Sequence-based genotyping of extra-intestinal pathogenic Escherichia coli isolates from patients with suspected community-onset sepsis, Sweden.

Extra-intestinal pathogenic Escherichia coli (ExPEC) strains are responsible for a large number of human infections globally. The management of infections caused by ExPEC has been complicated by the emergence of antimicrobial resistance, most importantly the increasing recognition of isolates producing extended-spectrum ß-lactamases (ESBL). Herein, we used whole-genome sequencing (WGS) on ExPEC isolates for a comprehensive genotypic characterization. Twenty-one ExPEC isolates, nine with and 12 without ESBL-production, from 16 patients with suspected sepsis were sequenced on an Illumina MiSeq platform. Analysis of WGS data was performed with widely used bioinformatics software and tools for genotypic characterization of the isolates. A higher number of plasmids, virulence and resistance genes were observed in the ESBL-producing isolates than the non-ESBL-producing, although not statistically significant due to the low sample size. All nine ESBL-producing ExPEC isolates presented with at least one bla gene, as did three of the 12 without ESBL-production. Multi-locus sequence typing analysis revealed a diversity of sequence types whereas phylogroup A prevailed among isolates both with and without ESBL-production. In conclusion, this limited study shows that analysis of WGS data can be used for genotypic characterization of ExPEC isolates to obtain in-depth information of clinical relevance.

Impact of obesity on outcome of severe bacterial infections.

INTRODUCTION: Obesity is a rapidly growing global health concern with considerable negative impact on life-time expectancy. It has yet not been clarified if and how obesity impacts outcomes of severe bacterial infections. The aim of this study was to determine how body mass index impacts outcome of severe bacterial infections in a well-defined population-based cohort. METHODS: This study is based on a cohort of 2196 patients included in a Swedish prospective, population-based, consecutive observational study of the incidence of community-onset severe sepsis and septic shock in adults. All patients with weight and height documented in the medical records on admission were included. RESULTS: The case fatality rate (CFR) was negatively correlating with increasing BMI. Outcomes included 28-day CFR (p-value = 0.002), hospital CFR (p-value = 0.039) and 1-year CFR (p-value<0.001). When BMI was applied as continuous variable in a multiple logistic regression together with other possible covariates, we still could discern that BMI was associated with decreasing 28-day CFR (OR = 0.93, 95% CI 0.88-0.98, p-value = 0.009) and 1-year CFR (OR = 0.94, 95% CI 0.91-0.97, p-value<0.001). CONCLUSION: The hypothesis and paradox of obesity being associated with higher survival rates in severe bacterial infections was confirmed in this prospective, population-based observational study.

Early detection of sepsis using artificial intelligence: a scoping review protocol.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. To decrease the high case fatality rates and morbidity for sepsis and septic shock, there is a need to increase the accuracy of early detection of suspected sepsis in prehospital and emergency department settings. This may be achieved by developing risk prediction decision support systems based on artificial intelligence. METHODS: The overall aim of this scoping review is to summarize the literature on existing methods for early detection of sepsis using artificial intelligence. The review will be performed using the framework formulated by Arksey and O'Malley and further developed by Levac and colleagues. To identify primary studies and reviews that are suitable to answer our research questions, a comprehensive literature collection will be compiled by searching several sources. Constrictions regarding time and language will have to be implemented. Therefore, only studies published between 1 January 1990 and 31 December 2020 will be taken into consideration, and foreign language publications will not be considered, i.e., only papers with full text in English will be included. Databases/web search engines that will be used are PubMed, Web of Science Platform, Scopus, IEEE Xplore, Google Scholar, Cochrane Library, and ACM Digital Library. Furthermore, clinical studies that have completed patient recruitment and reported results found in the database ClinicalTrials.gov will be considered. The term artificial intelligence is viewed broadly, and a wide range of machine learning and mathematical models suitable as base for decision support will be evaluated. Two members of the team will test the framework on a sample of included studies to ensure that the coding framework is suitable and can be consistently applied. Analysis of collected data will provide a descriptive summary and thematic analysis. The reported results will convey knowledge about the state of current research and innovation for using artificial intelligence to detect sepsis in early phases of the medical care chain. ETHICS AND DISSEMINATION: The methodology used here is based on the use of publicly available information and does not need ethical approval. It aims at aiding further research towards digital solutions for disease detection and health innovation. Results will be extracted into a review report for submission to a peer-reviewed scientific journal. Results will be shared with relevant local and national authorities and disseminated in additional appropriate formats such as conferences, lectures, and press releases.

Incidences of community onset severe sepsis, Sepsis-3 sepsis, and bacteremia in Sweden - A prospective population-based study.

BACKGROUND: Sepsis is a major healthcare challenge globally. However, epidemiologic data based on population studies are scarce. METHODS: During a 9-month prospective, population-based study, the Swedish Sepsis-2 criteria were used to investigate the incidence of community onset severe sepsis in adults aged ≥18 years (N = 2,196; mean age, 69; range, 18-102 years). All the patients who were admitted to the hospital and started on intravenous antibiotic treatment within 48 hours were evaluated. Retrospectively the incidence of sepsis according to Sepsis-3 criteria was calculated on this cohort. RESULTS: The annual incidence of community onset severe sepsis in adults at first admission was 276/100,000 (95% CI, 254-300). The incidence increased more than 40-fold between the youngest and the oldest age group, and was higher for men than for women. The respiratory tract was the most common site of infection (41% of cases). Using the Sepsis-3 criteria, the annual incidence of sepsis was 838/100,000 (95% CI, 798-877), which is 3-fold higher than that of severe sepsis. The main reason for the discrepancy in incidences is the more generous criteria for respiratory dysfunction used in Sepsis-3. Bacteremia was seen in 13% of all the admitted patients, giving an incidence of 203/100,000/year (95%, CI 184-223), which is among the highest incidences reported. CONCLUSIONS: We found a high incidence of community onset severe sepsis, albeit lower than that seen in previous Scandinavian studies. The incidence increased markedly with age of the patient. The incidence of community onset sepsis according to the Sepsis-3 definition is the highest reported to date. It is 3-fold higher than that for severe sepsis, due to more generous criteria for respiratory dysfunction. A very high incidence of bacteremia was noted, partly explained by the high frequency of blood cultures.

Prehospital characteristics among patients with sepsis: a comparison between patients with or without adverse outcome.

BACKGROUND: The prehospital care of patients with sepsis are commonly performed by the emergency medical services. These patients may be critically ill and have high in-hospital mortality rates. Unfortunately, few patients with sepsis are identified by the emergency medical services, which can lead to delayed treatment and a worse prognosis. Therefore, early identification of patients with sepsis is important, and more information about the prehospital characteristics that can be used to identify these patients is needed. Based on this lack of information, the objectives of this study were to investigate the prehospital characteristics that are identified while patients with sepsis are being transported to the hospital by the emergency medical services, and to compare these values to those of the patients with and without adverse outcomes during their hospital stays. METHODS: This was a retrospective observational study. The patients' electronic health records were reviewed and selected consecutively based on the following: retrospectively diagnosed with sepsis and transported to an emergency department by the emergency medical services. Data were collected on demographics, prehospital characteristics and adverse outcomes, defined as the in-hospital mortality or treatment in the intensive care unit, and analysed by independent sample t-test and chi-square. Sensitivity, specificity and likelihood ratio, of prehospital characteristics for predicting or development of adverse outcome were analysed. RESULTS: In total, 327 patients were included. Of these, 50 patients had adverse outcomes. When comparing patients with or without an adverse outcome, decreased oxygen saturation and body temperature, increased serum glucose level and altered mental status during prehospital care were found to be associated with an adverse outcome. CONCLUSIONS: The findings suggests that patients having a decreased oxygen saturation and body temperature, increased serum glucose level and altered mental status during prehospital care are at risk of a poorer patient prognosis and adverse outcome. Recognizing these prehospital characteristics may help to identify patients with sepsis early and improve their long-term outcomes. However further research is required to predict limit values of saturation and serum glucose and to validate the use of prehospital characteristics for adverse outcome in patients with sepsis.

Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection.

BACKGROUND: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures. MATERIALS AND METHODS: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden. RESULTS: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH® assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4-98.3), when the causative agent was covered by the QuickFISH® assay. CONCLUSIONS: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.

The early chain of care in bacteraemia patients: Early suspicion, treatment and survival in prehospital emergency care.

INTRODUCTION: Bacteraemia is a first stage for patients risking conditions such as septic shock. The primary aim of this study is to describe factors in the early chain of care in bacteraemia, factors associated with increased chance of survival during the subsequent 28days after admission to hospital. Furthermore, the long-term outcome was assessed. METHODS: This study has a quantitative design based on data from Emergency Medical Services (EMS) and hospital records. RESULTS: In all, 961 patients were included in the study. Of these patients, 13.5% died during the first 28days. The EMS was more frequently used by non-survivors. Among patients who used the EMS, the suspicion of sepsis already on scene was more frequent in survivors. Similarly, EMS personnel noted the ESS code "fever, infection" more frequently for survivors upon arriving on scene. The delay time from call to the EMS and admission to hospital until start of antibiotics was similar in survivors and non-survivors. The five-year mortality rate was 50.8%. Five-year mortality was 62.6% among those who used the EMS and 29.5% among those who did not (p<0.0001). CONCLUSION: This study shows that among patients with bacteraemia who used the EMS, an early suspicion of sepsis or fever/infection was associated with improved early survival whereas the delay time from call to the EMS and admission to hospital until start of treatment with antibiotics was not. 50.8% of all patients were dead after five years.

Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis.

BACKGROUND: Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively. METHODS: Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC). RESULTS: For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker). CONCLUSIONS: Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

The Early Chain of Care in Patients with Bacteraemia with the Emphasis on the Prehospital Setting.

UNLABELLED: Purpose There is a lack of knowledge about the early phase of severe infection. This report describes the early chain of care in bacteraemia as follows: (a) compare patients who were and were not transported by the Emergency Medical Services (EMS); (b) describe various aspects of the EMS chain; and (c) describe factors of importance for the delay to the start of intravenous antibiotics. It was hypothesized that, for patients with suspected sepsis judged by the EMS clinician, the delay until the onset of antibiotic treatment would be shorter. Basic Procedures All patients in the Municipality of Gothenburg (Sweden) with a positive blood culture, when assessed at the Laboratory of Bacteriology in the Municipality of Gothenburg, from February 1 through April 30, 2012 took part in the survey. Main Findings/Results In all, 696 patients fulfilled the inclusion criteria. Their mean age was 76 years and 52% were men. Of all patients, 308 (44%) had been in contact with the EMS and/or the emergency department (ED). Of these 308 patients, 232 (75%) were transported by the EMS and 188 (61%) had "true pathogens" in blood cultures. Patients who were transported by the EMS were older, included more men, and suffered from more severe symptoms and signs. The EMS nurse suspected sepsis in only six percent of the cases. These patients had a delay from arrival at hospital until the start of antibiotics of one hour and 19 minutes versus three hours and 21 minutes among the remaining patients (P =.0006). The corresponding figures for cases with "true pathogens" were one hour and 19 minutes versus three hours and 15 minutes (P =.009). CONCLUSION: Among patients with bacteraemia, 75% used the EMS, and these patients were older, included more men, and suffered from more severe symptoms and signs. The EMS nurse suspected sepsis in six percent of cases. Regardless of whether or not patients with true pathogens were isolated, a suspicion of sepsis by the EMS clinician at the scene was associated with a shorter delay to the start of antibiotic treatment. Axelsson C , Herlitz J , Karlsson A , Sjöberg H , Jiménez-Herrera M , Bång A , Jonsson A , Bremer A , Andersson H , Gellerstedt M , Ljungström L . The early chain of care in patients with bacteraemia with the emphasis on the prehospital setting. Prehosp Disaster Med. 2016;31(3):272-277.

Systemic symptoms predict presence or development of severe sepsis and septic shock.

BACKGROUND: Severe sepsis is a major cause of mortality and morbidity globally. As the time to adequate treatment is directly linked to outcome, early recognition is of critical importance. Early, accessible markers for severe sepsis are desirable. The systemic inflammatory response in sepsis leads to changes in vital signs and biomarkers and to symptoms unrelated to the focus of infection. This study investigated whether the occurrence of any of six systemic symptoms could predict severe sepsis in a cohort of patients admitted to hospital for suspected bacterial infections. METHODS: A retrospective, consecutive study was conducted. All adult patients admitted during 1 month to a 550-bed secondary care hospital in western Sweden and given intravenous antibiotics for suspected community-acquired infection were included (n = 289). Symptoms (fever/chills, muscle weakness, localised pain, dyspnea, altered mental status and gastrointestinal symptoms) were registered along with age, sex, vital signs and laboratory values. Patients who fulfilled criteria of severe sepsis within 48 h were compared with patients who did not. Odds ratios for severe sepsis were calculated, adjusted for age, sex and comorbidities. RESULTS: Criteria for severe sepsis were fulfilled by 90/289 patients (31.1%). Altered mental status (OR = 4.29, 95% CI = 2.03-9.08), dyspnea (OR = 2.92, 95% CI = 1.69-5.02), gastrointestinal symptoms (OR = 2.31, 95% CI = 1.14-4.69) and muscle weakness (OR = 2.24, 95% CI = 1.06-4.75) were more common in patients who had or later developed severe sepsis. CONCLUSIONS: Systemic symptoms in combination with other signs of infection should be considered warning signs of severe sepsis.

Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis.

BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.

Faecal microbiota transplantation and bacteriotherapy for recurrent Clostridium difficile infection: a retrospective evaluation of 31 patients.

BACKGROUND: Recurrent Clostridium difficile infection (CDI) is a significant problem due to its increased incidence and severity. Failure rates for standard antibiotic therapies are high. In our hospital, faecal microbiota transplantation (FMT), or instillation of a culture mixture of known enteric bacteria in saline as rectal bacteriotherapy (RBT), has long been used as 'rescue therapy' in patients with recurrent disease, in whom repeated courses of standard antibiotic treatment have failed. We wanted to evaluate the effectiveness of FMT and RBT for recurrent CDI. METHODS: The records of 31 patients treated with either FMT or RBT for recurrent CDI were reviewed retrospectively. FMT was based on faecal donation by a close relative and RBT on a defined saline mixture of 10 individually cultured enteric bacterial strains originally isolated from healthy persons. Both types of instillation were carried out through a rectal catheter. FMT (500 ml) was given as 1 installation. RBT (200 ml) was given as 2 or 3 installations with an interval of 2 days between courses. Treatment success was defined as a sustained loss of symptoms and discontinuation of diarrhoea within 3 days. RESULTS: Of 31 patients, 23 (74%) responded successfully to the treatment: 16 of 23 (70%) receiving FMT and 7 of 8 (88%) receiving RBT. CONCLUSION: We found FMT to be effective in patients with recurrent CDI. RBT based on a predefined bacterial suspension was as effective as or better than FMT based on faecal donation; however, multiple installations may be needed.

Suspicion and treatment of severe sepsis. An overview of the prehospital chain of care.

BACKGROUND: Sepsis is a life-threatening condition where the risk of death has been reported to be even higher than that associated with the major complications of atherosclerosis, i.e. myocardial infarction and stroke. In all three conditions, early treatment could limit organ dysfunction and thereby improve the prognosis. AIM: To describe what has been published in the literature a/ with regard to the association between delay until start of treatment and outcome in sepsis with the emphasis on the pre-hospital phase and b/ to present published data and the opportunity to improve various links in the pre-hospital chain of care in sepsis. METHODS: A literature search was performed on the PubMed, Embase (Ovid SP) and Cochrane Library databases. RESULTS: In overall terms, we found a small number of articles (n = 12 of 1,162 unique hits) which addressed the prehospital phase. For each hour of delay until the start of antibiotics, the prognosis appeared to become worse. However, there was no evidence that prehospital treatment improved the prognosis.Studies indicated that about half of the patients with severe sepsis used the emergency medical service (EMS) for transport to hospital. Patients who used the EMS experienced a shorter delay to treatment with antibiotics and the start of early goal-directed therapy (EGDT). Among EMS-transported patients, those in whom the EMS staff already suspected sepsis at the scene had a shorter delay to treatment with antibiotics and the start of EGDT.There are insufficient data on other links in the prehospital chain of care, i.e. patients, bystanders and dispatchers. CONCLUSION: Severe sepsis is a life-threatening condition. Previous studies suggest that, with every hour of delay until the start of antibiotics, the prognosis deteriorates. About half of the patients use the EMS. We need to know more about the present situation with regard to the different links in the prehospital chain of care in sepsis.