77), especially of C5l2, which was originally termed a 'default receptor', remains a controversial topic. Here we investigated the role of each receptor in the setting of cecal ligation and puncture–induced sepsis by using antibody-induced blockade of C5a receptors and knockout mice. In 'mid-grade' sepsis (30–40%

Daniel Rittirsch; Michael A Flierl; Brian A Nadeau; Danielle E Day; Markus Huber-Lang; Charles R Mackay; Firas S Zetoune; Norma P Gerard; Katherine Cianflone; Jörg Köhl; Craig Gerard; J Vidya Sarma; Peter A Ward

2008-01-01

359

Molecular diagnosis of sepsis: New aspects and recent developments  

PubMed Central

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

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

2014-01-01

360

Role of Circulating Lymphocytes in Patients with Sepsis  

PubMed Central

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

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

2014-01-01

361

New Approaches to Sepsis: Molecular Diagnostics and Biomarkers  

PubMed Central

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

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

2012-01-01

362

Spontaneous Neutrophil Migration Patterns during Sepsis after Major Burns  

PubMed Central

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

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

363

[Prognosis of acute dialysis dependent renal failure].  

PubMed

In a retrospective study of 116 patients with acute renal failure treated by hemodialysis the prognostic value of various clinical data was evaluated by discriminant analysis. With a letality of 73.6% the patient survival was dependent on the frequency of associated organ disorders. The following order was prognostical important: respiratory insufficiency, age, cardio-vascular complications and infection or sepsis. Other problems like gastrointestinal complications, coagulation disorders and hepatic failure were without significant value. PMID:2100088

Nieter, B; Haesner, M; Precht, K

1990-11-01

364

[A case of prostate abscess with sepsis, infectious endocarditis and pyogenic spondylitis].  

PubMed

A 65-year-old man with diabetes mellitus (DM) presented with an indwelling urethral catheter placed for urinary retention by his previous doctor. Thereafter, he had fever, vomiting and general fatigue. His blood examination showed severe inflammatory findings. He was diagnosed with acute prostatitis and immediately admitted to our hospital. Pelvic computerized tomography (CT) showed a prostate abscess. We performed transrectal ultrasonographic-guided puncture of the prostate abscess for drainage and blood culture was tested. Methicillin-sensitive Staphylococcus aureus (MSSA) was cultured from the puncture fluid and blood. We administered antibiotics with strict control of DM. After the prostate abscess improved and the urethral catheter was removed, the patient was systematically examined for potential sepsis-related disease caused by MSSA septic infection. Magnetic resonance imaging (MRI) of the head indicated multiple cerebral infarction, abdominal CT indicated splenetic infarction, ultrasonography of the heart indicated vegetation on the mitral valve and aortic valve, and chest X-ray indicated pulmonary congestion. Furthermore, MRI of the lumbar spine showed a high intensity lesion at the 4th and 5th lumbar spine, indicating pyogenic spondylitis. We diagnosed prostate abscess with sepsis, infectious endocarditis, congestive heart failure and pyogenic spondylitis. Aortic valve replacement, mitral annuloplasty, tricuspid valvuloplasty and ovale hole closure surgeries were performed to treat these conditions. PMID:23235281

Matsumoto, Minori; Shigemura, Katsumi; Yamamichi, Fukashi; Nakano, Yuzo; Miyake, Hideaki; Tanaka, Kazushi; Arakawa, Soichi; Fujisawa, Masato

2012-10-01

365

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

PubMed Central

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

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

2012-01-01

366

Low-dose heparin as treatment for early disseminated intravascular coagulation during sepsis: A prospective clinical study  

PubMed Central

The present study aimed to investigate whether low-dose heparin improves the condition of patients suffering from early disseminated intravascular coagulation (pre-DIC) during sepsis. In total, 37 patients were randomly divided into low-dose heparin intervention and control groups. The heparin group received a low-dose of heparin for 5–7 days, while the other group received only saline. The two groups were treated for sepsis. Blood samples were collected at various times and acute physiology and chronic health evaluation (APACHE)-II scores were recorded at day 1 and 7. In addition, the number of days applying mechanical ventilation and in the intensive care unit (ICU) were recorded, as well as the 28-day mortality rate. APACHE-II scores in the two groups decreased following treatment, however, scores in the heparin group decreased more significantly. Prothrombin fragment and thrombin-antithrombin complex levels in the heparin group were significantly decreased. In addition, the number of days applying a ventilator was fewer and the total stay in ICU was significantly shorter compared with the control group. Significantly fewer complications were observed in the heparin group, however, there was no significant difference in the 28-day mortality rate. In conclusion, low-dose heparin improves the hypercoagulable state of sepsis, which subsequently reduces the incidence of DIC or multiple organ dysfunction syndrome, decreasing the number of days of mechanical ventilation and hospitalization. PMID:24520253

LIU, XIAO-LI; WANG, XIAO-ZHI; LIU, XIU-XIANG; HAO, DONG; JALADAT, YASAMAN; LU, FENG; SUN, TING; LV, CHANG-JUN

2014-01-01

367

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

PubMed

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

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

2014-10-01

368

Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.  

PubMed

Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis. PMID:24619519

Steelman, Samantha M; Johnson, Philip; Jackson, Amy; Schulze, James; Chowdhary, Bhanu P

2014-05-15

369

Phlegmonous gastritis associated with group A streptococcal toxic shock syndrome.  

PubMed

Phlegmonous gastritis (PG) is a rare, acute, severe infectious disease of the gastric wall that is often fatal due to Streptococcus spp. A 77-year-old man with diabetes and a gastric ulcer was urgently admitted due to prolonged nausea and vomiting. Computed tomography revealed widespread diffuse thickening of the gastric wall, and PG was suspected. The patient expired less than 9 hours after admission despite intensive treatments. Later, an analysis of the blood and gastric juice revealed group A streptococcus (GAS) and virulence factors associated with toxic shock syndrome (TSS). We herein diagnosed a patient with an extremely aggressive course of PG caused by GAS TSS. PMID:25400190

Morimoto, Masaya; Tamura, Shinobu; Hayakawa, Takahiro; Yamanishi, Hirofumi; Nakamoto, Chiaki; Nakamoto, Hiromichi; Ikebe, Tadayoshi; Nakano, Yoshio; Fujimoto, Tokuzo

2014-01-01

370

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

PubMed Central

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

Houston, C W; Ferretti, J J

1981-01-01

371

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

PubMed Central

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

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

2012-01-01

372

Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis.  

PubMed

Despite recent advances in the prospective identification of the patient with sepsis who may benefit from anti-inflammatory or antithrombotic therapies, successful treatment regimens have been fairly modest. We have explored whether determination of several proinflammatory cytokine or mediator concentrations can complement physiologic scoring systems to identify patients with severe sepsis who will survive or expire within 28 days. The design of the study included an exploratory analysis performed in conjunction with a prospective, randomized, double-blind, placebo-controlled, multicenter, clinical trial and involved 33 academic institutions in the United States. One hundred twenty-four patients with severe sepsis with or without septic shock were included in this analysis. Blood samples were obtained at baseline and on days 1 through 4, and were evaluated for proinflammatory and anti-inflammatory cytokine concentrations, as well as for procalcitonin and total protein C levels. Baseline concentrations and changes in the concentrations of these mediators were evaluated in relationship to the Acute Physiology and Chronic Health Evaluation (APACHE) II and multiple organ dysfunction (MOD) scores, and 28-day all-cause mortality. Using univariate logistic regression analyses, APACHE II and MOD scores, age (but not gender), and baseline plasma interleukin (IL)-6 and soluble tumor necrosis factor receptor (sTNFR) 1 (log transformed) concentrations were all predictive of increased 28-day all-cause mortality (P < 0.01). Baseline total protein C, IL-8, IL-10, TNF-alpha, and procalcitonin concentrations, and the change in plasma cytokine concentrations from baseline over the initial 4 days were not useful in predicting outcome. Selected baseline proinflammatory cytokine concentrations and APACHE II score were correlated (P < 0.01). IL-6 concentration is a strong candidate for predicting clinical outcome in patients with severe sepsis alone, or when combined with the APACHE II or MOD scores. The potential usefulness of the combination of cytokine measurements and prognostic scores to identify patients who may benefit from treatment with anti-inflammatory or antithrombotic therapies should be further evaluated. PMID:15897799

Oberholzer, Andreas; Souza, Sonia M; Tschoeke, Sven K; Oberholzer, Caroline; Abouhamze, Amer; Pribble, John P; Moldawer, Lyle L

2005-06-01

373

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

PubMed

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

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

2013-01-01

374

Late-onset neonatal sepsis: recent developments.  

PubMed

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

Dong, Ying; Speer, Christian P

2015-05-01

375

Polymorphisms in the SUFU gene are Associated with Organ Injury Protection and Sepsis Severity in Patients with Enterobacteriacea Bacteremia  

PubMed Central

Background Organ injury including acute kidney injury (AKI) and acute lung Injury (ALI) are major contributors to mortality and morbidity in the setting of sepsis. Hedgehog pathway has been recognized as an important mediator in repair of organ injury. There are some clinical predictors associated with the development of organ injury in sepsis; however few host genetic risk factors have been identified and candidate genes for organ injury susceptibility and severity are largely unknown. Methods A prospective cohort study in a tertiary care hospital included 250 adult hospitalized patients with Enterobacteriacea bacteremia. We selected a panel of 69 tagging SNPs for genes in the Hedgehog signaling pathway using the TagSNP functionality of the SNPInfo web server and designed a panel on the GoldenGate Veracode genotyping assay (Illumina). We confirmed Illumina data using Taqman allelic discrimination assays. We assessed SNPs in combination with clinical variables for associations with outcomes and organ injury. Results Significant associations were identified using logistic regression models, controlling for age, race and gender. From the 69 tagging SNPs, 5 SNPs were associated with renal function and 2 with APACHEII score after false discovery rate correction. After multivariate analysis SNPs rs10786691 (p=0.03), rs12414407 (p=0.026), rs10748825 (p=0.01), and rs7078511 (p=0.006), all in the suppressor of fused homolog (SUFU) gene, correlated with renal function. Likewise, SUFU SNPs rs7907760 (p=0.009) and rs10748825 (p=0.029) were associated with APACHEII score. SNPs rs12414407 and rs1078825 are in linkage disequilibrium (LD) with rs2296590, a SNP in the 5?-UTR region that is within a predicted transcription factor bind site for CCAAT-enhancer-binding proteins. In multivariate analyses functional SNP rs2296590 was correlated with renal function (p=0.004) and APACHEII score (p=0.049). Conclusions Host susceptibility factors play an important role in sepsis development and sepsis related organ injury. Polymorphisms in the SUFU gene (encoding for a negative regulator of the hedgehog signaling pathway) are associated with protection from Enterobacteriacea bacteremia related organ injury and sepsis severity. PMID:23538333

Henao-Martínez, Andrés F.; Agler, Anne Hermetet; LaFlamme, Daniel; Schwartz, David A.; Yang, Ivana V.

2013-01-01

376

HLA-DR expression, cytokines and bioactive lipids in sepsis  

PubMed Central

Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock. PMID:24904669

2014-01-01

377

Early and Late Onset Sepsis in Late Preterm Infants  

PubMed Central

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

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

2009-01-01

378

Discriminative Value of Inflammatory Biomarkers for Suspected Sepsis  

PubMed Central

Background Circulating biomarkers can facilitate sepsis diagnosis enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers. Methods Adults with suspected sepsis in the Emergency Department were enrolled. PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care. Results Of 336 enrolled subjects, 60% had definite infection, 13% possible infection and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were significantly higher in septicemia (median PCT 2.3 vs. 0.2ng/mL; IL-6 178 vs. 72pg/mL; CRP 106 vs. 62mg/dL, p<0.001). Biomarker concentrations increased with greater likelihood of infection and sepsis severity. Using ROC analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67) but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cut-off of 0.5ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length-of-stay (p=0.015), but no biomarker independently predicted discharge to a higher level of care. Conclusions In adult Emergency Department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but do not meaningfully predict length-of-stay or need for discharge to a higher level of care. PMID:22056545

Tsalik, Ephraim L.; Jaggers, L. Brett; Glickman, Seth W.; Langley, Raymond J.; van Velkinburgh, Jennifer C.; Park, Lawrence P.; Fowler, Vance G.; Cairns, Charles B.; Kingsmore, Stephen F.; Woods, Christopher W.

2011-01-01

379

Serum Procalcitonine Levels as an Early Diagnostic Indicator of Sepsis  

PubMed Central

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

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

2013-01-01

380

Pharmacologic targeting of sphingosine-1-phosphate receptor 1 improves the renal microcirculation during sepsis in the mouse.  

PubMed

Microvascular failure is hallmark of sepsis in humans and is recognized as a strong predictor of mortality. In the mouse subjected to cecal ligation and puncture (CLP) to induce a clinically relevant sepsis, renal microvascular permeability increases and peritubular capillary perfusion declines rapidly in the kidney leading to acute kidney injury (AKI). Sphingosine-1-phosphate (S1P) is a key regulator of microvascular endothelial function. To investigate the role of S1P in the development of microvascular permeability and peritubular capillary hypoperfusion in the kidney during CLP-induced AKI, we used a pharmacologic approach and a clinically relevant delayed dosing paradigm. Evans blue dye was used to measure renal microvascular permeability and intravital video microscopy was used to quantitate renal cortical capillary perfusion. The S1P receptor 1 (S1P1) agonist SEW2871 [5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole] and S1P2 antagonist JTE-013 [N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide] were administered at the time of CLP and produced a dose-dependent but partial reduction in renal microvascular permeability at 6 hours after CLP. However, neither agent improved capillary perfusion at 6 hours. With delayed administration at 6 hours after CLP, only SEW2871 reversed microvascular permeability when measured at 18 hours. Importantly, SEW2871 also restored capillary perfusion and improved renal function. These data suggest that S1P1 and S1P2 do not regulate the early decline in renal capillary perfusion. However, later in the course of sepsis, pharmacologic stimulation of S1P1, even when delaying therapy until after injury has occurred, improves capillary and renal function, suggesting this approach should be evaluated as an adjunct therapy during sepsis. PMID:25355645

Wang, Zhen; Sims, Clark R; Patil, Naeem K; Gokden, Neriman; Mayeux, Philip R

2015-01-01

381

Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation  

PubMed Central

Background and the purpose of the study sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU). Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management. Methods This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-?), Interleukin (IL)-1? and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR) status. Cytokines (TNF-?, IL-1? and IL-6) were assayed in the first, third and seventh days in blood of patients. Results and major conclusion Among three measured cytokines, sequential levels of TNF-? and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC) curve indicated that APACHE II (0.858, 0.848, 0.861) and IL-6 (0.797, 0.799, 0.899) had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-? in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients. PMID:22615611

Hamishehkar, H.; Beigmohammadi, M.T.; Abdollahi, M.; Ahmadi, A.; Mahmoodpour, A.; Mirjalili, M.R.; Abrishami, R.; Khoshayand, M.R.; Eslami, K.; Kanani, M.; Baeeri, M.; Mojtahedzadeh, M.

2010-01-01

382

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

PubMed Central

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

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

2014-01-01

383

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

PubMed Central

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

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

2014-01-01

384

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

PubMed

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

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

2015-03-01

385

Gram-negative sepsis: a dilemma of modern medicine.  

PubMed Central

Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis. PMID:8457980

Bone, R C

1993-01-01

386

Proteome changes in mesenteric lymph induced by sepsis  

PubMed Central

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

ZHANG, PING; LI, YAN; ZHANG, LIAN-DONG; WANG, LIANG-HUA; WANG, XI; HE, CHAO; LIN, ZHAO-FEN

2014-01-01

387

Experimental and emerging therapies for sepsis and septic shock.  

PubMed

The underlying principles of sepsis therapy have remained unchanged for decades. These include: prompt institution of antimicrobial agents aimed at the inciting pathogen, source control directed at removal of the infection nidus whenever possible, and support of organ dysfunction. Despite advances in antibiotics, surgical techniques and organ support technology, the morbidity and mortality from sepsis-related diseases have remained substantially unchanged (30 - 50%). Immunomodulation of the inflammatory cascade has been suggested as a crucial but inadequately addressed element in the treatment of sepsis. The list of potential therapeutic targets has been growing as more and more mediators are identified in the pathogenesis of sepsis. To date, numerous anti-inflammatory agents, found to have favourable effects in animal models of septic shock, have been tested in a number of clinical trials on thousands of patients. In this first of a three part series, we go through some of the background and current strategies in sepsis therapy. In this review, we include the two novel therapies that have shown clear survival benefit in large, randomised, placebo-controlled, multi-centre trials, low-dose steroids and recombinant activated protein C. Also included in this review are studies on antithrombin III, platelet-activating factor antagonists, complement modulators, nitric oxide synthase inhibitors and caspase inhibitors (apoptosis inhibitors). PMID:11772263

Añel, R L; Kumar, A

2001-08-01

388

Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding  

PubMed Central

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

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

2013-01-01

389

Molecular microbiological methods in the diagnosis of neonatal sepsis  

PubMed Central

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

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

2010-01-01

390

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

PubMed Central

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

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

2015-01-01

391

Systemic group B streptococcal disease in neonates and young infants in Norway 1985-94.  

PubMed

In the period 1985-94, 237 out of 575,248 (0.41 per 1000) live born infants in Norway were reported to suffer culture-confirmed systemic group B streptococcal disease before their 90th day of life. The annual incidence increased from 0.20 per 1000 live births in 1985 to 0.64 in 1994, due solely to an increase in cases with an onset before the seventh day of life. Future studies should address the possible causes of this increase. PMID:8834989

Aavitsland, P; Høiby, E A; Lystad, A

1996-01-01

392

Bacteriological and serological aspects of group A streptococcal pharyngotonsillitis caused by group A streptococci.  

PubMed

Several bacteriological and serological variables were studied in connection with a clinical treatment trial in 212 patients with group A streptococcal pharyngotonsillitis. Anaerobic incubation was not superior to incubation in 5% CO2 in air for the detection of group A streptococci. Saliva cultures were inferior to conventional throat cultures in detecting group A streptococci. No strains from patients with recurrences were found to be tolerant to penicillin. In several patients (all asymptomatic), group C and G streptococci were found in follow-up cultures. Group A streptococci serology was more often positive after two months than after one month, also in patients without recurrence. PMID:3134205

Strömberg, A; Schwan, A; Cars, O

1988-04-01

393

Penicillin-Susceptible Group B Streptococcal Clinical Isolates with Reduced Cephalosporin Susceptibility  

PubMed Central

We characterized penicillin-susceptible group B streptococcal (PSGBS) clinical isolates exhibiting no growth inhibition zone around a ceftibuten disk (CTBr PSGBS). The CTBr PSGBS isolates, for which augmented MICs of cefaclor and ceftizoxime were found, shared a T394A substitution in penicillin-binding protein 2X (PBP 2X) and a T567I substitution in PBP 2B, together with an additional G429S substitution in PBP 2X or a T145A substitution in PBP 1A, although the T145A substitution in the transglycosidase domain of PBP 1A would have no effect on the level of resistance to ceftibuten. PMID:24920773

Nagano, Noriyuki; Nagano, Yukiko; Toyama, Masami; Kimura, Kouji; Shibayama, Keigo

2014-01-01

394

Nitric oxide (NO) production correlates with renal insufficiency and multiple organ dysfunction syndrome in severe sepsis  

Microsoft Academic Search

Objective: To investigate whether the production of nitric oxide (NO) relates to the develop- ment of renal insufficiency and multiple organ dysfunction syn- drome (MODS) in patients with severe sepsis. Design: Prospective study in 23 patients with severe sepsis. Setting.\\

P. H. P. Groeneveld; K. M. C. Kwappenberg; J. A. M. Langermans; P. H. Nibbering; L. Curtis

1996-01-01

395

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

PubMed

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

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

2014-01-01

396

Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis  

PubMed Central

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

Liu, Lingling; Yu, Yonghao; Wang, Guolin

2014-01-01

397

Proteolytic inactivation of plasma C1- inhibitor in sepsis.  

PubMed Central

Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis. Because C1 inhibitor (C1-Inh) regulates the activation of both cascade systems, we studied the characteristics of plasma C1-Inh in 48 patients with severe sepsis on admission to the Intensive Care Unit at the Free University of Amsterdam. The ratio between the level of functional and antigenic C1-Inh (functional index) was significantly reduced in the patients with sepsis compared with healthy volunteers (P = 0.004). The assessment of modified (cleaved), inactive C1-Inh (iC1-Inh), and complexed forms of C1-Inh (nonfunctional C1-Inh species) revealed that the reduced functional index was mainly due to the presence of iC1-Inh. On SDS-PAGE, iC1-Inh species migrated with a lower apparent molecular weight (Mr 98,000, 91,000, and 86,000) than native C1-Inh (Mr 110,000). Elevated iC1-Inh levels (greater than or equal to 0.13 microM) were found in 81% of all patients, sometimes up to 1.6 microM. Levels of iC1-Inh on admission appeared to be of prognostic value: iC1-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003). The mortality in 15 patients with iC1-Inh levels up to 0.2 microM was 27%, but in 12 patients with plasma iC1-Inh exceeding 0.44 microM, the mortality was 83%. The overall mortality in the patients with sepsis was 56%. We propose that the cleavage of C1-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis. Images PMID:2668333

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

1989-01-01

398

IRAK1-dependent signaling mediates mortality in polymicrobial sepsis  

PubMed Central

IRAK1 is a key regulatory protein in TLR/IL1R-mediated cell activation during the inflammatory response. Studies indicated that pending on the nature of the used inflammatory model, down-regulation of IRAK1 may be beneficial or detrimental. However the role of IRAK1 in affecting outcome in polymicrobial sepsis is unknown. We tested this question using an IRAK1 deficient mouse strain and the cecal ligation and puncture (CLP) procedure, which is a clinically relevant rodent septic model. Sepsis-induced mortality was markedly lower in IRAK1-deficient mice (35%) compared to WT (85%). Sepsis-induced increases in blood IL-6 and IL-10 levels were blunted at 6h post-CLP in IRAK1 deficiency compared to WT but cytokine levels were similar at 20h post-CLP. Sepsis induced blood granulocytosis and depletion of splenic B cells were also blunted in IRAK1 deficient mice as compared to WT. Analysis of TLR-mediated cytokine responses by IRAK1 deficient and WT macrophages ex vivo indicated a TLR4-dependent down-regulation of IL-6 and IL1? in IRAK1 deficiency, whereas TLR2 dependent responses were unaffected. TLR7/8-mediated IL-6, IL1? and IL-10 production was also blunted in IRAK1 macrophages as compared to WT. The study shows that IRAK1 deficiency impacts multiple TLR-dependent pathways and decreases early cytokine responses following polymicrobial sepsis. The delayed inflammatory response caused by the lack of IRAK1 expression is beneficial, as it manifests a markedly increased chance of survival after polymicrobial sepsis. PMID:23856940

Chandra, Rachna; Federici, Stephanie; Bishwas, Tripti; Németh, Zoltán H.; Deitch, Edwin A.; Thomas, James A.; Spolarics, Zoltán

2013-01-01

399

What are the latest recommendations for managing severe sepsis and septic shock?  

PubMed

Severe sepsis is a continuum of physiologic stages characterized by infection, systemic inflammation, and hypoperfusion leading to tissue injury and organ failure. The primary goal of sepsis treatment is to prevent morbidity and mortality. Crystalloids are now recommended over colloids for volume resuscitation, one of the key interventions for patients with sepsis. PMID:25251649

Bland, Christopher M; Sutton, S Scott; Dunn, Brianne L

2014-10-01

400

The Epidemiology of Sepsis in the United States from 1979 through 2000  

Microsoft Academic Search

background Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its inci- dence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of pa- tients, and the incidence and outcome. methods

Greg S. Martin; David M. Mannino; Stephanie Eaton; Marc Moss

2003-01-01

401

What is the role of interleukin 10 in polymicrobial sepsis: Anti-inflammatory agent or immunosuppressant?  

Microsoft Academic Search

Background: Controversy exists concerning the role of interleukin 10 (IL-10) in sepsis. When IL-10 is used in models of endotoxemia, it appears to protect (by anti-inflammatory effects), whereas in models of polymicrobial sepsis it seems to be deleterious (by immunosuppression?). However, little direct evidence for such an immunosuppressive role is available for polymicrobial sepsis. Thus the aim of this study

Grace Y. Song; Chun-Shiang Chung; Irshad H. Chaudry; Alfred Ayala

1999-01-01

402

Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet fever  

Microsoft Academic Search

Streptococcal toxic shock syndrome (STSS) is an illness with high mortality. To obtain clues to understanding the pathogenesis of STSS, we investigated the expression of several pathogenic factors in ten group A streptococcus (GAS) isolates from ten patients with STSS in Japan, in comparison with ten GAS isolates from children with scarlet fever. The ten scarlet fever-derived GAS isolates were

Masayuki Shiseki; Keishi Miwa; Yuko Nemoto; Hideto Kato; Jun Suzuki; Kachiko Sekiya; Teiko Murai; Tatsuo Kikuchi; Naoya Yamashita; Kyoichi Totsuka; Kenji Ooe; Yoshikata Shimizu; Takehiko Uchiyama

1999-01-01

403

Rapid detection of group B streptococcal antigen from vaginal specimens using a new Optical ImmunoAssay technique  

Microsoft Academic Search

A total of 531 vaginal specimens were used to evaluate a new Optical ImmunoAssay (OIA) screening technique for the rapid detection of group B streptococcal antigen. The results of the OIA test, the ICON Strep B membrane immunoassay (Hybritech ICON), and conventional culture on sheep blood agar (direct TSA) were compared to broth enhanced culture. Results obtained from the OIA

Choong H. Park; Davinder Ruprai; Nancy M. Vandel; Deborah L. Hixon; Fred E. Mecklenburg

1996-01-01

404

Direct Probing by Atomic Force Microscopy of the Cell Surface Softness of a Fibrillated and Nonfibrillated Oral Streptococcal Strain  

Microsoft Academic Search

In this paper, direct measurement by atomic force microscopy (AFM) of the cell surface softness of a fibrillated oral streptococcal strain Streptococcus salivarius HB and of a nonfibrillated strain S. salivarius HBC12 is presented, and the data interpretation is validated by comparison with results from independent techniques. Upon approach of the fibrillated strain in water, the AFM tip experienced a

Henny C. van der Mei; Henk J. Busscher; Rolf Bos; Joop de Vries; Christophe J. P. Boonaert; Yves F. Dufrêne

2000-01-01

405

Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.  

PubMed

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

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

2015-02-01

406

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

ERIC Educational Resources Information Center

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…

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

407

Comparative Genomics of the Mucoid and Nonmucoid Strains of Streptococcus pyogenes, Isolated from the Same Patient with Streptococcal Meningitis.  

PubMed

Mucoid (MTB313) and nonmucoid (MTB314) strains of group A streptococcus emm type 1 were simultaneously isolated from a single patient suffering from streptococcal meningitis. Whole-genome sequencing revealed that MTB313 carried a nucleotide substitution within rocA, which generated an amber termination codon. PMID:25883280

Yoshida, Haruno; Ishigaki, Yasuhito; Takizawa, Asako; Moro, Kunihiko; Kishi, Yuki; Takahashi, Takashi; Matsui, Hidenori

2015-01-01

408

Group C streptococcal endocarditis presenting as clinical meningitis: Report of a case and review of the literature  

PubMed Central

Lancefield group C streptococci are known to be pathogenic in a number of animal species, but cause human disease much less commonly than do streptococci of scrogroups A or B. Reported cases of bacteremic infection, pneumonia or meningitis in humans have been very severe with a grave prognosis. The authors describe a patient who presented with classic clinical and laboratory evidence of bacterial meningitis which proved to be a complication of endocarditis caused by a group C streptococcus. This is the first reported case in which meningitis was the presenting manifestation of group C streptococcal endocarditis and is only the second case in which group C streptococcal meningitis and endocarditis have been associated in the same patient. A total of 13 cases of group C streptococcal meningitis have now been reported in the medical literature. Five of these patients died, and four others recovered only to be left with neurological sequelae. The current case confirms the seriousness of group C streptococcal infections in humans. Such infections are associated with a poor prognosis despite apparently adequate antimicrobial therapy. PMID:22416199

Huang, Allen R; Briedis, Dalius J

1992-01-01

409

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...

410

Sepsis attenuates the anabolic response to skeletal muscle contraction.  

PubMed

Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ?24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor ? (TNF-?) mRNA in muscle was increased by sepsis, and contraction increased TNF-? to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent. PMID:25423127

Steiner, Jennifer L; Lang, Charles H

2015-04-01

411