Criteria For Sepsis Research Articles

Serum Neutrophil Gelatinase-associated Lipocalin: A Potential Marker of Impending Acute Kidney Injury in Sepsis

Abstract Introduction: Kidney injury is an inherent component of sepsis. Serum creatinine (S. Cr) as a marker of kidney injury has certain pitfalls and may not rise until significant kidney function has been lost. This study evaluated neutrophil gelatinase-associated lipocalin (NGAL) as a marker of impending acute kidney injury (AKI) in sepsis. Materials and Methods: A hospital-based cross-sectional, observational analytic study was conducted during one calendar year among patients admitted to medicine wards/intensive care units of a tertiary care hospital in Western India. A total of 80 study participants of age above 18 years fulfilling the criteria of sepsis were recruited in the study according to the Sepsis-3 criteria. Patients below 18 years of age, pregnant women, patients with known kidney diseases, malignancies, autoimmune diseases, and exposure to nephrotoxic agents (i.e. aminoglycoside, angiotensin-converting-enzyme inhibitors, and contrast agents) within the past 2 months, and patients who failed to give consent were excluded from the study. Clinical and biochemical data were collected till Day 7. Sequential organ failure assessment (SOFA) scores were calculated on Day 1 and Day 3. NGAL levels were measured on Day 3. Results: The mean age was 48 ± 19 years, with a male preponderance (63.8%). The mean of SOFA score on Day 1 and Day 3 was 9.84 ± 3.19 and 13.75 ± 3.14, respectively. The mean serum NGAL levels on Day 3 were 436.78 ± 242.23 ng/ml. The mean serum urea on Day 7 (86.99 ± 22.88 mg/dL) was significantly higher than on Day 3 (38.64 ± 9.49 mg/dL) (P = 0.004). Similarly, the mean S. Cr on Day 7 (2.97 ± 1.45 mg/dL) was significantly higher than on Day 3 (0.82 ± 0.23 mg/dL) (P = 0.033). The estimated glomerular filtration rate (eGFR) on Day 7 (35.42 ± 18.99 mL/min/1.73 m2) was also significantly lower in comparison to Day 3 (117.67 ± 56.10 mL/min/1.73 m2) (P < 0.05). Serum NGAL showed a significant positive correlation with S. Cr on Day 3 (r = 0.3257, P = 0.003), Day 7 (r = 0.5944, P < 0.00001), and mean change in S. Cr (r = 0.5562, P < 0.00001). Serum NGAL showed a significant negative correlation with eGFR on Day 3 (r = −0.3061, P = 0.005), Day 7 (r = −0.4362, P = 0.00005), and mean change in eGFR (r = −0.1629, P < 0.0001). Receiver-operating curve analysis showed 90.9% sensitivity and 98.3% specificity of NGAL (cutoff value 152 ng/ml) to predict impending AKI. Conclusion: Traditional marker of renal dysfunction (S. Cr, eGFR) had a significant correlation with NGAL. NGAL can predict impending AKI in sepsis patients earlier than S. Cr or eGFR.

Serum monocyte chemotactic protein 1 and soluble mannose receptor aid predictive diagnosis of pediatric sepsis.

To investigate the value of serum monocyte chemotactic protein 1 (MCP-1) and soluble mannose receptor (sMR) for predictive diagnosis of pediatric sepsis. This study retrospectively analyzed the data of 82 children with acute and severe signs of inflammation. According to the diagnostic criteria of sepsis, these children were divided into a sepsis group (40 cases) and a non-sepsis group (42 cases). In addition, 50 children who received health examinations during the same time period in Cangzhou Central Hospital were selected as a control group. According to the prognosis of the children in the sepsis group, they were further divided into a survival group (33 cases) and a death group (7 cases). The levels of blood indicators, inflammatory markers, liver and kidney function indicators, MCP-1 level, and sMR were collected from the children. The efficacy of using sMR and MCP-1 levels in the predictive diagnosis of sepsis was analyzed by using the area under the ROC curve (AUC). Serum levels of MCP-1 and sMR were (452.32±2.79) μg/ml and (97.23±.15) μg/ml, respectively, in the sepsis group, significantly higher than those in all controls (P<0.001). In the death group, the levels of white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), sMR, and MCP-1 were significantly higher compared to the survival group (P<0.05). The AUC for CRP in predictive diagnosis of sepsis was 0.9075; the AUC for PCT was 0.8759; the AUC for sMR was 0.9244; and the AUC for MCP-1 was 0.9406. Serum sMR and MCP-1 levels can help predict the diagnosis of pediatric sepsis.

Presepsin as a predictor of septic shock and mortality in patients with urinary tract infection according to the Sepsis-3 definitions

The objective of this study was to investigate whether presepsin can serve as a useful biomarker for predicting septic shock and mortality rates in patients with urinary tract infections (UTI) as defined by the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). This single-center and prospective observational study was carried out between December 2019 and December 2022 and included 171 UTI patients divided into two groups: a non-septic shock group (n = 121) and a septic shock group (n = 50). The primary outcome of this study was the development of septic shock; the secondary outcome was 30-day hospital mortality. Receiver operating characteristic (ROC) curves and multivariate regression analyses were performed to investigate the predictive value of presepsin levels for septic shock and the Cox proportional hazards model was used to determine the risk factors for 30-day hospital mortality in UTI patients. Septic shock patients had significantly higher serum levels of presepsin when compared to the non-septic shock group (p &lt; 0.001). In multivariate logistic regression analysis, presepsin demonstrated its independent role as a risk factor for septic shock (odds ratio (OR): 1.002; 95% confidence interval (CI): 1.001–1.002; p &lt; 0.001). The multivariate Cox proportional hazards model indicated that presepsin represents a significant predictor of 30-day hospital mortality in septic shock patients (hazard ratio (HR): 1.0005; 95% CI: 1.0001–1.001; p &lt; 0.05). The ROC curve for diagnosing septic shock had an area under the curve (AUC) of 0.739 with a cutoff value of 447 pg/mL for presepsin. For the prediction of 30-day hospital mortality in patients with UTI, an optimal presepsin cutoff of 709 pg/mL was determined; ROC curve analysis yielded an AUC of 0.744. When applying the Sepsis-3 criteria, presepsin levels represented a significant independent risk factor for septic shock and 30-day hospital mortality in UTI patients.

Characteristics and Cluster Analysis of 18,030 Sepsis Patients Who Were Admitted to Thailand's Largest National Tertiary Referral Center during 2014-2020 to Identify Distinct Subtypes of Sepsis in Thai Population.

This study aimed to investigate the demographic, clinical, and laboratory characteristics of sepsis patients who were admitted to our center during 2014-2020 and to employ cluster analysis, which is a type of machine learning, to identify distinct types of sepsis in Thai population. Demographic, clinical, laboratory, medicine, and source of infection data of patients admitted to medical wards of Siriraj Hospital (Bangkok, Thailand) during 2014-2020 were collected. Sepsis was diagnosed according to the Sepsis-3 criteria. Nineteen demographic, clinical, and laboratory variables were analyzed using hierarchical clustering to identify sepsis subtypes. Of 98,359 admissions, 18,030 (18.3%) had sepsis. Respiratory tract was the most common site of infection. The mean Sequential Organ Failure Assessment (SOFA) score was 4.21 ± 2.24, and the median serum lactate level was 2.7 mmol/L [range: 0.4-27.5]. Twenty percent of admissions required vasopressor. In-hospital mortality was 19.6%. Ten sepsis subtypes were identified using hierarchical clustering. Three clusters (clusters L1-L3) were considered low risk, and seven clusters (clusters H1-H7) were considered high risk for in-hospital mortality. Cluster H1 had prominent hematologic abnormalities. Clusters H3 and H5 had younger ages and significant hepatic dysfunction. Cluster H5 had multiple organ dysfunctions, and a higher proportion of cluster H5 patients required vasopressor, mechanical ventilation, and renal replacement therapy. Cluster H6 had more respiratory tract infection and acute respiratory failure and a lower SpO2/FiO2 value. Cluster analysis revealed 10 distinct subtypes of sepsis in Thai population. Furthermore, the study is needed to investigate the value of these sepsis subtypes in clinical practice.

Clinical prognostic models in children with sepsis in low- and middle-income countries: a systematic review and meta-analysis.

Sepsis is the leading cause of child death worldwide, with the majority of these deaths occurring in low- and middle-income countries (LMICs). The aim of this systematic review and meta-analysis was to describe clinical prognostic scores and models for pediatric sepsis outcomes and assess the performance of these scores for predicting mortality in LMICs. Ovid Medline, CINAHL, Cochrane Library, EBSCO Global Health, and Web of Science, were searched through September 2022 for citations related to the development or validation of a clinical prognostic score or model among children with sepsis, conducted in LMIC. Titles, abstracts, and full texts were screened by two independent reviewers and data extracted included population characteristics, variables included, outcomes, and model performance. Risk of bias was assessed with the Prediction Model Risk of Bias Assessment Tool (PROBAST). 4,251 titles/abstracts and 315 full-text studies were screened, with 12 studies meeting inclusion criteria. Study countries included India, China, Egypt, Indonesia, Tanzania, and a multi-site study in Latin America. Prognostic scores/models included existing scores such as PELOD-2, pSOFA, PRISM, P-MODS, refractory shock criteria. There was high risk of bias in all studies. Meta-analysis was possible for pSOFA, PELOD-2, PRISM, and P-MODS, with pooled area under the receiver-operator characteristic curve of 0.86 (95%CI 0.78-0.94), 0.83 (95% CI 0.76-0.91), respectively. Relatively few clinical scores and models have been externally validated for prognostication and risk-stratification among children with sepsis in diverse LMIC settings. Notably there were no studies from low-income countries. Some potentially relevant studies were excluded due to lack of clarity regarding the presence of sepsis in the study populations. More widespread and standardized use of sepsis criteria may aid in better understanding the burden of sepsis and prognostic model performance at the bedside among children in LMICs. Further research to externally validate, implement and adapt these models is needed to account for challenges in use of these scores in resource-limited settings. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340126, PROSPERO [CRD42022340126].

Sepsis-like HPeV encephalitis in young infants – case series

Human parechovirus is the most common underrecognised aetiological agent of encephalitis in children younger than 90 days. The aim of this study is to describe the clinical manifestation, laboratory features, and potential risk factors for severe parechovirus-related sepsis-like encephalitis. The case series included five infants aged below three months diagnosed with sepsis-like parechovirus encephalitis. The diagnosis was based on the patients’ neurological symptoms, the criteria of sepsis defined by the National Institute for Health and Care Excellence, and parechovirus-positive cerebrospinal fluid polymerase chain reaction (PCR). The majority of patients presented with irritability, fever, abnormal muscle tone, mottling, decreased activity, tachycardia, abdominal distension, and absence of neonatal developmental reflexes. No abnormalities in the cerebrospinal fluid were identified. Abnormal blood laboratory measurements included lymphopaenia, leukopaenia, and anaemia. The case series highlights the necessity to perform cerebrospinal fluid PCR for parechovirus in infants with sepsis-like illness and neurological signs but without cerebrospinal fluid signs of inflammation.

Bacteremia Following Alkalihalobacillus clausii (Formerly Bacillus clausii) Administration in Immunosuppressed Adults: A Case Series

(1) Background: Given the widespread use of Alkalihalobacillus clausii (A. clausii) as a probiotic in recent decades and the detection of bacteremia cases in a group of patients, we sought to analyze cases of A. clausii bacteremia following oral probiotic use (2) Methods: A retrospective observational study was conducted at a private hospital in San Jose, Costa Rica. Cases of bacteremia caused by A. clausii confirmed by the microbiology laboratory were analyzed in patients who received oral treatment with this probiotic between January 2020 and January 2022. In addition, an isolate (HCB-AC2) was compared through whole genome sequencing to demonstrate the correlation of bacteremia and A. clausii. Possible vulnerability factors related to the development of this condition were determined. (3) Results: Four cases were identified in this hospital over 2 years. Genomic analysis of isolate HCB-AC2, using two different methods, showed identical results. This indicates that HCB-AC2 is genomically identical to ENTpro and the Enterogermina® reference genome. The median age was 71 years, and all patients had some degree of immunosuppression. All patients met at least three sepsis criteria at the time of bacterial identification. Most patients were treated with vancomycin and levofloxacin. Three of the identified patients died. (4) Conclusion: A. clausii can be used as a probiotic, but caution is advised when used in immunosuppressed and elderly patients. These findings align with those reported in similar case studies.

Pediatric Sepsis Diagnosis, Management, and Sub-phenotypes.

Sepsis and septic shock are major causes of morbidity, mortality, and health care costs for children worldwide, including >3 million deaths annually and, among survivors, risk for new or worsening functional impairments, including reduced quality of life, new respiratory, nutritional, or technological assistance, and recurrent severe infections. Advances in understanding sepsis pathophysiology highlight a need to update the definition and diagnostic criteria for pediatric sepsis and septic shock, whereas new data support an increasing role for automated screening algorithms and biomarker combinations to assist earlier recognition. Once sepsis or septic shock is suspected, attention to prompt initiation of broad-spectrum empiric antimicrobial therapy, fluid resuscitation, and vasoactive medications remain key components to initial management with several new and ongoing studies offering new insights into how to optimize this approach. Ultimately, a key goal is for screening to encompass as many children as possible at risk for sepsis and trigger early treatment without increasing unnecessary broad-spectrum antibiotics and preventable hospitalizations. Although the role for adjunctive treatment with corticosteroids and other metabolic therapies remains incompletely defined, ongoing studies will soon offer updated guidance for optimal use. Finally, we are increasingly moving toward an era in which precision therapeutics will bring novel strategies to improve outcomes, especially for the subset of children with sepsis-induced multiple organ dysfunction syndrome and sepsis subphenotypes for whom antibiotics, fluid, vasoactive medications, and supportive care remain insufficient.

Impact of the empirical therapy timing on the clinical progress of septic shock patients

AimTo evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock. Materials and MethodWe included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis. ResultsAntibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality. ConclusionTraining programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation.

Correlation of systemic immune-inflammation index with immature to total neutrophil ratio (IT Ratio) in septic neonates admitted to Wangaya Regional General Hospital Denpasar

Introduction: Early diagnosis and management of neonatal sepsis plays an important role in determining patient outcomes. The Immature to Total Neutrophil Ratio (IT ratio) is one of the diagnostic criteria for neonatal sepsis. However, the IT ratio examination is separate from the complete blood examination, and must be carried out manually or with an automatic microscope. The systemic immune-inflammation index (SII) is calculated by multiplying the number of platelets by the number of neutrophils and dividing by the number of lymphocytes derived from the complete blood count (CBC) examination. Recent studies have shown that SII values increase significantly at the time of diagnosis of neonatal sepsis. This study aims to find the correlation between the IT ratio and SII in septic neonates. Methods: This cross-sectional analytical observational study was conducted at the Wangaya Regional General Hospital, Denpasar. Data was taken from medical records of patients admitted from June 2022 to September 2023. Neonates with major congenital abnormalities, autoimmune diseases, immunodeficiency conditions and incomplete medical record data were excluded from the study. The correlation between the SII value and the IT ratio was analyzed using the Pearson correlation test. Data analysis was carried out using the SPSS version 25 software. Results: This study consisted of 31 septic neonates who met the inclusion and exclusion criteria. Most of the subjects in this study were male and preterm neonates. The median IT ratio and SII were 0.20 and 875.92 x103/ul respectively. The correlation value or r value between SII and the IT ratio was 0.386 with a P value of 0.060. Conclusion: Increased SII in septic neonates occurs due to thrombocytosis and neutrophilia as a response to systemic inflammation. Meanwhile, lymphocyte activation is inhibited which causes a decrease in immune function. Although no correlation between the IT ratio and SII was observed, further diagnostic research needs to be carried out to analyze the ability of SII to diagnose neonatal sepsis.

271. Epidemiology of ESBL Klebsiella pneumoniae Clonal Group 307 in Stony Brook, NY

Abstract Background According to the most recent CDC threat report infections caused by ESBL and carbapenem-resistant Klebsiella pneumoniae (CRKp) remain a persistent challenge. In the US dissemination of CRKp has been largely attributed to clonal group (CG) 258 with recent evidence that CG307, a dominant Klebsiella Extended Spectrum Beta-Lactamase (ESBL-Kp) clone is also emerging as CRKp. CG307 strains uniformly express a wzi-173 type capsular polysaccharide (CPS) whereas other Klebsiella strains including those of the CG258 express a wide variety of wzi-type CPS. A paper from Houston, TX provided evidence of divergent evolution between CG258 and CG307. CG258 evolves upfront as carbapenem resistant whereas CG307 may initially emerge as ESBL. CR-Kp that belong to the CG307 have also been identified in SBU. Our objective was to determine if among ESBL-Kp CG307 is a common clone and to characterize the demographics of the infected patient population. Methods Molecular typing of the wzi gene alleles of 78 sequentially collected ESBL-Kp was performed. Demographic, microbiological and clinical data were extracted from the medical record. Results Wzi typing indicated that 43% of ESBLKp strains express a wzi173 type CPS indicating they belong to CG307 the remainder of ESBL strains expressed variable wzi-types. Preliminary data analysis showed that wzi173 expressing ESBL strains were predominantly derived from urine. The median age of patients was 64 years old with male predominance (60.8% males). The average length of stay is 41.6 days. Among these patients, 30.4% required ICU admission. Sepsis criteria were met in 56.5% of these patients within 2 days of positive culture. The mortality rate was 21.7%. Conclusion Our data provides evidence that CG307 is the most dominant ESBL Kp clone in hospitalized patients at Stony Brook University. Although the majority of cultures were from urinary source, ICU admission rates and mortality rates were also elevated. These data raise concern that high prevalence of ESBL CG307 in hospitalized patients may ultimately lead to emergence of carbapenem resistant CG307 strains especially if they emerge in patients who are treated with broad spectrum antibiotics. Disclosures All Authors: No reported disclosures

Final-year medical students’ perspective: a survey on the use of computed tomography in sepsis

ObjectivesTo determine the perspective of final-year medical students on the use of computed tomography (CT) in patients with sepsis.MethodsA total of 207 questionnaires were distributed to final-year medical students at a large university medical center, and 113 returned questionnaires met the criteria for inclusion in the analysis. Questions referred to sepsis guidelines, CT indications, and the use of contrast agents. Control variables included a level of practical experience as a final-year student (trimester of student’s practical year) and previous radiological experience. Statistical hypothesis tests such as the Mann-Whitney U test and chi-square test were performed.ResultsThe majority of participating students, 85% (n = 91/107), considered a Systemic Organ Failure Assessment (SOFA) score ≥ 2 as a diagnostic criterion for sepsis. The presence of ≥ 2 positive systemic inflammatory response syndrome (SIRS) criteria was considered relevant for diagnosing sepsis by 34% (n = 34/100). Ninety-nine percent (n = 64/65) of the participants who fully agreed with a SOFA score ≥ 2 being relevant for diagnosing sepsis would also use it as an indication for a CT scan. Seventy-six percent (n = 78/103) of the students rated a known severe allergic reaction to contrast agents as an absolute contraindication for its administration. Ninety-five percent (n = 78/82) considered radiation exposure as problematic in CT examinations, especially in repeat CTs.ConclusionMost final-year medical students were familiar with the sepsis criteria. Still, some referred to outdated diagnostic criteria. Participants saw the ability to plan further patient management based on CT as a major benefit. Most participants were aware of radiation as a risk of CT.Critical relevance statementMore detailed knowledge of CT in septic patients should be implemented in the medical curriculum. Retraining of medical students could help increase student confidence potentially improving patient care.Key points1. Whereas the majority of final-year medical students were familiar with sepsis criteria, some referred to outdated diagnostic criteria.2. Participants saw the ability to plan further patient management based on CT as a major benefit.3. Most participants were aware of radiation as a risk of CT.Graphical

Upfront endoscopic necrosectomy or step-up endoscopic approach for infected necrotising pancreatitis (DESTIN): a single-blinded, multicentre, randomised trial

Although the preferred management approach for patients with infected necrotising pancreatitis is endoscopic transluminal stenting followed by endoscopic necrosectomy as step-up treatment if there is no clinical improvement, the optimal timing of necrosectomy is unclear. Therefore, we aimed to compare outcomes between performing upfront necrosectomy at the index intervention versus as a step-up measure in patients with infected necrotising pancreatitis. This single-blinded, multicentre, randomised trial (DESTIN) was done at six tertiary care hospitals (five hospitals in the USA and one hospital in India). We enrolled patients (aged ≥18 years) with confirmed or suspected infected necrotising pancreatitis with a necrosis extent of at least 33% who were amenable to endoscopic ultrasound-guided drainage. By use of computer-generated permuted block randomisation (block size four), eligible patients were randomly assigned (1:1) to receive either upfront endoscopic necrosectomy or endoscopic step-up treatment. Endoscopists were not masked to treatment allocation, but participants, research coordinators, and the statistician were. Lumen-apposing metal stents (20 mm diameter; 10 mm saddle length) were used for drainage in both groups. In the upfront group, direct necrosectomy was performed immediately after stenting in the same treatment session. In the step-up group, direct necrosectomy or additional drainage was done at a subsequent treatment session if there was no clinical improvement (resolution of any criteria of systemic inflammatory response syndrome or sepsis or one or more organ failure and at least a 25% percentage decrease in necrotic collection size) 72 h after stenting. The primary outcome was the number of reinterventions per patient to achieve treatment success from index intervention to 6 months' follow-up, which was defined as symptom relief in conjunction with disease resolution on CT. Reinterventions included any endoscopic or radiological procedures performed for necrosectomy or additional drainage after the index intervention, excluding the follow-up procedure at 4 weeks for stent removal. All endpoints and safety were analysed by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT05043415 and NCT04113499, and recruitment and follow-up have been completed. Between Nov 27, 2019, and Oct 26, 2022, 183 patients were assessed for eligibility and 70 patients (24 [34%] women and 46 [66%] men) were randomly assigned to receive upfront necrosectomy (n=37) or step-up treatment (n=33) and included in the intention-to-treat population. At the time of index intervention, seven (10%) of 70 patients had organ failure and 64 (91%) patients had walled-off necrosis. The median number of reinterventions was significantly lower for upfront necrosectomy (1 [IQR 0 to 1] than for the step-up approach (2 [1 to 4], difference -1 [95% CI -2 to 0]; p=0·0027). Mortality did not differ between groups (zero patients in the upfront necrosectomy group vs two [6%] in the step-up group, difference -6·1 percentage points [95% CI -16·5 to 4·5]; p=0·22), nor did overall disease-related adverse events (12 [32%] patients in the upfront necrosectomy group vs 16 [48%] patients in the step-up group, difference -16·1 percentage points [-37·4 to 7·0]; p=0·17), nor procedure-related adverse events (four [11%] patients in the upfront necrosectomy group vs eight [24%] patients in the step-up group, difference -13·4 percentage points [-30·8 to 5·0]; p=0·14). In stabilised patients with infected necrotising pancreatitis and fully encapsulated collections, an approach incorporating upfront necrosectomy at the index intervention rather than as a step-up measure could safely reduce the number of reinterventions required to achieve treatment success. None.

Effect of a quality improvement program on compliance to the sepsis bundle in non-ICU patients: a multicenter prospective before and after cohort study.

Sepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a "simplified 1-h bundle" (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU). Emergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort). The effect of QIP on bundle compliance and hospital mortality was evaluated in a before-after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the "simplified rapid (1 h) intervention bundle" (the Sepsis 6 bundle - S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p < 0.001). We then analyzed compliance with S6 and hospital mortality in the before- and after-QIP periods, stratifying the two patients' cohorts by admission characteristics. Adherence to the S6 bundle was increased in patients with severe sepsis in the absence of shock, in patients with serum lactate <4.0 mmol/L, and in patients with hypotension at the time of enrollment, regardless of the type of admission (from EDs or MWs). Subsequently, in an observational analysis, we also investigated the relation between bundle compliance and hospital mortality by logistic regression. In the after-QIP cohort, we observed a lower in-hospital mortality than that observed in the before-QIP cohort. This finding was reported in subgroups where a higher adherence to the S6 bundle in the after-QIP period was found. After adjustment for confounders, the QIP appeared to be independently associated with a significant improvement in hospital mortality. Among the single S6 procedures applied within the first hour of sepsis diagnosis, compliance with blood culture and antibiotic therapy appeared significantly associated with reduced in-hospital mortality. A multi-faceted QIP aimed at promoting an early simplified bundle of care for the management of septic patients out of the ICU was associated with improved compliance with sepsis bundles and lower in-hospital mortality.

Association between chronic obstructive pulmonary disease and 28-day mortality in patients with sepsis: a retrospective study based on the MIMIC-III database

BackgroundSepsis is a common cause of mortality in critically ill patients, and chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in septic patients. However, the impact of COPD on patients with sepsis remained unclear. Therefore, the purpose of this study aimed to assess the effect of COPD on the prognosis of septic patients based on Medical Information Mart for Intensive Care (MIMIC-III) database.MethodsIn this retrospective study based on the (MIMIC)-III database version 1.4 (v1.4), we collected clinical data and 28-day all-cause mortality from patients with sepsis in intensive care unit (ICU) and these patients met the diagnostic criteria of Sepsis 3 on ICU admission between 2008 and 2012. International Classification of Diseases (ICD-9) (4660, 490, 4910, 4911, 49120, 49121, 4918, 4919, 4920, 4928, 494, 4940, 4941, 496) was used to identified COPD. We applied Kaplan–Meier analysis to compare difference of 28-day all-cause mortality between septic patients with and without COPD. Cox proportional-hazards model was applied to explore the risk factor associated with 28-day all-cause mortality in patients with sepsis.ResultsSix thousand two hundred fifty seven patients with sepsis were included in this study, including 955 (15.3%) patients with COPD and 5302 patients without COPD (84.7%). Compared with patients without COPD, patients with COPD were older (median: 73.5 [64.4, 82.0] vs 65.8 [52.9, 79.1], P < 0.001), had higher simplified acute physiology score II (SAPSII) (median: 40.0 [33.0, 49.0] vs 38.0 [29.0,47.0], P < 0.001) and greater proportion of mechanical ventilatory support (MV) (55.0% vs 48.9%, P = 0.001). In our study, septic patients with COPD had higher 28-day all-cause mortality (23.6% vs 16.4%, P < 0.001) than patients without COPD. After adjusting for covariates, the results showed that COPD was an independent risk factor for the 28-day all-cause mortality of patients with sepsis (HR 1.30, 95%CI: 1.12–1.50, P = 0.001).ConclusionsCOPD was an independent risk factor of 28-day all-cause mortality in septic patients. Clinically, septic patients with COPD should be given additional care.

Characteristics and Outcomes of Obstetric Sepsis by Three Sets of Clinical Diagnostic Criteria: A Retrospective Study.

Pregnancy-related mortality in the United States is the highest of all developed nations with a reported rate of 17 deaths per 100,000 live births in 2014 to 2017. Sepsis-related mortality is a major component of pregnancy-related mortality. Similar to nonpregnancy-related sepsis, the criteria for pregnancy-related sepsis are evolving. The purposes of this study were to compare three criteria for sepsis (Sepsis-2, Sepsis-3, California Maternal Quality Care Collaborative [CMQCC]) with one another and to determine patient outcomes using those three sets of criteria. Using the electronic medical record, we obtained granular data on all patients at University of Michigan Medical Center from July 10, 2009 to September 4, 2019 with suspected sepsis (blood cultures and administration of antibiotics) during pregnancy until the 42nd postpartum day. Agreement between the three criteria were assessed with kappa and shown by a Venn diagram. Groups were compared using standardized differences and chi square, rank sum, or independent t-tests. Of the 228 patients having sepsis by any criteria, 191 (83%) patients met the criteria for Sepsis-2, 131 (57%) for Sepsis-3, and 62 (27%) met criteria according to CMQCC. Agreement between the three criteria ranged from kappa = 0.13 (95% confidence interval [CI]: 0.09, 0.18) to kappa = 0.31 (95% CI: 0.23, 0.39). Patients who met CMQCC criteria tended to have more comorbidities and higher APACHE II (Acute Physiology And Chronic Health Evaluation) scores. Mortality (by 90 days) among the groups was low with 10 (4%) patients dying. Patients meeting criteria for CMQCC sepsis had higher mortality than the non-CMQCC patients with sepsis (10 vs. 2%, standardized difference = 0.31, p = 0.027). The agreement among Sepsis-2, Sepsis-3, and CMQCC diagnostic criteria is weak. CMQCC criteria identifies patients with sepsis at higher risk of death. · Agreements (kappa) between the three criteria are poor.. · CMQCC sepsis patients have more comorbidities.. · Endometritis was the most common cause of sepsis.. · CMQCC mortality was 10%; non-CMQCC mortality was 2%..

Epidemiological and bacteriological profile of sepsis in burns patients: A report from tertiary care hospital, India

Background: Burns are one of the most prevalent and mortifying forms of trauma. Patients burn with significant thermal injury require immediate intensive care unit (ICU) care to minimize morbidity and mortality. Burns patients are generally more predisposed to sepsis because of two main reasons, i.e., burn wound infection and catheter-related bloodstream infection (CRBSI). Due to extensive skin barrier disruption and an alteration in the cellular and humoral immune responses burn wounds has a much higher incidence of sepsis as compared to other forms of trauma. Aims and Objectives: The present study was undertaken to study the bacteriological profile and sources of sepsis in burns patients and their antimicrobial susceptibility pattern. Materials and Methods: It is a prospective observational study conducted in the Department of Burns, Plastic and Maxillofacial Surgery, ICU and Department of Microbiology of a tertiary care hospital, Uttar Pradesh, India, between January 2020 and June 2022. Adult patients with 30–70% of total body surface area burns with central venous catheter (CVC) inserted during ICU admission were enrolled in the study. The presence of clinical sepsis in the burn patients was evaluated using the American Burn Association Sepsis criteria. For all patients with suspected clinical sepsis, paired blood cultures were collected simultaneously; one from the CVC and another from a peripheral site and were sent for bacteriological culture. Blood culture samples were processed as per standard procedures. CRBSI was defined if the same organism was isolated in paired blood cultures. Burn wound biopsy was sent for quantitative culture and 105 organisms/g of tissue were considered significant. Results: In the present study, the overall incidence of clinical sepsis was 28.4% (39/137), out of which 48.7% of cases were found to be due to CRBSI and the most common organism involved was Klebsiella spp. (42.1%), 33.3% of cases were due to burn wound sepsis and the most common organism involved was Pseudomonas spp. (61.5%); and 18.0% of cases were those in which no known source could be found. Possible explanations for these cases could be sepsis without bacteremia due to endotoxins and Gram-negative endotoxemia. Conclusion: To find out microorganisms causing burn wound infection by culture and provide suitable antibiotics according to their antibiotic sensitivity patterns helping us in managing these infection and decreasing overall morbidity and mortality in burn patients.

Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis

BackgroundSepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients.MethodsWe determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients.ResultsThe 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135–2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131–2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075–5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients.ConclusionWe suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

Kinetics and Role of Pancreatic Stone Protein and Midregional Proadrenomedullin as Predictors of Sepsis and Bacteremia in Children with Hematological Malignancies.

To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with hematological malignancies. We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. CRP, PSP, and MR-proADM levels were measured at the onset of the febrile episode (day 1), day 3, and day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as an area under a receiver operating characteristic (ROC) curve. ROC curves were used for each biomarker to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis. During the 2-year study period, 70 febrile neutropenia episodes in 70 children with hematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%), a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers on day 1 differed significantly between patients with and without sepsis. PSP, MR-proADM, and CRP specificity were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM, and CRP were 0.84, 0.74, and 0.88, respectively. PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with hematological malignancies. However, PSP has a higher sensitivity and specificity.

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.