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Sample records for acute streptococcal sepsis

  1. Streptococcal acute pharyngitis.

    PubMed

    Anjos, Lais Martins Moreira; Marcondes, Mariana Barros; Lima, Mariana Ferreira; Mondelli, Alessandro Lia; Okoshi, Marina Politi

    2014-07-01

    Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine. PMID:25229278

  2. Failure of the urinary group B streptococcal antigen test as a screen for neonatal sepsis.

    PubMed Central

    Williamson, M.; Fraser, S. H.; Tilse, M.

    1995-01-01

    The accuracy of the urinary group B streptococcal antigen latex agglutination (LA) test for screening infants at risk of group B streptococcal (GBS) sepsis in the first 24 hours of life was prospectively studied in 236 infants for six months. Infection with GBS was defined by a positive blood culture while colonisation was defined by GBS cultured from any other site. The combination of infection and colonisation was used as the gold standard for the LA test. Although the LA test had a sensitivity of 90%, the specificity was only 70%, the positive predictive value 12% and the false positive rate 30%. The overall accuracy was only 71%. The LA test was unable to predict GBS sepsis in infants at risk of the disease. The false positive rate was unacceptably high and could not be potentially accounted for in 11 infants. However, a negative test was useful in excluding GBS disease. PMID:7583596

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

    PubMed Central

    Parida, Lalit

    2016-01-01

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

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

    PubMed

    Parida, Lalit

    2016-01-01

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

  5. Antibiotics for acute group A streptococcal pharyngitis.

    PubMed

    2004-12-01

    (1) Since the 1940s, a large number of comparative randomised placebo-controlled trials have evaluated antibiotic therapy for pharyngitis, initially parenteral benzathine benzylpenicillin, then oral phenoxymethylpenicillin (penicillin V). Our literature search identified a Cochrane meta-analysis of all these trials, with the exception of one published in 2003. (2) When group A betahemolytic streptococci (group A streptococci) are present in the throat, antibiotic therapy accelerates symptom relief (particularly fever and pain) by a day or two. This has been shown with 7-day treatments but not with 3-day treatments. There is no convincing evidence that antibiotics relieve symptoms in children. (3) According to the Cochrane meta-analysis, signs of progression to locoregional suppuration were noted in 1% of patients receiving placebo, compared to 0.09% of patients receiving antibiotics in the most recent trials (statistically significant difference). (4) Comparative trials done in the 1950s showed that benzathine benzylpenicillin helped prevent acute rheumatic fever, reducing the risk by about 75%. Since 1985 nearly 1000 patients with pharyngitis have been given a placebo in clinical trials, and none have developed acute rheumatic fever. (5) There is no firm evidence that antibiotics reduce the risk of acute glomerulonephritis. (6) The adverse effects associated with most antibiotics are mild. This is especially true for penicillin. However, there is a risk of rare but serious adverse effects: anaphylaxis is estimated to occur in 5 per 10 000 patients treated with injectable penicillin, while the risk associated with oral penicillin used to treat pharyngitis has not been quantified. Moreover, antibiotics affect the bacterial ecology, encouraging resistance among some bacterial species other than group A streptococci. (7) A strategy based on the use of a clinical diagnostic score, followed by a rapid test if the score is intermediate, seems to be the best way of restricting antibiotics to patients with pharyngitis due to group A streptococci. (8) In patients with group A streptococcal pharyngitis, a strategy of starting antibiotics only after 48 hours of symptoms delays symptom control but seems to reduce the risk of relapse. According to a clinical trial in patients with pharyngitis from all causes, advising patients to postpone antibiotic therapy reduces antibiotic use by about 85%, without increasing the risk of serious clinical complications. (9) In practice, immediate antibiotic therapy is justified for patients with severe symptoms or signs of progression to locoregional suppuration, and when the local incidence of acute rheumatic fever is high. In other situations, whether or not group A streptococci are involved, antibiotic therapy should be started only if symptoms do not begin to improve after 48 hours of symptomatic treatments. PMID:15612147

  6. Sepsis-Associated Acute Kidney Injury

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    1995-01-01

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

  8. Sepsis and Acute Respiratory Distress Syndrome: Recent Update

    PubMed Central

    Kim, Won-Young

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-04-01

    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

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

    PubMed Central

    Kafle, Sumitra; Nath, Navdeep

    2014-01-01

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

  13. Sepsis

    MedlinePlus

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

  14. Sepsis

    MedlinePlus

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. Sepsis

    PubMed Central

    Karnatovskaia, Lioudmila V.; Festic, Emir

    2012-01-01

    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

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

    PubMed

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

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment. PMID:26141259

  19. Update in sepsis and acute kidney injury 2014.

    PubMed

    Schortgen, Frédérique; Asfar, Pierre

    2015-06-01

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

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

    PubMed

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

    2015-01-01

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

  1. Sepsis

    MedlinePlus

    ... toxins they create can change a person's body temperature, heart rate, and blood pressure, and prevent the body's organs from working properly. Sepsis may lead to serious complications that affect the kidneys, lungs, brain, and heart, and can ...

  2. Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome

    PubMed Central

    2014-01-01

    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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2011-01-01

    The effect of extracorporeal blood purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal blood purification that did not result in acute changes in a panel of common cytokines associated with inflammation (TNF-α, IL-1β, 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-02-01

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

  8. High levels of antibodies to streptococcal cell membrane antigens specifically bound to monoclonal antibodies in acute poststreptococcal glomerulonephritis.

    PubMed Central

    Yoshimoto, M; Hosoi, S; Fujisawa, S; Sudo, M; Okuda, R

    1987-01-01

    We produced 15 immunoglobulin G class monoclonal antibodies against antigens of the streptococcal cell membrane (SCM) of Streptococcus pyogenes (T type 12, Tanaka strain) and determined the levels in human sera of antibodies against Triton-X-extracted antigens specifically bound to each of these 15 monoclonal antibodies by enzyme-linked immunosorbent assay. Sample sera were obtained from 10 normal controls (group 1), 10 patients with streptococcal pharyngitis without sequelae (group 2), and 8 patients with acute poststreptococcal glomerulonephritis (APSGN) (group 3). Anti-streptolysin O (ASO) titers of the sera increased in the order of groups 1, 2, and 3. There was no relationship between ASO titer and the level of anti-SCM antibodies, and there was no significant difference in the level of anti-SCM antibodies determined with each of the 15 monoclonal antibodies between group 1 and group 2 sera. Group 3 sera had higher levels of antibodies to SCM antigens specifically bound to each of 14 of these 15 monoclonal antibodies than group 1 or group 2 sera did. Of these 14 monoclonal antibodies, 9 reacted with the four SCM antigens separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretically transferred to a nitrocellulose sheet. These results suggest that high levels of antibodies to SCM antigens are related to the development of APSGN and that the systemic immune response to SCM antigens is involved in the pathogenesis of APSGN. Images PMID:3553232

  9. Early diverting colostomy for perianal sepsis in children with acute leukemia.

    PubMed

    Pini Prato, Alessio; Castagnola, Elio; Micalizzi, Concetta; Dufour, Carlo; Avanzini, Stefano; Pio, Luca; Guida, Edoardo; Mattioli, Girolamo; Jasonni, Vincenzo; Disma, Nicola; Mameli, Leila; Montobbio, Giovanni; Buffa, Piero

    2012-10-01

    Perineal sepsis is a life-threatening complication of acute leukemia. Although conservative management (antibiotics, incision, and drainage, alone or in combination) is considered the criterion standard, it provides an outcome that is not fully satisfactory, with an overall mortality of roughly 30%. This report presents a case series of 4 children who underwent early defunctioning colostomy for the treatment of perineal sepsis during leukemia. This management proved to be successful and allowed prompt reestablishment of chemotherapy, thus improving overall results. Routine application of this "aggressive" management in these cases will presumably increase overall survival of children with leukemia. PMID:23084226

  10. Group A streptococcal infections in children.

    PubMed

    Steer, Andrew C; Danchin, Margaret H; Carapetis, Jonathan R

    2007-04-01

    The group A streptococcus causes the widest range of disease in humans of all bacterial pathogens. Group A streptococcal diseases are more common in children than adults with diseases ranging from pharyngitis and impetigo to invasive infections and the post-streptococcal sequelae--acute rheumatic fever and acute post-streptococcal glomerulonephritis. The global burden of severe group A streptococcal disease is concentrated largely in developing countries and Indigenous populations such as Aboriginal Australians. Control of group A streptococcal disease is poor in these settings and the need for a vaccine has been argued. With an ever-increasing understanding of the group A streptococcus at a molecular level, new and sophisticated vaccines are currently in human trials and the next decade holds exciting prospects for curbing group A streptococcal diseases. PMID:17444820

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

    PubMed Central

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

    2013-01-01

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

  12. Infusion-related sepsis in dogs undergoing acute cardiopulmonary surgery.

    PubMed

    Slattum, M M; Maggio-Price, L; DiGiacomo, R F; Russell, R G

    1991-04-01

    During acute cardiopulmonary studies, 33 of 170 (19.4%) dogs developed uncontrollable acidosis accompanied by varying degrees of diarrhea and hypotension. Affected dogs had evidence of gram-negative bacteremia and septic shock. Intravenously administered fluids were contaminated with gram-negative bacteria. Since the experimental procedure entailed nonsurvival surgery, aseptic techniques were not employed. Although aseptic surgical techniques are to be used in animals undergoing survival surgery, such techniques also may be warranted in non-survival surgeries. PMID:1658443

  13. [Invasive streptococcal infections].

    PubMed

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

    2007-12-01

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

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

    PubMed Central

    2013-01-01

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

  15. Clinical evaluation of sivelestat for acute lung injury/acute respiratory distress syndrome following surgery for abdominal sepsis

    PubMed Central

    Tsuboko, Yoshiaki; Takeda, Shinhiro; Mii, Seiji; Nakazato, Keiko; Tanaka, Keiji; Uchida, Eiji; Sakamoto, Atsuhiro

    2012-01-01

    Background The efficacy of sivelestat in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has not been established. In part, this is due to the wide variety of factors involved in the etiology of ALI/ARDS. In this study, we examined the efficacy of sivelestat in patients with ALI/ARDS associated with abdominal sepsis. Methods The subjects were 49 patients with ALI/ARDS after surgery for abdominal sepsis. The efficacy of sivelestat was retrospectively assessed in two treatment groups, ie, a sivelestat group (n = 34) and a non-sivelestat group (n = 15). Results The sivelestat group showed significant improvements in oxygenation, thrombocytopenia, and multiple organ dysfunction score. The number of ventilator days (6.6 ± 6.1 versus 11.1 ± 8.4 days; P = 0.034) and length of stay in the intensive care unit (8.5 ± 6.2 versus 13.3 ± 9.5 days; P = 0.036) were significantly lower in the sivelestat group. The hospital mortality rate decreased by half in the sivelestat group, but was not significantly different between the two groups. Conclusion Administration of sivelestat to patients with ALI/ARDS following surgery for abdominal sepsis resulted in early improvements of oxygenation and multiple organ dysfunction score, early ventilator weaning, and early discharge from the intensive care unit. PMID:23091371

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

    PubMed

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

    2016-04-28

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    Iwashita, Yoshiaki; Imai, Hiroshi

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed

    O'Doherty, B

    1996-09-01

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

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

    PubMed

    Tetta, C; Bellomo, R; Ronco, C

    2003-03-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

    Shah, Birju A; Padbury, James F

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  9. Ketamine attenuates sepsis-induced acute lung injury via regulation of HMGB1-RAGE pathways.

    PubMed

    Li, Kehan; Yang, Jianxue; Han, Xuechang

    2016-05-01

    High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10mL/kg), sham-operation+ketamine (10mg/kg), CLP/HMGB1+NS (10mL/kg), CLP/HMGB1+ketamine (5mg/kg), CLP/HMGB1+ketamine (7.5mg/kg), and CLP/HMGB1+ketamine (10mg/kg) groups. NS and ketamine were administered at 3 and 12h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK. PMID:26945830

  10. Resveratrol reduces acute lung injury in a LPS‑induced sepsis mouse model via activation of Sirt1.

    PubMed

    Li, Tongxun; Zhang, Jinglan; Feng, Jiliang; Li, Qiang; Wu, Lisong; Ye, Qing; Sun, Jianping; Lin, Yi; Zhang, Mengran; Huang, Rui; Cheng, Jun; Cao, Yongmei; Xiang, Guoan; Zhang, Jinqian; Wu, Qinghua

    2013-06-01

    The development of acute lung injury (ALI) during sepsis almost doubles the mortality rate of patients. The efficacy of current treatment strategies is low as treatment is usually initiated following the onset of symptoms. Inflammation is one of the main mechanisms of autoimmune disorders and is a common feature of sepsis. The suppression of inflammation is therefore an important mechanism for the treatment of sepsis. Sirtuin 1 (Sirt1) has been demonstrated to play a role in the regulation of inflammation. Resveratrol, a potent Sirt1 activator, exhibits anti‑inflammatory properties. However, the role of resveratrol for the treatment of ALI during sepsis is not fully understood. In the present study, the anti‑inflammatory role of Sirt1 in the lipopolysaccharide (LPS)‑induced TC‑1 cell line and its therapeutic role in ALI was investigated in a mouse model of sepsis. The upregulation of matrix metalloproteinase-9, interleukin (IL)‑1β, IL‑6 and inducible nitric oxide synthase was induced by LPS in the mouse model of sepsis and the TC‑1 cell line, and resveratrol suppressed the overexpression of these proinflammatory molecules in a dose‑dependent manner. Resveratrol decreased pulmonary edema in the mouse model of sepsis induced by LPS. In addition, resveratrol improved lung function and reduced pathological alterations in the mouse model of sepsis. Knockdown of Sirt1 by RNA interference resulted in an increased susceptibility of TC‑1 cells to LPS stimulation and diminished the anti‑inflammatory effect of resveratrol. These results demonstrated that resveratrol inhibits LPS‑induced ALI and inflammation via Sirt1, and indicated that Sirt1 is an efficient target for the regulation of LPS‑induced ALI and inflammation. The present study provides insights into the treatment of ALI during sepsis. PMID:23625030

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

    Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV. The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle. Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced. Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment. We further found that the beneficial effects of AICAR on septic mice were diminished in AMPKα2 deficient mice, showing that AMPK mediates these effects. In conclusion, our findings reveal a new functional role of activating AMPK in the CNS to attenuate inflammatory responses and acute lung injury in sepsis. PMID:26252187

  13. Acute Post-Streptococcal Glomerulonephritis in the Northern Territory of Australia: A Review of 16 Years Data and Comparison with the Literature

    PubMed Central

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

    2011-01-01

    Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0–54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6–94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed. PMID:21976576

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2007-08-01

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

  16. Macrolide treatment failure in streptococcal pharyngitis resulting in acute rheumatic fever.

    PubMed

    Logan, Latania K; McAuley, James B; Shulman, Stanford T

    2012-03-01

    Macrolide resistance (MR) in group A Streptococcus (GAS) has been well documented in several countries and has become clinically significant since the large increases in macrolide usage during the 1970s. Macrolides are recommended as an alternative therapy for GAS pharyngitis, the most common cause of bacterial pharyngitis. Macrolide resistance has been associated with certain emm types, a sequence-based typing system of the hypervariable region of the GAS M-protein gene. Clinical failure of macrolide treatment of GAS infections can be associated with complications including acute rheumatic fever and rheumatic heart disease, the leading cause of acquired heart disease in children worldwide. Here we report 2 pediatric cases of MR and/or treatment failure in the treatment of GAS pharyngitis with the subsequent development of acute rheumatic fever. We also review the literature on worldwide MR rates, molecular classifications, and emm types, primarily associated with GAS pharyngeal isolates between the years of 2000 and 2010. The use of macrolides in the management of GAS pharyngitis should be limited to patients with significant penicillin allergy. PMID:22311996

  17. Successfully treated severe obstetric sepsis and acute respiratory distress syndrome with extracorporeal membrane oxygenation.

    PubMed

    Benetis, Rimantas; Nadisauskiene, Ruta; Sirvinskas, Edmundas; Lenkutis, Tadas; Siudikas, Adakrius; Kadusauskaitė, Vytaute; Railaitė, Dalia; Sukovas, Arturas; Abraitis, Vytautas

    2016-05-01

    We report a unique clinical case about an 18-year-old woman, immediately post-partum after an urgent C-section, who survived severe sepsis, acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) and was successfully treated with 11 different antibiotics, massive blood transfusions and repetitive surgeries and was on extracorporeal membrane oxygenation (ECMO) support for 22 days. Although, ECMO is a time-limited procedure and most manufacturers do not advise more than 14 days of use,(1)the situation for this patient was life-threatening and ECMO, despite the dangerous risks listed above, was the only way to win time for the lungs to recover and for treatment of the underlying disease, while maintaining adequate oxygenation and circulation. Fortunately, the condition of this woman was stabilized and she achieved complete physical recovery, despite minor neurological deficit in the fingers of her right hand. PMID:26373682

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

    PubMed Central

    Chen, Lin

    2015-01-01

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

  19. Protective Effects of Growth Arrest-Specific Protein 6 (Gas6) on Sepsis-Induced Acute Kidney Injury.

    PubMed

    Chen, Long-Wang; Chen, Wei; Hu, Zhi-Qiang; Bian, Jia-Lan; Ying, Lan; Hong, Guang-Liang; Qiu, Qiao-Meng; Zhao, Guang-Ju; Lu, Zhong-Qiu

    2016-04-01

    Acute kidney injury (AKI) is a serious complication of sepsis, which has a high mortality rate. Growth arrest-specific protein 6 (Gas6), the protein product of the growth arrest specific gene 6, has been shown to have an anti-apoptotic effect as well as pro-survival capability. Here, we investigated the effects of Gas6 on sepsis-associated AKI in mice subjected to cecal ligation and puncture (CLP). We found that the administration of rmGas6 significantly reduced serum urea nitrogen and creatinine and improved the survival of septic mice. Furthermore, the renal pathological damage induced by CLP was attenuated by rmGas6 treatment. Finally, rmGas6 reduced the renal tissue apoptotic index and the expression of Bax, while it upregulated the expression of Bcl-2. The data suggest that rmGas6 might be used as a potential therapeutic agent for sepsis-induced AKI. PMID:26552404

  20. Definitions and pathophysiology of sepsis.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. Acute Lung Injury and Acute Kidney Injury Are Established by Four Hours in Experimental Sepsis and Are Improved with Pre, but Not Post, Sepsis Administration of TNF-α Antibodies

    PubMed Central

    Webb, Ryan G.; Okamura, Kayo; Yang, Yimu; Falk, Sandor; Schmidt, Eric P.; Faubel, Sarah

    2013-01-01

    Introduction Acute kidney injury (AKI) and acute lung injury (ALI) are serious complications of sepsis. AKI is often viewed as a late complication of sepsis. Notably, the onset of AKI relative to ALI is unclear as routine measures of kidney function (BUN and creatinine) are insensitive and increase late. In this study, we hypothesized that AKI and ALI would occur simultaneously due to a shared pathophysiology (i.e., TNF-α mediated systemic inflammatory response syndrome [SIRS]), but that sensitive markers of kidney function would be required to identify AKI. Methods Sepsis was induced in adult male C57B/6 mice with 5 different one time doses of intraperitoneal (IP) endotoxin (LPS) (0.00001, 0.0001, 0.001, 0.01, or 0.25 mg) or cecal ligation and puncture (CLP). SIRS was assessed by serum proinflammatory cytokines (TNF-α, IL-1β, CXCL1, IL-6), ALI was assessed by lung inflammation (lung myeloperoxidase [MPO] activity), and AKI was assessed by serum creatinine, BUN, and glomerular filtration rate (GFR) (by FITC-labeled inulin clearance) at 4 hours. 20 µgs of TNF-α antibody (Ab) or vehicle were injected IP 2 hours before or 2 hours after IP LPS. Results Serum cytokines increased with all 5 doses of LPS; AKI and ALI were detected within 4 hours of IP LPS or CLP, using sensitive markers of GFR and lung inflammation, respectively. Notably, creatinine did not increase with any dose; BUN increased with 0.01 and 0.25 mg. Remarkably, GFR was reduced 50% in the 0.001 mg LPS dose, demonstrating that dramatic loss of kidney function can occur in sepsis without a change in BUN or creatinine. Prophylactic TNF-α Ab reduced serum cytokines, lung MPO activity, and BUN; however, post-sepsis administration had no effect. Conclusions ALI and AKI occur together early in the course of sepsis and TNF-α plays a role in the early pathogenesis of both. PMID:24265742

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2013-02-01

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

  6. Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury

    PubMed Central

    2012-01-01

    Introduction Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI). Methods This prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days. Results Median renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P=0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI (P=0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (ρ= -0.47; P=0.002), PaO2/FiO2 ratio (ρ= -0.33; P=0.04) and age (ρ=0.35; P=0.015) only in patients without AKI. Conclusions A poor correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain. PMID:22971333

  7. Glycyrrhizic acid pretreatment prevents sepsis-induced acute kidney injury via suppressing inflammation, apoptosis and oxidative stress.

    PubMed

    Zhao, Hongyu; Liu, Zhenning; Shen, Haitao; Jin, Shuai; Zhang, Shun

    2016-06-15

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. The aim of our study was to investigate the molecular mechanism involved in the protective effects of GA in lipopolysaccharide (LPS) stimulated rat mesangial cells (HBZY-1) and septic rats. Sepsis model was established by injection of 5mg/kg LPS in rats or incubation with 1μg/ml LPS for 24h in HBZY-1 cells. A variety of molecular biological experiments were carried out to assess the effects of GA on inflammation, apoptosis, and oxidative stress. First we found that GA alleviated sepsis-induced kidney injury in vivo. Furthermore, GA suppressed inflammatory response in vivo and in vitro. Additionally, GA inhibited cell apoptosis and the changes in expressions of apoptosis related proteins induced by LPS. Moreover, GA markedly inhibited oxidative stress induced by LPS via activation of ERK signaling pathway. Finally GA could inhibit the activation of NF-κ B induced by LPS. Our present study indicates that GA has a protective effect against sepsis-induced inflammatory response, apoptosis, and oxidative stress damage, which provides a molecular basis for a new medical treatment of septic acute kidney injury. PMID:27063444

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2014-10-15

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

  11. 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 Central

    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.

    2014-01-01

    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

  12. [Microbiology of streptococcal infections].

    PubMed

    Peuckert, W

    1985-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

    PubMed Central

    2010-01-01

    Introduction Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)≈70 mmHg; 2) normovolemia (MAP≈100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP≈130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H2O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1β, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est,L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic responses. Conclusions Volemic status should be taken into account during RMs, since in this sepsis-induced ALI model hypervolemia promoted and potentiated lung injury compared to hypo- and normovolemia. PMID:20546573

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

    PubMed

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

    2008-12-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

  20. The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis.

    PubMed

    Gerin, Fethullah; Sener, Umit; Erman, Hayriye; Yilmaz, Ahsen; Aydin, Bayram; Armutcu, Ferah; Gurel, Ahmet

    2016-04-01

    Experimental studies indicate that sepsis causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative damage, and inflammation on lung injury, following sepsis model by cecal ligation and puncture, and the effects of quercetin, antioxidant, and anti-inflammatory flavonoid, in the lung tissue were investigated. In the present study, we found that administration of single-dose quercetin before cecal ligation and puncture procedure, while markedly diminishing the levels of YKL-40 and oxidant molecules (xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA)), increases the antioxidant enzymes levels. Quercetin is beneficial to acute lung injury by decreasing the levels of oxidative stress markers and increasing the antioxidant enzyme activities. Quercetin also causes a decrease in the serum levels of YKL-40 and periostin in the oxidative lung injury induced by the experimental sepsis model. PMID:26670180

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

    PubMed Central

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

    2015-01-01

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

  2. Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome

    PubMed Central

    Sun, Xiaoguang; Ma, Shwu-Fan; Wade, Michael S.; Acosta-Herrera, Marialbert; Villar, Jesús; Pino-Yanes, Maria; Zhou, Tong; Liu, Bin; Belvitch, Patrick; Moitra, Jaideep; Han, Yoo-Jeong; Machado, Roberto; Noth, Imre; Natarajan, Viswanathan; Dudek, Steven M.; Jacobson, Jeffrey R.; Flores, Carlos

    2013-01-01

    The genetic mechanisms underlying the susceptibility to acute respiratory distress syndrome (ARDS) are poorly understood. We previously demonstrated that sphingosine 1-phosphate (S1P) and the S1P receptor S1PR3 are intimately involved in lung inflammatory responses and vascular barrier regulation. Furthermore, plasma S1PR3 protein levels were shown to serve as a biomarker of severity in critically ill ARDS patients. This study explores the contribution of single nucleotide polymorphisms (SNPs) of the S1PR3 gene to sepsis-associated ARDS. S1PR3 SNPs were identified by sequencing the entire gene and tagging SNPs selected for case-control association analysis in African- and ED samples from Chicago, with independent replication in a European case-control study of Spanish individuals. Electrophoretic mobility shift assays, luciferase activity assays, and protein immunoassays were utilized to assess the functionality of associated SNPs. A total of 80 variants, including 29 novel SNPs, were identified. Because of limited sample size, conclusive findings could not be drawn in African-descent ARDS subjects; however, significant associations were found for two promoter SNPs (rs7022797 −1899T/G; rs11137480 −1785G/C), across two ED samples supporting the association of alleles −1899G and −1785C with decreased risk for sepsis-associated ARDS. In addition, these alleles significantly reduced transcription factor binding to the S1PR3 promoter; reduced S1PR3 promoter activity, a response particularly striking after TNF-α challenge; and were associated with lower plasma S1PR3 protein levels in ARDS patients. These highly functional studies support S1PR3 as a novel ARDS candidate gene and a potential target for individualized therapy. PMID:23911438

  3. THE ENDOTHELIUM IN SEPSIS.

    PubMed

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

    2016-03-01

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

  4. Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) Outperforms Serum Creatinine in Detecting Sepsis-Induced Acute Kidney Injury, Experiments on Bilateral Nephrectomy and Bilateral Ureter Obstruction Mouse Models.

    PubMed

    Leelahavanichkul, Asada; Somparn, Poorichaya; Issara-Amphorn, Jiraphorn; Eiam-Ong, Somchai; Avihingsanon, Yingyos; Hirankarn, Nattiya; Srisawat, Nattachai

    2016-05-01

    Serum neutrophil gelatinase associated lipocalin (sNGAL), a promising acute kidney injury (AKI) biomarker produced by renal and non-renal tissues, might be affected by sepsis. We evaluated sNGAL in zero glomerular filtration rate models [bilateral ureter obstruction (BUO) and bilateral nephrectomy (BiNx)] with subsequent cecal ligation and puncture (CLP)-induced sepsis in 6 to 8-week-old ICR mice. We found that sNGAL increased earlier than serum creatinine (Scr) in BiNx/BUO with and without CLP. The earliest time-point of increased sNGAL in BiNx+CLP was 1 h after surgery. Scr, but not sNGAL, was lower at 18 h after BiNx/BUO+CLP compared with BiNx/BUO alone. Compared with BUO, BiNx had higher, and equal sNGAL at 1 to 18 h and 36 h, respectively. Additionally, similar NGAL expression in internal organs (heart, lung, liver, and spleen) and survival rates indicated the comparable severity of BiNx and BUO. Serum interleukin (IL)-6 was increased and correlated with sNGAL in BiNx/BUO with and without sepsis. In summary, we demonstrated: sNGAL is an early AKI biomarker, which is not affected by sepsis; sNGAL is mainly produced by extrarenal sources as demonstrated by the comparable sNGAL in BiNx and BUO; the saturation of renal NGAL re-absorption in BUO is demonstrated by lower sNGAL in BUO at 1 to 18 h, but not at 36 h when compared with BiNx; and a correlation of sNGAL and IL-6 implied sNGAL is a good sepsis prognostic biomarker. Therefore, sNGAL is a more beneficial sepsis-AKI biomarker than Scr. PMID:26863120

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    1994-03-18

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  10. Streptococcal pharyngitis in children.

    PubMed

    Klein, M D

    1989-12-01

    Children with suspected group A beta-hemolytic streptococcal pharyngitis are encountered daily in outpatient settings. Despite the ubiquity of this condition, important management issues still remain unresolved. This article will review selected epidemiologic, diagnostic, and therapeutic topics germane to clinical practice. PMID:2690022

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2013-11-01

    Ulinastatin is a potent multivalent serine protease inhibitor, which was recently found with therapeutic potentials in treating sepsis, and the most life-threatening complication of critically ill population. However, the pharmacological features and possible mechanisms need to be further elucidated in reliable and clinical relevant sepsis models. As known, sepsis induced by surgery of cecal ligation and puncture (CLP) is widely accepted as the gold standard animal model, but the inconsistency of outcomes is the most obvious problem. In the present experiments, we reported an improved rat CLP model with much more consistent outcomes using self-made three edged puncture needles in our lab. Results from this optimized model revealed that ulinastatin improved survivals of CLP rats, attenuated proinflammatory response and prevented systemic disorder and organ dysfunction. Ulinastatin was also found to be effective in ameliorating sepsis-related ALI, a syndrome most frequent and fatal in sepsis. The molecular mechanism investigation showed that ulinastatin's protection against ALI was probably related to the down-regulation of NF-κB activity and inhibition of TNF-α, IL-6 and elastase expressions in the lung tissue. In conclusion, based on a successful establishment of optimized rat CLP model ulinastatin is proved to be an effective candidate for sepsis treatment, due to its anti-inflammation and anti-protease activities that ameliorate systemic disorders, prevent organ injuries and thus improve the survival outcomes of sepsis in animals. PMID:24075864

  13. [Catheter associated Staphylococcus sciuri sepsis in a patient with acute myeloid leukemia].

    PubMed

    Koçoğlu, Esra; Karabay, Oğuz

    2006-10-01

    The coagulase-negative bacterial species Staphylococcus sciuri is widely distributed in the natural environment. Although principally found in animals, S. sciuri is occasionally isolated from human samples. In this paper, S. sciuri bacteremia which was associated with an indwelling catheter of a patient with acute myeloid leukemia (AML) and neutropenia was presented. An empirical intravenous antibiotic therapy (meropenem, vancomycin) was initiated with the preliminary diagnosis of febrile neutropenia and catheter infection. The catalase and oxidase positive, tube coagulase negative strain isolated from three of the concurrent blood cultures and intravenous catheter culture has been identified as S. sciuri. The isolate was found resistant to penicilin and oxacilline. This case has emphasized the importance of identification of coagulase-negative staphylococci isolated from the cultures of patients with haematological malignancy. PMID:17205699

  14. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    PubMed Central

    SEPEHR, REYHANEH; AUDI, SAID H.; MALEKI, SEPIDEH; STANISZEWSKI, KEVIN; EIS, ANNIE L.; KONDURI, GIRIJA G.; RANJI, MAHSA

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure. PMID:24672581

  15. [Manchincel poisoning complicated by streptococcal pharyngitis and impetigo].

    PubMed

    Bygbjerg, I C; Johansen, H K

    1991-12-30

    A Danish tourist to Antigua in the West Indies, ate a fruit of Hippomane mancinella and developed acute poisoning with blistering of the oral mucosa and diarrhoea and a streptococcal superinfection. Ignorant tourists and their travel advisers are warned against this potentially deadly apple-tree-like plant and its tempting fruits. PMID:1781062

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

    PubMed Central

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

    2014-01-01

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

  17. Streptococcal diseases worldwide: present status and prospects*

    PubMed Central

    Rotta, J.; Tikhomirov, E.

    1987-01-01

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

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

    PubMed

    Sosa, Mary Ellen Burke

    2016-01-01

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

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

    PubMed Central

    2012-01-01

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

  20. [Neonatal sepsis].

    PubMed

    Luoto, Raakel; Holmberg, Kaisa; Ruuskanen, Olli; Lehtonen, Liisa

    2014-01-01

    Many newborns are exposed to diagnostic or treatment procedures due to a suspicion of sepsis. Since non-specific signs of neonatal sepsis can quickly proceed to a life-threatening condition, it is essential to have a low threshold to diagnostic procedures and to provide antimicrobial therapy while waiting for the test results. After sepsis has been ruled out, antimicrobial therapy should be discontinued without delay. Good clinical practice includes avoiding unnecessarily broad-spectrum antibiotics. The future challenge is to develop a sensitive and specific marker for early detection of the disease and for avoiding unnecessary antibiotics, hospital care days and mother-infant separation. PMID:24772783

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

    PubMed

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

    2015-01-01

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

  2. Management of streptococcal pharyngitis reconsidered.

    PubMed

    Gerber, M A; Markowitz, M

    1985-01-01

    Adequate treatment of GABHS pharyngitis with penicillin shortens the course of illness, reduces the spread of streptococci and prevents suppurative complications. It has also been a major factor in the markedly accelerated decline in the incidence of acute rheumatic fever in this country. Difficulties in the clinical diagnosis of GABHS pharyngitis make bacteriologic confirmation highly desirable. Currently a properly performed throat culture is the best way to obtain this bacteriologic confirmation. However, it is possible that rapid antigen detection tests will replace the throat culture in the future. These diagnostic tools should be used more selectively and only in conjunction with clinical and epidemiologic data. Greater selectivity will help control costs and will increase the chances of identifying patients who are truly infected and are not merely streptococcal carriers. Penicillin is still the drug of choice and an oral preparation given twice daily is as effective as more frequent doses. Patients at risk for noncompliance should be treated with a single injection of benzathine penicillin combined with procaine penicillin to lessen the local discomfort. Routine follow-up cultures of asymptomatic patients should be abandoned. Persistence of GABHS following a course of treatment may no longer be an important risk factor for the development of rheumatic fever. However, there are exceptional cases, as noted in the text, in which eradication of GABHS carriage with a short course of rifampicin may be desirable. PMID:3931060

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

    PubMed Central

    2012-01-01

    Background Recent studies showed that overwhelming inflammatory response mediated by the toll-like receptor (TLR)-related pathway was important in the development of acute lung injury (ALI). The aim of this study was to determine whether common genetic variation in four genes of the TLR signaling pathway were associated with sepsis-induced ALI susceptibility and risk of death in Chinese Han population. Methods Fourteen tag single nucleotide polymorphisms (tagSNPs) in MyD88, IRAK1, IRAK4 and TRAF6 were genotyped in samples of sepsis-induced ALI (n = 272) and sepsis alone patients (n = 276), and tested for association in this case-control collection. Then, we investigated correlation between the associated SNP and the mRNA expression level of the corresponding gene. And we also investigated correlation between the associated SNP and tumor necrosis factor alpha (TNF-α) as well as interleukin-6 (IL-6) concentrations in peripheral blood mononuclear cells (PBMCs) exposed to lipopolysaccharides (LPS) ex vivo. The mRNA expression level was determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Results The association analysis revealed that rs4755453, an intronic SNP of TRAF6, was significantly associated with susceptibility to sepsis-induced ALI. The C allele frequency of rs4755453 in the sepsis alone group was significantly higher than that in the sepsis-induced ALI group (P = 0.00026, odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.37–0.74). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. TRAF6 mRNA expression levels in PBMCs from homozygotes of the rs4755453G allele were significantly higher than that in heterozygotes and homozygotes of the rs4755453C allele at baseline (P = 0.012 and P = 0.003, respectively) as well as after LPS stimulation (P = 0.009 and P = 0.005). Moreover, the concentrations of TNF-α and IL-6 in cell culture supernatants were also significantly higher in the subjects with rs4755453GG genotype than in subjects with CG and CC genotype. None of the 14 tagSNPs showed associations with risk of death and severity among ALI cases. Conclusions Our findings indicated that common genetic variants in TRAF6 were significantly associated with susceptibility to sepsis-induced ALI in Chinese Han population. This was the first genetic evidence supporting a role for TRAF6 in ALI. PMID:22901274

  4. Pediatric sepsis

    PubMed Central

    Randolph, Adrienne G; McCulloh, Russell J

    2014-01-01

    Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the 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

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

    PubMed Central

    2013-01-01

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

  6. Pathogenesis of Group A Streptococcal Infections

    PubMed Central

    Cunningham, Madeleine W.

    2000-01-01

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

  7. Coagulation abnormalities in sepsis.

    PubMed

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

    2015-03-01

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

  8. Group A Streptococcal (GAS) Disease

    MedlinePlus

    ... Cancel Submit Search The CDC Group A Streptococcal (GAS) Disease Note: Javascript is disabled or is not ... No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232- ...

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

    PubMed

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

    2016-01-01

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

  10. [Group A streptococcal meningitis].

    PubMed

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

    2012-12-01

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

  11. Streptococcal infections of skin and PANDAS.

    PubMed

    Carelli, Rosanna; Pallanti, Stefano

    2014-01-01

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

  12. MITOCHONDRIAL FUNCTION IN SEPSIS.

    PubMed

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

    2016-03-01

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

  13. Senegenin Ameliorate Acute Lung Injury Through Reduction of Oxidative Stress and Inhibition of Inflammation in Cecal Ligation and Puncture-Induced Sepsis Rats.

    PubMed

    Liu, Chun-Hong; Zhang, Wei-Dong; Wang, Jian-Jie; Feng, Shan-Dan

    2016-04-01

    The purpose of this study was to assess the protective effect of senegenin on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into five groups: group 1 (control), group 2 (CLP), group 3 (CLP + senegenin 15 mg/kg), group 4 (CLP + senegenin 30 mg/kg), and group 5 (CLP + senegenin 60 mg/kg). CLP + senegenin groups received senegenin by gavage daily for consecutive 5 days, respectively, while the mice in control and CLP groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of lung tissue myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) levels were studied. The results demonstrated that senegenin treatment significantly attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, protein leak, infiltration of leukocytes, and MPO activity. In addition, senegenin markedly decreased MDA content and increased SOD activity and GSH level. Serum levels of TNF-α and IL-1β were also decreased by senegenin administration. Furthermore, senegenin administration inhibited the nuclear translocation of NF-κB in the lungs. These findings indicate that senegenin exerts protective effects on CLP-induced septic rats. Senegenin may be a potential therapeutic agent against sepsis. PMID:26945584

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

    PubMed Central

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

    2015-01-01

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

  15. Staphylococcal and Streptococcal Superantigen Exotoxins

    PubMed Central

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

    2013-01-01

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

  16. Sepsis Questions and Answers

    MedlinePlus

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

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

    PubMed

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

    2015-10-01

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

  18. Microbiological diagnosis of streptococcal pharyngitis: lacunae and their implications.

    PubMed

    Brahmadathan, K N; Gladstone, P

    2006-04-01

    Post-streptococcal sequelae, especially acute rheumatic fever/rheumatic heart disease continue to occur in significant proportions in many parts of the world. Despite several attempts with various intervention strategies, little success has been achieved in the control of acute rheumatic fever/rheumatic heart disease in India. The success of the control programmes depends upon timely primary prophylaxis with benzathine penicillin for which a microbiological confirmation of group A streptococcal pharyngitis is essential. Isolation of beta hemolytic streptococci from throat cultures and their identification as GAS in the laboratory, clinches the microbiological diagnosis while demonstration of a 'significant rise' in antibody titers such as Anti-streptolysin O and Anti-deoxyribonuclease B differentiates it from a group A streptococcal carrier state or pharyngitis of a viral etiology. Despite the easiness with which these can be achieved, many laboratories in India are not equipped to do so. Enhancing bacteriological and serological facilities in laboratories across the country will drastically improve the clinician's ability to diagnose bona fide GAS pharyngitis and help to institute penicillin prophylaxis at the appropriate time. This will go a long way in enhancing the compliance to penicillin prophylaxis which is the cornerstone of any RF/RHD control program. PMID:16687857

  19. Host-pathogen interactions in streptococcal immune sequelae.

    PubMed

    Nitsche-Schmitz, D Patric; Chhatwal, Gursharan S

    2013-01-01

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

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

    PubMed

    Brackel, Caroline L H; Noordzij, Jeroen G

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Streptococcal meningitis following myelogram procedures.

    PubMed

    Hsu, Jennifer; Jensen, Bette; Arduino, Matthew; Bergeron, Toni; Fox, Teresa; Gum, Greg; Pischke, Vera; Potts, David; Townes, John; Srinivasan, Arjun

    2007-05-01

    In September of 2004, we investigated 7 cases of post-myelography meningitis. Streptococcal species were recovered from blood or cerebrospinal fluid in all cases. Our findings suggest that droplet transmission of the oral flora of the clinician performing the procedure was the most likely source of these infections. The Centers for Disease Control and Prevention recommends the use of face masks by those performing myelograms. PMID:17464927

  3. A possible post-streptococcal movement disorder with chorea and tics.

    PubMed

    Kerbeshian, J; Burd, L; Pettit, R

    1990-07-01

    A 14-year-old girl developed a movement disorder after a streptococcal infection. In the acute phase of the illness she exhibited simple and complex motor tics and chorea, but all abnormal movements ceased over the following eight months, without recurrence. This case raises questions about the relationship between tics, chorea and auto-immune reactivity. PMID:2391015

  4. Dilemmas of streptococcal pharyngitis.

    PubMed

    Raz, R; Bitnun, S

    1987-04-01

    Although the Group A beta-hemolytic streptococcus is the most common cause of acute bacterial pharyngitis in childhood, the clinical diagnosis is often not straightforward and throat cultures are advisable. To avoid unnecessary antibiotics, treatment should be delayed until culture results are available. Patients with negative cultures should discontinue any antibiotics already started on clinical grounds. Positive cultures may represent a carrier state, which can be identified by serologic studies. PMID:3105301

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Kohannim, Omid; Rubin, Zachary; Taylor, Mihaela

    2011-03-01

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

  7. Group G streptococcal endocarditis: two case reports, a review of the literature and recommendations for treatment.

    PubMed

    Smyth, E G; Pallett, A P; Davidson, R N

    1988-03-01

    Two cases of endocarditis caused by a group G streptococcus are reported and the literature on group G streptococcal endocarditis is reviewed. The onset of illness is usually acute and the portal of entry for the organism through the skin. The left side of the heart is mainly involved and in about 50% cases the endocarditis arises on a normal valve. Most patients develop complications, both embolic and cardiac, and the mortality is high (36%). We suggest that patients with proven group G streptococcal endocarditis should be treated with large doses of benzyl penicillin and with an aminoglycoside for not less than 4 weeks. Patients with complications should be referred to a cardiothoracic centre. We should be glad to know details of complications, treatment and outcome in other cases of group G streptococcal endocarditis. PMID:3280691

  8. Group A streptococcal infections as related to rheumatic fever.

    PubMed

    Kawakita, S; Takeuchi, T; Uemura, Y; Onishi, T; Saito, K

    1976-09-01

    Beta-hemolytic streptococci were recovered frequently, particularly from the throats of children, and the same type of group A strains was isolated from both throats and tonsils. A significant antibody response to streptolysin O was observed in 44.8 to 43.5 % of the children whom group A streptococci were recovered. It is considered that these children had the definite evidence of acute streptococcal infections, and administration of josamycin, penicillin G, and benzyl penicillin V benzathine decreases the frequency of recovery of beta-hemolytic streptococci and prevents rheumatic fever. PMID:994338

  9. Group G streptococcal lymphadenitis in rats.

    PubMed

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

    1991-12-01

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

  10. Rapidly progressive glomerulonephritis complicating acute rheumatic fever.

    PubMed Central

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

    1995-01-01

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

  11. Rapidly progressive glomerulonephritis complicating acute rheumatic fever.

    PubMed

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

    1995-09-01

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

  12. [Streptococcal rheumatic fever in adults].

    PubMed

    Lemaire, V; Peyrou, D; Ryckewaert, A

    1982-10-01

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

  13. Human pathogenic streptococcal proteomics and vaccine development.

    PubMed

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

    2008-03-01

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

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

    PubMed

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

    2012-07-01

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

  15. Diagnosis of streptococcal pharyngotonsillitis in children and adolescents: clinical picture limitations☆

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2005-01-01

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

  17. Streptococcal toxic shock syndrome complicating a peritonsillar abscess.

    PubMed

    Aalling, Mathilde; Klug, Tejs Ehlers

    2015-02-01

    A 68-year-old man was admitted to hospital in an acute confusional state with a 2-week history of fever, influenza-like illness and sore throat. He quickly developed coagulation disturbances, hypotension and renal function impairment. Despite broad-spectrum antibiotic therapy, he deteriorated. Group A streptococcus (GAS) was recovered from blood cultures, which gave the diagnosis streptococcal toxic shock syndrome (STSS). A computed tomography scan showed a right-sided peritonsillar abscess (PTA). Acute tonsillectomy was carried out and the patient recovered. STSS complicating PTA has not previously been described in the literature, but GAS is a common pathogen in PTA. Clinicians should be aware that STSS can develop secondary to tonsillar infections and that abscess development should be suspected in STSS patients who do not respond to antibiotic treatment. PMID:25342572

  18. Sepsis biomarkers: a review

    PubMed Central

    2010-01-01

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

  19. IMMUNE CELL PHENOTYPE AND FUNCTION IN SEPSIS.

    PubMed

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

    2016-03-01

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

  20. Severe sepsis bundles

    PubMed Central

    Khan, Parvez; Divatia, J. V.

    2010-01-01

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

  1. [Patients with sepsis].

    PubMed

    Oppert, M

    2016-05-01

    Sepsis is still the leading cause of mortality in noncardiac intensive care units. The new definition of sepsis emphasizes the importance of organ dysfunction. The Sepsis-related Organ Failure Assessment (SOFA) score is an indicator for organ dysfunction. The diagnosis of sepsis is for the most part made on clinical parameters with an altered mental status being a very sensitive indicator. Microbiological work-up is essential and two sets of blood cultures are the recommended minimum. Management includes prompt initiation of adequate antibiotic treatment and swift fluid resuscitation. Overinfusion is to be avoided as this itself can have a negative impact on patient outcome. PMID:27160262

  2. Pulmonary Renal Syndrome After Streptococcal Pharyngitis

    PubMed Central

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

    2016-01-01

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

  3. A case of canine streptococcal meningoencephalitis diagnosed using universal bacterial polymerase chain reaction assay.

    PubMed

    Messer, Jeannette S; Wagner, Susan O; Baumwart, Ryan D; Colitz, Carmen M

    2008-01-01

    A 3-year-old, spayed female, mixed-breed dog was evaluated for acute, progressive neurological disease. Analysis of cerebrospinal fluid (CSF) showed neutrophilic pleocytosis. The dog later developed liver disease, thrombocytopenia, and anemia that were presumably secondary to ceftriaxone administration. Bacterial cultures of blood, urine, and CSF were negative. However, a universal bacterial polymerase chain reaction assay of CSF identified deoxyribonucleic acid from Streptococcus spp. The dog recovered with therapy for streptococcal encephalitis. PMID:18593857

  4. Pediatric sepsis: challenges and adjunctive therapies.

    PubMed

    Hanna, William; Wong, Hector R

    2013-04-01

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

  5. TLR2, TLR4 and the MYD88 Signaling Pathway Are Crucial for Neutrophil Migration in Acute Kidney Injury Induced by Sepsis

    PubMed Central

    Castoldi, Angela; Braga, Tárcio Teodoro; Correa-Costa, Matheus; Aguiar, Cristhiane Fávero; Bassi, Ênio José; Correa-Silva, Reinaldo; Elias, Rosa Maria; Salvador, Fábia; Moraes-Vieira, Pedro Manoel; Cenedeze, Marcos Antônio; Reis, Marlene Antônia; Hiyane, Meire Ioshie; Pacheco-Silva, Álvaro; Gonçalves, Giselle Martins; Câmara, Niels Olsen Saraiva

    2012-01-01

    The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2−/−, TLR4−/− and MyD88−/− male mice were subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2−/−, TLR4−/− and MyD88−/− mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT). MyD88−/− mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1+low cells migration compared with the knockout mice and decreased in GR1+high cells migration into the peritoneal cavity. The TLR2−/−, TLR4−/−, and MyD88−/− mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells. PMID:22655058

  6. Adult Zebrafish model of streptococcal infection

    PubMed Central

    Phelps, Hilary A.; Runft, Donna L.

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Neurology of Sepsis.

    PubMed

    Sweis, Rochelle; Ortiz, Jorge; Biller, José

    2016-03-01

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

  9. Defensins and Sepsis

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    1991-01-01

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

  11. Properties and Biological Role of Streptococcal Fratricins

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Streptococcal pharyngitis: an uncommon cause of subdural empyema.

    PubMed

    Walden, Jeffrey Howard; Hess, Bryan; Rigby, Michael

    2015-01-01

    A 7-year-old girl with an unremarkable medical history presented to a local paediatric emergency department with a 7-day history of fever, sore throat and vomiting, and a 1-day history of rash. She was admitted to the hospital, with presumed Kawasaki disease. A few hours after admission, the patient had sudden onset of two witnessed tonic-clonic seizures and subsequent decreased mental status. She was transferred to the paediatric intensive care unit and started on broad-spectrum antibiotics. On hospital day 2, cerebral spinal fluid cultures and blood cultures grew Streptococcus pyogenes, and repeat physical examination was consistent with acute streptococcal pharyngitis. On hospital day 3, the patient developed left-sided hemiparesis and had another witnessed seizure. A CT scan was obtained and revealed a subdural abscess. She was transferred to a tertiary care centre and underwent craniotomy with evacuation of her subdural abscess. Surgical cultures eventually grew S. pyogenes. PMID:26385939

  14. [LABORATORY MARKERS FOR EARLY DIAGNOSIS OF NEONATAL SEPSIS].

    PubMed

    Kucherov, Y I; Zhirkova, Y V; Chebotaeva, L I; Shishkina, T V

    2015-01-01

    Sepsis in neonates still remains difficult issue for clinicians. This review observes literature data about early laboratory diagnosis of neonatal sepsis. The paper considers the latest information about well-known methods of sepsis diagnosis in neonates such as complete blood count, acute phase reactants, cytokine markers, their advantages and disadvantages, as well as statistical value based on different meta-analysis and large multicenter investigations in many countries. We notified the newest methods in sepsis diagnosis such as plasma amyloid A, DAMP molecules, cell surface markers CD64, CD11b, and inter-a inhibitor proteins. The review informs about analysis of genomic and proteomic profile, nucleic acids tools. This data considering for early and late neonatal sepsis and their statistical values: sensitivity, specificity, positive and negative predictive value. PMID:26415288

  15. Biomarkers of sepsis

    PubMed Central

    2013-01-01

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

  16. Personalized Medicine for Sepsis.

    PubMed

    Pinheiro da Silva, Fabiano; César Machado, Marcel Cerqueira

    2015-11-01

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

  17. Sepsis Pathophysiology and Anesthetic Consideration

    PubMed Central

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

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

  18. Sepsis pathophysiology and anesthetic consideration.

    PubMed

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

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

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

    PubMed

    Floret, D

    2001-09-01

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

  20. Streptococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Streptococcal Infections - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) Korean (한국어) Spanish (español) Arabic (العربية) Strep ...

  1. Microvascular blood flow is altered in patients with sepsis.

    PubMed

    De Backer, Daniel; Creteur, Jacques; Preiser, Jean-Charles; Dubois, Marc-Jacques; Vincent, Jean-Louis

    2002-07-01

    Microvascular blood flow alterations are frequent in animal models of sepsis and may impair tissue oxygenation. We hypothesized that alterations of the microcirculation are present in patients with sepsis. We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 10 healthy volunteers, 16 patients before cardiac surgery, 10 acutely ill patients without sepsis (intensive care unit control subjects), and 50 patients with severe sepsis. The effects of topical application of acetylcholine (10(-2) M) were tested in 11 patients with sepsis. In each subject, five to seven sublingual areas were recorded and analyzed semiquantitatively. Data were analyzed with nonparametric tests and are presented as medians (25th-75th percentiles). No significant difference in microvascular blood flow was observed between healthy volunteers and patients before cardiac surgery or intensive care unit control subjects. The density of all vessels was significantly reduced in patients with severe sepsis (4.5 [4.2-5.2] versus 5.4 [5.4-6.3]/mm in volunteers, p < 0.01). The proportion of perfused small (< 20 microm) vessels was reduced in patients with sepsis (48 [33-61] versus 90 [89-92]% in volunteers, p < 0.001). These alterations were more severe in nonsurvivors. The topical application of acetylcholine totally reversed these alterations. In conclusion, microvascular blood flow alterations are frequent in patients with sepsis and are more severe in patients with a worse outcome. PMID:12091178

  2. Late mortality after sepsis: propensity matched cohort study

    PubMed Central

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

    2016-01-01

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

  3. Vitamin D and sepsis

    PubMed Central

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

    2012-01-01

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

  4. SEPSIS CHRONICALLY IN MARS: SYSTEMIC CYTOKINE RESPONSES ARE ALWAYS MIXED REGARDLESS OF THE OUTCOME, MAGNITUDE OR PHASE OF SEPSIS 1

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

    Popovic, Nada; Djordjevic, Dragan

    2013-01-01

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

  7. Medical treatment of multiple streptococcal liver abscesses

    SciTech Connect

    Matlow, A.; Vellend, H.

    1983-04-01

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

  8. Translational research and biomarkers in neonatal sepsis.

    PubMed

    Delanghe, Joris R; Speeckaert, Marijn M

    2015-12-01

    As neonatal sepsis is a severe condition, there is a call for reliable biomarkers to differentiate between infected and noninfected newborns. Although blood culture has been considered as the gold standard, this analysis is still too slow and limited by false negative results. Use of CRP is hampered by a physiological 3-day increase, resulting in a low sensitivity to detect sepsis at an early stage. A moderate diagnostic accuracy of other acute phase proteins has been demonstrated (serum amyloid A, procalcitonin, lipopolysaccharide binding protein, mannose binding lectin and hepcidin). In neonatal sepsis, changed chemokine/cytokine levels are observed before those of acute phase reactants. High IL-6, IL-8, IL-10 and TNF-α concentrations are detected in infected infants. Soluble interleukin-2 receptor has been used to identify bacteremia, whereas low plasma RANTES concentrations are characteristic for septicemia. Several cell adhesion molecules contribute to the pathogenesis of sepsis. As an upregulated CD64 expression on granulocytes is found within 1-6h after bacterial invasion, serial CD64 measurements could guide antibiotic therapy. An increased CD11b/CD18 density can improve the diagnosis, and a positive correlation between CD11b and the severity of systemic inflammation has been reported. An early increase in sCD14-ST presepsin is also observed during sepsis, whereas high sTREM-1 values in early-onset neonatal sepsis (EOS) have been associated with mortality. Biomarkers resulting from proteomics are also promising. A 4-biomarker 'mass restricted' score has been validated as diagnostic for intra-amniotic infection and/or inflammation. S100A8 in amniotic fluid is a strong predictor of an increased incidence of EOS. Proteomic analysis of cord blood has revealed altered protein expression patterns. The ApoSAA score is useful for identifying sepsis and could guide prescription of antibiotics. (1)H-NMR and GC-MS metabolomics allow to diagnose septic shock, which is associated with increased concentrations of 2-hydroxybutyrate, 2-hydroxyisovalerate, 2-methylglutarate, creatinine, glucose and lactate. PMID:25661089

  9. Group B streptococcal phospholipid causes pulmonary hypertension

    NASA Astrophysics Data System (ADS)

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

    2003-04-01

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

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

    PubMed

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

    2015-08-01

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

  11. Efficacy of benzathine penicillin G in group A streptococcal pharyngitis: reevaluation.

    PubMed

    Feldman, S; Bisno, A L; Lott, L; Dodge, R; Jackson, R E

    1987-05-01

    The rate of streptococcal eradication after intramuscular administration of benzathine penicillin G in 66 children with acute group A streptococcal pharyngitis was determined and possible reasons for treatment failure explored. Bacteriologic treatment failure, defined as isolation of the same serotype at 3- or 6-weeks follow-up, occurred in eight (12%) patients. The treatment failure rate was 21% in those with immunologically significant infection, versus 8% in those without antibody rises (P greater than 0.1). All group A beta-hemolytic streptococcal (GABS) strains isolated from patients with treatment failure, both before and after benzathine penicillin G therapy, were exquisitely susceptible to penicillin G (minimum inhibitory concentration less than or equal to 0.02 microgram/mL), and none showed evidence of tolerance (minimum bactericidal concentration less than or equal to 0.04 microgram/mL). Thus, we found GABS eradication rates to exceed 10% in children given benzathine penicillin G. The failure rate did not appear to be related to enrichment of the patient population with a high proportion of asymptomatic carriers nor to the presence of penicillin-tolerant GABS. PMID:3553513

  12. Biomarkers for Sepsis

    PubMed Central

    Henriquez-Camacho, Cesar; Losa, Juan

    2014-01-01

    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

  13. Group B streptococcal neonatal parotitis.

    PubMed

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

    2015-01-01

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

  14. Essentials of sepsis management.

    PubMed

    Green, John M

    2015-04-01

    Despite remarkable advances in the knowledge of infection and human response to it, sepsis continues to be one of the most common challenges surgeons and critical care providers face. Surgeons confront the problem of infection every day, in treating established infections or reacting to a consequence of surgical intervention. Infections after surgery continue to be a problem despite massive efforts to prevent them. Patients rely on the surgeon's ability to recognize infection and treat it. Also, preventing nosocomial infection and antibiotic resistance is a primary responsibility. This article describes diagnostic and therapeutic measures for sepsis in the perioperative surgical patient. PMID:25814111

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

    PubMed

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

    2010-11-19

    Despite substantial progress in prevention of perinatal group B streptococcal (GBS) disease since the 1990s, GBS remains the leading cause of early-onset neonatal sepsis in the United States. In 1996, CDC, in collaboration with relevant professional societies, published guidelines for the prevention of perinatal group B streptococcal disease (CDC. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR 1996;45[No. RR-7]); those guidelines were updated and republished in 2002 (CDC. Prevention of perinatal group B streptococcal disease: revised guidelines from CDC. MMWR 2002;51[No. RR-11]). In June 2009, a meeting of clinical and public health representatives was held to reevaluate prevention strategies on the basis of data collected after the issuance of the 2002 guidelines. This report presents CDC's updated guidelines, which have been endorsed by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the American College of Nurse-Midwives, the American Academy of Family Physicians, and the American Society for Microbiology. The recommendations were made on the basis of available evidence when such evidence was sufficient and on expert opinion when available evidence was insufficient. The key changes in the 2010 guidelines include the following: • expanded recommendations on laboratory methods for the identification of GBS, • clarification of the colony-count threshold required for reporting GBS detected in the urine of pregnant women, • updated algorithms for GBS screening and intrapartum chemoprophylaxis for women with preterm labor or preterm premature rupture of membranes, • a change in the recommended dose of penicillin-G for chemoprophylaxis, • updated prophylaxis regimens for women with penicillin allergy, and • a revised algorithm for management of newborns with respect to risk for early-onset GBS disease. Universal screening at 35-37 weeks' gestation for maternal GBS colonization and use of intrapartum antibiotic prophylaxis has resulted in substantial reductions in the burden of early-onset GBS disease among newborns. Although early-onset GBS disease has become relatively uncommon in recent years, the rates of maternal GBS colonization (and therefore the risk for early-onset GBS disease in the absence of intrapartum antibiotic prophylaxis) remain unchanged since the 1970s. Continued efforts are needed to sustain and improve on the progress achieved in the prevention of GBS disease. There also is a need to monitor for potential adverse consequences of intrapartum antibiotic prophylaxis (e.g., emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens). In the absence of a licensed GBS vaccine, universal screening and intrapartum antibiotic prophylaxis continue to be the cornerstones of early-onset GBS disease prevention. PMID:21088663

  16. Intra-abdominal sepsis.

    PubMed

    Holliday, R L

    1976-01-01

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

  17. Sepsis Associated Encephalopathy

    PubMed Central

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

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

  18. Revisiting caspases in sepsis.

    PubMed

    Aziz, M; Jacob, A; Wang, P

    2014-01-01

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

  19. Revisiting caspases in sepsis

    PubMed Central

    Aziz, M; Jacob, A; Wang, P

    2014-01-01

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

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

    PubMed Central

    2014-01-01

    In 1991, a well-meaning consensus group of thought leaders derived a simple definition for sepsis which required the breach of only a few static thresholds. More than 20 years later, this simple definition has calcified to become the gold standard for sepsis protocols and research. Yet sepsis clearly comprises a complex, dynamic, and relational distortion of human life. Given the profound scope of the loss of life worldwide, there is a need to disengage from the simple concepts of the past. There is an acute need to develop 21st century approaches which engage sepsis in its true form, as a complex, dynamic, and relational pattern of death. PMID:24383420

  1. Streptococcal infection in a Junior Detention Centre: a five-year study.

    PubMed Central

    Colling, A.; Kerr, I.; Maxted, W. R.; Widdowson, J. P.

    1980-01-01

    In 1972 more than 20% of boys admitted to a closed community (Junior Detention Centre) developed acute tonsillitis and group-A streptococci were isolated from more than 40% of all boys at some time during their stay of two months. The most common serotype was M-type 5, which has frequently been associated with rheumatic fever in other epidemics; four cases of rheumatic fever occurred between 1972 and 1977. Various methods were tried to eliminate the infection, but only full penicillin prophylaxis (0.25 g oral penicillin 4 times a day for 10 days) to all boys on entry appeared to be effective. In a sample of cases of acute tonsillitis, group-A haemolytic streptococci were isolated from 31.7% by the use of dry swabs or unenriched transport medium, but with enrichment medium duplicate swabs, 77.6% yielded positive results. We question the current practice in some laboratories of reporting positive cultures only when more than ten colonies of beta-haemolytic streptococci are present. In this survey viruses did not appear to be an important cause of acute tonsillitis. High titres of streptococcal antibodies (antistreptolysin O, anti-desoxyribonuclease B and anti-M associated protein) were found, not only in cases and carriers, but in boys on entry to the centre. This supports epidemiological evidence that adolescent boys are particularly prone to streptococcal throat infections. PMID:7007484

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

    PubMed Central

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

    2014-01-01

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

  3. Neuroinflammation in sepsis: sepsis associated delirium.

    PubMed

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

    2015-01-01

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

  4. Streptococcal vertebral osteomyelitis: multiple faces of the same disease.

    PubMed

    Murillo, O; Roset, A; Sobrino, B; Lora-Tamayo, J; Verdaguer, R; Jiménez-Mejias, E; Nolla, J M; Colmenero, J de D; Ariza, J

    2014-01-01

    The role of Streptococcus species as an aetiological microorganism of vertebral osteomyelitis (VO) is considered to be of little relevance. We aimed to describe a large number of cases of streptococcal vertebral osteomyelitis (SVO), to analyze the clinical features associated with different Streptococcus species, and to compare them with a cohort of patients with VO caused by Staphylococcus aureus. An incidence study and a retrospective, multicenter, observational clinical study of cases of SVO (1991-2011) were performed. Statistical comparison of SVO by different species and between them and staphylococcal VO was carried out. Over the whole period there was an increasing incidence in the number of VOs and SVOs per year (p <0.05). Among 58 cases of SVO, those caused by non-viridans streptococcus (Streptococcus pneumoniae, Streptococcus agalactiae and Streptococcus pyogenes; n = 26) mimicked VO by S. aureus, and presented with more fever, neurological symptoms and paravertebral abscesses in comparison with those caused by the viridans group (remaining species). In contrast, the latter have a sub-acute clinical picture and were associated with the presence of endocarditis (p <0.05). Among non-viridans SVOs, concomitant infection was specifically related to S. pneumoniae (p <0.05). In conclusion, SVO presents a wide range of clinical patterns. The relationship between VO and diagnosis of endocarditis was established with SVO caused by the viridans group. Whereas non-viridans SVO mimics acute characteristics of VO caused by S. aureus, cases of viridans SVO are significantly more likely to have a sub-acute clinical presentation. The increased incidence of SVO during the last decades could support a new epidemiological scenario. PMID:23889700

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

    PubMed Central

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

    2016-01-01

    Background Although Streptococcal bacteremia is common in diarrheal children with high morbidity and mortality, no systematic data are available on Streptococcal bacteremia in diarrheal children. We sought to evaluate the factors associated with Streptococcal bacteremia in diarrheal children under five years of age and their outcome. Methods We used an unmatched case-control design to investigate the associated factors with Streptococcal bacteremia in all the diarrheal children under five years of age through electronic medical record system of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. We had simultaneously used a retrospective cohort design to further evaluate the outcome of our study children. All the enrolled children had their blood culture done between January 2010 and December 2012. Comparison was made among the children with (cases = 26) and without Streptococcal bacteremia (controls = 78). Controls were selected randomly from hospitalized diarrheal children under five years of age. Results Cases had proportionately higher deaths compared to controls, but it was statistically insignificant (15% vs. 10%, p = 0.49). The cases more often presented with severe dehydration, fever, respiratory distress, severe sepsis, and abnormal mental status compared to the controls (for all p<0.05). In the logistic regression analysis, after adjusting for potential confounders, it has been found that Streptococcal bacteremia in diarrheal children under five years of age was independently associated with nutritional edema (OR: 5.86, 95% CI = 1.28–26.80), hypoxemia (OR: 19.39, 95% CI = 2.14–175.91), fever (OR: 4.44, 95% CI = 1.13–17.42), delayed capillary refill time (OR: 7.00, 95% CI = 1.36–35.93), and respiratory distress (OR: 2.69, 95% CI = 1.02–7.12). Conclusions and Significance The results of our analyses suggest that diarrheal children under five years of age presenting with nutritional edema, hypoxemia, fever, delayed capillary refill time, and respiratory distress may be at risk of Streptococcal bacteremia. It underscores the importance of identification of these simple clinical parameters for the prompt recognition and management in order to reduce the morbidity and death of such children especially in resource limited settings. PMID:27135829

  6. New paradigms in sepsis: from prevention to protection of failing microcirculation.

    PubMed

    Hawiger, J; Veach, R A; Zienkiewicz, J

    2015-10-01

    Sepsis, also known as septicemia, is one of the 10 leading causes of death worldwide. The rising tide of sepsis due to bacterial, fungal and viral infections cannot be stemmed by current antimicrobial therapies and supportive measures. New paradigms for the mechanism and resolution of sepsis and consequences for sepsis survivors are emerging. Consistent with Benjamin Franklin's dictum 'an ounce of prevention is worth a pound of cure', sepsis can be prevented by vaccinations against pneumococci and meningococci. Recently, the NIH NHLBI Panel redefined sepsis as 'severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure'. Microvascular endothelial injury underlies sepsis-associated hypotension, edema, disseminated intravascular coagulation, acute respiratory distress syndrome and acute kidney injury. Microbial genome products trigger 'genome wars' in sepsis that reprogram the human genome and culminate in a 'genomic storm' in blood and vascular cells. Sepsis can be averted experimentally by endothelial cytoprotection through targeting nuclear signaling that mediates inflammation and deranged metabolism. Endothelial 'rheostats' (e.g. inhibitors of NF-κB, A20 protein, CRADD/RAIDD protein and microRNAs) regulate endothelial signaling. Physiologic 'extinguishers' (e.g. suppressor of cytokine signaling 3) can be replenished through intracellular protein therapy. Lipid mediators (e.g. resolvin D1) hasten sepsis resolution. As sepsis cases rose from 387 330 in 1996 to 1.1 million in 2011, and are estimated to reach 2 million by 2020 in the US, mortality due to sepsis approaches that of heart attacks and exceeds deaths from stroke. More preventive vaccines and therapeutic measures are urgently needed. PMID:26190521

  7. Sepsis-induced Cardiomyopathy

    PubMed Central

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

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

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

    PubMed Central

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

    2014-01-01

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

  9. Complicated Perianal Sepsis.

    PubMed

    Mitra, Abhishek; Yadav, Amitabh; Mehta, Naimish; Varma, Vibha; Kumaran, Vinay; Nundy, Samiran

    2015-12-01

    Management of benign anorectal conditions like abscesses and haemorrhoids is usually uneventful. However, complicated perianal complications can result and have sparsely been reported in literature. Hereby, we report a series of seven patients who presented with rare sequelae like necrotising fasciitis, intraperitoneal or retroperitoneal involvement. All patients responded well to surgical management. Accordingly, complicated perianal sepsis warrants a timely and aggressive surgical intervention. PMID:27011454

  10. Glycocalyx in Sepsis Resuscitation.

    PubMed

    Chen, Leon

    2016-01-01

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

  11. Endotoxin in the pathogenesis of sepsis.

    PubMed

    Marshall, John C

    2010-01-01

    The word 'sepsis' is a descriptive term that denotes the clinical syndrome resulting from the activation of an innate host response to infection. Sepsis is a useful concept that underlines the fact that the morbidity of serious infection arises through the response of the host, rather than through intrinsic cytopathic effects of the microorganism. However, it has proven inadequate as a means to delineate a population of patients who might benefit from therapies that modulate this response. The syndrome is variable in its clinical expression, and not specific for infection as a cause. Emerging insights into the biology of the innate host immune response reveal that the cellular response can be evoked by a variety of stimuli - including both microbial products and host-derived molecules that are normally intracellular - that signal danger to the host. The disconnect between concept and disease that has hampered the conduct of clinical trials is nicely exemplified in the host response to endotoxin. Endotoxemia occurs in many patients with sepsis, but also in many clinical settings that are noninfectious in nature. Moreover, the biologic behavior of endotoxin resembles that of a hormone more than that of a toxin, suggesting that low level endotoxemia may, under some circumstances, be beneficial. Future studies of antiendotoxin strategies in acute illness are more likely to succeed if they recruit patients with endotoxemia, and titrate therapy to an optimal level. PMID:20519894

  12. Therapeutic iron restriction in sepsis.

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    1992-01-01

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

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

    PubMed Central

    2010-01-01

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

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

    ERIC Educational Resources Information Center

    Markowitz, Milton

    1979-01-01

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

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

    PubMed Central

    Kaufman, David; Fairchild, Karen D.

    2004-01-01

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

  18. Group A streptococcal infections in obstetrics and gynecology.

    PubMed

    Rimawi, Bassam H; Soper, David E; Eschenbach, David A

    2012-12-01

    Group A streptococcal (GAS) infections continue to be an infrequent, but potentially lethal infections in women despite the victory over childbed fever in the 1800s. Invasive group A streptococcal infection still causes 40% of septic deaths among patients with postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome. Many times symptoms and signs of this infection are nonspecific, but laboratory evaluation can suggest serious infection. The prudent combination of antibiotic and surgical therapy can be lifesaving. PMID:23090455

  19. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    PubMed

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

    2016-06-01

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

  20. Alcoholic leukopenic pneumococcal sepsis.

    PubMed

    Alraiyes, Abdul Hamid; Shaheen, Khaldoon; Alraies, M Chadi

    2013-04-01

    Alcohol abuse has been associated with an increased mortality and morbidity due to increased aspiration, delirium tremens, and seizures. The association of pneumococcal lung infections and leukopenia in the setting of alcohol abuse are rarely reported; however, when present, severe lung infections can happen with severe lung injury and poor response to conventional therapy and ultimately, death. We are reporting a case of 55-year-old-man presented with shortness of breath, cough and altered mental status and eventually found with severe pneumococcal lung infection in the setting of leukopenia and long-term alcohol abuse representing alcoholic leukopenic pneumococcal sepsis syndrome. PMID:23930244

  1. Prevention of sepsis after splenectomy.

    PubMed

    Aguilar, Rizalea B; Keister, Kathy J; Russell, Anne C

    2010-01-01

    Individuals who do not have a spleen are highly susceptible to severe infections. The purpose of this article was to present vaccination guidelines for prophylactic treatment of sepsis following splenectomy. Nursing considerations for the prevention of sepsis after splenectomy are discussed. PMID:20160541

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

    PubMed Central

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

    2012-01-01

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

  3. Surgical wound sepsis

    PubMed Central

    Cruse, P. J. E.

    1970-01-01

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

  4. Early Onset Sepsis.

    PubMed

    Johnson, Kyrsten; Messier, Stephen

    2016-01-01

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

  5. Sepsis and ARDS: The Dark Side of Histones

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Dyagilev, Kirill; Saria, Suchi

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2015-01-01

    Background In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. Methods In this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. Results The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). Conclusion and Significance We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children. PMID:26440279

  11. The management of sepsis.

    PubMed

    Zawistowski, Christine A

    2013-01-01

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

  12. Sepsis Resuscitation: Consensus and Controversies.

    PubMed

    Montanaro, Nicholas

    2016-01-01

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

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

    PubMed

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

    2014-09-01

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

  14. The Role of Nephritis-Associated Plasmin Receptor (NAPlr) in Glomerulonephritis Associated with Streptococcal Infection

    PubMed Central

    Oda, Takashi; Yoshizawa, Nobuyuki; Yamakami, Kazuo; Sakurai, Yutaka; Takechi, Hanako; Yamamoto, Kojiro; Oshima, Naoki; Kumagai, Hiroo

    2012-01-01

    It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate. We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected by in situ zymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity. PMID:23118507

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

    PubMed

    Macerollo, Antonella; Martino, Davide

    2013-01-01

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

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

    PubMed Central

    Macerollo, Antonella; Martino, Davide

    2013-01-01

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

  17. [Experience of application of meronem in the treatment of severe purulent sepsis in children].

    PubMed

    Sleptsov, V P; Kirsanov, A I; Usachenko, V P; Ivanova, O V; Stepkina, O I; Belkina, Iu E; Bondarenko, I V; Panasenko, V V

    2002-01-01

    Results of antibacterial therapy with application of meropenem (meronem by firm Astra Zeneca, Great Britain) in 29 childs with severe purulent-septic state, including 5 with toxic peritonitis, in 2--with sepsis, in 3 newborn childs--with esophageal atresia and in 19--with the blood disease (nonhodgkin's lymphoma, an acute lymphoblastic or myeloblastic leucosis, reccurrent of acute lymphoblastic leucosis, nephroblastoma). PMID:11944296

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

    PubMed

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

    2012-01-01

    The results achieved with 80% reduction in the incidence of early-onset neonatal group B streptococcal (GBS) sepsis following the implementation of the preliminary (1996, 2002) and subsequently the revised (2010) guidelines for intrapartum antibiotic prophylaxis imposed the discussion on a large scale of the updated:--algorithms for GBS screening (35-37 weeks of gestation) with the recommended dosage of penicillin-G for intrapartum antibiotic prophylaxis for women having normal labor and delivery;--algorithms for GBS screening and intrapartum antibiotic prophylaxis for women with preterm labor (PPROM) or premature rupture of membranes (PROM);--intrapartum antibiotic prophylaxis regimens for women with penicillin allergy;--algorithm for management of newborns with respect to risk of early-onset GBS disease. The present study is aimed at studying the distribution of the early-onset GBS disease in our country based on the data of leading obstetrics & gynecology clinics and wards. The aim is to diferrentiate clinically the cases and investigate the influence of the known risk factors on the part of the mother. A special accent is put over the microbiological diagnostics of cases in view of CDC expanded recommendations on the laboratory methods for identification of GBS. As a final conclusion the necessity for introduction of an official registration of the early- and late-onset GBS disease in the country is emphasized. PMID:23390859

  19. Neonatal sepsis and inflammatory mediators.

    PubMed

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

    2014-01-01

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

  20. Diagnosis and treatment of streptococcal pharyngitis.

    PubMed

    Choby, Beth A

    2009-03-01

    Common signs and symptoms of streptococcal pharyngitis include sore throat, temperature greater than 100.4 degrees F (38 degrees C), tonsillar exudates, and cervical adenopathy. Cough, coryza, and diarrhea are more common with viral pharyngitis. Available diagnostic tests include throat culture and rapid antigen detection testing. Throat culture is considered the diagnostic standard, although the sensitivity and specificity of rapid antigen detection testing have improved significantly. The modified Centor score can be used to help physicians decide which patients need no testing, throat culture/rapid antigen detection testing, or empiric antibiotic therapy. Penicillin (10 days of oral therapy or one injection of intramuscular benzathine penicillin) is the treatment of choice because of cost, narrow spectrum of activity, and effectiveness. Amoxicillin is equally effective and more palatable. Erythromycin and first-generation cephalosporins are options in patients with penicillin allergy. Increased group A beta-hemolytic streptococcus (GABHS) treatment failure with penicillin has been reported. Although current guidelines recommend first-generation cephalosporins for persons with penicillin allergy, some advocate the use of cephalosporins in all nonallergic patients because of better GABHS eradication and effectiveness against chronic GABHS carriage. Chronic GABHS colonization is common despite appropriate use of antibiotic therapy. Chronic carriers are at low risk of transmitting disease or developing invasive GABHS infections, and there is generally no need to treat carriers. Whether tonsillectomy or adenoidectomy decreases the incidence of GABHS pharyngitis is poorly understood. At this time, the benefits are too small to outweigh the associated costs and surgical risks. PMID:19275067

  1. Group A β-hemolytic streptococcal pharyngotonsillitis outbreak.

    PubMed

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

    2014-04-01

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

  2. Group A β-hemolytic streptococcal pharyngotonsillitis outbreak

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-02-01

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

  4. Heparanase mediates renal dysfunction during early sepsis in mice

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

    Martin, Greg S

    2012-01-01

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

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

    PubMed

    Barash, Judith

    2013-06-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Antimicrobial Peptides in Human Sepsis

    PubMed Central

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

    2015-01-01

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

  11. Antimicrobial Peptides in Human Sepsis.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-08-01

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

  14. Immunomodulatory Effect of Continuous Venovenous Hemofiltration during Sepsis: Preliminary Data

    PubMed Central

    Servillo, Giuseppe; Pastore, Antonio; Procino, Alfredo; Iannuzzi, Michele; Capuano, Alfredo; Memoli, Andrea; Memoli, Bruno

    2013-01-01

    Introduction. Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many pro- and anti-inflammatory mediators, such as interleukin-6 (IL-6), play a strategic role in septic syndrome. Continuous renal replacement therapy (CRRT) removes in a nonselective way pro- and anti-inflammatory mediators. Objective. To investigate the effects of continuous venovenous hemofiltration (CVVH) as an immunomodulatory treatment of sepsis in a prospective clinical study. Methods. High flux hemofiltration (Qf = 60 ml/Kg/hr) was performed for 72 hr in thirteen critically ill patients suffering from severe sepsis or septic shock with acute renal failure (ARF). IL-6 gene expression was measured by real-time PCR analysis on RNA extracted from peripheral blood mononuclear cell before beginning of treatment (T0) and after 12, 24, 48, and 72 hours (T1–4). Results. Real-time PCR analysis demonstrated in twelve patients IL-6 mRNA reduction after 12 hours of treatment and a progressive increase after 24, 48, and 72 hours. Conclusions. We suggest that an immunomodulatory effect might exist during CVVH performed in critically ill patients with severe sepsis and septic shock. Our data show that the transcriptional activity of IL-6 increases during CVVH. PMID:23971020

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

    PubMed

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

    2003-11-01

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

  16. Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis.

    PubMed

    Hikone, Mayu; Kobayashi, Ken-Ichiro; Washino, Takuya; Ota, Masayuki; Sakamoto, Naoya; Iwabuchi, Sentaro; Ohnishi, Kenji

    2015-12-01

    Streptococcal toxic shock syndrome (TSS) is a systemic illness usually caused in the setting of infection by group A Streptococcus (GAS). The primary infections are often invasive infections of the respiratory tract or necrotizing infections of the skin and soft tissue, but some infections occur without relevant focus. GAS vaginitis is a rare condition among adult women and is accordingly thought to be uncommon as a cause of streptococcal TSS. Here we report the cases of two postmenopausal women with streptococcal TSS secondary to GAS vaginitis, one aged 55 and one aged 60. Both came to our emergency department with complaints or symptoms of abdominal pain, fever, hypotension, and multi-organ failure. In both cases, the relevant factor associated with streptococcal infection was a recent episode of GAS vaginitis. Both underwent fluid management and 14 days of antibiotic treatment and fully recovered without complications. Vaginitis was likely to be the primary infectious trigger of TSS in these two cases. Intrauterine device insertion, endometrial biopsy, and post-partum state have all been previously reported in TSS patients, and the female genital tract has been described as a portal of entry. GAS vaginitis warrants appropriate treatment as it may progress to severe systemic infection as described. PMID:26386777

  17. Post-streptococcal autoimmune disorders of the central nervous system.

    PubMed

    Dale, Russell C

    2005-11-01

    Group A Streptococcus can induce autoimmune disease in humans with particular involvement of the heart, joints, and brain. The spectrum of post-streptococcal disease of the central nervous system (CNS) has been widened recently and includes movement disorders (chorea, tics, dystonia, and Parkinsonism), psychiatric disorders (particularly emotional disorders), and associated sleep disorders. Neuroimaging and pathological studies indicate that the most vulnerable brain region is the basal ganglia. The immunopathogenesis of the disease is incompletely defined, and although there is some support for autoantibody-mediated disease, several conflicting studies cast doubt on the autoantibody hypothesis. It has been speculated that post-streptococcal autoimmunity has a role in common neuropsychiatric disease but the evidence is conflicting and routine screening of patients with Tourette syndrome and obsessive-compulsive disorder for post-streptococcal autoimmune abnormalities is not be recommended at present. However, post-streptococcal disorders of the CNS remain a useful model of neuropsychiatric disease, which may improve our understanding of abnormal movements and behaviours in children. PMID:16225745

  18. Treatment of streptococcal pharyngitis with amoxycillin once a day.

    PubMed Central

    Shvartzman, P; Tabenkin, H; Rosentzwaig, A; Dolginov, F

    1993-01-01

    OBJECTIVE--To evaluate treatment of group A beta haemolytic streptococcal pharyngitis with amoxycillin once daily compared with phenoxymethylpenicillin three or four times a day. DESIGN--Randomised controlled study of consecutive patients presenting with symptoms suggestive of group A beta haemolytic streptococcal pharyngitis in whom culture of a throat swab yielded positive results. SETTING--Five family medicine practices. SUBJECTS--157 patients aged over 3 years who required treatment with antibiotics. MAIN OUTCOME MEASURES--Clinical response, bacteriological response, days at work and school lost, and compliance. RESULTS--During the period of the study 393 patients presented with symptoms suggesting streptococcal pharyngitis; 157 of them had throat swabs that yielded positive results on culture. Eighty two were treated with phenoxymethylpenicillin and 75 with amoxycillin. No difference was observed in the clinical response, days at work and school lost (139 days for 64 patients taking phenoxymethylpenicillin v 100 days for 57 patients taking amoxycillin; p > 0.2), or residual positive cultures after two days (6 (7.3%) v 3 (4%); p > 0.5). A significant difference in the bacteriological response was found after 14 days (5 (6.1%) v 0; p < 0.04) with no positive cultures observed in the amoxycillin group. CONCLUSIONS--These findings support the hypothesis that amoxycillin once daily is as effective as phenoxymethylpenicillin in the treatment of group A beta haemolytic streptococcal pharyngitis. PMID:8499823

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2013-07-01

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

  2. Transfusion-associated bacterial sepsis.

    PubMed Central

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

    1994-01-01

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

  3. Diagnostic criteria of acute rheumatic fever.

    PubMed

    Burke, Rebecca J; Chang, Christopher

    2014-01-01

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

  4. Early identification and treatment of sepsis.

    PubMed

    McClelland, Heather; Moxon, Alex

    Sepsis is a potentially fatal condition and is becoming increasingly frequent, yet health professionals are often unable to recognise its symptoms. It is the body's exaggerated response to infection and, if left untreated, will lead to severe sepsis, multi-organ failure and death. Nurses play a vital role in identifying patients with sepsis and starting essential treatment. This article looks at how sepsis can be identified and effectively treated to improve survival. PMID:24592630

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2015-03-01

    Neonatal sepsis is a major cause of morbidity and mortality. Early diagnosis and treatment of the neonate with suspected sepsis are essential to prevent life-threatening complications. Diagnosis of neonatal sepsis is a challenge due to non-specific clinical signs and the fact that infection markers are difficult to interpret in the first and critical phase of neonatal sepsis. The objective of the present study was to systematically evaluate existing evidence of the diagnostic utility of biomarkers for prediction of sepsis in neonates. We conducted a systematic literature search performed in PubMed and Embase. The study population was neonates with gestation age > 24 weeks in their first 28 days of life with suspected sepsis. The included manuscripts were rated due to criteria from a modified rating scale developed by Douglas Altman. Of 292 potentially relevant manuscripts, 77 fulfilled the inclusion and exclusion criteria; 16 (21%) were rated as high-quality studies. C-reactive protein (CRP) was the most extensively studied biomarker evaluated. The high-quality studies indicated that the acute phase protein serum amyloid A had high sensitivity, both at onset of symptoms and 2 days after. The studies evaluating serum amyloid A presented a variable positive predictive value (PPV, 0.67 and 0.92) with a high negative predictive value (NPV, 0.97 and 1.00). The existing evidence of the diagnostic value of serum amyloid A for neonatal sepsis showed promising results, and should be further investigated in clinical settings. PMID:25522182

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Cunningham, Madeleine W

    2014-01-01

    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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

    2014-01-01

    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

  11. Which Biomarkers Reveal Neonatal Sepsis?

    PubMed Central

    Wang, Kun; Bhandari, Vineet; Chepustanova, Sofya; Huber, Greg; O′Hara, Stephen; O′Hern, Corey S.; Shattuck, Mark D.; Kirby, Michael

    2013-01-01

    We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA) and sparse support vector machine (SSVM) classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU). CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance): Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression. PMID:24367543

  12. Which biomarkers reveal neonatal sepsis?

    PubMed

    Wang, Kun; Bhandari, Vineet; Chepustanova, Sofya; Huber, Greg; O'Hara, Stephen; O'Hern, Corey S; Shattuck, Mark D; Kirby, Michael

    2013-01-01

    We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA) and sparse support vector machine (SSVM) classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU). CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance): Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression. PMID:24367543

  13. Restless legs syndrome: association with streptococcal or mycoplasma infection.

    PubMed

    Matsuo, Muneaki; Tsuchiya, Katsunori; Hamasaki, Yuhei; Singer, Harvey S

    2004-08-01

    Group A beta-hemolytic streptococcal infections have been reported to cause neuropsychiatric symptoms, such as chorea, tics, and obsessive-compulsive disorder, presumably through autoimmune damage to basal ganglia. Mycoplasma pneumoniae infections have also been reported to cause damage to the basal ganglia. Restless legs syndrome is a movement disorder with focal restlessness, an irresistible desire to move, and exacerbation by long periods of sitting or lying. We present three children with transient restless legs syndrome-like symptoms possibly associated with group A beta-hemolytic streptococcal infection or Mycoplasma pneumoniae infection. One of three patients had persistently elevated enzyme-linked immunosorbent optical density values against human caudate and putamen. PMID:15301831

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

    PubMed

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

    2006-05-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. 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

  18. Substrate Specificity of Streptococcal Unsaturated Glucuronyl Hydrolases for Sulfated Glycosaminoglycan*

    PubMed Central

    Maruyama, Yukie; Nakamichi, Yusuke; Itoh, Takafumi; Mikami, Bunzo; Hashimoto, Wataru; Murata, Kousaku

    2009-01-01

    Unsaturated glucuronyl hydrolase (UGL) categorized into the glycoside hydrolase family 88 catalyzes the hydrolytic release of an unsaturated glucuronic acid from glycosaminoglycan disaccharides, which are produced from mammalian extracellular matrices through the β-elimination reaction of polysaccharide lyases. Here, we show enzyme characteristics of pathogenic streptococcal UGLs and structural determinants for the enzyme substrate specificity. The putative genes for UGL and phosphotransferase system for amino sugar, a component of glycosaminoglycans, are assembled into a cluster in the genome of pyogenic and hemolytic streptococci such as Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes, which produce extracellular hyaluronate lyase as a virulent factor. The UGLs of these three streptococci were overexpressed in Escherichia coli cells, purified, and characterized. Streptococcal UGLs degraded unsaturated hyaluronate and chondroitin disaccharides most efficiently at approximately pH 5.5 and 37 °C. Distinct from Bacillus sp. GL1 UGL, streptococcal UGLs preferred sulfated substrates. DNA microarray and Western blotting indicated that the enzyme was constitutively expressed in S. agalactiae cells, although the expression level increased in the presence of glycosaminoglycan. The crystal structure of S. agalactiae UGL (SagUGL) was determined at 1.75 Å resolution by x-ray crystallography. SagUGL adopts α6/α6-barrel structure as a basic scaffold similar to Bacillus UGL, but the arrangement of amino acid residues in the active site differs between the two. SagUGL Arg-236 was found to be one of the residues involved in its activity for the sulfated substrate through structural comparison and site-directed mutagenesis. This is the first report on the structure and function of streptococcal UGLs. PMID:19416976

  19. Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings

    PubMed Central

    Seidlitz, Jakob; Kovacevic, Miro; Latimer, M. Elizabeth; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul

    2015-01-01

    Abstract Background: The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described>15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. Methods: A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). Results were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48). Results: As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86–92%), school issues (75–81%), sleep disruptions (71%), tics (60–65%), urinary symptoms (42–81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. Conclusions: The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS). PMID:25695941

  20. Office diagnosis and management of group A streptococcal pharyngitis employing the rapid antigen detecting test. A 1-year prospective study of reliability and cost in primary care centres.

    PubMed

    Majeed, H A; al-Doussary, L; Moussa, M M; Yusuf, A R; Suliman, A H

    1993-01-01

    The impact of introducing the rapid antigen detecting test for the diagnosis of group A streptococcal pharyngitis in primary care centres and the direct and comprehensive cost-effectiveness of four alternative strategies for the management of group A streptococcal pharyngitis and the prevention of rheumatic fever were assessed in a 1-year prospective randomized study, carried out in children between the ages of 5 and 14 years. Data from the study showed that the test was easy to perform and reliable when introduced as a service in primary care. The strategy of using the rapid antigen detecting test and a 10-day oral penicillin course for diagnosis and treatment proved to be the safest and most cost-effective. If compliance with a 10-day course of oral penicillin is unlikely to be achieved, the strategy of introducing the test and treatment by intramuscular benzathin penicillin G proved to be the second best cost-effective alternative. In developing countries, where acute rheumatic fever is still common and the cost of the test and a 10-day course of penicillin may prove to be formidable, a strategy of treating all children with pharyngitis with intramuscular benzathin penicillin G seems to be the most cost-effective. The strategy of diagnosing group A streptococcal pharyngitis on clinical grounds proved to be the worst. PMID:7681647

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

    PubMed Central

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

    1978-01-01

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

  2. Functional brain imaging in Sydenham's chorea and streptococcal tic disorders.

    PubMed

    Citak, Elvan Caglar; Gücüyener, Kivilcim; Karabacak, Nese Ilgin; Serdaroğlu, Ayşe; Okuyaz, Cetin; Aydin, Kurşad

    2004-05-01

    Group A streptococcal infections cause a wide range of neuropsychiatric disorders, such as Sydenham's chorea, tics, obsessive-compulsive disorders, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography, single-photon emission computed tomography) imaging studies in patients with Sydenham's chorea have suggested reversible striatal abnormalities. The objective of this study was to investigate the cerebral perfusion patterns of the subcortical structures by using hexamethylpropylenamine oxime single-photon emission computed tomography (HMPAO-SPECT) in seven cases of Sydenham's chorea and two cases of streptococcal tic disorder. HMPAO-SPECT studies revealed a hyperperfusion pattern in two and a hypoperfusion pattern in five of the chorea patients and in two patients with tic disorder. The results are discussed in relation to the duration and severity of the symptoms and the response to therapy. Functional imaging findings can be variable in Sydenham's chorea, and hyperperfusion of the striatum and thalamus could be an indicator of the response to therapy and the severity of symptoms. However, the number of cases so far investigated by either SPECT or positron emission tomography is still too limited to draw any firm conclusions. PMID:15224712

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

    PubMed

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

    2015-02-01

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

  4. Sepsis: Medical errors in Poland.

    PubMed

    Rorat, Marta; Jurek, Tomasz

    2016-01-01

    Health, safety and medical errors are currently the subject of worldwide discussion. The authors analysed medico-legal opinions trying to determine types of medical errors and their impact on the course of sepsis. The authors carried out a retrospective analysis of 66 medico-legal opinions issued by the Wroclaw Department of Forensic Medicine between 2004 and 2013 (at the request of the prosecutor or court) in cases examined for medical errors. Medical errors were confirmed in 55 of the 66 medico-legal opinions. The age of victims varied from 2 weeks to 68 years; 49 patients died. The analysis revealed medical errors committed by 113 health-care workers: 98 physicians, 8 nurses and 8 emergency medical dispatchers. In 33 cases, an error was made before hospitalisation. Hospital errors occurred in 35 victims. Diagnostic errors were discovered in 50 patients, including 46 cases of sepsis being incorrectly recognised and insufficient diagnoses in 37 cases. Therapeutic errors occurred in 37 victims, organisational errors in 9 and technical errors in 2. In addition to sepsis, 8 patients also had a severe concomitant disease and 8 had a chronic disease. In 45 cases, the authors observed glaring errors, which could incur criminal liability. There is an urgent need to introduce a system for reporting and analysing medical errors in Poland. The development and popularisation of standards for identifying and treating sepsis across basic medical professions is essential to improve patient safety and survival rates. Procedures should be introduced to prevent health-care workers from administering incorrect treatment in cases. PMID:26113542

  5. Randomized, single-blind evaluation of cefadroxil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis.

    PubMed

    Pichichero, M E; Disney, F A; Aronovitz, G H; Talpey, W B; Green, J L; Francis, A B

    1987-06-01

    A total of 150 children from two pediatric practices with clinical and bacteriologic evidence of acute group A beta-hemolytic streptococcal (GABHS) pharyngitis randomly received cefadroxil monohydrate (75 children) or phenoxymethyl penicillin (75 children). Cefadroxil was given once daily, while penicillin was given three times daily. The treatment groups were similar in age, sex, race, illness severity, and acute GABHS symptomatology. Throat cultures were routine 3 to 5 days after the start of therapy and 2 and 14 days after the end of therapy. The bacterial cure rates were 90% (62 of 69) for cefadroxil-treated patients and 76% (52 of 68) for penicillin-treated patients. This difference was significant (P less than 0.04). The clinical response was satisfactory in 91% of cefadroxil-treated patients and 89% of penicillin-treated patients. We conclude that once-daily cefadroxil is at least as effective as three-times-daily penicillin in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS pharyngitis. PMID:3113329

  6. Effectiveness of clinical guidelines for the presumptive treatment of streptococcal pharyngitis in Egyptian children.

    PubMed

    Steinhoff, M C; Abd el Khalek, M K; Khallaf, N; Hamza, H S; el Ayadi, A; Orabi, A; Fouad, H; Kamel, M

    1997-09-27

    In developing country settings without access to bacterial culture and rapid diagnostic tests, the prevention of acute rheumatic fever depends on clinicians' presumptive treatment of streptococcal pharyngitis. This study evaluated the effectiveness of World Health Organization (WHO) acute respiratory infection guidelines in a large pediatric clinic (Abu Reesh Children's Hospital) in Cairo, Egypt. 451 children 2-13 years of age with sore throat and pharyngeal erythema were enrolled, 107 (24%) of whom had group A beta-hemolytic streptococci on throat culture. Purulent exudate, present in 99 (22%) of these children, was 31% sensitive and 81% specific for a positive culture. The WHO guidelines, which recommend treatment for pharyngeal exudate plus enlarged and tender cervical node, were 12% sensitive and 94% specific. Based on these guidelines, 13 of 107 children with a positive throat culture would correctly receive antibiotics and 323 of 344 with a negative culture would not receive antibiotics. A modified guideline in which exudate or large cervical nodes would indicate antibiotic treatment would be 84% sensitive and 40% specific. With this modification, 90 of 107 children with a positive throat culture would correctly receive antibiotics and 138 out of 344 with a negative culture would not receive treatment. However, additional prospective studies from other regions of Egypt are necessary before modified guidelines are implemented. PMID:9314870

  7. Early-Onset Neonatal Sepsis

    PubMed Central

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

    2014-01-01

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

  8. Biosensor of endotoxin and sepsis

    NASA Astrophysics Data System (ADS)

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

    2001-09-01

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

  9. Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters

    PubMed Central

    Goldman, John; Cheriyath, Pramil; Nookala, Vinod

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  13. Epigenetic coordination of acute systemic inflammation: potential therapeutic targets

    PubMed Central

    Vachharajani, Vidula; Liu, Tiefu; McCall, Charles E.

    2015-01-01

    Epigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator Sirtuin 1 (SIRT-1), a NAD+ sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper and hypo inflammatory responses of sepsis at the microvascular interface, which disseminates inflammatory injury to cause multiple organ failure. Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way treat sepsis by epigenetically restoring immunometabolic homeostasis. PMID:25088223

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

    PubMed

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

    2009-06-01

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

  15. [Massive intravascular hemolysis secondary to sepsis due to Clostridium perfringens].

    PubMed

    Pita Zapata, E; Sarmiento Penide, A; Bautista Guillén, A; González Cabano, M; Agulla Budiño, J A; Camba Rodríguez, M A

    2010-05-01

    Massive hemolysis secondary to sepsis caused by Clostridium perfringens is a rare entity but appears fairly often in the literature. In nearly all published reports, the clinical course is rapid and fatal. We describe the case of a 75-year-old woman with diabetes who was admitted with symptoms consistent with acute cholecystitis. Deteriorating hemodynamics and laboratory findings were consistent with intravascular hemolysis, coagulation disorder, and renal failure. Gram-positive bacilli of the Clostridium species were detected in blood along with worsening indicators of hemolysis. In spite of antibiotic and surgical treatment, hemodynamic support and infusion of blood products, the patient continued to decline and died in the postoperative recovery unit 14 hours after admission. Mortality ranges from 70% to 100% in sepsis due to Clostridium perfringens, and risk of death is greater if massive hemolysis is present, as in the case we report. Only a high degree of clinical suspicion leading to early diagnosis and treatment can improve the prognosis. This bacterium should therefore be considered whenever severe sepsis and hemolysis coincide. PMID:20527348

  16. [Assessment of severity of meningococcal sepsis in children].

    PubMed

    Oom, Paulo; Rossi, Renata; Correia, Manuela; Rodrigues, Gustavo

    2003-01-01

    Despite advances in critical care medicine, acute meningococcal infection remains complicated by high mortality. Different prognostic scoring systems have been developed but none of them is largely used. The objective of this study was to evaluate the performance at admission to the pediatric intensive care unit (PICU) of five severity scores in children with proven and unproven meningococcal infection. Our results seem to indicate that the Neisseria Sepsis Index (NESI) and the Rotterdam Score (RS) perform better than the other scores, being appropriate tools to assess severity of illness at admission to the PICU in children with proven or presumed meningococcal infection. PMID:14750274

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

    PubMed

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

    2013-08-01

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

  18. Development and Implementation of Sepsis Alert Systems.

    PubMed

    Harrison, Andrew M; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

    2016-06-01

    Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload, and alert fatigue, due to suboptimal alert performance. Outside the ICU, barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Current evidence does not support routine use of sepsis alert systems in clinical practice. Continuous improvement in the afferent and efferent aspects will help translate theoretic advantages into measurable patient benefit. PMID:27229639

  19. Systems for Paediatric Sepsis: A Global Survey

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Chronic Sepsis Mortality Characterized by an Individualized Inflammatory Response1

    PubMed Central

    Osuchowski, Marcin F.; Welch, Kathy; Yang, Huan; Siddiqui, Javed; Remick, Daniel G.

    2015-01-01

    Late mortality in septic patients often exceeds the lethality occurring in acute sepsis, yet the immunoinflammatory alterations preceding chronic sepsis mortality are not well defined. We studied plasma cytokine concentrations preceding late septic deaths (days 6–28) in a murine model of sepsis induced by polymicrobial peritonitis. The late prelethal inflammatory response varied from a virtually nonexistent response in three of 14 to a mixed response in eight of 14 mice to the concurrent presence of nearly all measured cytokines, both proinflammatory and anti-inflammatory in three of 14 mice. In responding mice a consistent prelethal surge of plasma MIP-2 (1.6 vs 0.12 ng/ml in survivors; mean values), MCP-1 (2.0 vs 1.3 ng/ml), soluble TNF receptor type I (2.5 vs 0.66 ng/ml), and the IL-1 receptor antagonist (74.5 vs 3.3 ng/ml) was present, although there were infrequent increases in IL-6 (1.9 vs 0.03 ng/ml) and IL-10 (0.12 vs 0.04 ng/ml). For high mobility group box 1, late mortality was signaled by its decrease in plasma levels (591 vs 864 ng/ml). These results demonstrate that impeding mortality in the chronic phase of sepsis may be accurately predicted by plasma biomarkers, providing a mechanistic basis for individualized therapy. The pattern of late prelethal responses suggest that the systemic inflammatory response syndrome to compensatory anti-inflammatory response syndrome transition paradigm fails to follow a simple linear pattern. PMID:17579084

  5. Cytokine profile in elderly patients with sepsis

    PubMed Central

    Kumar, Anil T.; Sudhir, U.; Punith, K.; Kumar, Rahul; Ravi Kumar, V. N.; Rao, Medha Y.

    2009-01-01

    Context: Sepsis is a serious health problem in the elderly with a high degree of mortality. There is very limited data available in elderly subjects regarding the markers for sepsis. Development of good markers will help in overall management and prediction of sepsis. Objectives: Serial estimation of Interleukin-6 (IL-6) and Tumor Necrosis Factor-Alpha (TNF-α) and their correlation with mortality in sepsis in elderly patients and to determine the influence of gender on cytokine production and mortality in elderly patients with sepsis. Settings and Design: The prospective study was conducted at our tertiary care center from April 2007 to September 2008. Elderly Patients satisfying the Systemic Inflammatory Response Syndrome (SIRS) criteria were included. Methods and Material: TNF-α and IL-6 were estimated in 30 elderly patients admitted to our intensive care unit with SIRS and sepsis. The estimations were done on day 1, 3 and 7 of admission. Statistical Analysis Used: Student and paired ‘t’ tests, and ANOVA, which were further followed up by post-hoc ‘t’ tests with Bonferroni correction using SPSS. Results: Reducing levels of IL-6 levels from day 1 to 7 was found in the survivor group. TNF-α level was significantly low on day 1 in the nonsurvivor female group. Conclusions: Serial estimation of cytokines in elderly patients with sepsis will help in prediction of mortality. Female gender was an independent predictor of increased morality in critically ill patients with sepsis. PMID:19881187

  6. Clostridium perfringens sepsis following a molar pregnancy.

    PubMed

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

    2014-01-01

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

  7. Estrogen sulfotransferase ablation sensitizes mice to sepsis

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2004-10-01

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

  9. Type-Specific Opsonic Antibodies in Streptococcal Pyoderma

    PubMed Central

    Bisno, Alan L.; Nelson, Kenrad E.

    1974-01-01

    Prospective studies of streptococcal pyoderma were carried out among black children enrolled in Project Headstart centers in Holmes County, Miss. Sera collected from 28 of these children in early October were tested for opsonic antibodies to one of two prevalent skin strains of group A streptococci isolated from them on one or more occasions over the preceding 3 months. The two streptococcal strains (A and B) belong to M-types previously unrecognized. Ten subjects (36%) had antibody to their homologous serotypes detectable by the indirect bactericidal test: this included 6 of 10 subjects infected with strain B but only 4 of 18 infected with strain A (P < 0.05). Of 17 children who had strains A or B isolated from skin lesions only, 12% developed type-specific antibodies (TSA) against the infecting serotype. In contrast, 11 subjects had these strains isolated from throat cultures (either with or without associated pyoderma), and 72% had detectable TSA (P < 0.01). There was no demonstrable relationship between the development of antibodies to streptococcal extracellular products or to non-type-specific cellular antigens and the development of TSA. These results demonstrate that type-specific immune responses do occur following infection with pyoderma streptococci. The frequency with which such antibodies develop is variable and appears related to a number of factors, including the immunologic properties of the infecting strain and the site of bacterial colonization. Pharyngeal carriage may represent an important mechanism for development of acquired immunity to skin strains of group A streptococci. PMID:4435959

  10. AMP-Activated Protein Kinase and Glycogen Synthase Kinase 3β Modulate the Severity of Sepsis-Induced Lung Injury

    PubMed Central

    Liu, Zhongyu; Bone, Nathaniel; Jiang, Shaoning; Park, Dae Won; Tadie, Jean-Marc; Deshane, Jessy; Rodriguez, Cilina Ann; Pittet, Jean-Francois; Abraham, Edward; Zmijewski, Jaroslaw W

    2015-01-01

    Alterations in metabolic and bioenergetic homeostasis contribute to sepsis-mediated organ injury. However, how AMP-activated protein kinase (AMPK), a major sensor and regulator of energy expenditure and production, affects development of organ injury and loss of innate capacity during polymicrobial sepsis remains unclear. In the present experiments, we found that cross-talk between the AMPK and GSK3β signaling pathways controls chemotaxis and the ability of neutrophils and macrophages to kill bacteria ex vivo. In mice with polymicrobial abdominal sepsis or more severe sepsis induced by the combination of hemorrhage and intraabdominal infection, administration of the AMPK activator metformin or the GSK3β inhibitor SB216763 reduced the severity of acute lung injury (ALI). Improved survival in metformin-treated septic mice was correlated with preservation of mitochondrial complex V (ATP synthase) function and increased amounts of ETC complex III and IV. Although immunosuppression is a consequence of sepsis, metformin effectively increased innate immune capacity to eradicate P. aeruginosa in the lungs of septic mice. We also found that AMPK activation diminished accumulation of the immunosuppressive transcriptional factor HIF-1α as well as the development of endotoxin tolerance in LPS-treated macrophages. Furthermore, AMPK-dependent preservation of mitochondrial membrane potential also prevented LPS-mediated dysfunction of neutrophil chemotaxis. These results indicate that AMPK activation reduces the severity of polymicrobial sepsis-induced lung injury and prevents the development of sepsis-associated immunosuppression. PMID:26650187

  11. Post-streptococcal vasculopathy with evolution to Degos' disease.

    PubMed

    Pati, Sandipan; Muley, Suraj A; Grill, Marie F; Coons, Stephen; Walker, Russell

    2011-01-15

    Degos' disease or malignant atrophic papulosis is a rare disseminated occlusive vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and less often other organ systems. The exact etiology of this vasculopathy has not been established. Infections, autoimmune disease and coagulation defects have been proposed as underlying pathogenic mechanisms, but none have been confirmed. Here, we report the clinical, radiological and histopathologic features of Degos' disease in a 41-year-old man following streptococcal throat infection. Prior postulated hypothesis as post-infectious immunologic mechanism may be further supported by this case. PMID:21035145

  12. Streptococcal cellulitis following preparation of fresh raw seafood.

    PubMed

    Koh, T H; Sng, L-H; Yuen, S M; Thomas, C K; Tan, P L; Tan, S H; Wong, N S

    2009-05-01

    We describe three zoonotic streptococcal soft tissue infections resulting from fresh seafood contact. One was a localized thumb infection with Streptococcus iniae in an immunocompetent healthy young male resulting from a puncture wound from a crab pincer. The other two were cases of ascending upper limb cellulitis associated with bacteraemia in mastectomy patients. One of these infections was caused by S. iniae while the other was caused by Streptococcus dysgalactiae subsp. dysgalactiae, a species that has not been previously described as a cause of zoonotic infection. Hence when cleaning raw seafood, protective equipment should be used to minimize the risk of percutaneous injuries. PMID:19309483

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

    PubMed

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

    1999-01-01

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

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

    PubMed

    Squires, R L; Ellison, G C

    1986-08-01

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

  15. Identifying severe sepsis via electronic surveillance.

    PubMed

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

    2015-01-01

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

  16. Renal Mitochondrial Lipid Peroxidation during Sepsis

    PubMed Central

    Singh, P; Parajuli, N; Mayeux, PR; MacMillan-Crow, LA

    2016-01-01

    Sepsis can provoke kidney injury, which increases mortality. Human and animal studies have documented increased renal oxidative injury and mitochondrial damage during sepsis. However, few studies have attempted to dissect specific renal targets and/or types of oxidative injury using the cecal ligation and puncture (CLP) murine model of sepsis. The purpose of this short communication is to examine the extent of lipid peroxidation within renal mitochondria using CLP and blue native gel electrophoresis which separates intact mitochondrial respiratory complexes. Our results show that CLP induced increased 4-hydroxy-nonenal protein adduction (marker of lipid peroxidation) in renal homogenates and mitochondrial fractions. Blue native gel electrophoresis revealed that respiratory complex III was selectively targeted within mitochondrial fractions. This supports our prior report showing renal complex III inactivation following CLP. Future studies will identify specific renal proteins within complex III that are modified during sepsis to provide mechanistic insight on how mitochondrial respiration is inhibited during sepsis. PMID:27104220

  17. Mobilization in Severe Sepsis: An Integrative Review

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Suetrong, Bandarn; Walley, Keith R

    2016-01-01

    Increased blood lactate concentration (hyperlactatemia) and lactic acidosis (hyperlactatemia and serum pH < 7.35) are common in patients with severe sepsis or septic shock and are associated with significant morbidity and mortality. In some patients, most of the lactate that is produced in shock states is due to inadequate oxygen delivery resulting in tissue hypoxia and causing anaerobic glycolysis. However, lactate formation during sepsis is not entirely related to tissue hypoxia or reversible by increasing oxygen delivery. In this review, we initially outline the metabolism of lactate and etiology of lactic acidosis; we then address the pathophysiology of lactic acidosis in sepsis. We discuss the clinical implications of serum lactate measurement in diagnosis, monitoring, and prognostication in acute and intensive care settings. Finally, we explore treatment of lactic acidosis and its impact on clinical outcome. PMID:26378980

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  1. Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis.

    PubMed

    Mertineit, C; Samlalsingh-Parker, J; Glibetic, M; Ricard, G; Noya, F J; Aranda, J V

    2000-03-01

    Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS damage during neonatal meningitis. We tested (i) the hypothesis that cerebrovascular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive mediators such as prostaglandins and (or) nitric oxide (NO), and (iii) whether this impairment is preventable by specific and (or) nonspecific inhibitors: dexamethasone, ibuprofen, and Nomega-nitro-L-arginine, a NO inhibitor. Sterile saline or 10(9) colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets. CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon-tipped catheters placed in the aorta. GBS produced a narrow range of CBF autoregulation due to an impairment at the upper limit of CPP. We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GBS impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen, dexamethasone, and Nomega-nitro-L-arginine not only prevent this GBS-induced autoregulatory impairment but improve the range of cerebrovascular autoregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the induction of NO synthase gene expression. Thus, acute early onset GBS-induced impairment of the upper limit of CBF autoregulation can be correlated with increases of NO synthase production, suggesting that NO is a vasoactive mediator of CBF. PMID:10721813

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-03-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring postburn inflammation is of paramount importance but, so far, there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As interleukin 8 (IL-8) is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict postburn sepsis, infections, and mortality. Plasma cytokines, acute-phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days after injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure [MOF], and mortality) were recorded. A cutoff level for IL-8 was determined using receiver operating characteristic analysis. Statistical significance is set at P < 0.05. Receiver operating characteristic analysis identified a cutoff level of 234 pg/mL for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cutoff and stratified into high (H) (n = 133) and low (L) (n = 335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area burned and incidence of MOF (P < 0.001). In the H group, IL-8 levels were able to predict sepsis (P < 0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute-phase responses compared with the L group (P < 0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients. PMID:25514427

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

    PubMed Central

    2012-01-01

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

  5. Sepsis

    MedlinePlus

    ... the vital organs, and prevent a drop in blood pressure. Many patients receive oxygen and intravenous fluids. Other types of treatment, such as respirators or kidney dialysis, may be necessary. Sometimes, surgery is needed to clear up an infection. NIH: National Institute of General Medical Sciences

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2014-04-01

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

  8. Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans

    PubMed Central

    Schultz, Aylit; Yuan, Hai-Tao; Christiani, David; Karumanchi, S. Ananth; Sukhatme, Vikas P

    2006-01-01

    Background Acute respiratory distress syndrome (ARDS) is a devastating complication of numerous underlying conditions, most notably sepsis. Although pathologic vascular leak has been implicated in the pathogenesis of ARDS and sepsis-associated lung injury, the mechanisms promoting leak are incompletely understood. Angiopoietin-2 (Ang-2), a known antagonist of the endothelial Tie-2 receptor, was originally described as a naturally occurring disruptor of normal embryonic vascular development otherwise mediated by the Tie-2 agonist angiopoietin-1 (Ang-1). We hypothesized that Ang-2 contributes to endothelial barrier disruption in sepsis-associated lung injury, a condition involving the mature vasculature. Methods and Findings We describe complementary human, murine, and in vitro investigations that implicate Ang-2 as a mediator of this process. We show that circulating Ang-2 is significantly elevated in humans with sepsis who have impaired oxygenation. We then show that serum from these patients disrupts endothelial architecture. This effect of sepsis serum from humans correlates with measured Ang-2, abates with clinical improvement, and is reversed by Ang-1. Next, we found that endothelial barrier disruption can be provoked by Ang-2 alone. This signal is transduced through myosin light chain phosphorylation. Last, we show that excess systemic Ang-2 provokes pulmonary leak and congestion in otherwise healthy adult mice. Conclusions Our results identify a critical role for Ang-2 in disrupting normal pulmonary endothelial function. PMID:16417407

  9. Nephrilin peptide modulates a neuroimmune stress response in rodent models of burn trauma and sepsis

    PubMed Central

    Mascarenhas, Desmond D; ElAyadi, Amina; Singh, Baljit K; Prasai, Anesh; Hegde, Sachin D; Herndon, David N; Finnerty, Celeste C

    2013-01-01

    Sepsis occurs three times more often in burns than in other types of trauma, suggesting an overlap or synergy between underlying immune mechanisms in burn trauma and sepsis. Nephrilin peptide, a designed inhibitor of mTORC2, has previously been shown to modulate a neuroimmune stress response in rodent models of xenobiotic and metabolic stress. Here we investigate the effect of nephrilin peptide administration in different rodent models of burn trauma and sepsis. In a rat scald burn model, daily subcutaneous bolus injection of 4 mg/kg nephrilin significantly reduced the elevation of kidney tissue substance P, S100A9 gene expression, PMN infiltration and plasma inflammatory markers in the acute phase, while suppressing plasma CCL2 and insulin C-peptide, kidney p66shc-S36 phosphorylation and PKC-beta and CGRP in dorsal root ganglia at 14 days (chronic phase). In the mouse cecal ligation and puncture model of sepsis, nephrilin fully protected mice from mortality between surgery and day 7, compared to 67% mortality in saline-treated animals, while significantly reducing elevated CCL2 in plasma. mTORC2 may modulate important neuroimmune responses in both burn trauma and sepsis. PMID:24273694

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

    PubMed Central

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

    2008-01-01

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

  11. Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection.

    PubMed

    Pavone, Piero; Bianchini, Rio; Parano, Enrico; Incorpora, Gemma; Rizzo, Renata; Mazzone, Luigi; Trifiletti, Rosario R

    2004-02-01

    The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection. PMID:14984902

  12. The changing immune system in sepsis

    PubMed Central

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

    2014-01-01

    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

  13. Biomarkers for late-onset neonatal sepsis.

    PubMed

    Polin, Richard A; Randis, Tara M

    2010-01-01

    The diagnosis of healthcare-associated infections is problematic because of the overlap between clinical signs associated with 'normal' physiological disturbances and those of bacteremia or fungemia. Earlier diagnosis of sepsis in critically ill infants would enable timely administration of antibiotics and discontinuation of treatment in infants with a low probability of sepsis. A recent study by Ng et al. identified two novel biomarkers for late-onset neonatal sepsis: the des-arginine variant of serum amyloid A and apolipoprotein C-II. These markers may be of value in the identification of neonates with bacteremia or fungemia. PMID:20828428

  14. Biomarkers for late-onset neonatal sepsis

    PubMed Central

    2010-01-01

    The diagnosis of healthcare-associated infections is problematic because of the overlap between clinical signs associated with 'normal' physiological disturbances and those of bacteremia or fungemia. Earlier diagnosis of sepsis in critically ill infants would enable timely administration of antibiotics and discontinuation of treatment in infants with a low probability of sepsis. A recent study by Ng et al. identified two novel biomarkers for late-onset neonatal sepsis: the des-arginine variant of serum amyloid A and apolipoprotein C-II. These markers may be of value in the identification of neonates with bacteremia or fungemia. PMID:20828428

  15. A prospective treatment for sepsis.

    PubMed

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

    Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7–89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06–1.43] vs. 1.50 [95%CI 1.30–1.71], respectively, rate ratio 0.82 [95%CI 0.67–1.01]; LOD 1.04 [95% CI 0.90–1.23] vs. 1.22 [95%CI 1.05–1.42], rate ratio 0.85 [95% CI 0.68–1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a probe to better quantify the burden of invasive GBS disease in low-middle resourced settings such as ours. From our study passive systems are important to monitor trends over time as long as they are interpreted with caution; active systems give better detailed information and will have greater representivity when expanded to other surveillance sites. PMID:27055184

  18. Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis

    PubMed Central

    Kountchev, Jordan; Bijuklic, Klaudija; Bellmann, Romuald; Wiedermann, Christian J; Joannidis, Michael

    2005-01-01

    Introduction In acute disseminated intravascular coagulation, the effect of antithrombin (AT) administration on elevated levels of D-dimer is not well established. In the present study, we report on changes in circulating levels of D-dimer in response to administration of AT in a series of patients with acquired AT deficiency due to severe sepsis. Methods Eight consecutive critically ill medical patients presenting with acute disseminated intravascular coagulation associated with severe sepsis/septic shock received a single bolus infusion of AT over 30 minutes, aiming to achieve physiological AT levels. Haemostatic parameters including D-dimer were assessed prior to, 6 and 24 h after AT administration. An average of 42 ± 9 U/kg body weight was infused. Results Following AT substitution, elevated levels of D-dimer fell whereas AT levels rose. Conclusion These observations support the notion that AT can favourably affect fibrin degradation accompanying disseminated intravascular coagulation of severe sepsis. PMID:16280058

  19. Post-streptococcal 'complex' movement disorders: unusual concurrence of psychogenic and organic symptoms.

    PubMed

    Squintani, Giovanna; Tinazzi, Michele; Gambarin, Mattia; Bravi, Elena; Moretto, Giuseppe; Buttiglione, Maura; Defazio, Giovanni; Martino, Davide

    2010-01-15

    Post-streptococcal neuropsychiatric disorders encompass a broad spectrum of movement disorders, including tics, stereotypies, dystonia and tremor. We report the case of a 15-year-old boy who presented with a relapsing-remitting combination of psychogenic and organic movement disorders. Both relapses occurred after an episode of streptococcal pharyngitis and consisted in motor and phonic tics, an atypical gait disorder, and severe worsening of a pre-existing psychogenic tremor of the right hand. After each relapse, both psychogenic and 'organic' symptoms concomitantly remitted after the administration of an association of oral steroids and antibiotics. The peculiarity of this case consists in the coexistence of psychogenic and organic symptoms subsequent to streptococcal infection, and broadens the clinical spectrum of post-streptococcal neuropsychiatric disorders. PMID:19896680

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

    PubMed

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

    2011-06-01

    Children with obsessive compulsive disorder or tic disorders that are associated with streptococcal infections (Group A beta-hemolytic) in the oro-pharyngeal region are given the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Tonsillectomy has been reported to resolve the neuro-psychiatric symptoms in these children. We have a case of a 9-year-old boy who was seen in our clinic with multiple recurrent streptococcal infections of the oro-pharyngeal cavity. He also exhibited neuro-psychiatric symptoms including agitation, hyperactivity, and tics. These symptoms followed his recurrent infections. Tonsillectomy was performed and in one year follow-up the patient did not have any recurrent streptococcal infections, and his neuro-psychiatric symptoms resolved completely. Guidelines for medical and surgical management of recurrent strep infections in the face of PANDAS are reviewed. PMID:21466900

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

    PubMed Central

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

    2014-01-01

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

  2. Sepsis in Pregnancy: Identification and Management.

    PubMed

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

    2016-01-01

    Sepsis accounts for up to 28% of all maternal deaths. Prompt, appropriate treatment improves maternal and fetal morbidity and mortality. To date, there are no validated tools for identification of sepsis in pregnant women, and tools used in the general population tend to overestimate mortality. Once identified, management of pregnancy-associated sepsis is goal-directed, but because of the lack of studies of sepsis management in pregnancy, it must be assumed that modifications need to be made on the basis of the physiologic changes of pregnancy. Key to management is early fluid resuscitation and early initiation of appropriate antimicrobial therapy directed toward the likely source of infection or, if the source is unknown, empiric broad-spectrum therapy. Efforts directed at identifying the source of infection and appropriate source control measures are critical. Development of an illness severity scoring system and treatment algorithms validated in pregnant women needs to be a research priority. PMID:26825620

  3. Intracompartmental Sepsis With Burn: A Case Report.

    PubMed

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

    2016-03-01

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

  4. Improving the Odds of Surviving Sepsis

    MedlinePlus

    ... weak electric voltages to an acupuncture point on mice with a sepsis-like condition. The "electro-acupuncture" ... gland to produce the chemical dopamine, and the mice experienced reduced inflammation and greatly improved survival. But ...

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

    PubMed Central

    2014-01-01

    Introduction Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis. Methods Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥65 years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured. Results The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P < 0.05). Serum IL-6 levels in elderly sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P < 0.01). Ex vivo stimulation decreased CD25 expression, IL-2 production, and proliferation to a greater extent in CD4+ T cells from elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased detection of gram-negative bacteria at days 14–16 and 28–32 after sepsis (P < 0.05). Conclusions Persistent inflammation and T cell exhaustion may be associated with decreased survival in elderly patients and mice after sepsis. PMID:24962182

  6. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

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

  7. Clinical features and outcome of bone and joint infections with streptococcal involvement: 5-year experience of interregional reference centres in the south of France.

    PubMed

    Seng, P; Vernier, M; Gay, A; Pinelli, P-O; Legré, R; Stein, A

    2016-07-01

    Streptococcal bone and joint infections are less common than staphylococcal cases. Few studies have reported the cases with well-identified Streptococcus species. Their clinical features and prognosis are not clearly known to date. Moreover, no treatment regimen has yet been clarified. We reviewed the streptococcal bone and joint infection cases managed in our centres from January 2009 to December 2013. We described the epidemiology, clinical and microbiologic characteristics, treatment approach and outcome. Among the 93 cases, 83% of patients were men with a median age of 60 years, and 90% of patients had comorbidities or risk factors. Bacteraemia occurred in 14% of cases. Serious complications occurred in six patients, including severe sepsis (two cases) and infective endocarditis (two cases). Orthopaedic device infections were observed in 35% of cases, including 17 patients with internal osteosynthesis device infection, 14 with prosthetic joint infection and three with vertebral osteosynthesis device infection. The median time between orthopaedic device implantation and onset of infection was 447 days. Fourteen species of Streptococcus were identified, including 97 isolates using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and three isolates using molecular identification. The five most represented species included S. agalactiae (37%), S. dysgalactiae (12%), S. anginosus (11%), S. constellatus (10%) and S. pneumoniae (9%). Streptococci isolates were susceptible to amoxicillin, with the exception of one S. mitis isolate. Remission 1 year after the end of treatment was recorded in 83%. One patient died of infection; eight patients had infections that failed to respond to treatment; and seven patients experienced relapse. Twenty patients (22%) had an unfavourable functional outcome, including 19 amputations and one arthrodesis. Five significant prognostic factors associated with an unfavourable clinical outcome were identified, including peripheral neuropathy (p 0.009), peripheral arterial disease (p 0.019), diabetes mellitus (p 0.031), location in the femur (p 0.0036), location in the foot (p 0.0475), osteitis without an orthopaedic device (p 0.041) and infection caused by S. dysgalactiae (p 0.020). The rate of poor outcomes remains high despite the low number of Streptococcus isolates resistant to antibiotics. Some prognostic factors, such as the presence of S. dysgalactiae, are associated with an unfavourable clinical outcome. Antibiotic regimens of streptococcal bone and joint infections are not standardized and need to be further investigated. PMID:27222712

  8. Sepsis: From Pathophysiology to Individualized Patient Care.

    PubMed

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

    2015-01-01

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

  9. Physician-led sepsis quality improvement team.

    PubMed

    Hampe, Holly M

    2015-01-01

    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 (e.g., 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 (i.e., 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

  10. Hospital variations in severe sepsis mortality.

    PubMed

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

    2015-01-01

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

  11. [Sepsis. Update on pathophysiology, diagnostics and therapy].

    PubMed

    Bauer, M; Brunkhorst, F; Welte, T; Gerlach, H; Reinhart, K

    2006-08-01

    Sepsis results from the host response to infection. While a localized and controlled inflammatory reaction helps to control infection, a dysregulated response may lead to multiple organ failure and determines the course and prognosis of the septic patient. Despite intensive care, mortality remains as high as 54% for severe sepsis and septic shock. As the mechanisms are becoming better defined, interventions aiming to interfere with the host response have been undertaken, largely with disappointing results. Thus, many evidence-based recommendations suggest waiving of resource-consuming interventions. Nevertheless, several seminal studies have indicated that early and systematic supportive therapy according to pathophysiological principles, most notably early goal-directed therapy, low-dose hydrocortisone and activated protein C, can disrupt dysfunctional cascades and can favourably influence the course of the disease. In parallel, efforts to better define nationwide epidemiology and treatment habits for severe sepsis by the German competence network "SepNet" indicate that therapy of severe sepsis is generally in poor compliance with guidelines, while the personal perception of physicians in charge would suggest high rates of adherence. Thus, strategies of change management, such as implementation of sepsis bundles are warranted to achieve a better standard of care toward the aim of the "surviving sepsis campaign", i.e. a reduction of mortality by 25% within the next 5 years. PMID:16810538

  12. Sepsis: From Pathophysiology to Individualized Patient Care

    PubMed Central

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

    2015-01-01

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

  13. Etiology of pediatric fever in western Kenya: a case-control study of falciparum malaria, respiratory viruses, and streptococcal pharyngitis.

    PubMed

    O'Meara, Wendy P; Mott, Joshua A; Laktabai, Jeremiah; Wamburu, Kabura; Fields, Barry; Armstrong, Janice; Taylor, Steve M; MacIntyre, Charles; Sen, Reeshi; Menya, Diana; Pan, William; Nicholson, Bradly P; Woods, Christopher W; Holland, Thomas L

    2015-05-01

    In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1-3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed. PMID:25758648

  14. Streptococcal M1 protein constructs a pathological host fibrinogen network

    PubMed Central

    Macheboeuf, Pauline; Buffalo, Cosmo; Fu, Chi-yu; Zinkernagel, Annelies S.; Cole, Jason N.; Johnson, John E.; Nizet, Victor; Ghosh, Partho

    2012-01-01

    M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen (Fg) that, unlike M1 or Fg alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the M1-Fg complex. A conformationally dynamic coiled-coil dimer of M1 was found to organize four Fg molecules into a specific cross-like pattern. This pattern supported the construction of a supramolecular network that was required for neutrophil activation but was distinct from a fibrin clot. Disruption of this network into other supramolecular assemblies was not tolerated. These results have bearing on the pathophysiology of streptococcal toxic shock. PMID:21475196

  15. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

    PubMed

    LaRock, Christopher N; Nizet, Victor

    2015-11-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Witkowski, J A; Parish, L C

    1982-10-01

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

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

    PubMed Central

    LaRock, Christopher N.; Nizet, Victor

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. Pediatric sepsis: preparing for the future against a global scourge.

    PubMed

    Riley, Carley; Basu, Rajit K; Kissoon, Niranjan; Wheeler, Derek S

    2012-10-01

    Sepsis is a leading cause of morbidity and mortality among children worldwide. As consensus statements emerge regarding early recognition and goal-directed management of sepsis, scrutiny should be given to the unique characteristics of sepsis in children. Pediatric patients are not small adults! Sepsis epidemiology, pathophysiology, and management strategy can vary significantly from those for adults. Herein, we describe the epidemiology of pediatric sepsis, in both resource-rich and resource-poor worlds, and discuss how the pathophysiology of pediatric sepsis differs from that for adults. We discuss the timeline of management of pediatric sepsis, studying how discoveries over the past 50 years have changed the way sepsis is treated. Finally, we discuss the future of pediatric sepsis. We focus on approaches that carry the most substantive impact on the global burden of disease. PMID:22864953

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

    PubMed Central

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

    2015-01-01

    Background Early recognition and timely intervention significantly reduce sepsis-related mortality. Objective Describe the development, implementation and impact of an Early Warning and Response System (EWRS) for Sepsis. Design After tool derivation and validation, a pre/post study with multivariable adjustment measured impact. Setting Urban academic healthcare system Patients Adult non-ICU patients admitted to acute inpatient units from: 10/01–10/31/2011 for tool derivation, 06/06–07/05/2012 for tool validation, and 06/06–09/04/2012 and 06/06–09/04/2013 for the pre/post analysis. Intervention An EWRS in our electronic health record monitored laboratory values and vital signs in real time. If a patient had >= 4 predefined abnormalities at any one time, the provider, nurse, and rapid response coordinator were notified and performed an immediate bedside patient evaluation. Measurements Screen positive rates, test characteristics, predictive values and likelihood ratios; system utilization; and resulting changes in processes and outcomes. Results The tool’s screen positive, sensitivity, specificity, and positive and negative predictive values and likelihood ratios for our composite of intensive care unit (ICU) transfer, rapid response team call or death in the derivation cohort was 6%, 16%, 97%, 26%, 94%, 5.3 and 0.9, respectively. Validation values were similar. The EWRS resulted in a statistically significant increase in early sepsis care, ICU transfer, and sepsis documentation, and decreased sepsis mortality and increased discharge to home, although neither of these latter two findings reached statistical significance. Conclusions An automated prediction tool identified at risk patients and prompted a bedside evaluation resulting in more timely sepsis care, improved documentation, and a suggestion of reduced mortality. PMID:25263548

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

    The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785–0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores. PMID:24303815

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

    PubMed Central

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

    2013-01-01

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

  7. Streptococcal necrotising fasciitis from diverse strains of Streptococcus pyogenes in tropical northern Australia: case series and comparison with the literature

    PubMed Central

    Hassell, Marilyn; Fagan, Peter; Carson, Phillip; Currie, Bart J

    2004-01-01

    Background Since the mid-1980's there has been a worldwide resurgence of severe disease from group A streptococcus (GAS), with clonal clusters implicated in Europe and the United States. However GAS associated sepsis and rheumatic fever have always remained at high levels in many less developed countries. In this context we aimed to study GAS necrotising fasciitis (NF) in a region where there are high background rates of GAS carriage and disease. Methods We describe the epidemiology, clinical and laboratory features of 14 consecutive cases of GAS NF treated over a seven year period from tropical northern Australia. Results Incidence rates of GAS NF in the Aboriginal population were up to five times those previously published from other countries. Clinical features were similar to those described elsewhere, with 7/14 (50%) bacteremic and 9/14 (64%) having associated streptococcal toxic shock syndrome. 11/14 (79%) had underlying chronic illnesses, including all four fatalities (29% mortality overall). Important laboratory differences from other series were that leukocytosis was absent in 9/14 (64%) but all had substantial lymphopenia. Sequence typing of the 14 NF-associated GAS isolates showed no clonality, with only one emm type 1 and two emm type 3 strains. Conclusions While NF clusters can occur from a single emergent GAS clone, this was not evident in our tropical region, where high rates of NF parallel high overall rates of GAS infection from a wide diversity of strains. The specific virulence factors of GAS strains which do cause NF and the basis of the inadequate host response in those patients who develop NF on infection with these GAS require further elucidation. PMID:15601476

  8. Biomarkers for late-onset neonatal sepsis: cytokines and beyond.

    PubMed

    Ng, Pak C; Lam, Hugh S

    2010-09-01

    Acute phase reactants, pro and antiinflammatory mediators including chemokines and cytokines, and cell-surface antigens are nonspecific biomarkers that have been extensively studied for the diagnosis and management of late-onset neonatal sepsis (LONS) and necrotizing enterocolitis. It is expected that the next generation of biomarkers and tests will be more specific, will pinpoint the precise disease entity, and will provide crucial information on the exact pathogen or category of microorganism and its antibiotic profile within hours of clinical presentation. Research on molecular pathogen detection and proteomic profiling has shown promising results. Academic-industry partnerships are vital for successful development of new diagnostic biomarkers for LONS, which are sensitive, inexpensive, fully automated, and easy to measure, allowing a quick turnaround time for clinical decision making. PMID:20813273

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. A blueprint for a sepsis protocol.

    PubMed

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

    2005-04-01

    Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is viewed. Although complex and challenging, these therapies must be brought to the patient's bedside. We propose and describe the Multiple Urgent Sepsis Therapies (MUST) protocol as a practical way to implement a comprehensive treatment plan using available evidence-based therapies. PMID:15805328

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

    PubMed Central

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

    1990-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Sepsis guidelines: Suggestions to improve adherence.

    PubMed

    Kissoon, Niranjan

    2015-06-01

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

  17. Anticoagulant modulation of inflammation in severe sepsis

    PubMed Central

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

    2015-01-01

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

  18. Role of immunoglobulins in neonatal sepsis

    PubMed Central

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

    2015-01-01

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

  19. Host innate immune responses to sepsis

    PubMed Central

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

    2014-01-01

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

  20. Group A streptococcal tonsillopharyngitis: cost-effective diagnosis and treatment.

    PubMed

    Pichichero, M E

    1995-03-01

    Most patients who seek medical attention for sore throat are concerned about streptococcal tonsillopharyngitis, but fewer than 10% of adults and 30% of children actually have a streptococcal infection. Group A beta-hemolytic streptococci (GAS) are most often responsible for bacterial tonsillopharyngitis, although Neisseria gonorrhea, Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum), Chlamydia pneumoniae (TWAR agent), and Mycoplasma pneumoniae have also been suggested as possible, infrequent, sporadic pathogens. Viruses or idiopathic causes account for the remainder of sore throat complaints. Reliance on clinical impression to diagnose GAS tonsillopharyngitis is problematic; an overestimation of 80% to 95% by experienced clinicians typically occurs for adult patients. Overtreatment promotes bacterial resistance, disturbs natural microbial ecology, and may produce unnecessary side effects. Existing data suggest that rapid GAS antigen testing as an aid to clinical diagnosis can be very useful. When used appropriately, it is sensitive (79% to 88%) in detecting GAS-infected patients and is specific (90% to 96%) and cost-effective. Penicillin has been the treatment of choice for GAS tonsillopharyngitis since the 1950s; 10 days of treatment are necessary for bacterial eradication. A single IM injection of benzathine penicillin is effective and obviates compliance issues. Until the early 1970s, the bacteriologic failure rate for the treatment of GAS tonsillopharyngitis ranged from 2% to 10% and was attributed to chronic GAS carriers. Since the late 1970s, the penicillin failure rate has frequently exceeded 20% in published reports. Explanations for recurrent GAS tonsillopharyngitis include poor patient compliance; reacquisition from a family member or peer, copathogenic colonization by Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, anaerobes that inactivate penicillin with beta-lactamase, or all these organisms; suppression of natural immune response by too-early administration of antibiotics; GAS tolerance to penicillin; antibiotic eradication of normal pharyngeal flora that normally act as natural host defenses; and establishment of a true carrier state. When therapy fails, milder symptoms may occur during the relapse. Several antimicrobials have demonstrated superior efficacy compared with penicillin in eradicating GAS and are administered less frequently to enhance patient compliance. In previously untreated GAS throat infections, cephalosporins produce a 5% to 22% higher bacteriologic cure rate; after a penicillin treatment failure, these differences are greater. Amoxicillin/clavulanate and the extended-spectrum macrolides clarithromycin and azithromycin may also produce enhanced bacteriologic eradication in comparison to penicillin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7864482

  1. Current concept of abdominal sepsis: WSES position paper

    PubMed Central

    2014-01-01

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

  2. Neutrophil Cd64 as a Diagnostic Marker in Neonatal Sepsis

    PubMed Central

    Streimish, Iris; Bizzarro, Matthew; Northrup, Veronika; Wang, Chao; Renna, Sara; Koval, Nancy; Li, Fang-Yong; Ehrenkranz, Richard; Rinder, Henry M.; Bhandari, Vineet

    2012-01-01

    We assessed neutrophil CD64 as a diagnostic marker for neonatal sepsis. For early-onset sepsis, the CD64 index with a cut-point value of 2.38 had sensitivity, specificity and a negative predictive values of 100%, 68%, and 100%, respectively. For late-onset sepsis, the respective values were 3.62, 75%, 77%, and 96%. Neutrophil CD64 index can be incorporated as a valuable marker for excluding neonatal sepsis. PMID:22481422

  3. Molecular mechanisms in the pathogenesis of sepsis.

    PubMed

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

    2014-01-01

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

  4. Fluid Resuscitation in Sepsis: Reexamining the Paradigm

    PubMed Central

    Tirupakuzhi Vijayaraghavan, Bharath Kumar; Cove, Matthew Edward

    2014-01-01

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

  5. Fatal Yersinia enterocolitica sepsis after blood transfusion.

    PubMed

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

    1985-11-01

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

  6. The Use of Fluids in Sepsis.

    PubMed

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

    2016-01-01

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

  7. The Use of Fluids in Sepsis

    PubMed Central

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

    2016-01-01

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

  8. Hepatosplanchnic circulation in cirrhosis and sepsis

    PubMed Central

    Prin, Meghan; Bakker, Jan; Wagener, Gebhard

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-08-01

    In this incidence study, of 16 074 patients admitted to the intensive care unit (ICU) from 1/1/2003 to 7/31/2011, 161 cases of candidemia were identified. The incidence of sepsis (27%), severe sepsis (31%), and septic shock (40%) was remarkably high in these cases of candidemia, as was the all-cause in-hospital mortality for sepsis (30%), severe sepsis (44%), and septic shock (65%). PMID:25811137

  11. Soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) in neonatal sepsis: new clinical and analytical perspectives for two old biomarkers.

    PubMed

    Mussap, Michele; Noto, Antonio; Fravega, Marco; Fanos, Vassilios

    2011-10-01

    Several biochemical markers have been proposed over the past years to manage critically ill newborns with acute inflammation and sepsis. The state of the art in diagnosing and monitoring neonatal sepsis, severe sepsis and septic shock consists of the measurement of plasma C-reactive protein (CRP) and procalcitonin (PCT) at the onset and in the course of the disease. CRP and PCT in combination are clinically significant in diagnosing and monitoring septic newborns; however, CRP and PCT have a very limited value for risk stratification and in predicting outcome. The availability of commercial methods for the automated measurement of the soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) represent a challenge for the evaluation in clinical practice of reliable markers of neonatal sepsis, specifically for the very early diagnosis, the classification into class of severity, and the prediction of complications and death. PMID:21740312

  12. Clinical Characteristics of Community-Acquired Viridans Streptococcal Pneumonia

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2003-01-01

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

  14. [Management of severe invasive group A streptococcal infections].

    PubMed

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

    2014-11-01

    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 β-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

  15. Pressure Sensitivity of Streptococcal Growth in Relation to Catabolism

    PubMed Central

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

    1971-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2001-11-24

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

  19. Group B streptococcal epidemiology and vaccine needs in developed countries.

    PubMed

    Melin, Pierrette; Efstratiou, Androulla

    2013-08-28

    Development of a group B streptococcal vaccine (GBS) vaccine is the most promising approach for the prevention of GBS infections in babies, given the potential adverse effects of intrapartum antibiotic prophylaxis as well as the need for effective prevention of both adult and late perinatal disease. There are numerous prevention strategies at this time but none are 100% effective in the eradication of neonatal early onset GBS disease and there are no preventative strategies for late onset disease. The need for a GBS vaccine is therefore, of utmost importance. Efforts applying genomics to GBS vaccine development have led to the identification of novel vaccine candidates. The publication of GBS whole genomes coupled with new technologies including multigenome screening and bioinformatics has also allowed researchers to overcome the serotype limitation of earlier vaccine preparations in the search of a universal effective vaccine against GBS. This review brings together the key arguments concerning the potential need of a GBS vaccine in developed countries and describes the current status with GBS epidemiology and microbiology in these countries. PMID:23973345

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

    PubMed Central

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

    1976-01-01

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

  1. Case report: group B streptococcal bacteremia and sacroiliitis after mid-trimester dilation and evacuation.

    PubMed

    McKenna, T; O'Brien, K

    2009-09-01

    Group B streptococcal bacteremia with septic arthritis is a rare complication of second trimester dilation and evacuation, and may cause substantial post-operative morbidity. A 37-year-old gravida 4 para 1-0-2-1 presented with fever and right hip pain on post-operative day 11 from a second trimester dilation and evacuation for fetal trisomy 21. She was initially found to have septic arthritis involving the right sacroiliac joint and group B streptococcal bacteremia. Transesophageal echocardiogram showed a tricuspid valve, vegetation consistent with endocarditis. After prolonged parenteral antibiotic therapy, she developed septic pulmonary emboli that were successfully treated with anticoagulation therapy. Group B streptococcal infection is a potentially serious post-abortion complication that can cause sacroiliitis, endocarditis and septic pulmonary emboli. PMID:19710658

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

    PubMed

    Bloos, Frank

    2015-01-01

    Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can be given. PMID:25319792

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. Role of biomarkers in sepsis care

    PubMed Central

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

    2013-01-01

    Sepsis is one of the leading causes of mortality and morbidity, even with the current availability of extended spectrum antibiotics and advanced medical care. Biomarkers offer a tool in facilitating early diagnosis, in identifying patient populations at high risk of complications, and in monitoring progression of the disease, which are critical assessments for appropriate therapy and improvement in patient outcomes. Several biomarkers are already available for clinical use in sepsis; however, their effectiveness in many instances is limited by the lack of specificity and sensitivity to characterize the presence of an infection and the complexity of the inflammatory and immune processes, and to stratify patients into homogenous groups for specific treatments. Current advances in molecular techniques have provided new tools facilitating the discovery of novel biomarkers, which can vary from metabolites and chemical products present in body fluids to genes and proteins in circulating blood cells. The purpose of this review is to examine the current status of sepsis biomarkers, with special emphasis on emerging markers, which are undergoing validation and may transition into clinical practice for their informative value in diagnosis, prognosis or response to therapy. We will also discuss the new concept of combination biomarkers and biomarker risk models, their existing challenges, and their potential use in the daily management of the sepsis patients. PMID:24088989

  7. Effective Biomarkers for Diagnosis of Neonatal Sepsis.

    PubMed

    Bhandari, Vineet

    2014-09-01

    Infection in neonates continues to be a global problem with significant morbidity and mortality. The diagnosis of neonatal sepsis is complicated by nonspecific clinical symptomatology, a high-false negative rate, and a delay in obtaining blood culture results. An ideal biomarker needs to have a high degree of accuracy in recognizing the presence or absence of definite infection at an early stage, to guide the initiation and duration of antibiotic therapy. The diagnostic utility of the following biomarkers seems to be most practical in the early (interleukin [IL]-6, IL-8, tumor necrosis factor-alpha, neutrophil CD64), mid (procalcitonin) and late (C-reactive protein) phases of neonatal sepsis. Future research studies to assess reliability of these biomarkers should be (1) adequately powered for sample size and (2) use the gold-standard definition of blood-culture proven pathogen-specific sepsis. Significant advances in diagnostic accuracy of novel biomarkers to allow early, accurate, and cost-effective identification of pathogens responsible for neonatal sepsis is anticipated in the next 5 years. PMID:26625387

  8. Clinical review: Blood purification for sepsis

    PubMed Central

    2011-01-01

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

  9. Leclercia adecarboxylata Sepsis and Cerebral Herniation.

    PubMed

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

    2014-03-01

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

  10. [Pharmaconutrition with parenteral selenium in sepsis].

    PubMed

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. PMID:24021703

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Gimzal, Aylan; Topçuoğlu, Volkan; Yazgan, M Yanki

    2002-01-01

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

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

    PubMed Central

    Colling, R G; Brown, J C

    1981-01-01

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

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

    DOEpatents

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

    2009-09-15

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

  15. From juvenile parkinsonism to encephalitis lethargica, a new phenotype of post-streptococcal disorders: case report.

    PubMed

    Beleza, Pedro; Soares-Fernandes, João; Jordão, Maria J; Almeida, Fátima

    2008-11-01

    We report the case of a 16-year-old boy presented with a mild akinetic-rigid parkinsonism shortly after a post-streptococcal infection. After stopping corticoids, he had a rapid neurological deterioration to a fatal encephalitis lethargica-like syndrome. Serum analysis demonstrated consistently elevated anti-streptolysin-O. This case illustrates a new severe phenotype in the spectrum of the post-streptococcal disorders. This etiology should be considered in the differential diagnosis of a movement disorder with a rapid detrimental evolution. PMID:18221898

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

    PubMed Central

    Tarakçı, Nuriye; Dağı, Hatice Türk; Uğur, Ayşe Rüveyda; Tuncer, İnci; Taştekin, Ayhan

    2014-01-01

    Apnea, cyanosis, lethargy and prolongation in capillary filling time developed on the postnatal 37th day in a preterm baby who was born at the 30th gestational week with a birth weight of 1 300 g. Acute phase reactants and immature/total neutrophil count ratio were found to be high. The patient who was diagnosed with sepsis was successfully treated with meropenem which was started empirically. In his blood culture Streptococcus pasteurianus grew. S. pasteurianus is in the subgroup of streptococcus bovis which is one of the D group streptococci and its previous name is S. bovis type II/2. In the literature, there are very few cases of neonatal infection related with this bacterium. As far as we know, this is first case of neonatal sepsis caused by S. pasteurianus in Turkey. In addition, we tried to determine the clinical properties of neonatal infections arising from S. pasteurianus by reviewing the literature. PMID:26078653

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

    PubMed

    Schorr, Christa A; Dellinger, R Phillip

    2014-04-01

    The Surviving Sepsis Campaign (SSC) was created in 2002 and consists of severe sepsis management guidelines and a sepsis performance improvement program. The second revision of the guidelines, published in 2013, are sponsored by 30 international scientific organizations and contain changes in recommendations for fluids and vasopressor administration. The new 3- and 6-hour sepsis 'bundles' (sets of care elements) include a software program that can be downloaded free from the Surviving Sepsis Campaign website (www.survivingsepsis.org). The traditional intensive care unit and emergency department champion-driven sepsis performance improvement program continues internationally with the kick off of a new grant-funded hospital floor sepsis performance improvement initiative. PMID:24698888

  18. Abdominal sepsis managed by leaving abdomen open.

    PubMed

    Duff, J H; Moffat, J

    1981-10-01

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

  19. Objective Sepsis Surveillance Using Electronic Clinical Data

    PubMed Central

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

    2016-01-01

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

  20. Prognostic utility and characterization of cell-free DNA in patients with severe sepsis

    PubMed Central

    2012-01-01

    Introduction Although sepsis is the leading cause of death in noncoronary critically ill patients, identification of patients at high risk of death remains a challenge. In this study, we examined the incremental usefulness of adding multiple biomarkers to clinical scoring systems for predicting intensive care unit (ICU) mortality in patients with severe sepsis. Methods This retrospective observational study used stored plasma samples obtained from 80 severe sepsis patients recruited at three tertiary hospital ICUs in Hamilton, Ontario, Canada. Clinical data and plasma samples were obtained at study inclusion for all 80 patients, and then daily for 1 week, and weekly thereafter for a subset of 50 patients. Plasma levels of cell-free DNA (cfDNA), interleukin 6 (IL-6), thrombin, and protein C were measured and compared with clinical characteristics, including the primary outcome of ICU mortality and morbidity measured with the Multiple Organ Dysfunction (MODS) score and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Results The level of cfDNA in plasma at study inclusion had better prognostic utility than did MODS or APACHE II scores, or the biomarkers measured. The area under the receiver operating characteristic (ROC) curves for cfDNA to predict ICU mortality is 0.97 (95% CI, 0.93 to 1.00) and to predict hospital mortality is 0.84 (95% CI, 0.75 to 0.94). We found that a cfDNA cutoff value of 2.35 ng/μl had a sensitivity of 87.9% and specificity of 93.5% for predicting ICU mortality. Sequential measurements of cfDNA suggested that ICU mortality may be predicted within 24 hours of study inclusion, and that the predictive power of cfDNA may be enhanced by combining it with protein C levels or MODS scores. DNA-sequence analyses and studies with Toll-like receptor 9 (TLR9) reporter cells suggests that the cfDNA from sepsis patients is host derived. Conclusions These studies suggest that cfDNA provides high prognostic accuracy in patients with severe sepsis. The serial data suggest that the combination of cfDNA with protein C and MODS scores may yield even stronger predictive power. Incorporation of cfDNA in sepsis risk-stratification systems may be valuable for clinical decision making or for inclusion into sepsis trials. PMID:22889177

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

    PubMed

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

    1984-03-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2015-09-01

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

  4. Cytokines and Signaling Molecules Predict Clinical Outcomes in Sepsis

    PubMed Central

    Fjell, Christopher D.; Thair, Simone; Hsu, Joseph L.; Walley, Keith R.; Russell, James A.; Boyd, John

    2013-01-01

    Introduction Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST) compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment) and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission. Hypothesis Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure. Methods Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups. Results Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks. Conclusions A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from small numbers of cytokines. Design of clinical trials and interventions may benefit from consideration of cytokine levels. PMID:24244449

  5. Towards Prevention of Acute Syndromes

    PubMed Central

    Ahmed, A.; Thongprayoon, C.; Pickering, B.W.; Akhoundi, A.; Wilson, G.; Pieczkiewicz, D.; Herasevich, V.

    2014-01-01

    Summary Background Identifying patients at risk for acute respiratory distress syndrome (ARDS) before their admission to intensive care is crucial to prevention and treatment. The objective of this study is to determine the performance of an automated algorithm for identifying selected ARDS predisposing conditions at the time of hospital admission. Methods This secondary analysis of a prospective cohort study included 3,005 patients admitted to hospital between January 1 and December 31, 2010. The automated algorithm for five ARDS predisposing conditions (sepsis, pneumonia, aspiration, acute pancreatitis, and shock) was developed through a series of queries applied to institutional electronic medical record databases. The automated algorithm was derived and refined in a derivation cohort of 1,562 patients and subsequently validated in an independent cohort of 1,443 patients. The sensitivity, specificity, and positive and negative predictive values of an automated algorithm to identify ARDS risk factors were compared with another two independent data extraction strategies, including manual data extraction and ICD-9 code search. The reference standard was defined as the agreement between the ICD-9 code, automated and manual data extraction. Results Compared to the reference standard, the automated algorithm had higher sensitivity than manual data extraction for identifying a case of sepsis (95% vs. 56%), aspiration (63% vs. 42%), acute pancreatitis (100% vs. 70%), pneumonia (93% vs. 62%) and shock (77% vs. 41%) with similar specificity except for sepsis and pneumonia (90% vs. 98% for sepsis and 95% vs. 99% for pneumonia). The PPV for identifying these five acute conditions using the automated algorithm ranged from 65% for pneumonia to 91 % for acute pancreatitis, whereas the NPV for the automated algorithm ranged from 99% to 100%. Conclusion A rule-based electronic data extraction can reliably and accurately identify patients at risk of ARDS at the time of hospital admission. PMID:24734124

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

    PubMed

    Arzanlou, Mohsen

    2016-04-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. The utility of affinity-tags for detection of a streptococcal protein from a variety of streptococcal species

    PubMed Central

    Zhou, Meixian; Fives-Taylor, Paula; Wu, Hui

    2008-01-01

    There is no systematic examination of affinity tag utility in Gram-positive bacteria, which limits the investigation of protein function in this important group of bacteria as specific antibodies for many of native proteins are generally not available. In this study, we utilized an E. coli-streptococcal shuttle vector pVT1666 and constructed two sets of expression plasmids pVPT-CTag and pVPT-NTag, with each set containing five affinity tags (GST, GFP, HSV, T7 and Nano) that can be fused to either the C- or N-terminus of a target protein. A putative glycosyltransferase (Gtf2) essential for Fap1 glycosylation was used to demonstrate the utility of the cassettes in detection of Gtf2 fusion proteins, and the biological relevance of the proteins in our working strain Streptococcus parasanguinis. GFP and T7 tags were readily expressed in S. parasanguinis as either an N- or C-terminal fusion to Gtf2. Only the C- terminal fusion of GST and HSV were able to be identified in S. parasanguinis. The Nano tag was not detected in either E. coli or S. parasanguinis. Genetic complementation experiments indicated that all the tagged Gtf2 fusion proteins could restore the Gtf2 function in the null mutant except for the Nano-tagged Gtf2 at its N-terminal fusion. Using a T7-tagged Gtf2 fusion construct, we demonstrated that the fusion cassette is also useful in detection of the fusion tag expression in other streptococci including S. mutans, S. pneumoniae and S. sanguinis. Therefore, the expression cassettes we constructed will be a useful tool not only to investigate protein-protein interactions in Fap1 biogenesis in S. parasanguinis, but also to study protein functions in other gram-positive bacteria in which pVT1666 replicates. PMID:18201786

  13. Staged exchange arthroplasty for shoulder sepsis.

    PubMed

    Seitz, William H; Damacen, Harvey

    2002-06-01

    Eight patients with shoulder sepsis were treated with staged exchange arthroplasty using antibiotic-impregnated polymethyl methacrylate spacers shaped and fitted to the patient's anatomy after extensive joint débridement. Intravenous antibiotic therapy followed for a minimum of 3 months. At the end of 6 months, the patients were evaluated for any clinical or laboratory signs of infection; none were encountered. Exchange prosthetic reconstructions were performed using standard implants fixed with antibiotic-impregnated polymethyl methacrylate cement. Three patients underwent a revision to total shoulder arthroplasty, whereas 5 underwent hemiarthroplasty of the humerus with local capsular flap covering of the glenoid. All patients experienced substantial pain relief and improvement in function despite limited total overhead motion, showing this technique to be a satisfactory salvage procedure for managing sepsis of the glenohumeral joint primarily and after total shoulder arthroplasty. PMID:12068401

  14. Lemierre's syndrome: two cases of postanginal sepsis.

    PubMed

    Lustig, L R; Cusick, B C; Cheung, S W; Lee, K C

    1995-06-01

    Lemierre's disease consists of suppurative thrombophlebitis of the IJV in the presence of oropharyngeal infection and can be complicated by septic pulmonary emboli. If a patient has an oropharyngeal or deep neck infection and neck pain suspicious for IJV thrombosis, a CT or MRI is warranted to establish the diagnosis. Blood cultures should be obtained to establish the responsible organism. In most cases F. necrophorum, an anaerobic bacterium, is responsible for the sepsis. Once the diagnosis of Lemierre's disease is made, long-term, high-dose intravenous antibiotics with beta-lactamase anaerobic activity should be initiated. In cases with persistent sepsis and emboli despite appropriate medical management, ligation or excision of the IJV should be performed. Finally, if there is clinical or radiologic evidence of retrograde cavernous sinus thrombosis, the use of anticoagulants should be considered. PMID:7777368

  15. Emergency department antimicrobial considerations in severe sepsis.

    PubMed

    Green, Robert S; Gorman, Sean K

    2014-11-01

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

  16. Sepsis and Meningitis due to Listeria Monocytogenes

    PubMed Central

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

    2007-01-01

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

  17. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

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

    2016-03-01

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

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

    PubMed

    Maslove, David M; Wong, Hector R

    2014-04-01

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

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

    PubMed

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

    2013-05-01

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

  20. Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury

    PubMed Central

    Patil, Naeem K.; Parajuli, Nirmala; Mayeux, Philip R.

    2014-01-01

    Acute kidney injury (AKI) is a complication of sepsis and leads to a high mortality rate. Human and animal studies suggest that mitochondrial dysfunction plays an important role in sepsis-induced multi-organ failure; however, the specific mitochondrial targets damaged during sepsis remain elusive. We used a clinically relevant cecal ligation and puncture (CLP) murine model of sepsis and assessed renal mitochondrial function using high-resolution respirometry, renal microcirculation using intravital microscopy, and renal function. CLP caused a time-dependent decrease in mitochondrial complex I and II/III respiration and reduced ATP. By 4 h after CLP, activity of manganese superoxide dismutase (MnSOD) was decreased by 50% and inhibition was sustained through 36 h. These events were associated with increased mitochondrial superoxide generation. We then evaluated whether the mitochondria-targeted antioxidant Mito-TEMPO could reverse renal mitochondrial dysfunction and attenuate sepsis-induced AKI. Mito-TEMPO (10 mg/kg) given at 6 h post-CLP decreased mitochondrial superoxide levels, protected complex I and II/III respiration, and restored MnSOD activity by 18 h. Mito-TEMPO also improved renal microcirculation and glomerular filtration rate. Importantly, even delayed therapy with a single dose of Mito-TEMPO significantly increased 96-h survival rate from 40% in untreated septic mice to 80%. Thus, sepsis causes sustained inactivation of three mitochondrial targets that can lead to increased mitochondrial superoxide. Importantly, even delayed therapy with Mito-TEMPO alleviated kidney injury, suggesting that it may be a promising approach to treat septic AKI. PMID:24500690

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

    PubMed Central

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

    2015-01-01

    Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis. PMID:24754535

  2. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study

    PubMed Central

    Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-01-01

    Objective To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Design Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients’ designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Setting Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Participants Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. Main outcome measure ‘Suspected infection’ was the established gold standard to assess clinical decision support clinimetric performance. Results A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying ‘suspected infection’ as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. Conclusion A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis. PMID:26688744

  3. Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

    PubMed Central

    Kojic, Dubravka; Siegler, Benedikt H; Uhle, Florian; Lichtenstern, Christoph; Nawroth, Peter P; Weigand, Markus A; Hofer, Stefan; Brenner, Thorsten

    2015-01-01

    Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects - i.e., sepsis induced immunosuppression - but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. PMID:25992320

  4. Anesthesia in a patient with undiagnosed salicylate poisoning presenting as intraabdominal sepsis.

    PubMed

    Chui, P T

    1999-05-01

    An 81-year-old woman with unintentional salicylate intoxication presented with features of sepsis, abdominal pain, and tenderness. Laparotomy was performed to rule out acute cholecystitis. Anesthesia was complicated by severe hypercarbia despite hyperventilation, and progressive cardiovascular and neurologic deterioration postoperatively. The adverse neurologic, respiratory, and hepatic effects of abdominal surgery and general anesthesia probably potentiated salicylate toxicity and increased patient morbidity. Anesthesiologists should be aware of the protean manifestations of salicylate poisoning and consider it as a cause of "medical abdomen." PMID:10434224

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

    PubMed Central

    Takeuchi, Muneyuki; Tachibana, Kazuya

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Oxidative mitochondrial damage is closely linked to inflammation and cell death, but low levels of reactive oxygen and nitrogen species serve as signals that involve mitochondrial repair and resolution of inflammation. More specifically, cytoprotection relies on the elimination of damaged mitochondria by selective autophagy (mitophagy) during mitochondrial quality control. This aim of this study was to identify and localize mitophagy in the mouse lung as a potentially upregulatable redox response to Staphylococcus aureus sepsis. Fibrin clots loaded with S. aureus (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-1β and TNF-α 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

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

    PubMed Central

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

    2014-01-01

    Background Oxidative mitochondrial damage is closely linked to inflammation and to cell death, but low levels of reactive oxygen and nitrogen species serve as signals that involve mitochondrial repair and resolution of inflammation. More specifically, cytoprotection relies on the elimination of damaged mitochondria by selective autophagy (mitophagy) during mitochondrial quality control. Objective To identify and localize mitophagy in mouse lung as a potentially up-regulatable redox response to S. aureus sepsis. Methods Anesthetized C57BL/6 and B6.129X1-Nfe2l2tm1Ywk/J (Nrf2−/−) mice had fibrin clots loaded with S. aureus (1×107 CFU) implanted abdominally. At the time of implantation, mice were given Vancomycin (6mg/kg) and fluid resuscitation. Mouse lungs were harvested at 0, 6, 24, and 48 hours for bronchoalveolar lavage (BAL), Western blot analysis and qRT-PCR. To localize mitochondria with autophagy protein LC3, we used lung immunofluorescence staining in LC3-GFP transgenic mice. Results In C57BL/6 mice, sepsis-induced pulmonary inflammation was detected by significant increases in mRNA for the inflammatory markers IL-1β and TNF-α at 6h and 24h respectively hours. BAL cell count and protein increased. Sepsis suppressed lung Beclin-1 protein, but not mRNA, suggesting activation of canonical autophagy. Notably sepsis also increased the LC3-II autophagosome marker, as well as the lung’s non-canonical autophagy pathway as evidenced by loss of p62, a redox-regulated scaffolding protein of the autophagosome. In LC3-GFP mice lungs, immunofluorescence staining showed co-localization of LC3-II to mitochondria, mainly in Type 2 epithelium and alveolar macrophages. In contrast, marked accumulation of p62, as well as attenuation of LC3-II in Nrf2 KO mice supported an overall decrease in autophagic turnover. Conclusions The down-regulation of canonical autophagy during sepsis may contribute to lung inflammation while the switch to non-canonical autophagy selectively removes damaged mitochondria and accompanies tissue repair and cell survival. Furthermore, mitophagy in the alveolar region appears to depend on activation of Nrf2. Thus, efforts to promote mitophagy may be a useful therapeutic adjunct for acute lung injury in sepsis. PMID:25450328

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

    PubMed Central

    Bodkin, Jennifer Victoria; Fernandes, Elizabeth Soares

    2013-01-01

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

  9. Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia

    PubMed Central

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

    2014-01-01

    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

  10. Public Awareness of Sepsis Is Low in Sweden

    PubMed Central

    Mellhammar, Lisa; Christensson, Bertil; Linder, Adam

    2015-01-01

    Background. Sepsis is a serious and common condition with high mortality and morbidity. The public awareness, knowledge, and perception of sepsis in Sweden are unknown. Methods. A survey was performed using an online interview distributed to adults, aged 18–74, between March 6 and 9, 2015. Results. A total of 1001 people responded to the survey. Twenty-one percent of participants had heard of sepsis, whereas more than 86% had heard of each of the other conditions listed; for example, stroke (95%), chronic obstructive pulmonary disease (COPD) (95%), and leukemia (92%). Of those who had heard of sepsis, 93% responded that it is an infection or blood poisoning in an open question. The respondents who had heard of each disease estimated its mortality. For sepsis, the mortality was estimated at an average of 30%, which was at the same level as estimated mortalities for prostate and breast cancer but lower than for stroke, COPD, and leukemia. Conclusions. The awareness and knowledge of sepsis is low. The mortality for sepsis is not as overestimated as for many other diseases. The lack of awareness of sepsis might be a target to improve the outcome for sepsis patients by reducing the prehospital delay and hence enable early interventions. An increased general awareness might also raise interest for funding for research in this area and for its priority in healthcare support. PMID:26634220

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-09-01

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

  13. Efficacy of traditional Chinese medicine on sepsis: a systematic review and Meta-Analysis

    PubMed Central

    Liang, Xiao; Zhou, Miao; Ge, Xin-Yu; Li, Cheng-Bao; Fang, Shang-Ping; Tang, Ling; Shao, Dong-Hua; Xu, Guo

    2015-01-01

    Background: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. Methods: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. Results: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU-stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = -0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-α [SMD = -0.61; 95% CI: -0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. Conclusion: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion. PMID:26884914

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

    PubMed Central

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

    2015-01-01

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

  15. MFHAS1 Is Associated with Sepsis and Stimulates TLR2/NF-κB Signaling Pathway Following Negative Regulation

    PubMed Central

    Zhong, Jing; Shi, Qi-Qing; Zhu, Min-Min; Shen, Jian; Wang, Hui-Hui; Ma, Duan; Miao, Chang-Hong

    2015-01-01

    Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) has a potential immunoregulatory role dependent on Toll-like receptors (TLRs). TLR2, associated with deleterious systemic inflammation, cardiac dysfunction, and acute kidney injury, acts synergistically in sepsis. The role of MFHAS1 in targeting TLR2 involved in sepsis has not been examined thus far. This study aimed to examine the relationship of MFHAS1 and sepsis, and the effect of MFHAS1 on the TLR2 signaling pathway. Blood samples were collected from eight sepsis patients after surgery and eight patients undergoing selective surgery to determine blood MFHAS1 levels. HEK 293 cells, RAW 264.7 macrophages and THP-1 monocytes were used to confirm the effect of MFHAS1 on TLR2 signaling pathway. Our study showed that blood MFHAS1 was significantly elevated in septic patients, and MFHAS1 was more increased in mononuclear cells from septic patients. Pam3CSK4 (TLR2 ligand) was found to induce MFHAS1 production in RAW 264.7 murine macrophages and THP-1 human monocytes in a time-dependent manner. MFHAS1 has dual effects on TLR2 signaling pathway and inflammation, i.e., inhibitory effect at 6 hours, and then stimulatory effect after 24 hours through the activation of TLR2/NF-κB signaling pathway, and MFHAS1 induced the phosphorylation of JNK and p38 after TLR2 stimulation. PMID:26599367

  16. Designing a Pediatric Severe Sepsis Screening Tool

    PubMed Central

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

    2014-01-01

    We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). “Gold standard” SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2 months. The 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

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

    PubMed Central

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

    2015-01-01

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

  18. Administration of bone marrow stromal cells in sepsis attenuates sepsis-related coagulopathy.

    PubMed

    Tan, Lifei; Huang, Yueyue; Pan, Xiaojun; Quan, Shichao; Xu, Shunyao; Li, Dequan; Song, Lijun; Zhang, Xiaomin; Chen, Wanzhou; Pan, Jingye

    2016-06-01

    Introduction Coagulopathy plays an important role in sepsis. The aim of this study was to determine whether bone marrow stromal cell (BMSC) administration could attenuate coagulopathy in sepsis. Materials and methods In vitro: endothelial cells were cultured with/without BMSCs for 6 h following LPS stimulation and were collected for thrombomodulin (TM) and endothelial protein C receptor (EPCR) measurements. In vivo: Thirty-six mice were randomized into sham, sepsis, and sepsis + BMSC groups (n = 12 each group). Sepsis was induced through cecal ligation and puncture (CLP). BMSC infusion was started at 6 h after CLP. Lung tissues and plasma samples were collected at 24 h after CLP for enzyme-linked immunosorbent assay (ELISA), quantitative real-time RT-PCR, western blot, and immunohistochemistry analysis. Results In vitro: BMSCs attenuated the decrease in TM and EPCR mRNA and protein expression levels in LPS-stimulated endothelial cells. In vivo: BMSC treatment decreased lung injury and mesenteric perfusion impairment, and ameliorated coagulopathy, as suggested by the reduction in elevated TF, vWF, and TAT circulation levels. BMSC infusion decreased TF mRNA transcription and protein expression levels in lung tissues, and increased TM and EPCR mRNA transcription and expression levels. Discussion BMSC administration attenuated coagulopathy, and decreased lung injury and mesenteric perfusion impairment in sepsis. Key messages BMSCs increased the expression of TM and EPCR from endothelium cells exposed to LPS in vitro. BMSC treatment attenuated lung injury and coagulopathy in the mice cecal ligation and puncture (CLP) model. BMSC administration-attenuated coagulopathy is related to the reduced expression of TF and increased expression of TM and EPCR. PMID:26969493

  19. Disruption of tight junctions during polymicrobial sepsis in vivo.

    PubMed

    Li, Qiurong; Zhang, Qiang; Wang, Chenyang; Liu, Xiaoxiang; Li, Ning; Li, Jieshou

    2009-06-01

    The disruption of intestinal epithelial tight junctions may result in barrier function dysfunction during polymicrobial sepsis. The pathophysiology of sepsis involves breakdown of barrier integrity, which correlates with adverse outcome during sepsis. However, the mechanisms underlying loss of barrier function in sepsis remain unknown. In the present study in mice, tight junction (TJ) structure was analysed by transmission electron microscopy; intestinal permeability was assessed using molecular tracer measurement; and the distribution of TJ proteins was investigated by immunofluorescence microscopy. The membrane microdomains of TJs were isolated using discontinuous sucrose density gradients and the expression of TJ proteins in these was determined by western blot. Immunofluorescence microscopy revealed that claudins 1, 3, 4, 5, and 8 were present predominantly in the microvillous surface of epithelial cells and along the lateral membranes of the cells; in sepsis, however, labelling of these proteins was present diffusely within cells and was no longer focused at the lateral cell boundaries. Moreover, the expression of claudin-2 was markedly up-regulated in sepsis. Using western blot analysis, we found that occludin and claudins were displaced from raft fractions to non-raft fractions in membrane microdomains of TJs in sepsis. In addition, the disruption of TJ structure was accompanied by increased intestinal permeability. Our results demonstrate for the first time that redistribution of TJ proteins in TJ membrane microdomains and redistribution of claudins in epithelial cells of the colon lead to alteration of TJ architecture and TJ barrier dysfunction during the development of polymicrobial sepsis. PMID:19235836

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

    PubMed

    Nasa, Prashant; Juneja, Deven; Singh, Omender

    2012-02-01

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

  1. Prognosis of AKI in malignant diseases with and without sepsis

    PubMed Central

    2013-01-01

    Background AKI significantly worsens prognosis of hospitalized patients. This is particularly the case in patients with sepsis. The risk for aquiring sepsis is significantly increased in malignant diseases. Aim of the present retrospective study was to analyze outcomes of tumor patients with sepsis and AKI. Methods One-thousand and seventeen patients, treated at the ICU of the Department of Nephrology and Rheumatology of the University Hospital Göttingen from 2009 to 2011 were retrospectively analyzed for mortality, sepsis, AKI, need for renal replacement therapy (dialysis) and malignancies. Results AKI occurred significantly more frequent in septic than in non-septic patients and in tumor as oposed to non-tumor patients. Mortaliy rates were higher in the respective latter groups. Mortality increased even further if patients suffered from a malignant disease with sepsis and AKI. Mortality rates peaked if dialysis treatment became mandatory. In non-solid tumors 100% of the patients died if they suffered drom sepsis and AKI. This was not the case in solid malignancies (mortality rate 56%). Conclusions We conclude that prognosis of tumor patients with AKI and sepsis is very poor. Mortality increases to almost 70% if diaylsis therapy is initiated. Non-solid tumors are associated with a 100% mortality if sepsis and AKI conincide. PMID:24168374

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

    PubMed

    de Oliveira, Sheila Knupp Feitosa; Pelajo, Christina Feitosa

    2010-03-01

    Despite more than a decade of studying pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), it is still not possible to confirm its existence and whether it is a poststreptococcal autoimmune disorder. Many controversies remain: the diagnostic criteria have not been validated, evidence of autoimmunity remains inconclusive, evidence of a genetic predisposition is weak, and streptococcal infections are common in childhood and could represent only a trigger of exacerbations of tics and obsessive-compulsive disorder. Patients who fit the PANDAS criteria appear to represent a subgroup of children with chronic tic disorder and/or obsessive-compulsive disorder who may experience symptom exacerbations after group A β-hemolytic streptococci infections; however, those infections are not the sole or even the most common antecedent of exacerbations. There is not enough evidence to support PANDAS as a unique clinical entity. PMID:21308506

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

    PubMed

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

    2000-06-01

    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

  4. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis.

    PubMed

    Cizmeci, Mehmet Nevzat; Kara, Semra; Kanburoglu, Mehmet Kenan; Simavli, Serap; Duvan, Candan Iltemur; Tatli, Mustafa Mansur

    2014-03-01

    Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism's access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min-max: 118.1-8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis. PMID:24424393

  5. Targeting HMGB1 in the treatment of sepsis

    PubMed Central

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

    2013-01-01

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

  6. Therapeutic potential of HMGB1-targeting agents in sepsis

    PubMed Central

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

    2008-01-01

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

  7. Improving the management and care of people with sepsis.

    PubMed

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

    2014-04-01

    Many hospitals struggle to implement the full sepsis care bundle, but research suggests that many patients with sepsis are transported to hospital by ambulance. In 2011, the Scottish Ambulance Service introduced a pre-hospital sepsis screening tool (PSST) to expedite sepsis identification and care delivery. However, ambulance clinicians have reported varying degrees of interest and enthusiasm from hospital staff during handover. Therefore, an online survey was set up to investigate medical and nursing staff perceptions and experiences of the introduction of a PSST. This article discusses the results, which show that participants perceive the PSST reduces time to treatment, improves continuity of care, benefits patients and is accurately applied by ambulance clinicians, but which also highlight problems with communication. The delivery of in-hospital and pre-hospital sepsis care is challenging, but simple measures such as improving and standardising communication and alert systems between ambulance services and receiving hospitals could improve the clinical effects of a PSST. PMID:24689480

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

    PubMed Central

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

    2005-01-01

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

  9. Coagulation dysfunction in sepsis and multiple organ system failure.

    PubMed

    Nimah, Marianne; Brilli, Richard J

    2003-07-01

    In patients diagnosed with sepsis, severe sepsis or septic shock, cytokine-mediated endothelial injury, and TF activation initiate a cascade of events that culminate in the development of coagulation dysfunction characterized as procoagulant and antifibrinolytic. This abnormal state predisposes the patient to develop microvascular thrombosis, tissue ischemia, and organ hypoperfusion. Multiple organ dysfunction syndrome may be a product of this pertubation in coagulation regulation. Treatments aimed at correcting this coagulation dysfunction have met with mixed success. Current data suggest that AT III replacement therapy has limited efficacy in adults with severe sepsis. In contrast, adult patients diagnosed with severe sepsis and organ failure and treated with aPC (drotrecogin alfa activate) have a significantly reduced risk of death when compared with placebo-treated patients. A phase III trial examining the efficacy of protein C replacement therapy in pediatric patients with severe sepsis and organ failure is underway. PMID:12848314

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

    PubMed Central

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

    2012-01-01

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

  11. The Economic and Humanistic Burden of Severe Sepsis.

    PubMed

    Tiru, Bogdan; DiNino, Ernest K; Orenstein, Abigail; Mailloux, Patrick T; Pesaturo, Adam; Gupta, Abhinav; McGee, William T

    2015-09-01

    Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases "severe sepsis" and "septic shock" and the MeSH terms "epidemiology", "statistics", "mortality", "economics", and "quality of life". Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use. PMID:25935211

  12. Hypomagnesemia in Critically Ill Sepsis Patients.

    PubMed

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

    2015-12-01

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

  13. Lactoferrin for prevention of neonatal sepsis

    PubMed Central

    Turin, Christie G.; Zea-Vera, Alonso; Pezo, Alonso; Cruz, Karen; Zegarra, Jaime; Bellomo, Sicilia; Cam, Luis; Llanos, Raul; Castañeda, Anne; Tucto, Lourdes; Ochoa, Theresa J.

    2015-01-01

    Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF´s role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide. PMID:24935001

  14. The effects of the rapid strep test on physician management of streptococcal pharyngitis.

    PubMed

    Bryars, C H; deGruy, F V; Dickinson, L C; Waller, A M

    1991-01-01

    Management of pharyngitis remains an important and controversial subject. A retrospective chart review at the University of South Alabama Family Practice Center was undertaken to assess changes in physician prescribing and testing patterns since the advent of rapid testing of streptococcal pharyngitis (rapid strep tests [RST]). Charts for study were identified by encounter form coding of a diagnosis of streptococcal pharyngitis or pharyngitis not otherwise specified. Control and test groups were formed based on the availability of the RST, and a stratified sample was drawn from each group. In the group of patients studied after the RST became available, data analysis showed a significantly increased likelihood that patients received antibiotics with a positive RST (odds ratio [OR] = 6.42), whereas those patients with a negative or no RST were significantly less likely to receive antibiotics (OR = 2.50 and 2.48, respectively). Group assignment was a significant predictor of test-ordering behavior (P less than 0.05). A higher than expected rate of streptococcal pharyngitis was noted in the group of patients who had the RST available to them. The RST plays an important though not fully defined role in the current management of pharyngitis. PMID:2053452

  15. Induction of human gamma interferon by structurally defined polypeptide fragments of group A streptococcal M protein.

    PubMed Central

    Weigent, D A; Beachey, E H; Huff, T; Peterson, J W; Stanton, G J; Baron, S

    1984-01-01

    The presence of interferon (IFN) has been demonstrated previously (i) in fluids obtained from the middle ears of children with Streptococcus pneumoniae infections, (ii) from the serum of mice injected intraperitoneally with either S. pneumoniae or Streptococcus pyogenes, and (iii) from human lymphoid cell cultures treated with a variety of bacteria. In this study, we showed that highly purified peptic extracts of three different serotypes of group A streptococcal M protein (pep M5, pep M6, and pep M24) stimulated human peripheral leukocytes to produce IFN. IFN production was apparent by 10 h and peaked 24 h after exposure. Dose-response experiments indicated that IFN could be detected in cultures treated with concentrations of M protein as low as 6 micrograms/ml, whereas maximum IFN production occurred at a concentration of 200 micrograms/ml. The IFN had antigenic and physicochemical characteristics of IFN-gamma. Preliminary leukocyte fractionation studies revealed that the IFN-producing cell was a nonadherent lymphocyte with receptors for sheep erythrocytes (T cell). Rabbit antisera specific for these structurally defined polypeptide fragments of streptococcal M protein (pep M5, pep M6, and pep M24) blocked IFN induction by each of the polypeptides. The data suggest that the different serotypes of streptococcal M protein may induce IFN by a common structural determinant shared by each of the polypeptide fragments tested. PMID:6418655

  16. Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants.

    PubMed

    Pavone, Piero; Parano, Enrico; Rizzo, Renata; Trifiletti, Rosario R

    2006-09-01

    Streptococcal infection in children is usually benign and self-limited. In a small percentage of children, prominent neurologic and/or psychiatric sequelae can occur. Sydenham chorea is the best defined and best recognized. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a group A beta-hemolytic streptococcal infection. PANDAS constitutes a subset of children with tics, Tourette syndrome, and obsessive-compulsive disorder. In addition to strictly defined PANDAS, we and others have recognized several PANDAS variants, including adult-onset variant, a dystonic variant, a myoclonic variant, and a "chronic" PANDAS variant. The nosology and classification of these entities are rapidly evolving. The recognition that some pediatric neurobehavioral syndromes have infectious and/or immunologic triggers points to important new avenues of disease treatment. In this review, we summarize this complex and rapidly evolving area of clinical research. PMID:16970875

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

    PubMed

    Pavone, P; Rapisarda, V; Serra, A; Nicita, F; Spalice, A; Parano, E; Rizzo, R; Maiolino, L; Di Mauro, P; Vitaliti, G; Coco, A; Falsaperla, A; Trifiletti, R R; Cocuzza, S

    2014-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS. PMID:25280028

  18. Continuous evaluation of changes in the serum proteome from early to late stages of sepsis caused by Klebsiella pneumoniae.

    PubMed

    Raju M, Swathi; V, Jahnavi; Kamaraju, Ratnakar S; Sritharan, Venkataraman; Rajkumar, Karthik; Natarajan, Sumathi; Kumar, Anil D; Burgula, Sandeepta

    2016-06-01

    Serum protein profiles of patients with bacterial sepsis from the day of diagnosis until recovery/mortality were compared from early to late stages in response to severe sepsis using two dimensional electrophoresis. The proteins exhibiting changes during the course of sepsis (20‑28 day mortality) were selected and identified by matrix‑assisted laser desorption ionization‑time of flight‑tandem mass spectrometry. Among the proteins identified, haptoglobin (Hp), transthyretin (TTR), orosomucoid 1/α1 acid glycoprotein (ORM1), α1 antitrypsin (A1AT), serum amyloid A (SAA) and S100A9 exhibited differential expression patterns between survivors (S; n=6) and non‑survivors (NS; n=6), particularly during the early stages of sepsis. Expression factors (EFs), taken as the ratio between the NS and S during early stages, showed ratios of Hp, 0.39 (P≤0.012); TTR, 3.96 (P≤0.03); ORM1, 0.69 (P≤0.79); A1AT, 0.92 (P≤0.87) and SAA, 0.69 (P≤0.01). S100A9, an acute phase protein, exhibited an EF ratio of 1.68 (P≤0.004) during the end stages of sepsis. A delayed rise in levels was observed in Hp, A1AT, ORM1, S100A9 and SAA, whereas TTR levels increased during the early stages of sepsis in NS. Analysis of inflammatory responses in the early stages of sepsis revealed increased mRNA expression in leukocytes of interleukin (IL)‑6 (EF, 2.50), IL‑10 (EF, 1.70) and prepronociceptin (EF, 1.6), which is a precursor for nociceptin in NS compared with S, and higher Toll‑like receptor‑4 (EF, 0.30) levels in S compared with NS. Therefore, a weaker acute phase response in the early stages of sepsis in NS, combined with an inefficient inflammatory response, may contribute to sepsis mortality. PMID:27082932

  19. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS. PMID:25466727

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

    PubMed Central

    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

    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

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

    PubMed Central

    Weeks, C R; Ferretti, J J

    1984-01-01

    The infection of Streptococcus pyogenes T25(3) with the temperate bacteriophage T12 results in the conversion of the nontoxigenic strain to type A streptococcal exotoxin (erythrogenic toxin) production. Although previous research has established that integration of the bacteriophage genome into the host chromosome is not essential for exotoxin production, the location of the gene on the bacteriophage or bacterial chromosome had not been determined. In the present investigation, recombinant DNA techniques were used to determine whether the gene specifying type A streptococcal exotoxin (speA) production is located on the bacteriophage chromosome. Bacteriophage T12 was obtained from S. pyogenes T25(3)(T12) by induction with mitomycin C, and after isolation of bacteriophage DNA by phenol-chloroform extraction, the DNA was digested with restriction enzymes and ligated with Escherichia coli plasmid pHP34 or the Streptococcus-E. coli shuttle vector pSA3. Transformation of E. coli HB101 with the recombinant molecules allowed selection of E. coli clones containing bacteriophage T12 genes. Immunological assays with specific antibody revealed the presence of type A streptococcal exotoxin in sonicates of E. coli transformants. Subcloning experiments localized the speA gene to a 1.7-kilobase segment of the bacteriophage T12 genome flanked by SalI and HindIII sites. Introduction of the pSA3 vector containing the speA gene into Streptococcus sanguis (Challis) resulted in transformants that secreted the type A exotoxin. Immunological analysis showed that the type A streptococcal exotoxin produced by E. coli and S. sanguis transformants was identical to the type A exotoxin produced by S. pyogenes T25(3)(T12). Southern blot hybridizations with the cloned fragment confirmed its presence in the bacteriophage T12 genome and its absence in the T25(3) nonlysogen. Therefore, the gene for type A streptococcal exotoxin is located in the bacteriophage genome, and conversion of S. pyogenes T25(3) to toxigenicity occurs in a manner similar to the conversion of Corynebacterium diphtheriae to toxigenicity by bacteriophage beta. Images PMID:6389348

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

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

    2015-08-01

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

  4. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

    PubMed Central

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T.; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  5. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve.

    PubMed

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  6. Proteomic and epigenomic markers of sepsis-induced delirium (SID).

    PubMed

    Sfera, Adonis; Price, Amy I; Gradini, Roberto; Cummings, Michael; Osorio, Carolina

    2015-01-01

    In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143-152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis? PMID:26579527

  7. Mortality in Sepsis and its relationship with Gender

    PubMed Central

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

    2015-01-01

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

  8. Proteomic and epigenomic markers of sepsis-induced delirium (SID)

    PubMed Central

    Sfera, Adonis; Price, Amy I.; Gradini, Roberto; Cummings, Michael; Osorio, Carolina

    2015-01-01

    In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143–152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis? PMID:26579527

  9. Challenges in the diagnosis and management of neonatal sepsis

    PubMed Central

    Zea-Vera, Alonso

    2015-01-01

    Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries. PMID:25604489

  10. Serum Calprotectin: A Potential Biomarker for Neonatal Sepsis

    PubMed Central

    Decembrino, Lidia; De Amici, Mara; Pozzi, Margherita; De Silvestri, Annalisa; Stronati, Mauro

    2015-01-01

    Introduction. The correct diagnosis of neonatal sepsis is a relevant problem because sepsis is one of the most important causes of neonatal morbidity, mortality, and prolonged hospital stay. Calprotectin is an antimicrobial, calcium and zinc binding heterocomplex protein that could be used as a nonspecific marker for activation of granulocytes and mononuclear phagocytes. Calprotectin has been proposed for the diagnosis of inflammatory conditions. Our aim is to study serum calprotectin as a biomarker for neonatal sepsis diagnosis. Methods. 41 (20 females, 21 males) infants who underwent blood culture due to suspected sepsis were enrolled in the study. Serum calprotectin was measured by a commercial ELISA assay (Calprest, Eurospital, Trieste, Italy). Statistical analysis was performed using the statistical software package Stata 13.1 (Stata Corporation, College Station, Texas, USA). Results. 8 neonates (19.51%) showed sepsis with positive culture and 33 (80.49%) showed suspected sepsis. The optimal cut-off for calprotectin is 2.2 μg/mL with a sensitivity of 62.5% and a specificity of 69.7%. Conclusions. Calprotectin may be considered a promising early, sensitive, specific marker of sepsis thanks to the importance of calprotectin in defense mechanisms and physiological functions of the immune system. PMID:26380313

  11. Activated Complement Factors as Disease Markers for Sepsis

    PubMed Central

    Charchaflieh, Jean; Rushbrook, Julie; Worah, Samrat; Zhang, Ming

    2015-01-01

    Sepsis is a leading cause of death in the United States and worldwide. Early recognition and effective management are essential for improved outcome. However, early recognition is impeded by lack of clinically utilized biomarkers. Complement factors play important roles in the mechanisms leading to sepsis and can potentially serve as early markers of sepsis and of sepsis severity and outcome. This review provides a synopsis of recent animal and clinical studies of the role of complement factors in sepsis development, together with their potential as disease markers. In addition, new results from our laboratory are presented regarding the involvement of the complement factor, mannose-binding lectin, in septic shock patients. Future clinical studies are needed to obtain the complete profiles of complement factors/their activated products during the course of sepsis development. We anticipate that the results of these studies will lead to a multipanel set of sepsis biomarkers which, along with currently used laboratory tests, will facilitate earlier diagnosis, timely treatment, and improved outcome. PMID:26420913

  12. Biomarkers for pediatric sepsis and septic shock

    PubMed Central

    Standage, Stephen W; Wong, Hector R

    2011-01-01

    Sepsis is a clinical syndrome defined by physiologic changes indicative of systemic inflammation, which are likely attributable to documented or suspected infection. Septic shock is the progression of those physiologic changes to the extent that delivery of oxygen and metabolic substrate to tissues is compromised. Biomarkers have the potential to diagnose, monitor, stratify and predict outcome in these syndromes. C-reactive protein is elevated in inflammatory and infectious conditions and has long been used as a biomarker indicating infection. Procalcitonin has more recently been shown to better distinguish infection from inflammation. Newer candidate biomarkers for infection include IL-18 and CD64. Lactate facilitates the diagnosis of septic shock and the monitoring of its progression. Multiple stratification biomarkers based on genome-wide expression profiling are under active investigation and present exciting future possibilities. PMID:21171879

  13. Interprofessional sepsis education module: a pilot study.

    PubMed

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

    2016-03-01

    Although there is an increasing emphasis on interprofessional collaboration for safer health care systems, there remains a paucity of opportunities for postgraduate trainees to engage in formal interprofessional education (IPE). Current opportunities for interprofessional learning, such as simulation sessions, typically do not provide true IPE because they often utilize actors or confederates as support staff, making residents the only stakeholders in the education experience. Here, we describe a flexible educational module designed to provide genuine IPE for physicians, nurses, and respiratory therapists. We outline how simulation, feedback, and group discussions can be used to teach interprofessional team communication, collaboration, and crew resource management skills-while, at the same time, also teaching a highly relevant medical topic (sepsis management) and thus resulting in learner engagement and motivation. PMID:26063312

  14. An Immunological Perspective on Neonatal Sepsis.

    PubMed

    Kan, Bernard; Razzaghian, Hamid Reza; Lavoie, Pascal M

    2016-04-01

    Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more-accurate age-adapted diagnostic and preventive strategies for neonatal sepsis. PMID:26993220

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

    PubMed

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

    2016-02-01

    Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis and offers recommendations for monitoring and treating sepsis in the older adult population. PMID:26687340

  16. Management and Treatment Guidelines for Sepsis in Pediatric Patients

    PubMed Central

    El-wiher, Nidal; Cornell, Timothy T.; Kissoon, Nranjany; Shanley, Thomas P.

    2012-01-01

    Sepsis remains one of the leading causes of morbidity and mortality in children despite improved understanding of the pathophysiology leading to better clinical management and survival. Recent studies have identified several areas that must be addressed by the clinician in order to continue to impact the morbidity and mortality associated with sepsis. In this review, we discuss the evidence in several of these areas including initial resuscitation, pathogen eradication, maintenance of oxygen delivery, and directed modifiers of the inflammatory response. Our overall goal is to provide the bedside clinician with an updated systematic approach to treat sepsis in children. PMID:23125881

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

    PubMed

    Csete, Marie; Hunt, William D

    2013-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  20. In-111 WBC imaging in musculoskeletal sepsis

    SciTech Connect

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

    1984-01-01

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

  1. Incorporating Interprofessional Evidenced-Based Sepsis Simulation Education for Certified Nursing Assistants (CNAs) and Licensed Care Providers Within Long-term Care Settings for Process and Quality Improvement.

    PubMed

    Mihaljevic, Susan E; Howard, Valerie M

    2016-01-01

    Improving resident safety and quality of care by maximizing interdisciplinary communication among long-term care providers is essential in meeting the goals of the United States' Federal Health care reform. The new Triple Aim goals focus on improved patient outcomes, increasing patient satisfaction, and decreased health care costs, thus providing consumers with quality, efficient patient-focused care. Within the United States, sepsis is the 10th leading cause of death with a 28.6% mortality rate in the elderly, increasing to 40% to 60% in septic shock. As a result of the Affordable Care Act, the Centers for Medicare & Medicaid services supported the Interventions to Reduce Acute Care Transfers 3.0 program to improve health care quality and prevent avoidable rehospitalization by improving assessment, documentation, and communication among health care providers. The Interventions to Reduce Acute Care Transfers 3.0 tools were incorporated in interprofessional sepsis simulations throughout 19 long-term care facilities to encourage the early recognition of sepsis symptoms and prompt communication of sepsis symptoms among interdisciplinary teams. As a result of this simulation training, many long-term care organizations have adopted the STOP and WATCH and SBAR tools as a venue to communicate resident condition changes. PMID:26633155

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

    PubMed Central

    Houston, C W; Ferretti, J J

    1981-01-01

    We describe the detection and quantitation of type A streptococcal exotoxin (erythrogenic toxin, streptococcal pyrogenic exotoxin) by an enzyme-linked immunosorbent assay. This sensitive and specific technique detected microgram amounts of type A exotoxin and was useful for studying the kinetics and regulation of type A exotoxin production during the growth of Streptococcus pyogenes NY5. Maximum production of type A exotoxin was observed during the mid-log phase of growth, similar to the production of other streptococcal extracellular products. When S. pyogenes NY5 was grown at 42 degrees C, decreases in both growth and type A exotoxin production were observed. The results obtained when we studied the influence of nutrient additives and metal ions on the production of type A exotoxin led to the conclusion that none of these factors significantly affected type A exotoxin synthesis and that regulation was constitutive. Images PMID:7026447

  3. [Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections].

    PubMed

    Beşiroğlu, Lütfullah; Ağargün, Mehmet Yücel; Ozbebit, Ozgür; Sözen, Mehmet; Dilek, Imdat; Güleç, Mustafa

    2007-01-01

    The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections. PMID:17853982

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

    PubMed Central

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

    2016-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2015-01-01

    Every year numerous individuals develop the morbid condition of sepsis. Therefore, novel biomarkers th