Outcome Of Sepsis Research Articles

Temperature control in sepsis.

Fever can be viewed as an adaptive response to infection. Temperature control in sepsis is aimed at preventing potential harms associated with high temperature (tachycardia, vasodilation, electrolyte and water loss) and therapeutic hypothermia may be aimed at slowing metabolic activities and protecting organs from inflammation. Although high fever (>39.5°C) control is usually performed in critically ill patients, available cohorts and randomized controlled trials do not support its use to improve sepsis prognosis. Finally, both spontaneous and therapeutic hypothermia are associated with poor outcomes in sepsis.

Sepsis Outcome after Major Abdominal Surgery Does Not Seem to Be Improved by the Use of Pentameric Immunoglobulin IgM: A Single-Center Retrospective Analysis.

Sepsis still represents a major public health issue worldwide, and the immune system plays a main role during infections; therefore, its activity is mandatory to resolve this clinical condition. In this report, we aimed to retrospectively verify in a real-life setting the possible usefulness of pentameric IgM plus antibiotics in recovering patients with sepsis after major abdominal surgery. We reviewed, from January 2013 until December 2019, all adult patients admitted to the ICU for sepsis or septic shock (2) after major abdominal surgery. Among these patients, were identified those that, according to legal indication and licenses in Italy, were treated with pentameric IgM plus antibiotics (Group A) or with antibiotics alone (Group B). The following parameters were evaluated: blood gas analysis, lactate, CRP, procalcitonin, endotoxin activity, liver and renal function, coagulation and blood cell count at different time points (every 48 h for at least 7 days). Differences between groups were analyzed using Fisher's exact test or a chi-square test for categorical variables. A Mann-Whitney U test or Kruskal-Wallis test were instead been performed to compare continuous variables. Univariate and multivariate analysis were also performed. Over a period of 30 months, 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects, no statistical differences were found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or according to inflammatory index, a score, lactate levels and mortality rate. A 48 h response was statistically more frequent in Group B than in Group A, while no differences were found in other clinical and laboratory evaluations. Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery.

Inoculum-Based Dosing: A Novel Concept for Combining Time with Concentration-Dependent Antibiotics to Optimize Clinical and Microbiological Outcomes in Severe Gram Negative Sepsis.

Certain classes of antibiotics show "concentration dependent" antimicrobial activity; higher concentrations result in increased bacterial killing rates, in contrast to "time dependent antibiotics", which show antimicrobial activity that depends on the time that antibiotic concentrations remain above the MIC. Aminoglycosides and fluoroquinolones are still widely used concentration-dependent antibiotics. These antibiotics are not hydrolyzed by beta-lactamases and are less sensitive to the inoculum effect, which can be defined as an increased MIC for the antibiotic in the presence of a relatively higher bacterial load (inoculum). In addition, they possess a relatively long Post-Antibiotic Effect (PAE), which can be defined as the absence of bacterial growth when antibiotic concentrations fall below the MIC. These characteristics make them interesting complementary antibiotics in the management of Multi-Drug Resistant (MDR) bacteria and/or (neutropenic) patients with severe sepsis. Global surveillance studies have shown that up to 90% of MDR Gram-negative bacteria still remain susceptible to aminoglycosides, depending on the susceptibility breakpoint (e.g., CLSI or EUCAST) being applied. This percentage is notably lower for fluoroquinolones but depends on the region, type of organism, and mechanism of resistance involved. Daily (high-dose) dosing of aminoglycosides for less than one week has been associated with significantly less nephro/oto toxicity and improved target attainment. Furthermore, higher-than-conventional dosing of fluoroquinolones has been linked to improved clinical outcomes. Beta-lactam antibiotics are the recommended backbone of therapy for severe sepsis. Since these antibiotics are time-dependent, the addition of a second concentration-dependent antibiotic could serve to quickly lower the bacterial inoculum, create PAE, and reduce Penicillin-Binding Protein (PBP) expression. Inadequate antibiotic levels at the site of infection, especially in the presence of high inoculum infections, have been shown to be important risk factors for inadequate resistance suppression and therapeutic failure. Therefore, in the early phase of severe sepsis, effort should be made to optimize the dose and quickly lower the inoculum. In this article, the authors propose a novel concept of "Inoculum Based Dosing" in which the decision for antibiotic dosing regimens and/or combination therapy is not only based on the PK parameters of the patient, but also on the presumed inoculum size. Once the inoculum has been lowered, indirectly reflected by clinical improvement, treatment simplification should be considered to further treat the infection.

Patient-reported penicillin allergy and intensive care unit outcomes in sepsis

Patient-reported penicillin allergy and intensive care unit outcomes in sepsis

Intersection of sepsis, atrial fibrillation, and severe obesity: a population-based analysis in the United States.

Atrial fibrillation (AF) is an indicator of poor prognosis in patients with sepsis and can increase the risk of stroke and mortality. Data on the impact of severe obesity on the outcomes of sepsis complicated by AF remains poorly understood. National Inpatient Sample (2018) and ICD-10 CM codes were used to identify the principal sepsis admissions with AF. We assessed comorbidities and outcomes of sepsis in people without obesity (BMI < 30) vs. non-severe obesity (BMI 30-35) and severe obesity (BMI > 35) cohorts. We also did a subgroup analysis to further stratify obesity based on metabolic health and analyzed the findings. The primary outcomes were the prevalence and adjusted odds of AF, AF-associated stroke, and all-cause mortality in sepsis by obesity status. Multivariable regression analyses were adjusted for patient- and hospital-level characteristics and comorbidities. Our main analysis showed that of the 1,345,595 sepsis admissions, the severe obesity cohort was the youngest (median age 59 vs. non-severe 64 and people without obesity 68 years). Patients with obesity, who were often female, were more likely to have hypertension, diabetes, congestive heart failure, chronic pulmonary disease, and chronic kidney disease. The crude prevalence of AF was highest in non-severe obesity (19.9%). The adjusted odds of AF in non-severe obesity (OR 1.21; 95% CI:1.16-1.27) and severe obesity patients with sepsis (OR 1.49; 95% CI:1.43-1.55) were significantly higher than in people without obesity (p < 0.001). Paradoxically, the rates of AF-associated stroke (1%, 1.5%, and 1.7%) and in-hospital mortality (3.3%, 4.9%, and 7.1%) were lowest in the severe obesity cohort vs. the non-severe and people without obesity cohorts, respectively. On multivariable regression analyses, the all-cause mortality revealed lower odds in sepsis-AF patients with severe obesity (OR 0.78; 95% CI:0.67-0.91) or non-severe obesity (OR 0.63; 95% CI:0.54-0.74) vs. people without obesity. There was no significant difference in stroke risk. A higher prevalence of cardiovascular comorbidities can be linked to a higher risk of AF in people with obesity and sepsis. Paradoxically, lower rates of stroke and all-cause mortality secondary to AF in people with obesity and sepsis warrant further investigation.

A Prospective Cohort Protocol for the Remnant Investigation in Sepsis Study.

Sepsis is a common and deadly syndrome, accounting for more than 11 million deaths annually. To mature a deeper understanding of the host and pathogen mechanisms contributing to poor outcomes in sepsis, and thereby possibly inform new therapeutic targets, sophisticated, and expensive biorepositories are typically required. We propose that remnant biospecimens are an alternative for mechanistic sepsis research, although the viability and scientific value of such remnants are unknown. The Remnant Biospecimen Investigation in Sepsis study is a prospective cohort study of 225 adults (age ≥ 18 yr) presenting to the emergency department with community sepsis, defined as sepsis-3 criteria within 6 hours of arrival. The primary objective was to determine the scientific value of a remnant biospecimen repository in sepsis linked to clinical phenotyping in the electronic health record. We will study candidate multiomic readouts of sepsis biology, governed by a conceptual model, and determine the precision, accuracy, integrity, and comparability of proteins, small molecules, lipids, and pathogen sequencing in remnant biospecimens compared with paired biospecimens obtained according to research protocols. Paired biospecimens will include plasma from sodium-heparin, EDTA, sodium fluoride, and citrate tubes. The study has received approval from the University of Pittsburgh Human Research Protection Office (Study 21120013). Recruitment began on October 25, 2022, with planned release of primary results anticipated in 2024. Results will be made available to the public, the funders, critical care societies, laboratory medicine scientists, and other researchers.

Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA/ACEP/PIDS/SHEA/SHM/SIDP Position Paper.

The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients.

Impact of pulmonary hypertension on outcomes of influenza pneumonia patients: A nationwide analysis

Background: Pulmonary hypertension can be a significant cause of morbidity and mortality for influenza pneumonia (IP) patients. We performed analysis from the multicentric National Inpatient Sample (NIS) datasets to study the influence of disorders of pulmonary hypertension on the outcomes in IP patients. Methods: We used NIS 2016–2019 to identify IP hospitalizations (between 22–90 years of age) and divided them into with and without pulmonary hypertension (herein PHDPC). We analyzed for differences in demographics, primary (all-cause mortality) and other secondary outcomes. Results: Of 353,460 IP hospitalizations, 6.5% had PHDPC. The PHDPC cohort had more elderly, females, African Americans, and Medicare enrollees predominantly with more hospitalizations to large bed sizes and urban teaching hospitals, and higher cardiovascular comorbidities than non-PHDPC cohort. PHDPC had higher primary outcomes for in-hospital mortality (8.9% vs. 5.8%, adjusted OR 1.4, 95% CI: 1.21–1.61). PHDPC also had higher secondary outcomes for sepsis, septic shock, cardiogenic shock and need for mechanical ventilation, prolonged ventilation, hospital resource utilization for longer mean length of stay, mean hospitalization cost, transfer to other facilities or need for home health care, and high risk for 30-day readmission than the non-PHDPC cohort. Conclusions: With our study, we provide contemporary data for the outcomes of IP inpatients with pulmonary hypertension and depict worse outcomes for mortality, complications, and hospital resource utilization. Although our study does not include stratification for vaccination status for the outcome, primary care physicians, cardiologists, and pulmonologists should pro-actively educate patients on preventive strategies during the flu season.

Sepsis Course and Outcome Depends on the Genetic Variant in the 3`-Region of Aquaporin 4 Gene &lt;i&gt;AQP4&lt;/i&gt; and Comorbidities

Aquaporins 4 and 5 are proteins that form water channels in the cell membrane, participate in the transfer and migration of immune cells, being expressed on many cell types including CNS astrocytes, kidney cells, lungs, and the immune system. We have previously shown that AQP5 genetic polymorphism is associated with different outcomes of abdominal sepsis. Since another common aquaporin protein, AQP4, is also expressed on the surface of immunocompetent cells, determining cell motility, it was suggested that AQP4 may also be important in the pathogenesis of sepsis, and that AQP4 polymorphism may predetermine sepsis severity and outcome. AQP4 rs1058427 genetic polymorphism has not been studied earlier. The aim of the study was to determine the effects of region 3` polymorphism in the AQP4 gene on the clinical course and outcome of sepsis.Materials and methods. The prospective study included 290 ICU patients from three clinical hospitals in Moscow aged 18–75 years with clinical signs of sepsis (SEPSIS-3, 2016).Results. It was found that the minor T allele of the AQP4 rs1058427 gene provides strong protection against septic shock, as among GG genotype carriers septic shock developed in 66%, but in presence of the minor T allele dropped to half of cases (P=0.009, Fisher’s exact test, OR=1.99, 95% CI: 1.12–3.55, N=290). There was a significant association between AQP4 rs1058427 genetic polymorphism and 30-day hospital mortality in a subgroup of patients with more severe organ dysfunction and higher comorbidity burden (cardiovascular diseases, type II diabetes mellitus) requiring extracorporeal treatment modalities and ventilator support for 5 or more days (N=66). Carriers of the minor T allele showed better survival rates as compared AQP4 rs1058427 GG genotype carriers (5 deaths out of 10 and 47 deaths out of 56, respectively, P=0.003, Fisher’s exact test, N=66, OR=5.22, 95% CI: 1.25–21.82, P=0.009, log-rank criterion).Conclusion. The minor AQP4 rs1058427 T allele is associated with protection against septic shock and better survival in sepsis in a group of ICU patients with high comorbidity burden requiring extracorporeal life support interventions.

Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.

DECIPHERING GUT MICROBIOTA IN PATIENTS WITH SEVERE SEPSIS AND SEPTIC SHOCK.

Introduction: Gut microbiota dysbiosis is associated with susceptibility to sepsis and poor outcomes. However, changes to the intestinal microbiota during sepsis and their value as biomarkers are unclear. In this study, we compared the intestinal microbiota of patients with sepsis and healthy controls. Methods: Stool was collected from patients with sepsis (subdivided according to mortality) and controls. Microbiome diversity and composition were analyzed by 16S rRNA gene pyrosequencing. The α-diversity of the intestinal microbiome was determined using operational taxonomic unit counts and the Chao1, Shannon, and ACE indices. Adjusted Cox regression analyses assessed 6-month mortality risk factors. Results: Fifty-nine patients (14 in-hospital deaths) and 29 healthy controls were enrolled. Operational taxonomic unit counts and Chao1 and ACE indices were lower in the nonsurvivor than in the other groups. The controls showed a higher Shannon and lower Simpson index than did the sepsis group. The genus Blautia was more abundant in controls than in the sepsis group, and Faecalibacterium less abundant in the nonsurvivor than in the other groups. Regression analysis associated low Shannon index with 6-month mortality. Conclusions: Survivors of sepsis, nonsurvivors, and healthy controls have different gut microbiomes, and a low Shannon index is a risk factor for 6-month mortality.

Is Carboxyhaemoglobin an Effective Bedside Prognostic Tool for Sepsis and Septic Shock Patients?

Proper management of sepsis poses a challenge even today, with early diagnosis and targeted treatment being the most important steps. Easy, cost-effective bedside tools are needed in order to pinpoint towards the outcome of sepsis or septic shock. This study aims to find a correlation between Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) severity scores, the Neutrophil-Lymphocytes Ratio (NLR) and carboxyhaemoglobin (COHb) levels in septic or septic shock patients with the scope of establishing a bed side cost-effective prognostic tool. A pilot, prospective, observational, and ongoing study was conducted on 61 patients admitted with sepsis or septic shock according to the SEPSIS 3 Consensus definition. We followed clinical and paraclinical parameters on day 1 (D1) and day 5 (D5) after meeting the inclusion criteria. On D1 we found a statistically significant positive correlation between each severity score (p <0.0001), r = 0.7287 for SOFA vs. APACHE II with CI: 0.5841-0.8285, r = 0.6862 for SOFA vs. SAPS II with CI: 0.5251-0.7998 and r = 0.8534 for APACHE II vs. SAPS II with CI: 0.7663 to 0.9097. On D5 we observed similar results: a significant positive correlation between each severity score (p <0.0001), with r = 0.7877 for SOFA vs. APACHE II with CI: 0.6283 to 0.8836, r = 0.8210 for SOFA vs. SAPS II with CI: 0.6822 to 0.9027 and r = 0.8880 for APACHE II vs. SAPS II., CI: 0.7952 to 0.9401. Nil correlation was found between the severity scores, NLR and COHb on D1 and D5. Cost-effective bedside tools to pinpoint towards the outcome of sepsis are yet to be found, however the positive correlation between the severity scores point out to a combination of such tools for prognosis prediction of septic or septic shock patients.

OC 66.4 Platelet Factor 4 (Pf4) Enhances Bacterial Uptake and Clearance by the Endothelium, Contributing to Improved Outcomes in Sepsis

OC 66.4 Platelet Factor 4 (Pf4) Enhances Bacterial Uptake and Clearance by the Endothelium, Contributing to Improved Outcomes in Sepsis

OC 78.3 Interferon-Induced Transmembrane Protein 3 in Platelets Mediates Granule Secretion, Thrombosis, and Pathophysiological Outcomes in Sepsis

OC 78.3 Interferon-Induced Transmembrane Protein 3 in Platelets Mediates Granule Secretion, Thrombosis, and Pathophysiological Outcomes in Sepsis

Prognostic value of platelet to lymphocyte ratio in sepsis outcome prediction

Prognostic value of platelet to lymphocyte ratio in sepsis outcome prediction

A novel opsonic eCIRP inhibitor for lethal sepsis.

Sepsis is a life-threatening inflammatory condition partly orchestrated by the release of various damage-associated molecular patterns such as extracellular cold-inducible RNA-binding protein (eCIRP). Despite advances in understanding the pathogenic role of eCIRP in inflammatory diseases, novel therapeutic strategies to prevent its excessive inflammatory response are lacking. Milk fat globule-epidermal growth factor-VIII (MFG-E8) is critical for the opsonic clearance of apoptotic cells, but its potential involvement in the removal of eCIRP was previously unknown. Here, we report that MFG-E8 can strongly bind eCIRP to facilitate αvβ3-integrin-dependent internalization and lysosome-dependent degradation of MFG-E8/eCIRP complexes, thereby attenuating excessive inflammation. Genetic disruption of MFG-E8 expression exaggerated sepsis-induced systemic accumulation of eCIRP and other cytokines, and consequently exacerbated sepsis-associated acute lung injury. In contrast, MFG-E8-derived oligopeptide recapitulated its eCIRP binding properties, and significantly attenuated eCIRP-induced inflammation to confer protection against sepsis. Our findings suggest a novel therapeutic approach to attenuate eCIRP-induced inflammation to improve outcomes of lethal sepsis.

Current knowledge of thrombocytopenia in sepsis and COVID-19.

Thrombocytopenia, characterized by a decrease in platelet count, is commonly observed in sepsis and COVID-19. In sepsis, thrombocytopenia can result from various mechanisms, including impaired platelet production in the bone marrow, accelerated platelet destruction due to increased inflammation, sequestration of platelets in the spleen, immune-mediated platelet destruction, or dysregulated host responses. Similarly, thrombocytopenia has been reported in COVID-19 patients, but the immune-related mechanisms underlying this association remain unclear. Notably, interventions targeting thrombocytopenia have shown potential for improving outcomes in both sepsis and COVID-19 patients. Understanding these mechanisms is crucial for developing effective treatments.

Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk

BackgroundSepsis-induced immunosuppression is a frequent cause of opportunistic infections and death in critically ill patients. A better understanding of the underlying mechanisms is needed to develop targeted therapies. Circulating bile acids with immunosuppressive effects were recently identified in critically ill patients. These bile acids activate the monocyte G-protein coupled receptor TGR5, thereby inducing profound innate immune dysfunction. Whether these mechanisms contribute to immunosuppression and disease severity in sepsis is unknown. The aim of this study was to determine if immunosuppressive bile acids are present in endotoxemia and septic shock and, if so, which patients are particularly at risk.MethodsTo induce experimental endotoxemia in humans, ten healthy volunteers received 2 ng/kg E. coli lipopolysaccharide (LPS). Circulating bile acids were profiled before and after LPS administration. Furthermore, 48 patients with early (shock onset within < 24 h) and severe septic shock (norepinephrine dose > 0.4 μg/kg/min) and 48 healthy age- and sex-matched controls were analyzed for circulating bile acids. To screen for immunosuppressive effects of circulating bile acids, the capability to induce TGR5 activation was computed for each individual bile acid profile by a recently published formula.ResultsAlthough experimental endotoxemia as well as septic shock led to significant increases in total bile acids compared to controls, this increase was mild in most cases. By contrast, there was a marked and significant increase in circulating bile acids in septic shock patients with severe liver failure compared to healthy controls (61.8 µmol/L vs. 2.8 µmol/L, p = 0.0016). Circulating bile acids in these patients were capable to induce immunosuppression, as indicated by a significant increase in TGR5 activation by circulating bile acids (20.4% in severe liver failure vs. 2.8% in healthy controls, p = 0.0139).ConclusionsCirculating bile acids capable of inducing immunosuppression are present in septic shock patients with severe liver failure. Future studies should examine whether modulation of bile acid metabolism can improve the clinical course and outcome of sepsis in these patients.Graphical abstract

Antimicrobial Resistance Pattern and Empirical Antibiotic Treatments in Neonatal Sepsis: A Retrospective, Single-Center, 12-Year Study.

Neonatal sepsis is an important cause of morbidity and mortality in neonatal intensive care units (NICUs). Continuous evaluation of antimicrobial resistance (AMR) profiles is advised to implement antimicrobial stewardship (AMS) programs and establish effective empiric antibiotic protocols. AMS may reduce AMR in NICUs and improve sepsis outcomes. In this retrospective observational study, we report data on culture-positive neonatal sepsis, assessing differences after the implementation of an AMS program (2011-2016 vs. 2017-2022). A total of 215 positive bacterial cultures from 169 infants were retrieved, with 79 early-onset (36.7%) and 136 late-onset (63.3%) sepsis episodes. Frequent causative agents for early-onset sepsis were S. agalactiae and E. coli, all susceptible to empiric treatment. Late-onset sepsis was mainly caused by Enterobacterales and S. aureus. Aminoglycosides, cefotaxime, and piperacillin-tazobactam resistance among Enterobacterales was substantially low; S. aureus was mostly susceptible to oxacillin and vancomycin. There were no differences in mortality and multidrug-resistant pathogens rates between the two study periods. There were five episodes of fungal late-onset sepsis, mostly due to C. albicans, of which one was fatal. The microbial distribution pattern and AMR profiles overlapped with other European studies. Because susceptibility patterns are rapidly changing worldwide, with the emerging threat of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases producers, infection prevention and control practices and AMS strategies require continuous optimization to limit selection pressure and AMR escalation.

A-155 Unlocking the Complete Blood Count: Derivation of a Single-Panel Laboratory Test That Includes Monocyte Distribution Width to Create a Universal Sepsis Screening Tool

Abstract Background Sepsis is the leading cause of in-hospital death. Outcome improvement requires rapid detection and early antimicrobial therapy. The complete blood count (CBC) is ordered for more than two-thirds of all patients in the emergency department (ED). Individual CBC components have limited utility for sepsis screening due to low specificity and sensitivity. We sought to create a reliable sepsis screening tool by combining components of the CBC differential. Methods In this single-center retrospective cohort study, all adult patients who had a CBC with differential performed within 6 h of ED arrival during a 20-month period were eligible for inclusion. Repeat ED visits by the same patient were excluded. Our primary outcome was manifestation of sepsis within 72 h of ED arrival, detected from timestamped electronic health records using a previously validated electronic phenotype based on Sepsis-3 consensus criteria. Multivariable logistic regression was performed to identify individual components of the CBC differential that were independently associated with our outcome and to identify optimal cutoffs for discretization. Odds ratios were used to assign weights to each component and to derive a 10-point system for scoring likelihood of sepsis. Results 34 864 patients were included; 1306 (3.7%) met sepsis outcome criteria within 72 h of ED arrival and 181 (0.5%) had septic shock. White blood cell (WBC) count, monocyte distribution width (MDW), and the neutrophil to lymphocyte count ratio were found to predict sepsis. As shown in the figure, there was a linear relationship between our CBC infection severity index and likelihood of developing sepsis and septic shock. Patients with a high risk score (8 or above) had a greater than one in four chance of developing sepsis within 72 h. Conclusion A simple ten-point index derived from the most commonly used laboratory panel in medicine reliably estimated likelihood of developing sepsis.