Early Diagnosis of Sepsis: The Role of Biomarkers and Rapid Microbiological Tests.

Sepsis is a medical emergency resulting from a dysregulated response to an infection, causing preventable deaths and a high burden of morbidity. Protocolized and accurate interventions in sepsis are time-critical. Therefore, earlier recognition of cases allows for preventive interventions, early treatment, and improved outcomes. Clinical diagnosis of sepsis by clinical scores cannot be considered an early diagnosis, given that underlying molecular pathophysiological mechanisms have been activated in the preceding hour or days. There is a lack of a widely available tool enhancing preclinical diagnosis of sepsis. Sophisticated technologies for sepsis prediction have several limitations, including high costs. Novel technologies for fast molecular and microbiological diagnosis are focusing on bedside point-of-care combined testing to reach most settings where sepsis represents a challenge.

External ventriculostomy-associated infection reduction after updating a care bundle.

BACKGROUND: Despite the clinical benefits of external ventricular drains (EVD), these devices can lead to EVD-related infections (EVDRI). The drainage insertion technique and standardized guidelines can significantly reduce the risk of infection, mainly caused by gram-positive bacteria. However, gram-negative microorganisms are the most frequent causative microorganisms of EVDRI in our hospital. We aimed to determine whether a new bundle of measures for the insertion and maintenance of a drain could reduce the incidence of EVDRI. This cohort study of consecutive patients requiring EVD from 01/01/2015 to 12/31/2018 compared the patients' characteristics before and after introducing an updated protocol (UP) for EVD insertion and maintenance in 2017. RESULTS: From 204 consecutive patients, 198 requiring EVD insertion were included (54% females, mean age 55 ± 15 years). The before-UP protocol included 87 patients, and the after-UP protocol included 111 patients. Subarachnoid (42%) and intracerebral (24%) hemorrhage were the main diagnoses at admission. The incidence of EVDRI fell from 13.4 to 2.5 episodes per 1000 days of catheter use. Gram-negative bacteria were the most frequent causative microorganisms. Previous craniotomy remained the only independent risk factor for EVDRI. EVDRI patients had increased mechanical ventilation durations, hospital and ICU stays, and percutaneous tracheostomy requirements. CONCLUSIONS: A care bundle focusing on fewer catheter sampling and more accurate antiseptic measures can significantly decrease the incidence of EVDRI. After implementing the management protocol, a decreased incidence of infections caused by gram-negative and gram-positive bacteria and reduced ICU and hospital lengths of stay were observed.

Time to decision in sepsis / Tiempo para la toma de decisiones en sepsis

Introduction: This study aimed to identify the common barriers leading to delayed initial management, microbiological diagnosis, and appropriate empirical antimicrobial treatment in sepsis. Patients and methods: A cross-sectional study was performed by the application of a population-based survey. Four different surveys were designed, targeting the healthcare personnel located in main hospital areas [emergency department (SEMES); infectious diseases and clinical microbiology-microbiological diagnosis (SEIMC-M); intensive care and infectious diseases, (SEMICYUC-GTEIS); and infectious diseases and clinical microbiology-clinical diagnosis, (SEIMC-C)]. Results: A total of 700 valid surveys were collected from June to November 2019: 380 (54.3%) of SEMES, 127 (18.1%) of SEIMC-M, 97 (13.9%) de SEMICYUC-GTEIS and 96 (13.7%) of SEIMC-C, in 270 hospitals of all levels of care. The qSOFA score was used as a screening tool. The most used biomarker was procalcitonin (n=92, 39.8%). The sepsis code was implemented in 157 of 235 participating centers (66.2%), particularly in tertiary level hospitals. The mean frequency of contaminated blood cultures was 8.9% (8.7). In 85 (78.7%) centers, positive results of blood cultures were available within the first 72 hours and were communicated to the treating physician effectively by phone or e-mail in 76 (81.7%) cases. The main reason for escalating treatment was clinical deterioration, and the reason for de-escalating antimicrobials was significantly different between the specialties. Quality indicators were not frequently monitored among the different participating centers. Conclusion: There are significant barriers that hinder adequate management processes in sepsis in Spanish hospitals. (AU)

Introducción: Este estudio tuvo como objetivo identificar las barreras comunes que conducen al retraso en el manejo inicial, el diagnóstico microbiológico y el tratamiento antimicrobiano empírico adecuado en la sepsis. Pacientes y métodos: Se realizó un estudio transversal mediante la aplicación de una encuesta de base poblacional. Se diseñaron cuatro encuestas diferentes, dirigidas al personal de salud ubicado en las principales áreas hospitalarias [urgencias (SEMES); enfermedades infecciosas y microbiología clínica-diagnóstico microbiológico (SEIMC-M); cuidados intensivos y enfermedades infecciosas (SEMICYUC-GTEIS); y enfermedades infecciosas y microbiología clínica-diagnóstico clínico, (SEIMC-C)]. Resultados: Se recogieron un total de 700 encuestas válidas de junio a noviembre de 2019: 380 (54,3%) de SEMES, 127 (18,1%) de SEIMC-M, 97 (13,9%) de SEMICYUC-GTEIS y 96 (13,7%) de la SEIMC-C, en 270 hospitales de todos los niveles de atención. El qSOFA se utilizó principalmente como herramienta de detección. El biomarcador más utilizado fue la procalcitonina (n=92, 39,8%). El código sepsis estaba implementado en 157 de 235 centros participantes (66,2%), particularmente en hospitales de tercer nivel. La frecuencia media de hemocultivos contaminados fue del 8,9% (8,7). En 85 (78,7%) de los centros, los resultados de los hemocultivos positivos estuvieron disponibles en las primeras 72 horas y se comunicaron al médico responsable del paciente por teléfono o correo electrónico en 76 casos (81,7%). El motivo principal de la escalada del tratamiento fue el deterioro clínico y el motivo de la desescalada de los antimicrobianos fue significativamente diferente entre las especialidades. Los indicadores de calidad no se monitorizaban con frecuencia en los diferentes centros. Conclusión: Existen importantes barreras que dificultan los procesos de manejo adecuado de la sepsis en los hospitales españoles. (AU)

Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit.

Objectives: To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency. Design: Prospective, observational, single-center study. Setting: Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021. Patients: Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included. Interventions: Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients. Measurement: Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2-5 mg/L; (normal plasma concentration: > 5 mg/L). Main results: Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1-4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10-22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO2/FIO2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients. Conclusion: This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period.

Current treatment of nosocomial pneumonia and ventilator-associated pneumonia

Hospital-acquired pneumonia and ventilator-associated pneumonia are severe nosocomial infections leading to high morbidity and mortality. Broad-spectrum antibiotics with coverage against all likely pathogens are recommended by the international guidelines. Inappropriate empirical treatment is one of the most important prognostic factors. Knowledge of local epidemiology and continuous microbiological surveillance is crucial for improving clinical approaches to empirical antimicrobial treatment. The development of protocols and policies for training healthcare professionals on preventive strategies, such as the “Pneumonia Zero” project, and improved implementation of antimicrobial stewardship practices, will aid early de-escalation of antibiotics and prevent resistance. (AU)

Case report: Cytokine hemoadsorption in a case of hemophagocytic lymphohistiocytosis secondary to extranodal NK/T-cell lymphoma.

We discuss a single case of Hemophagocytic lymphohistiocytosis (HLH) due to NK-type non-Hodgkin lymphoma and Epstein-Barr virus reactivation with multiorgan dysfunction and distributive shock in which we performed cytokine hemoadsorption with Cytosorb ®. A full microbiological panel was carried out, including screening for imported disease, standard serologies and cultures for bacterial and fungal infection. A liver biopsy and bone marrow aspirate were performed, confirming the diagnosis. The patients fulfilled the HLH-2004 diagnostic criteria, and according to the 2018 Consensus Statements by the HLH Steering Committee of the Histiocyte Society, dexamethasone and etoposide were started. There was an associated hypercytokinemia and, due to refractory distributive shock, rescue therapy with cytokine hemoadsorption was performed during 24 h (within day 2 and 3 from ICU admission). After starting this procedure, rapid hemodynamic control was achieved with a significant reduction in vasopressor support requirements. This case report highlights that cytokine hemoadsorption can be an effective since rapid decrease in IL-10 levels and a significant hemodynamic improvement was achieved.

Precision medicine in sepsis and septic shock: From omics to clinical tools.

Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.

Consequences of ICU Readmission After Lung Transplantation: Beyond the Early Postoperative Period / Consecuencias del reingreso en la UCI tras el trasplante de pulmón: más allá del periodo postoperatorio temprano

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Blood purification in sepsis and COVID-19: what´s new in cytokine and endotoxin hemoadsorption.

Sepsis and COVID-19 are two clinical conditions that can lead to a dysregulated inflammatory state causing multiorgan dysfunction, hypercytokinemia, and a high risk of death. Specific subgroups of critically ill patients with particular characteristics could benefit from rescue treatment with hemoadsorption. There is a lack of adequately designed randomized controlled trials evaluating the potential benefits of cytokine or endotoxin hemoadsorption. Critically ill COVID-19 patients with severe acute respiratory failure poorly responsive to conventional treatment could be candidates to receive cytokine hemoadsorption in the presence of high levels of interleukin 6. This treatment can also be suitable for patients with refractory septic shock and hypercytokinemia. In the context of high endotoxin activity, hemoadsorption with polymyxin B could improve clinical parameters and the prognosis of patients with refractory septic shock. Predictive enrichment, using biomarkers or other individual features, identifies potential responders to cytokine, endotoxin, or sequential hemoadsorption. Besides, recognizing the particular subsets of patients likely to respond to one or both types of hemoadsorption will aid the design of future studies that accurately validate the effectiveness of these therapies.

Antibiotic treatment in patients with sepsis: a narrative review.

Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, with unacceptably high morbidity and mortality. Similar to acute myocardial infarction or cerebral vascular accident, sepsis is a severe and continuous time-dependent condition. Thus, in the case of sepsis, early and adequate administration of antimicrobials must be a priority, ideally within the first hour of diagnosis, simultaneously with organ support.As a consequence of the emergence of multidrug-resistant pathogens, the choice of antimicrobials should be performed according to the local pathogen patterns of resistance. Individual antimicrobial optimization is essential to achieve adequate concentrations of antimicrobials, to reduce adverse effects, and to ensure successful outcomes, as well as preventing the emergence of multidrug-resistant pathogens. The loading dose is the administration of an initial higher dose of antimicrobials, regardless of the presence of organ dysfunction. Further doses should be implemented according to pharmacokinetics/pharmacodynamics of antimicrobials and should be adjusted according to the presence of renal or liver dysfunction. Extended or continuous infusion of beta-lactams and therapeutic drug monitoring can help to achieve therapeutic levels of antimicrobials. Duration and adequacy of treatment must be reviewed at regular intervals to allow effective de-escalation and administration of short courses of antimicrobials for most patients. Antimicrobial stewardship frameworks, leadership, focus on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches will help us to improve patients the process of care and overall quality of care.

[Pathophysiology of septic shock]. / Fisiopatología del shock séptico.

Sepsis and septic shock result from an inadequate host response to an infection, which causes organ dysfunction. The progression of this condition is manifested by the occurrence of successive clinical stages, resulting from the systemic inflammatory response secondary to the activation of different inflammatory mediators, leading to organ dysfunction. There is a high burden of evidence on the role of endotoxin in the pathogenesis of sepsis and its crucial role in triggering the inflammatory response in sepsis caused by gram-negative bacteria. The coagulation cascade activation in sepsis patients is part of the host's adaptive immune response to infection. The endothelium is the main target in sepsis, which is metabolically active and can.

Evidence for the Application of Sepsis Bundles in 2021.

Sepsis represents a severe condition that predisposes patients to a high risk of death if its progression is not ended. As with other time-dependent conditions, the performance of determinant interventions has led to significant survival benefits and quality-of-care improvements in acute emergency care. Thus, the initial interventions in sepsis are a cornerstone for prognosis in most patients. Even though the evidence supporting the hour-1 bundle is perfectible, real-life application of thoughtful and organized sepsis care has improved survival and quality of care in settings promoting compliance to evidence-based treatments. Current evidence for implementing the Surviving Sepsis Campaign bundles for early sepsis management is moving forward to better approaches as more substantial evidence evolves.

Sequential Organ Failure Assessment Score and the Need for Organ Support Predict Mortality in Allogeneic Stem Cell Transplant Patients Admitted to the Intensive Care Unit.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy resulting in increased definitive cure rates or extended disease-free survival in various malignant and nonmalignant hematologic diseases. However, because of the high risk of severe complications of this therapy, up to 50% of patients may require being admitted to the intensive care unit (ICU) to manage life-threatening conditions. We aimed to evaluate the in-hospital mortality of allo-HSCT recipients admitted to the ICU and to identify those variables associated with in-hospital mortality. A 10-year (January 2010 to December 2019), single-center, retrospective study was conducted in Vall d´Hebron University Hospital, Barcelona. We included all consecutive allo-HSCT patients who required admission to the ICU. Baseline and disease-related characteristics were registered. Severity scores and the need for organ support were also assessed on days 1, 3, and 5 of ICU admission. In-hospital mortality-associated independent variables were identified using the Cox proportional hazards regression model. Three hundred twenty-three patients underwent allo-HSCT during the study period, of whom 82 (25%) were admitted to the ICU; 53 (65%) male, with a median age of 51 (38-59) years. Most patients received allo-HSCT for the treatment of lymphoma (20 patients [24%]) or acute leukemia (44 patients [54%]). The median Acute Physiology And Chronic Health Evaluation II score was 23 (17-28), and the median Sequential Organ Failure Assessment (SOFA) score on admission was 9 (7-11). Forty-nine (60%) patients died in the ICU, and 11 (13%) died in the hospital after being discharged from the ICU. Disease-related characteristics were not associated with mortality. Yet, SOFA score on day 1 (hazard ratio [HR]: 1.11 [95% confidence interval {CI}: 1.04-1.02]; P = .002), the need for vasopressors on day 3 (HR: 2.35 [95% CI: 1.27-4.36]; P = .007), and a nondecreasing SOFA score on day 5 (HR: 2.13 [95% CI: 1.03-4.39]; P = .04), were independently associated with in-hospital mortality. Mortality in allo-HSCT patients who require ICU admission remains high. In the present study, SOFA score, the need for vasopressors on day 3, and a nondecreasing SOFA score on day 5 predicted in-hospital mortality.

Hemadsorption as a Treatment Option for Multisystem Inflammatory Syndrome in Children Associated With COVID-19. A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is characterized by hypercytokinemia leading to overwhelming inflammation. We describe the use of a hemadsorption device as part of the supportive treatment for cytokine storm.

Cytokine Hemoadsorption as Rescue Therapy for Critically Ill Patients With SARS-CoV-2 Pneumonia With Severe Respiratory Failure and Hypercytokinemia.

Introduction: A dysregulated inflammatory response, known as "cytokine storm", plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). Identifying patients with a dysregulated inflammatory response and at high risk for severe respiratory failure, organ dysfunction, and death is clinically relevant, as they could benefit from the specific therapies, such as cytokine removal by hemoadsorption. This study aimed to evaluate cytokine hemoadsorption as rescue therapy in critically ill patients with SARS-CoV-2 pneumonia, severe respiratory failure refractory to prone positioning, and hypercytokinemia. Methods: In this single center, observational and retrospective study, critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure, and hypercytokinemia were analyzed. All the patients underwent cytokine hemoadsorption using CytoSorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate clinical response to the prone position, and hypercytokinemia. Results: Among a total of 343 patients who were admitted to the intensive care unit (ICU) due to SARS-CoV-2 infection between March 3, 2020 and June 22, 2020, six patients received rescue therapy with cytokine hemoadsorption. All the patients needed invasive mechanical ventilation and prone positioning. A significant difference was found in the pre- and post-treatment D-dimer (17,868 mcg/ml [4,196-45,287] vs. 4,488 mcg/ml [3,166-17,076], p = 0.046), C-reactive protein (12.9 mg/dl [10.6] vs. 3.5 mg/dl [2.8], p = 0.028), ferritin (1,539 mcg/L [764-27,414] vs. 1,197 ng/ml [524-3,857], p = 0.04) and interleukin-6 (17,367 pg/ml [4,539-22,532] vs. 2,403 pg/ml [917-3,724], p = 0.043) levels. No significant differences in the pre- and post-treatment interleukin-10 levels (22.3 pg/ml [19.2-191] vs. 5.6 pg/ml [5.2-36.6], p = 0.068) were observed. Improvements in oxygenation (prehemoadsorption PaO2/FIO2 ratio 103 [18.4] vs. posthemoadsorption PaO2/FIO2 ratio 222 [20.9], p = 0.029) and in the organ dysfunction (prehemoadsorption SOFA score 9 [4.75] vs. posthemoadsorption SOFA score 7.7 [5.4], p = 0.046) were observed. ICU and in-hospital mortality was 33.7%. Conclusions: In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and SOFA score were also observed.

An approach to antibiotic treatment in patients with sepsis.

Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, which is time-dependent and associated with unacceptably high mortality. Thus, when treating suspicious or confirmed cases of sepsis, clinicians must initiate broad-spectrum antimicrobials within the first hour of diagnosis. Optimizing antibiotic use is essential to ensure successful outcomes and to reduce adverse antibiotic effects, as well as preventing drug resistance. All likely pathogens involved should be considered to provide an appropriate antibiotic coverage. Clinicians must investigate on the previous risk of multidrug-resistant (MDR) pathogens, and the principle of individualized dosing should replace the principle of standard dosing. The loading dose is an initial higher dose of an antibiotic for all patients, yet an individualized treatment approach for further doses should be implemented according to pharmacokinetics (PK)/pharmacodynamics (PD) and the presence of renal/liver dysfunction. Extended or continuous infusion of beta-lactams and therapeutic drug monitoring (TDM) can help to achieve therapeutic levels of antimicrobials. Reevaluation of duration and appropriateness of treatment at regular intervals are also necessary. De-escalation and shortened courses of antimicrobials must be considered for most patients, except in some justified circumstances. Leadership, teamwork, antimicrobial stewardship (AS) frameworks, guideline's recommendations on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches will help us to improve patients' quality of care.