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BACKGROUND: Sepsis is a medical emergency in which timely, appropriate antibiotic therapy improves patient outcomes. While the addition of emergency department (ED) pharmacists has been found to optimize timely antimicrobial therapy in patients with sepsis, the role of clinical staff pharmacists (CSPs) in the sepsis response has not been studied. METHODS: We implemented a process of incorporating CSPs in sepsis antimicrobial management in the ED. To evaluate the accuracy of antimicrobial selection by CSPs with a sepsis antibiotic algorithm and vancomycin dosing nomogram, a retrospective cohort study was conducted on patients with sepsis presenting to the ED from December 3, 2018 through March 31, 2020. RESULTS: Of the 157 sepsis alerts included in this study, CSPs correctly used the antibiotic selection algorithm in 154 (98%) instances and the vancomycin dosing nomogram in 147 (94%) instances. CONCLUSIONS: A process incorporating CSPs into the ED sepsis response resulted in high rates of accuracy for antibiotic selection and vancomycin dosing.

Introduction: Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in Intensive Care Unit (ICU) patients with circulatory shock are limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. Methods: We analyzed a dataset from an international, multicenter randomized clinical trial (RCT) evaluating protein dose in ICU patients. EEN was defined as initiating 48 hours. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. Results: We included 626 patients. Median age was 60 years [18-93], 55% had septic shock, 99% received norepinephrine alone and 91% received EN alone. Forty-two percent of EEN patients had persistent organ dysfunction syndrome-plus death at day 28, compared to 53% in the DEN group (p=0.04) (adjusted OR 0.60, 95% confidence intervals, 0.38-0.93, p=0.02). EEN was associated with more ICU-free days (9.3±9.2 vs. 5.7±7.9, p=0.0002), more days alive and free of vasopressors (7.1±3.1 vs. 6.3±3.2, p=0.007), and shorter duration of MV among survivors (9.8±10.9 vs. 13.8±14.5, p=0.0002). There were no differences in ICU/60-day mortality or feeding intolerance rates between groups.Conclusion: In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

Sepsis is the leading cause of death worldwide. Timely administration of antibiotics is recognized as the cornerstone in the management of sepsis. However, inappropriate use of antibiotics may lead to adverse effects and the selection of drug-resistant pathogens. Microbiological cultures remain the gold standard to diagnose infection despite their low sensitivity and the intrinsic delay to obtain the results. Certain biomarkers have the benefit of rapid turnover, potentially providing an advantage in timely diagnosis leading to accurate treatment. Over the last few decades, there is an ongoing quest for the ideal biomarker in sepsis. Procalcitonin (PCT), when used alone or alongside additional clinical information, has shown to be a promising tool to aid in the diagnosis and management of patients with sepsis. In February 2017, the Food and Drug Administration (FDA) approved the use of PCT to guide antibiotic treatment in lower respiratory tract infections and sepsis. Despite a good negative predictive value for bacterial infection, the utility of PCT-guided antibiotic initiation is conflicting at best. On the other hand, the use of PCT-guided antibiotic discontinuation has shown to reduce the duration of antibiotic use, the associated adverse effects, and to decrease the overall mortality. The current review discusses the history and pathophysiology of procalcitonin, synthesizes its utility in the diagnosis and management of sepsis, highlights its limitations and compares it with other biomarkers in sepsis.

Objective:Several studies have shown septic shock developing later during the hospital stay are associated with greater mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study aimed to evaluate the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock, as well as the optimal cut-off time period to categorize early and late-onset septic shock.Method: We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from 01/2011 to 12/2020. A multivariable Cox regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. A multivariable additive logistic regression was performed to estimate the odds ratio for mortality using the log-transformed admission-shock-onset-time. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality.The primary outcome was in-hospital mortality and the secondary outcome was ICU mortality.Results:A total of 2,520 patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital mortality [Hazard ratio (HR): 1.08, 95% confidence interval (CI): 1.05-1.11, p< 0.001] and ICU mortality (HR: 1.06, 95%CI: 1.03-1.10, pConclusion:In-hospital mortality continued to rise as admission-shock-onset-time increased in septic shock. No clear dichotomization between early and late septic shock can be ascertained and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.Trial RegistrationThis study was approved by Cleveland Clinic Institutional Review Board (IRB 15-1233).

Background\ud Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.\ud Methods\ud We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.\ud Results\ud The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.\ud Conclusion\ud The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.

Purpose of review The purpose of this study is to review the recent literature examining the clinical utility of markers of systemic oxygen extraction and perfusion in the diagnosis, treatment and prognosis of severe sepsis and septic shock. Recent findings When sepsis is accompanied by conditions in which systemic oxygen delivery does not meet tissue oxygen demands, tissue hypoperfusion begins. Tissue hypoperfusion leads to oxygen debt, cellular injury, organ dysfunction and death. Tissue hypoperfusion can be characterized using markers of tissue perfusion (central venous oxygen saturation and lactate), which reflect the interaction between systemic oxygen delivery and demands. For the last two decades, studies and quality initiatives incorporating the early detection and interruption of tissue hypoperfusion have been shown to improve mortality and altered sepsis care. Three recent trials, while confirming an all-time improvement in sepsis mortality, challenged the concept that rapid normalization of markers of perfusion confers outcome benefit. By defining and comparing haemodynamic phenotypes using markers of tissue perfusion, we may better understand which patients are more likely to benefit from early goal-directed haemodynamic optimization. Summary The phenotypic haemodynamic characterization of patients using perfusion markers has diagnostic, therapeutic and outcome implications in severe sepsis and septic shock. However, irrespective of haemodynamic phenotype, the outcome reflects the quality of care provided at the point of presentation. Utilizing these principles may allow more objective interpretation of resuscitation trials and translate these findings into current practice.

Frequently Blood Bank donors are found to have a presence of Total Anti-Bc in the serum in the absence of the Hepatitis B surface antigen (HBsAg) and the Hepatitis B Surface Antigen (Anti-Bs) antibody. This study was designed to determine the serological response to the vaccination against the Hepatitis B virus, and evaluate the effectiveness of the vaccine in such cases, taking into consideration that the protective antibody titers for Hepatitis B are measured in levels above 10 mUl/ml.Thirty-one patients with the HBsAg negative/Anti-Bs negative/Antil-Bc positive serological patterns received three doses of the recombinant DNA vaccine (Hepavax Gene 20 microg), in a 0, 1, 2 months vaccination schedule. Anti-HBs levels were taken 30 days after the application of the last dose. After the 3 doses of the vaccine, the Anti-HBs levels were100 mUl/ml in 89% of the cases,500 in 50% and1000 in 14.3% of the vaccinated patients. Only 3 patients (9.7%) did not show serological response 30 days after the application of the last dose of the vaccine. In conclusion, 90% of the patients administered the HBsAg negative/Anti-HBs negative/Anti-HBc positive serological patterns, obtained Anti-HBs levels considered protectors (10 mUl/m).