Risk factors for recurrent healthcare-facility associated Clostridioides difficile infection in a Swedish setting.

OBJECTIVE: The objectives were to determine the risk factors for recurrent healthcare facility-associated Clostridioides difficile infection (HCF-CDI) in a high CDI incidence, low antibiotic use setting and to determine if length of cefotaxime exposure is a risk factor for recurrent HCF-CDI. METHODS: The risk factors for recurrent HCF-CDI were evaluated with a retrospective nested case control study based on chart reading. The risk factors were evaluated univariately and multivariately. Length of risk antibiotic exposure was evaluated further in a subanalysis. RESULTS: Risk factors for recurrent HCF-CDI were renal insufficiency (25.4% of cases compared to 15.4% of controls p = 0.006) and metronidazole treatment of initial CDI episode (88.4% compared to 71.7% p = 0.01). Exposure to cefotaxime and risk for recurrent CDI showed a dose-dependent relationship (linear by linear p = 0.028). CONCLUSIONS: Renal insufficiency and metronidazole treatment were independent risk factors for recurrent HCF-CDI in our setting. The relationship between cefotaxime exposure and risk for recurrent HCF-CDI, dose-dependent, could be evaluated further in a setting with high cefotaxime use.

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales.

BACKGROUND: The possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections. METHODS: In 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points. RESULTS: 4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non-3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75-.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient. CONCLUSIONS: A prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.

Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. METHODS: During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. RESULTS: From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. CONCLUSIONS: In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.

Interventions for prudent antibiotic use in primary healthcare: an econometric analysis.

BACKGROUND: Rational antibiotic prescribing is crucial to combat antibiotic resistance. Optimal strategies to improve antibiotic use are not known. Strama, the Swedish strategic program against antibiotic resistance, has been successful in reducing antibiotic prescription rates. This study investigates whether two specific interventions directed toward healthcare centers, an informational visit and a self-evaluation meeting, played a role in observed reduction in rates of antibiotic prescriptions in primary healthcare. METHODS: The study was a retrospective, observational, empirical analysis exploiting the variation in the timing of the interventions and considering past prescriptions through use of estimations from dynamic panel data models. Primary healthcare data from 2011 to 2014 were examined. Data were from public and private primary healthcare centers in western Sweden. The key variables were prescription of antibiotics and indicator variables for the two interventions. RESULTS: The first intervention, an educational information intervention, decreased the number of prescriptions among public healthcare centers, but this effect was only temporary. We found no proof that the second intervention, a self-evaluation meeting at the healthcare center, had an impact on the reduction of prescriptions. CONCLUSIONS: Single educational interventions aimed at influencing rates of antibiotic prescriptions have limited impact. A multifaceted approach is needed in efforts to reduce the use of antibiotics in primary health care.

Clostridioides difficile incidence related to in-hospital cephalosporin use: a tale of two highly comparable hospitals.

Background: Antibiotic treatment is a well-known risk factor for healthcare facility-associated Clostridioides (Clostridium) difficile infection (HCF-CDI). Antibiotic stewardship programmes (ASPs) targeting high-risk antibiotics have been shown to decrease HCF-CDI incidence. HCF-CDI incidence is high in Nordic countries despite relatively low antibiotic use in hospital. Objectives: To determine if HCF-CDI incidence was modified by a hospital ASP that restricted cephalosporin use. Methods: The effects of an ASP on HCF-CDI incidence were evaluated in a two-centre setting using a retrospective design. We exploited a strategy of both individual case ascertainment based on chart reviews and aggregated data from the hospitals. Cases were attributed to the antibiotics given prior to disease onset, in proportion to the number of DDDs used. Three periods were studied: 2007 (before the ASP), 2012 and 2015. Results: At the ASP hospital, cephalosporin use decreased by 87% and the number of HCF-CDI/1000 hospital admissions decreased significantly from 2.25 (2007) to 1.16 (2015) (P = 0.0014). The corresponding results at the non-ASP hospital showed a non-significant increase from 2.09 to 2.38. A high number of cases could be attributed to cephalosporins at both hospitals. The increased use of other broad-spectrum antibiotics, e.g. piperacillin/tazobactam, at the ASP hospital was not associated with offsetting increases in attributable HCF-CDI cases. Conclusions: Decreased use of cephalosporins is an effective strategy to decrease HCF-CDI incidence over time in a setting with high incidence and low antibiotic use.

Staphylokinase Control of Staphylococcus aureus Biofilm Formation and Detachment Through Host Plasminogen Activation.

Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In the present study, we investigated the contribution of fibrin and staphylokinase (Sak) to biofilm formation. In both clinical S. aureus isolates and laboratory strains, high Sak-producing strains formed less biofilm than strains that lacked Sak, suggesting that Sak prevents biofilm formation. In addition, Sak induced detachment of mature biofilms. This effect depended on plasminogen activation by Sak. Host-derived fibrin, the main substrate cleaved by Sak-activated plasminogen, was a major component of biofilm matrix, and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Sak also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for Sak-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components.

Tissue Plasminogen Activator Coating on Implant Surfaces Reduces Staphylococcus aureus Biofilm Formation.

Staphylococcus aureus biofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role in S. aureus biofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating on S. aureus biofilm formation was tested with in vitro microplate biofilm assays and an in vivo mouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by various S. aureus strains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics. In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduce S. aureus biofilm formation both in vitro and in vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices.

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.

Staphylokinase promotes the establishment of Staphylococcus aureus skin infections while decreasing disease severity.

Skin infections are frequently caused by Staphylococcus aureus and can lead to a fatal sepsis. The microbial mechanisms controlling the initiation and progression from mild skin infection to a severe disseminated infection remain poorly understood. Using a combination of clinical data and in vitro and ex vivo assays, we show that staphylokinase, secreted by S. aureus, promoted the establishment of skin infections in humans and increased bacterial penetration through skin barriers by activating plasminogen. However, when infection was established, the interaction between staphylokinase and plasminogen did not promote systemic dissemination but induced the opening and draining of abscesses and decreased disease severity in neutropenic mice. Also, increased staphylokinase production was associated with noninvasive S. aureus infections in patients. Our results point out the dual roles of staphylokinase in S. aureus skin infections as promoting the establishment of infections while decreasing disease severity.

Antibiotic prescription: Knowledge among physicians and nurses in western Sweden.

Misuse and overuse of antibiotics are common in primary care. Guidelines for prescribing of antibiotics are often not followed We conducted a survey of 120 health centers in western Sweden to investigate to what extent physicians and nurses think they know and comply with the guidelines for prescribing of antibiotics. A large majority of the respondents answered that they know the guidelines well. However, many also believed that physicians/nurses in general know less about and are worse at following the guidelines than themselves, indicating optimism bias. According to the respondents the main reason for non-compliance with guidelines was patient expectations. The survey also showed that both physicians' and nurses' actual knowledge of when it is effective to prescribe antibiotics is incomplete. Interventions to reduce unnecessary antibiotic therapy in primary care should target the failing congruence between the perceived knowledge of guidelines for antibiotic therapy and actual knowledge.

Clostridioides difficile outbreak detection: Evaluation by ribotyping and whole-genome sequencing of a surveillance algorithm based on ward-specific cutoffs.

OBJECTIVE: We evaluated the performance of an early-warning algorithm, based on ward-specific incidence cutoffs for detecting Clostridioides difficile transmission in hospitals. We also sought to determine the frequency of intrahospital Clostridioides difficile transmission in our setting. DESIGN: Diagnostic performance of the algorithm was tested with confirmed transmission events as the comparison criterion. Transmission events were identified by a combination of high-molecular-weight typing, ward history, ribotyping, and whole-genome sequencing (WGS). SETTING: The study was conducted in 2 major and 2 minor secondary-care hospitals with adjacent catchment areas in western Sweden, comprising a total population of ∼480,000 and ∼1,000 hospital beds. PATIENTS: All patients with a positive PCR test for Clostridioides difficile toxin B during 2020 and 2021. METHODS: We conducted culturing and high-molecular-weight typing of all positive clinical samples. Ward history was determined for each patient to find possible epidemiological links between patients with the same type. Transmission events were determined by PCR ribotyping followed by WGS. RESULTS: We identified 4 clusters comprising a total of 10 patients (1.5%) among 673 positive samples that were able to be cultured and then typed by high-molecular-weight typing. The early-warning algorithm performed no better than chance; patient diagnoses were made at wards other than those where the transmission events likely occurred. CONCLUSIONS: In surveillance of potential transmission, it is insufficient to consider only the ward where diagnosis is made, especially in settings with high strain diversity. Transmission within wards occurs sporadically in our setting.

Long-term outcome of invasive Staphylococcus aureus infections.

BACKGROUND: Short-term mortality from invasive Staphylococcus aureus infections (ISA) is high. Death rates from 20% to 60% are reported. Long-term outcome has not been investigated. Studies of other critical illnesses have demonstrated incremental health effects that persist after hospital discharge. Several researchers have proposed that evaluation of mortality secondary to sepsis should take place after 1 y. METHODS: We performed an observational, prospective, population-based study of long-term mortality and recurrence in a cohort of ISA patients during 2 y. RESULTS: One hundred and fifty-seven patients were included. All-cause mortality after 1 y was 37.6% and after 3 y was 45.5%. The multivariate survival analysis explored different independent factors for short-term compared to long-term mortality. Age, comorbidity, and place of acquisition were the determinants of long-term outcome. In contrast, infection-related factors such as disease severity and systolic blood pressure determined short-term mortality. The relapse-reinfection rate was 11.2% (16 in 143 episodes in 127 patients living 4 weeks after inclusion). Predictive factors for relapse-reinfection in a univariate analysis were joint prosthesis (28.6%, p = 0.027), haemodialysis (27.8%, p = 0.017), kidney disease (22.2%, p = 0.015), and healthcare- and nosocomial-related infection (18.3%, p = 0.029). No association to length of antibiotic therapy and relapse-reinfection rate was observed, nor any sex differences. The majority of relapses-reinfections (11 of 16) occurred during the first 11 months after the initial episode. CONCLUSION: Patients with ISA infections, irrespective of age, suffer a high long-term mortality and recurrence rate.

Remote investigation and assessment of vital signs (RIA-VS)-proof of concept for contactless estimation of blood pressure, pulse, respiratory rate, and oxygen saturation in patients with suspicion of COVID-19.

BACKGROUND: Vital signs are critical in assessing the severity and prognosis of infections, for example, COVID-19, influenza, sepsis, and pneumonia. This study aimed to evaluate a new method for rapid camera-based non-contact measurement of heart rate, blood oxygen saturation, respiratory rate, and blood pressure. METHODS: Consecutive adult patients attending a hospital emergency department for suspected COVID-19 infection were invited to participate. Vital signs measured with a new camera-based method were compared to the corresponding standard reference methods. The camera device observed the patient's face for 30 s from ∼1 m. RESULTS: Between 1 April and 1 October 2020, 214 subjects were included in the trial, 131 female (61%) and 83 male (39%). The mean age was 44 years (range 18-81 years). The new camera-based device's vital signs measurements were, on average, very close to the gold standard but the random variation was larger than the reference methods. CONCLUSIONS: The principle of contactless measurement of blood pressure, pulse, respiratory rate, and oxygen saturation works, which is very promising. However, technical improvements to the equipment used in this study to reduce its random variability is required before clinical implementation. This will likely be a game changer once this is sorted out. CLINICAL TRIAL REGISTRATION: Universal Trial Number (UTN) U1111-1251-4114 and the ClinicalTrials.gov Identifier NCT04383457.

[Rational use of antibiotics in Region Västra Götaland]. / Från rött till grönt efter tio år med Strama i Västra Götaland.

Optimizing antibiotic use to control the spread of antimicrobial resistance is a global health priority. The Swedish strategic programme against antibiotic resistance (Strama) has for many years supported the rational use of antibiotics. A key element has been the bottom-up approach, working closely with prescribers at the local level. During the last decade, Strama VG has intensified the efforts in Region Västra Götaland, and a considerable reduction (45%) in antibiotic prescription rates has been achieved. Our aim is to facilitate the local process by engaging local ¼Strama doctors« at each of 200 Primary Health Care (PHC) Centres and at every hospital department. In PHC an appreciated educational model through reflective peer meetings including case discussion, comparison of individual prescribing and teamwork that include all staff, have contributed to the improvement. However, the work needs continuous support by Strama.

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.

Increasing incidence and antimicrobial resistance in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. METHODS: We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). RESULTS: We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. CONCLUSIONS: Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.

Invasive Staphylococcus aureus strains are highly variable in PFGE patterns, agr group and exoprotein production.

In the present study, we have investigated 37 invasive Staphylococcus aureus strains (collected between 1997 and 2005) from 33 human episodes of septicaemia causing either endocarditis or vertebral osteomyelitis. All S. aureus strains were typed using pulsed field gel electrophoresis (PFGE), and most strains belonged to any of 4 different PFGE clusters. There was no correlation between any of the PFGE clusters with site of infection. All strains showed highly different expression patterns of extracellular proteins, i.e. we found a vast variation in the number of proteins and amount of individual proteins expressed by the different strains. There was no correlation between any cluster of exoprotein patterns with endocarditis or with vertebral osteomyelitis. We did not find any correlation between agr group and endocarditis, as previously reported. On the other hand, a correlation between some of the PFGE clusters with a certain agr group was found. Known risk factors for S. aureus infections were observed in a majority of the patients.

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.