Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study.

BACKGROUND: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). RESULTS: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]. CONCLUSIONS: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).

Limits of the Glasgow Coma Scale When Assessing for Sepsis in Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: The well-documented association between acute mental status changes and sepsis development and progression makes acute mental status an attractive factor for sepsis screening tools. However, the usefulness of acute mental status within these criteria is limited to the frequency and accuracy of its capture. The Glasgow Coma Scale (GCS) score-the acute mental status indicator in many clinical sepsis criteria-is infrequently captured among allogeneic hematopoietic cell transplant recipients with suspected infections, and its ability to serve as an indicator of acute mental status among this high-risk population is unknown. OBJECTIVE: We evaluated the GCS score as an indicator of acute mental status during the 24 hours after suspected infection onset among allogeneic hematopoietic cell transplant recipients. METHODS: Using data from the first 100 days posttransplant for patients transplanted at a single center between September 2010 and July 2017, we evaluated the GCS score as an indicator of documented acute mental status during the 24 hours after suspected infection onset. From all inpatients with suspected infections, we randomly selected a cohort based on previously published estimates of GCS score frequency among hematopoietic cell transplant recipients with suspected infections and performed chart review to ascertain documentation of clinical acute mental status within the 24 hours after suspected infection onset. RESULTS: A total of 773 patients had ≥1 suspected infections and experienced 1,655 suspected infections during follow-up-625 of which had an accompanying GCS score. Among the randomly selected cohort of 100 persons with suspected infection, 28 were accompanied with documented acute mental status, including 18 without a recorded GCS. In relation to documented acute mental status, the GCS had moderate to high sensitivity and high specificity. DISCUSSION: These data indicate that, among allogeneic hematopoietic cell transplant recipients with suspected infections, the GCS scores are infrequently collected and have a moderate sensitivity. If sepsis screening tools inclusive of acute mental status changes are to be used, nursing teams need to increase measurement of GCS scores among high sepsis risk patients or identify a standard alternative indicator.

Sepsis and Septic Shock Definitions in Patients With Cancer Admitted in ICU.

INTRODUCTION: In 2016, a new definition of sepsis and septic shock was adopted. Some studies based on the general population demonstrated that the Sequential Organ Failure Assessment (SOFA) score is more accurate than the systemic inflammatory response syndrome (SIRS) criteria to predict hospital mortality of infected patients requiring intensive care. PATIENTS AND METHOD: We have analyzed all the records of patients with cancer admitted for a suspected infection between January 1, 2013, and December 31, 2016, in our oncological intensive care unit (ICU). Sequential Organ Failure Assessment score and quick SOFA (qSOFA) score as well as SIRS criteria were calculated. We analyzed the accuracy of each score to predict hospital mortality in the setting of the new and old definitions of septic shock. RESULTS: Our study includes 241 patients with a solid tumor and 112 with a hematological malignancy. The hospital mortality rate is 37% (68% in patients with septic shock according to the new definition and 60% according to old definition) between 2013 and 2016. To predict hospital mortality, the SOFA score has an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.68-0.79), the qSOFA of 0.65 (95% CI, 0.59-0.70), and the SIRS criteria of 0.58 (95% CI, 0.52-0.63). In multivariate analysis, a higher SOFA score or a higher qSOFA score indicates poor prognosis: odds ratio (OR) per 1-point increase by 1.28 (95% CI, 1.18-1.39) and 1.48 (95% CI, 1.04-2.11), respectively. Complete remission is a good prognostic factor for hospital mortality: OR 0.39 (95% CI, 0.22-0.67). CONCLUSION: The new definition of sepsis and septic shock is applicable in an ICU oncological population with the same reliability as in the general population. The SOFA score is more accurate than qSOFA and SIRS criteria to predict hospital mortality.

Development and utility assessment of a machine learning bloodstream infection classifier in pediatric patients receiving cancer treatments.

BACKGROUND: Objectives were to build a machine learning algorithm to identify bloodstream infection (BSI) among pediatric patients with cancer and hematopoietic stem cell transplantation (HSCT) recipients, and to compare this approach with presence of neutropenia to identify BSI. METHODS: We included patients 0-18 years of age at cancer diagnosis or HSCT between January 2009 and November 2018. Eligible blood cultures were those with no previous blood culture (regardless of result) within 7 days. The primary outcome was BSI. Four machine learning algorithms were used: elastic net, support vector machine and two implementations of gradient boosting machine (GBM and XGBoost). Model training and evaluation were performed using temporally disjoint training (60%), validation (20%) and test (20%) sets. The best model was compared to neutropenia alone in the test set. RESULTS: Of 11,183 eligible blood cultures, 624 (5.6%) were positive. The best model in the validation set was GBM, which achieved an area-under-the-receiver-operator-curve (AUROC) of 0.74 in the test set. Among the 2236 in the test set, the number of false positives and specificity of GBM vs. neutropenia were 508 vs. 592 and 0.76 vs. 0.72 respectively. Among 139 test set BSIs, six (4.3%) non-neutropenic patients were identified by GBM. All received antibiotics prior to culture result availability. CONCLUSIONS: We developed a machine learning algorithm to classify BSI. GBM achieved an AUROC of 0.74 and identified 4.3% additional true cases in the test set. The machine learning algorithm did not perform substantially better than using presence of neutropenia alone to predict BSI.

TNM: a simple classification system for complicated intra-abdominal sepsis after acute appendicitis.

BACKGROUND: Delayed diagnosis in case of acute appendicitis (AA) could lead to complicated intra-abdominal sepsis (IAS). Grading systems are not commonly employed in the clinical practice, because they are too complicated or too specific. Therefore, we suggest grading the severity of complicated IAS after AA with a simple system: TNM, an acronym borrowed by cancer staging where T indicates temperature, N neutrophils, and M multiple organ failure (MOF). This prospective observational study evaluates the predictive value of the TNM score on mortality of patients with complicated IAS after AA. METHODS: Sixty-eight patients with complicated IAS after AA were treated. Three classes of attributes were chosen: temperature (T), neutrophils count (N), and MOF (M). After defining the categories T (T0-T4), N (N0-N3) and M (M0-M2), these were grouped in stages (0-IV). Variables analyzed for their possible relation to death were age, sex, temperature, neutrophils count, preoperative organ failure, immunocompromised status, stage (0-IV). Odds ratios were calculated in a univariate and multivariate analysis. RESULTS: TNM staging was: one patient stage 0; 16 patients at stage I; 26 patients at stage II; 16 patients at stage III; nine patients at stage IV. Death occurred in 15 patients (22%). Neutrophil count, preoperative organ failure, immunocompromised status, stages III-IV were potential predictors of postoperative death in univariate analysis; only stage IV was significant independent predictor of postoperative mortality in multivariate analysis. CONCLUSIONS: TNM classification is very easy to use; it helps to define the mortality risk and is useful to objectively compare patients with sepsis.

The value of neutrophil gelatinase-associated lipocalin and citrullinated alpha enolase peptide-1 antibody in diagnosis, classification, and prognosis for patients with sepsis.

We examined the blood concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and citrullinated alpha enolase peptide-1 (CEP-1) antibody in sepsis patients to evaluate their potential diagnostic, classified and prognostic utility together with C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6).Sixty-nine patients admitted at the emergency department with sepsis were studied, on admission, their demographic and clinical information were recorded. Blood levels of CRP, PCT, IL-6, NGAL, and CEP-1 antibody were measured. Relationships between sequential [sepsis-related] organ failure assessment score and blood biomarkers, between acute physiology and chronic health evaluation II score and blood biomarkers were investigated. Additionally, the mutual correlation among CRP, PCT, IL-6, NGAL, and CEP-1 antibody were investigated. Diagnostic and predictive values for clinical outcomes for biomarkers were assessed by receiver operator characteristic curve.Sixty-nine participants (38 sepsis, 31 septic shock) were compared with 40 healthy controls. The levels of CRP, PCT, IL-6, and NGAL were significantly higher in sepsis patients ([59.49 ± 48.88]; 0.71, [0.13-11.72]; 60.46, [33.26-201.20]; 265.61, [185.79-500.96], respectively) compared with healthy controls ([2.05 ± 1.85]; 0.02, [0.02-0.03]; 12.08, [7.22-16.84]; 19.73, [7.66-34.39], respectively) (P < .001). CRP, PCT, IL-6, and NGAL had better discriminatory performance with an area under the receiver operator characteristic curve (AUC) of (0.98; 0.98; 0.90; 0.97, respectively), 95% confidence interval (CI) = ([0.95; 1.00]; [0.96; 1.00]; [0.84; 0.96]; [0.94; 1.00], respectively) (P < .001), with a cut off value of (8.02 mg/L [Se = 88.40%, Sp = 100.00%]; 0.06 ng/mL [Se = 94.20%, Sp = 75.00%]; 30.63 pg/mL [Se = 78.30%, Sp = 95.00%]; 95.72 ng/mL [Se = 99.00%, Sp = 92.00%], respectively). Between the sepsis group and septic shock group, PCT and NGAL were significantly higher in septic shock group (2.44, [0.49-20.36]; 294.65 [203.34-1262.47], respectively) compared with sepsis group (0.41, [0.11-2.63]; 219.94, [146.38-385.24], respectively) (P < .05). Between survivors group and nonsurvivors group, PCT was obviously elevated in nonsurvivors group (2.47, [0.70-12.49]) compare with survivors group (0.41, [0.11-8.16]) (P < .05), with an AUC of 0.69, 95% CI = (0.57; 0.81) (P < .05), while CEP-1 antibody was decreased in nonsurvivors group (14.03, [4.94-17.17]) contrast to survivors group (18.78, [8.08-39.72]) (P < .05), with an AUC of 0.67, 95% CI = (0.54; 0.80) (P < .05). Additionally, CEP-1 antibody demonstrated a negative correlation with either sequential [sepsis-related] organ failure assessment score (r = -0.31, P < .05) or PCT (r = -0.27, P < .05).As CRP, PCT, and IL-6, NGAL was valuable in sepsis diagnosis. With a classificatory value, PCT and NGAL correlated with the degree severity of sepsis. PCT and CEP-1 antibody were meaningful in sepsis prognosis. CEP-1 antibody may be a protective factor for sepsis.

Evaluation of sepsis using compensatory reserve measurement: A prospective clinical trial.

BACKGROUND: Sepsis, a leading cause of morbidity and mortality worldwide, characterized by metabolic and hemodynamic changes that can lead to multiorgan failure and death. The evaluation of a patient's condition is routinely performed by several objective criteria. The compensatory reserve measurement (CRM) represents a new paradigm that measures the total of all physiological compensatory mechanisms, using noninvasive photoplethysmography to read changes in arterial waveforms. The present study's aim was to evaluate the applicability and the predictive value of the CRM during sepsis. METHODS: Data were prospectively collected from patients hospitalized in the department of surgery because of different inflammatory illnesses. All subjects were evaluated with hemodynamic, laboratory measurements and CRM throughout hospitalization. RESULTS: Of 100 subjects enrolled, 84 patients were not septic. The remaining 16 patients were in sepsis (Sequential Organ Failure Assessment [SOFA] score, >2), 6 of whom were in septic shock and 4 died. When nonseptic patients were compared with septic patients, statistical differences were found in C-reactive protein level (p < 0.0005), SOFA score (p < 0.0005), and CRM (p < 0.0001). Other parameters did not show any difference between groups. The area under the receiver operating characteristic curve for CRM was 1, significantly higher than the area under the receiver operating characteristic for heart rate (0.78), systolic blood pressure (0.67), quick SOFA (0.81), and respiratory rate (0.56). CONCLUSION: Clinical criteria, imaging, and laboratory features used to identify a septic patient are suboptimal. This demonstrates the need for a monitoring device capable of detecting rapidly, constantly, and simply the sum condition of the ill patient. We have shown that CRM was able to distinguish between severe septic and nonseptic patients early in the course of hospitalization and was significantly more sensitive than the conventional diagnostic tools. Such capability to assess the septic patients or even to triage these patients will surely aid treatment of sepsis. LEVEL OF EVIDENCE: Care management, level II.

Implementation of a MEWS-Sepsis screening tool: Transformational outcomes of a nurse-led evidence-based practice project.

BACKGROUND: One in three patients who die in the hospital has sepsis. Alerting clinicians to early detection of high-risk patients before deterioration is a top health care priority. Modified Early Warning Scoring (MEWS) tools have assisted organizations in identifying at-risk patients at the first sign of subtle deterioration. AIM AND SETTING: In conjunction with an academic-clinical partner, we evaluated, revised and implemented a modified MEWS-Sepsis screening tool in an acute care facility. PARTICIPANTS: One hundred and thirty-nine direct-care nurses participated in tool evaluation. METHODS: Using a plan-do-study-act cycle of quality improvement, critical care scenarios from septic patient data were created and tested in a simulated setting. RESULTS: Upon implementation of the MEWS-Sepsis tool, the monthly risk-adjusted sepsis mortality rate immediately declined by 24%. The decline in mortality has been sustained from implementation to the present, spanning a 5-year period. CONCLUSIONS: The implementation of a MEWS-Sepsis screening tool contributed to early identification and implementation of time-sensitive interventions aimed at preventing sepsis-associated deaths. MEWS-Sepsis tools hold potential for scale-up and spreading out of evidence-based practice nursing innovations to transform care, improve patient outcomes, and save lives.

Implementation of an Artificial Intelligence Algorithm for sepsis detection / Implantación de Algoritmo de Inteligencia Artificial para la detección de la sepsis / Implantação de algoritmo de inteligência artificial para detecção da sepse

ABSTRACT Objectives: to present the nurses' experience with technological tools to support the early identification of sepsis. Methods: experience report before and after the implementation of artificial intelligence algorithms in the clinical practice of a philanthropic hospital, in the first half of 2018. Results: describe the motivation for the creation and use of the algorithm; the role of the nurse in the development and implementation of this technology and its effects on the nursing work process. Final Considerations: technological innovations need to contribute to the improvement of professional practices in health. Thus, nurses must recognize their role in all stages of this process, in order to guarantee safe, effective and patient-centered care. In the case presented, the participation of the nurses in the technology incorporation process enables a rapid decision-making in the early identification of sepsis.

RESUMEN Objetivos: presentar la experiencia de enfermeros con innovaciones tecnológicas computacionales en el apoyo a la identificación precoz de la sepsis. Métodos: relato de experiencia de pre y post implantación de algoritmos basados en inteligencia artificial para la práctica clínica en un hospital filantrópico, en el primer semestre de 2018. Resultados: describen la motivación para la creación y uso del algoritmo; el papel del enfermero en el desarrollo e implantación de esa tecnología y sus efectos en el proceso de trabajo de la enfermería. Consideraciones Finales: las innovaciones tecnológicas necesitan contribuir a la mejora de las prácticas profesionales en salud, así que los enfermeros deben reconocer su papel en todas las etapas de este proceso, con el fin de garantizar el cuidado seguro, efectivo, centrado en el paciente. En el caso presentado, la participación de los enfermeros en el proceso de incorporación tecnológica potencializa la rápida toma de decisión en la identificación precoz de la sepsis.

RESUMO Objetivos: apresentar a experiência de enfermeiros com inovações tecnológicas computacionais no apoio à identificação precoce da sepse. Métodos: relato de experiência de pré e pós-implantação de algoritmos baseados em inteligência artificial para a prática clínica em um hospital filantrópico, no primeiro semestre de 2018. Resultados: descrevem a motivação, para criação e uso do algoritmo, o papel do enfermeiro no desenvolvimento e na implantação dessa tecnologia e os seus efeitos no processo de trabalho da enfermagem. Considerações Finais: inovações tecnológicas precisam contribuir para a melhoria das práticas profissionais em saúde. Assim, enfermeiros devem reconhecer seu papel em todas as etapas desse processo, de modo a garantir o cuidado seguro, efetivo, centrado no paciente. No caso apresentado, a participação dos enfermeiros no processo de incorporação tecnológica potencializa a rápida tomada de decisão na identificação precoce da sepse.

Clinical Scores and Formal Triage for Screening of Sepsis and Adverse Outcomes on Arrival in an Emergency Department All-Comer Cohort.

BACKGROUND: Early recognition of sepsis remains a major challenge. The clinical utility of the Quick Sepsis-Related Organ Failure Assessment (qSOFA) score is still undefined. Several studies have tested its prognostic value. However, its ability to diagnose sepsis is still unknown. OBJECTIVE: Our aim was to compare the performance of qSOFA, systemic inflammatory response syndrome (SIRS) criteria, National Early Warning Score (NEWS), and formal triage with the Emergency Severity Index (ESI) algorithm to identify patients with sepsis and predict adverse outcomes on arrival in an emergency department (ED) all-comer cohort. METHODS: We included all patients presenting consecutively to the ED during a 3-week period. We used vital signs recorded at triage to calculate the study scores. Two independent assessors retrospectively assigned the primary outcome of sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock criteria in a chart review process. RESULTS: There were 2523 cases included in the analysis and 39 (1.6%) had the primary outcome of sepsis. The area under the curve for sepsis was 0.79 (95% confidence interval [CI] 0.71-0.86) for qSOFA, 0.81 (95% CI 0.73-0.87) for SIRS, 0.85 (95% CI 0.77-0.92) for NEWS, and 0.77 (95% CI 0.70-0.83) for ESI. CONCLUSIONS: qSOFA offered high specificity for the prediction of sepsis and adverse outcomes. However, its low sensitivity does not support widespread use as a screening tool for sepsis. NEWS outperformed qSOFA for prediction of adverse outcomes and screening for sepsis.

Characteristics and Outcomes of Pediatric Septic Patients With Cancer: A Retrospective Cohort Study.

BACKGROUND: Pediatric oncology patients may be at a higher risk of complications and mortality from sepsis compared with their nononcology counterpart. OBJECTIVES: The aim of this study is to compare characteristics, treatment, and sepsis-related mortality between oncology and nononcology patients presenting to the emergency department (ED). METHODS: This is a retrospective single-center cohort study including patients <18 years old with a diagnosis of sepsis, severe sepsis, septic shock, or bacteremia presenting to an academic ED between January 2009 and January 2015. A total of 158 patients were included with 53.8% having an underlying malignancy. The primary outcome of the study was in-hospital mortality. Secondary outcomes included ED vital signs, resuscitation parameters, laboratory work, infection site, general practitioner unit, intensive care unit length of stay, and hospital length of stay. RESULTS: Oncology patients had a higher in-hospital mortality (5.9% vs. 2.7%), however, it did not meet statistical significance (p = 0.45). On presentation, oncology patients had a lower respiratory rate (24.33 ± 9.48 vs. 27.45 ± 7.88; p = 0.04). There was a significant increase in the white blood count in oncology patients (4.011 ± 4.965 vs. 17.092 ± 12.806; p < 0.001) with this cohort receiving more intravenous fluids. In the first 6 hours (33.0 ± 27.7 mL/kg vs. 24.9 ± 16.1 mL/kg; p = 0.029) as well as having a higher percentage of vasopressor administration (15.3% vs. 1.4%; p = 0.002). Antibiotics were initiated at an earlier stage in the oncology cohort (1.25 ± 1.95 vs. 3.33 ± 1.97 hours; p < 0.0001). Cancer-free patients had a significantly higher rate of lung infections compared with cancer patients (68.5% vs. 32.9%; p < 0.0001). In terms of infection characteristics, cancer patients had a higher percentage of bacteremia (27.1% vs. 4.1%; p < 0.001). CONCLUSION: There was no statistical significance regarding mortality between the 2 cohorts. Pediatric cancer patients were found to have a higher incidence of bacteremia and received more aggressive treatment.

Intra-abdominal sepsis: new definitions and current clinical standards.

PURPOSE: The abdomen is the second most common source of sepsis and is associated with unacceptably high morbidity and mortality. Recently, the essential definitions of sepsis and septic shock were updated (Third International Consensus Definitions for Sepsis and Septic Shock, Sepsis-3) and modified. The purpose of this review is to provide an overview of the changes introduced by Sepsis-3 and the current state of the art regarding the treatment of abdominal sepsis. RESULTS: While Sepsis-1/2 focused on detecting systemic inflammation as a response to infection, Sepsis-3 defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The Surviving Sepsis Campaign (SSC) guideline, which was updated in 2016, recommends rapid diagnosis and initiating standardized therapy. New diagnostic tools, the establishment of antibiotic stewardship programs, and a host of new-generation antibiotics are new landmark changes in the sepsis literature of the last few years. Although the "old" surgical source control consisting of debridement, removal of infected devices, drainage of purulent cavities, and decompression of the abdominal cavity is the gold standard of surgical care, the timing of gastrointestinal reconstruction and closure of the abdominal cavity ("damage control surgery") are discussed intensively in the literature. The SSC guidelines provide evidence-based sepsis therapy. Nevertheless, treating critically ill intensive care patients requires individualized, continuous daily re-evaluation and flexible therapeutic strategies, which can be best discussed in the interdisciplinary rounds of experienced surgeons and intensive care medicals.

Streptococcus agalactiae - Distribuição sorotípica e relação com fatores de virulência e resistência antimicrobiana / Streptococcus agalactiae - Serotype distriburion and correlation with virulence factors and antibiotic resistance

Streptococcus agalactiae, ou Estreptococo do Grupo B, é um microrganismo que encontrado na microbiota intestinal, vaginal e/ou geniturinária de 10-30% de mulheres saudáveis. A principal infecção causada por S. agalactiae é a sepse neonatal. O bebê pode adquirir o microrganismo durante o parto ao passar pelo canal vaginal, ou até mesmo durante a gestação, caso haja ascensão de S. agalactiae para o útero. Existem diversos fatores associados à infecção do feto por S. agalactiae quando a mãe é colonizada, tais como fator CAMP, cápsula de polissacarídeos, hialuronidase, ß-citolisina/hemolisina e pili. Não existe consenso ou recomendação técnica sobre o tema no Brasil. Segundo o Caderno de Atenção Básica ao Pré-Natal, não existem estudos que levem à recomendação da antibioticoterapia intraparto. É necessário elucidar as características genotípicas de cepas de S. agalactiae isoladas no Brasil para alinhar as práticas clínicas às características fenotípicas do microrganismo. Desta forma, os objetivos deste projeto são: i) classificar cepas de S. agalactiae isoladas de gestantes e não gestantes quanto ao sorotipo capsular, por PCR Multiplex, ii) avaliar a presença e distribuição de fatores de virulência, por PCR e iii) avaliar o perfil de resistência antimicrobiana, pelo método de disco difusão e teste D. Os achados de virulência e resistência a antimicrobianos foram comparados com os sorotipos, gestação, localização geográfica e sítio de isolamento. Foram analisadas 292 cepas isoladas de gestantes e não gestantes em São Paulo, São José dos Campos e Rio de Janeiro. O sorotipo Ia foi o mais prevalente entre as cepas. Na cidade de São José dos Campos não houve diferença significativa entre a prevalência dos sorotipos Ia e V, sendo que o sorotipo V foi mais abundante do que nas cidades de São Paulo e Rio de Janeiro. O sorotipo II foi mais abundante em mulheres não gestantes do que gestantes. Não foram encontradas cepas resistentes à Penicilina e vancomicina; contudo a resistência a Cefepima, Eritromicina e Clindamicina ficou em torno de 22%. Foram encontradas diferenças entre os sorotipos quanto à resistência, genes de virulência e sítio de isolamento das cepas. Portanto essas diferenças podem se refletir no perfil epidemiológico da infecção por S. agalactiae quanto à localização geográfica também quanto à gestação. A incidência de sepse causada por S. agalactiae diminuiu muito nas últimas décadas, contudo o monitoramento constante é necessário para alinhar as práticas clínicas às características fenotípicas do microrganismo

Streptococcus agalactiae, or Group B Streptococcus, is a microorganism found in intestinal, vaginal and/or genitourinary microbiota from about 10-30% of all healthy women. The main infection caused by S. agalactiae is neonatal sepsis. The baby can contract the infection during labor when passing through the vaginal canal, or even during pregnancy, if S. agalactiae ascends from the vaginal canal to the uterus. There are several factors associated to the infection of the fetus by S. agalactiae when the mother is colonized, such as the CAMP factor, polysaccharide capsule, hyaluronidase, ß-cytolysin/hemolysin and pili. There is no consensus or technical recommendation regarding this theme in Brazil. According to the Brazilian guidelines to prenatal care, there is no research that justifies the implementation of intrapartum antibiotic therapy. There is a need to clarify genotype characteristics of S. agalactiae strains isolated in Brazil in order to align clinical practices to phenotypical characteristics of this microorganism. This way, the goals of this project are: i) to classify S. agalactiae strains isolated from pregnant and nonpregnant women according to their capsular serotype, using PCR Multiplex, ii) to evaluate the presence and distribution of virulence factors, using PCR and iii) to evaluate their antibiotic resistance profile, using disk-diffusion and D-zone tests. The findings regarding virulence and resistance were compared to serotypes, pregnancy, geographic localization and the site where the sample was isolated. A total of 292 strains from pregnant and nonpregnant women from the cities of São Paulo, São José dos Campos and Rio de Janeiro were analyzed. Serotype Ia was the most prevalent among the strains. In São José dos Campos there was no significate difference in the prevalence of serotypes Ia and V. Serotype V was the most abundant in São Paulo and Rio de Janeiro. Serotype II was most prevalent in nonpregnant women when compared to pregnant women. No resistance to Penicillin nor Vancomycin was found. However, resistance to Cefepime, Erythromycin or Clindamycin was found in around 22% of strains. There were differences among serotypes regarding resistance, virulence genes and site where the strain was isolated. Therefore these differences can reflect into the epidemiologic profile of S. agalactiae infection in regards to geographic localization and pregnancy. The incidence of sepsis caused by S. agalactiae has decrease in the last few decades, however constant monitoring is necessary in order to align clinical practice to the microorganisms phenotypical characteristics

Comparison of qSOFA with current emergency department tools for screening of patients with sepsis for critical illness.

OBJECTIVE: We sought to compare the quick sequential organ failure assessment (qSOFA) to systemic inflammatory response syndrome (SIRS), severe sepsis criteria and lactate levels for their ability to identify ED patients with sepsis with critical illness. METHODS: We conducted this multicenter retrospective cohort study at five US hospitals, enrolling all adult patients admitted to these hospitals from their EDs with infectious disease-related illnesses from 1 January 2016 to 30 April 2016. We abstracted clinical variables for SIRS, severe sepsis and qSOFA scores, using values in the first 6 hours of ED stay. Our primary outcome was critical illness, defined as one or more of the composite outcomes of death, vasopressor use or intensive care unit (ICU) admission within 72 hours of presentation. We determined diagnostic test characteristics for qSOFA scores, SIRS, severe sepsis criteria and lactate level thresholds. MAIN RESULTS: Of 3743 enrolled patients, 512 (13.7%) had the primary composite outcome. The qSOFA scores were ≥1, >2 and 3 in 1839 (49.1%), 626 (16.7%) and 146 (3.9%) patients, respectively; 2202 (58.8%) met SIRS criteria and 1085 (29.0%) met severe sepsis criteria. qSOFA ≥1 and SIRS had similarly high sensitivity [86.1% (95% CI 82.8% to 89.0%) vs 86.7% (95% CI 83.5% to 89.5%)], but qSOFA ≥1 had higher specificity [56.7% (95% CI 55.0% to 58.5%) vs 45.6% (43.9% to 47.3%); mean difference 11.1% (95% CI 8.7% to 13.6%)]. qSOFA ≥2 had higher specificity than severe sepsis criteria [89.1% (88.0% to 90.2%) vs 77.5% (76.0% to 78.9%); mean difference 11.6% (9.8% to 13.4%)]. qSOFA ≥1 had greater sensitivity than a lactate level ≥2 (mean difference 24.6% (19.2% to 29.9%)). CONCLUSION: For patients admitted from the ED with infectious disease diagnoses, qSOFA criteria performed as well or better than SIRS criteria, severe sepsis criteria and lactate levels in predicting critical illness.

Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria.

Background: Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. Methods: All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Results: Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). Conclusions: No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest "inclusion-criteria" to recognize patients with a high chance of mortality and ICU admission. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.

Raising concerns about the Sepsis-3 definitions.

The Global Alliance for Infections in Surgery appreciates the great effort of the task force who derived and validated the Sepsis-3 definitions and considers the new definitions an important step forward in the evolution of our understanding of sepsis. Nevertheless, more than a year after their publication, we have a few concerns regarding the use of the Sepsis-3 definitions.

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis.

BACKGROUND: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. METHODS: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. RESULTS: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1ß and IL-6). CONCLUSION: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.

Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis.

BACKGROUND: Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics. METHODS: We conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia. RESULTS: Of 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups. CONCLUSIONS: Neutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.