Dysregulation of the complement system has been proposed as a pathophysiological mechanism for Post-acute sequelae of SARS-CoV-2 (PASC). We analyzed the complement activation markers C3bc, C3bBbP and TCC in 48 PASC patients, grouped into whether they had a mild (n=38) or severe (n=10) acute SARS-CoV-2 infection, and 80 control subjects. Although the patients with a mild SARS-CoV-2 infection had a trend towards more severe PASC, we could not find any significant differences in complement activation markers between these patients and controls. In conclusion, we could not find convincing evidence of activation of the complement system in PASC patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by grants from Governmental Funds for Clinical Research (ALF), Interreg (EU), Sodra sjukvardsregionen, Skanes Universitetssjukhus, the Crafoord foundation, the Tegger Foundation and, the Alfred Osterlund Foundation all held by FK. MH was supported by grants from Sodra sjukvardsregionen. The funders played no role in the design of the study, data collection or analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Swedish Ethical Review Authority gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Chills and vomiting have traditionally been associated with severe bacterial infections and bacteremia. However, few modern studies have in a prospective way evaluated the association of these signs with bacteremia, which is the aim of this prospective, multicenter study. Patients presenting to the emergency department with at least one affected vital sign (increased respiratory rate, increased heart rate, altered mental status, decreased blood pressure or decreased oxygen saturation) were included. A total of 479 patients were prospectively enrolled. Blood cultures were obtained from 197 patients. Of the 32 patients with a positive blood culture 11 patients (34%) had experienced shaking chills compared with 23 (14%) of the 165 patients with a negative blood culture, P = 0.009. A logistic regression was fitted to show the estimated odds ratio (OR) for a positive blood culture according to shaking chills. In a univariate model shaking chills had an OR of 3.23 (95% CI 1.35-7.52) and in a multivariate model the OR was 5.9 (95% CI 2.05-17.17) for those without prior antibiotics adjusted for age, sex, and prior antibiotics. The presence of vomiting was also addressed, but neither a univariate nor a multivariate logistic regression showed any association between vomiting and bacteremia. In conclusion, among patients at the emergency department with at least one affected vital sign, shaking chills but not vomiting were associated with bacteremia.

OBJECTIVES:To assess whether the triage model Sepsis Alert for Emergency Departments results in improved initial care of patients with severe infections.DESIGN:Interventional study comparing patient care before and after the start of a new triage model, including 90-day follow-up.SETTING:Eight emergency departments in Skåne County, Sweden.SUBJECTS:Patients with suspected severe infection.INTERVENTIONS:Patients with severely deviating vital signs and suspected infection were triaged into a designated sepsis line called Sepsis Alert, for rapid evaluation supported by an infectious disease specialist. Also, all emergency department staff participated in a designated sepsis education before the model was introduced.MEASUREMENTS AND MAIN RESULTS:Medical records were evaluated for a 3-month period 1 year before the triage system was started in 2016 and for a 3-month period 1 year after. Of 195,607 patients admitted to these emergency departments during two 3-month periods, a total of 5,321 patients presented severely abnormal vital signs. Of these, 1,066 patients who presented with fever greater thanor equal to 38°C or history of fever/chills were considered to be patients at risk of having severe sepsis. Among patients triaged according to Sepsis Alert, 89.3% received antibiotic treatment within 1 hour after arrival to the emergency department (median time to antibiotics, 26 min), which was significantly better than before the start of the new triage: 67.9% (median time to antibiotics, 37 min) (p < 0.001). Additionally, sepsis treatment quality markers were significantly improved after the introduction of Sepsis Alert, including number of blood cultures and lactate measurements taken, percentage of patients receiving IV fluids, and appropriate initial antibiotic treatment. There were no differences in 28- or 90-day mortality rates.CONCLUSIONS:The implementation of the new triage model Sepsis Alert with special attention to severe sepsis patients led to faster and more accurate antibiotic treatment and improved diagnostic procedures and supportive care.

BACKGROUND:To allow early identification of patients at risk of sepsis in the emergency department (ED), a variety of risk stratification scores and/or triage systems are used. The first aim of this study was to develop a risk stratification score for sepsis based upon vital signs and biomarkers using a statistical approach. Second, we aimed to validate the Rapid Emergency Triage and Treatment System (RETTS) for sepsis. RETTS combines vital signs with symptoms for risk stratification. METHODS:We retrospectively analysed data from two prospective, observational, multicentre cohorts of patients from studies of biomarkers in ED. A candidate risk stratification score called Sepsis Heparin-binding protein-based Early Warning Score (SHEWS) was constructed using the Least Absolute Shrinkage and Selector Operator (LASSO) method. SHEWS and RETTS were compared to National Early Warning Score 2 (NEWS2) for infection-related organ dysfunction, intensive care or death within the first 72h after admission (i.e. sepsis). RESULTS:506 patients with a diagnosed infection constituted cohort A, in which SHEWS was derived and RETTS was validated. 435 patients constituted cohort B of whom 184 had a diagnosed infection where both scores were validated. In both cohorts (A and B), AUC for infection-related organ dysfunction, intensive care or death was higher for NEWS2, 0.80 (95% CI 0.76-0.84) and 0.69 (95% CI 0.63-0.74), than RETTS, 0.74 (95% CI 0.70-0.79) and 0.55 (95% CI 0.49-0.60), p = 0.05 and p <0.01, respectively. SHEWS had the highest AUC, 0.73 (95% CI 0.68-0.79) p = 0.32 in cohort B. CONCLUSIONS:Even with a statistical approach, we could not construct better risk stratification scores for sepsis than NEWS2. RETTS was inferior to NEWS2 for screening for sepsis.

Background The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. Objective The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. Methods The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. Conclusions The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.

Schinkel, Michiel MD; Boerman, Anneroos W. MD; Nanayakkara, Prabath W. B. MD, PhD, FRCP Author Information

International guidelines recommend that the treatment of patients with infective endocarditis (IE) should be directed by a multidisciplinary endocarditis team. The aim of this study was to describe the first-year experience of multidisciplinary rounds by the endocarditis team in Scania, Sweden. This was a retrospective study on all possible and definitive IE episodes that were assessed by the endocarditis team from January 1st to December 31st, 2017. Descriptive statistics were used. A total of 145 multidisciplinary rounds were held and addressed 100 episodes in 97 patients. The median age was 71 years and 66% were males. The most common causative pathogens were alpha-hemolytic streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and enterococci. The endocarditis team recommended surgery in 40 % of episodes. The transfer of patients between different hospitals was facilitated by the team. The IE team evaluated a large proportion of patients with IE in the region and provided a rapid expert opinion on the optimal management of complicated cases of IE. (Less)

International guidelines recommend that the treatment of patients with infective endocarditis (IE) should be directed by a multidisciplinary endocarditis team. The aim of this study was to describe the first-year experience of multidisciplinary rounds by the endocarditis team in Scania, Sweden. This was a retrospective study on all possible and definitive IE episodes that were assessed by the endocarditis team from January 1st to December 31st, 2017. Descriptive statistics were used. A total of 145 multidisciplinary rounds were held and addressed 100 episodes in 97 patients. The median age was 71 years and 66% were males. The most common causative pathogens were alpha-hemolytic streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and enterococci. The endocarditis team recommended surgery in 40 % of episodes. The transfer of patients between different hospitals was facilitated by the team.  The IE team evaluated a large proportion of patients with IE in the region and provided a rapid expert opinion on the optimal management of complicated cases of IE.

Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75–0.83) and 0.70 (95% CI 0.65–0.74), than qSOFA, AUC 0.70 (95% CI 0.66–0.75) and 0.62 (95% CI 0.57–0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.

ABSTRACT Objective: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department. Design: Prospective, international multicenter, convenience sample study. Setting: Four general emergency departments at academic centers in Sweden, Switzerland, and Canada. Patients: All emergency encounters among adults where one of the following criteria were fulfilled: respiratory rate >25 breaths per minute; heart rate >120 beats per minute; altered mental status; systolic blood pressure <100 mm Hg; oxygen saturation <90% without oxygen; oxygen saturation <93% with oxygen; reported oxygen saturation <90%. Intervention: None. Measurements and Main Results: A total of 524 emergency department patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a noninfectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 h, 54 patients (10%) were admitted to an intensive care unit, and 23 patients (4%) died within 72 h. For the primary outcome, detection of infected-related organ dysfunction within 72 h, the area under the receiver operating curve (AUC) for HBP was 0.73 (95% CI 0.68–0.78) among all patients and 0.82 (95% CI 0.76–0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12–24 h) HBP had an AUC of 0.87 (95% CI 0.79–0.95) among all patients and 0.88 (95% CI 0.77–0.99) among patients confidently adjudicated to either infection or noninfection. Conclusions: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.

AIM: Enterococci cause 2-11% of all prosthetic joint infections (PJI) and are generally considered difficult to treat. However, study-results are not consistent. In this study we present a population-based case series of 55 cases with enterococcal PJI, investigating treatment and outcome, as well as describing the affected patient population regarding demography and co-morbidities. METHODS: We identified all enterococcal PJIs in the Region of Skåne, Sweden, during a five-year period (2011-2015) and reviewed the patients' medical records. RESULTS: Fifty-five enterococcal PJIs were found. Enterococcus faecalis was the most frequently isolated species (84%), and poly-microbial infections were common (64%). Treatment with intention to cure was given to 43 (78%) cases. Debridement with retention of the implant and antibiotics (DAIR) was the most common surgical treatment strategy (71%), with a cure-rate of 72%. Overall cure-rate was 67%, and in cases where cure was intended, this was achieved in 80%. CONCLUSIONS: When cure is aimed for, the prognosis for enterococcal PJI is not so poor, and DAIR treatment can provide adequate results in many cases.

Antimicrobial peptides (AMPs) provide a first line of defense against bacterial infections. Here we report that urine levels of AMPs, locally produced in the urinary tract, are lower in individuals with asymptomatic bacteriuria (ABU) compared to patients with urinary tract infection (UTI).

Within emergency department (ED) sepsis patients, delayed deterioration resulting in shock is associated with increased risk of death. Heparin-binding protein (HBP), a neutrophil-released serum biomarker, has been shown to be elevated in patients developing delayed shock. The objective of this study was to assess the performance of HBP to predict delayed shock among sepsis sub-populations.

Abstract Objective: To study if a modified triage system at an Emergency Department (ED) combined with educational efforts resulted in reduced time to antibiotics and decreased length of hospital stay (LOS) for patients with severe infection. Methods: A retrospective, observational study comparing patients before and after the start of a new triage model at the ED of a University Hospital. After the implementation of the model, patients with fever and abnormal vital signs were triaged into a designated sepsis line (Sepsis Alert) for rapid evaluation by the attending physician supported by a infectious diseases (IDs) specialist. Also, all ED staff participated in a designated sepsis education before Sepsis Alert was introduced. Medical records were evaluated for patients during a 3-month period after the triage system was started in 2012, and also during the corresponding months in 2010 and 2014. Results: A total of 1837 patients presented with abnormal vital signs. Of these, 221 patients presented with fever and thus at risk of having severe sepsis. Among patients triaged according to the new model, median time to antibiotics was 58.5 at startup and 24.5 minutes at follow-up two years later. This was significantly less than for patients treated before the new model, 190 minutes. Also, median LOS was significantly decreased after introduction of the new triage model, from nine to seven days. Conclusions: A triage model at the ED with special attention to severe sepsis patients, led to sustained improvements of time to antibiotic treatment and LOS.

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonisation may prevent transmission of strains between patients and reduces the risk of clinical infection. Colonisation of the throat is associated with prolonged carriage and is more difficult to eradicate. An open randomised study was conducted to evaluate two eradication protocols. Patients with pharyngeal carriage of MRSA were enrolled at six Swedish centres during 4 years. One treatment group received oral rifampicin and either clindamycin or trimethoprim/sulfamethoxazole (SXT) for 7 days in combination with nasal mupirocin. Patients in the other group were treated with nasal mupirocin only. Patients in the same household were randomised together. Both groups followed a hygiene protocol including chlorhexidine washing. Cultures from the nares, perineum and throat were taken at baseline and then at 2 weeks, 2 months and 6 months after the end of treatment. A total of 28 patients received rifampicin-based systemic antibiotics and 24 subjects received mupirocin only. At follow-up 6 months after the end of treatment, 61% of patients and 50% of households in the systemic antibiotics group had culture results negative for MRSA. Significantly less patients (12%) and households (10%) became decolonised in the group receiving topical treatment only. A combination of rifampicin and either clindamycin or SXT was more effective in eliminating pharyngeal MRSA carriage compared with topical treatment with mupirocin only.

P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux

Asymptomatic bacteriuria (ABU) is highly prevalent among elderly patients. It can be difficult to distinguish ABU from symptomatic urinary tract infection (UTI) in this population, which leads to unnecessary antibiotic treatment. Urinary heparin-binding protein (U-HBP) and urinary interleukin-6 (U-IL-6) have previously been studied as diagnostic markers for UTI. In this study, biomarkers were measured in the urine of 134 nursing home residents. The prevalence of ABU in this population, excluding patients with urinary catheter, was 32.8%. Levels of U-HBP and IL-6 were significantly lower among residents with ABU when compared to 49 patients with verified UTI. When previously defined cut-off limits were used, U-HBP had a high negative predictive value for UTI (93%), however, the specificity for differentiating patients with UTI and ABU was low. Discriminatory values were better for U-IL-6 with a sensitivity of 80% and specificity of 82% for the differentiation between the subgroup of pyelonephritis and ABU.

Unfortunately, the original version of this supplement [1] contained errors in two of the abstracts; P037 and P127. Please see details below.

The aim of this study is to investigate the cost of treating recurrent Clostridium difficile infection in patients attending infectious disease clinics at 4 hospitals in Sweden. Following approval by the Central Ethical Review Board in Stockholm patient records of 120 patients were used to record the resources used to treat the latest recurrent infection. Recurrence was defined as a new toxin-positive Clostridium difficile infection within 12 weeks of the previous Clostridium difficile infection. The sample included 47 patients not hospitalized and 73 hospitalized patients. All resources used were itemized and a point estimate of the associated costs calculated using the average of two or more pricelists from county councils in Sweden. This study shows that the treatment costs at the four participating infectious disease clinics in Sweden for treating a single event of recurrent Clostridium difficile infection ranged from SEK 921 to SEK 278323. Median cost for non-hospitalized patients was SEK 5397 and for hospitalized patients SEK 68078. We found that the 10% of the patients with the highest resource use accounted for MSEK 2,38, or nearly 40% of the accumulated resource use of MSEK 6,25 used to treat the 120 studied patients. Significant costs are associated with treatment of recurrent Clostridium difficile infections, especially when hospitalization is needed. Minimizing the need for hospitalization during treatment is the single most important objective when minimizing the economic burden of recurrent Clostridium difficile infection.

OBJECTIVES:Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. DESIGN:A prospective international multicenter cohort study. SETTING:Seven different emergency departments in Sweden, Canada, and the United States. PATIENTS:Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). INTERVENTION:None. MEASUREMENTS AND MAIN RESULTS:Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort. CONCLUSION:In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.