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Background The recommended duration of antimicrobial treatment for Staphylococcus aureus bacteremia (SAB) is a minimum of 14 days. We compared the clinical outcomes of patients receiving short-course (SC; 6–10 days), or prolonged-course (PC; 11–16 days) antibiotic therapy for low-risk methicillin-susceptible SAB (MS-SAB). Methods Adults with MS-SAB in 1995–2018 were included from 3 independent retrospective cohorts. Logistic regression models fitted with inverse probability of treatment weighting were used to assess the association between the primary outcome of 90-day mortality and treatment duration for the individual cohorts as well as a pooled cohort analysis. Results A total of 645, 219, and 141 patients with low-risk MS-SAB were included from cohorts I, II, and III. Median treatment duration in the 3 SC groups was 8 days (interquartile range [IQR], 7–10), 9 days (IQR, 8–10), and 8 days (IQR, 7–10). In the PC groups, patients received a median therapy of 14 days (IQR, 13–15), 14 days (IQR, 13–15), and 13 days (IQR, 12–15). No significant differences in 90-day mortality were observed between the SC and PC group in cohort I (odds ratio [OR], 0.85 [95% confidence interval {CI}, .49–1.41]), cohort II (OR, 1.24 [95% CI, .60–2.62]), or cohort III (OR, 1.15 [95% CI, .24–4.01]). This result was consistent in the pooled cohort analysis (OR, 1.05 [95% CI, .71–1.51]). Furthermore, duration of therapy was not associated with the risk of relapse. Conclusions In patients with low-risk MS-SAB, shorter courses of antimicrobial therapy yielded similar clinical outcomes as longer courses of therapy.

Background Treatment with dabigatran, an oral direct thrombin inhibitor, reduces the virulence of Staphylococcus aureus in in vitro and in vivo models. However, it remains to be determined whether dabigatran reduces the risk of S. aureus infections in humans. We investigated the incidence rate of S. aureus bacteremia (SAB) in patients with atrial fibrillation treated with the direct thrombin inhibitor dabigatran compared with patients treated with the factor Xa-inhibitors rivaroxaban, apixaban, and edoxaban. Methods In this observational cohort study, 112 537 patients with atrial fibrillation who initiated treatment with direct oral anticoagulants (August 2011–December 2017) were identified from Danish nationwide registries. The incidence rates of SAB in patients treated with dabigatran versus patients treated with the factor Xa-inhibitors were examined by multivariable Cox regression accounting for time-dynamic changes in exposure status during follow-up. Results A total of 112 537 patients were included. During a median follow-up of 2.0 years, 186 patients in the dabigatran group and 356 patients in the factor Xa-inhibitor group were admitted with SAB. The crude incidence rate of SAB was lower in the dabigatran group compared with the factor Xa-inhibitor group (22.8 [95% confidence interval [CI], 19.7–26.3] and 33.8 [95% CI, 30.5–37.6] events per 10 000 person-years, respectively). In adjusted analyses, dabigatran was associated with a significantly lower incidence rate of SAB compared with factor Xa-inhibitors (incidence rate ratio, .76; 95% CI, .63–.93). Conclusions Treatment with dabigatran was associated with a significantly lower incidence rate of SAB compared with treatment with factor Xa-inhibitors.

Aims To investigate the 1-year risks of Staphylococcus aureus bacteraemia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor vs. clopidogrel. Methods and results In this nationwide observational cohort study, 26 606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011–December 2017) and initiated treatment with ticagrelor [N = 20 073 (75.5%); median age 64 years (25th–75th percentile 55–72 years); 74.8% men] or clopidogrel [N = 6533 (24.5%); median age 68 years (25th–75th percentile 58–77 years); 70.2% men] were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% confidence interval (CI), 0.05–0.15%] in the ticagrelor group and 0.29% (95% CI, 0.17–0.42%) in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB [absolute risk difference −0.19% (95% CI, −0.32% to −0.05%), P value 0.006]. Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis [0.99% (95% CI, 0.83–1.14%) vs. 1.49% (95% CI, 1.17–1.80%); absolute risk difference −0.50% (95% CI, −0.86% to −0.14%), P value 0.007] and pneumonia [3.13% (95% CI, 2.86–3.39%) vs. 4.56% (95% CI, 4.03–5.08%); absolute risk difference −1.43% (95% CI, −2.03% to −0.82%), P value < 0.001] compared with clopidogrel. Conclusion Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.

Background Although the vast majority of individuals succumbing to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are elderly, infection fatality rate (IFR) estimates for the age group ≥70 years are still scarce. To this end, we assessed SARS-CoV-2 seroprevalence among retired blood donors and combined it with national coronavirus disease 2019 (COVID-19) survey data to provide reliable population-based IFR estimates for this age group. Methods We identified 60 926 retired blood donors aged ≥70 years in the rosters of 3 regionwide Danish blood banks and invited them to fill in a questionnaire on COVID-19–related symptoms and behaviors. Among 24 861 (40.8%) responders, we invited a random sample of 3200 individuals for blood testing. Overall, 1201 (37.5%) individuals were tested for SARS-CoV-2 antibodies (Wantai) and compared with 1110 active blood donors aged 17–69 years. Seroprevalence 95% confidence intervals (CIs) were adjusted for assay sensitivity and specificity. Results Among retired (aged ≥70 years) and active (aged 17–69 years) blood donors, adjusted seroprevalences were 1.4% (95% CI, .3–2.5%) and 2.5% (95% CI, 1.3–3.8%), respectively. Using available population data on COVID-19–related fatalities, IFRs for patients aged ≥70 years and for 17–69 years were estimated at 5.4% (95% CI, 2.7–6.4%) and .083% (95% CI, .054–.18%), respectively. Only 52.4% of SARS-CoV-2–seropositive retired blood donors reported having been sick since the start of the pandemic. Conclusions COVID-19 IFR in the age group >69 years is estimated to be 65 times the IFR for people aged 18–69 years.

Background: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages. Methods: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion. Findings: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72–0·87; p

Purpose Staphylococcus aureus carriage poses an increased risk of S. aureus infection. The aim of this study was to investigate the colonization of S. aureus among healthy individuals and to establish a prospective cohort and biobank for research in the health consequences of colonization. Population and methods The Danish Blood Donor S. aureus Carriage Study (DBDSaCS) was established in 2014. So far, a total of 6082 healthy participants have been included with nasal swabs and repeated swabs are performed at subsequent donations. Samples from the first 2217 participants were cultured using a two-step method to evaluate the effect of using enrichment broth. Furthermore, 262 participants were sampled from both the nares and the throat. All participants completed a questionnaire with self-reported health, anthropometric measurements, current smoking status, and physical activity. Plasma samples, nasal swab transport media, and S. aureus isolates were stored. Results The prevalence of S. aureus nasal colonization was 41%. The prevalence of colonization was higher in men (46%) than women (34%), lower for smokers, and decreased with increasing age ( 55 years: 35%). In participants swabbed from the nose and throat, the prevalence of S. aureus colonization after enrichment was 55% with significantly higher prevalence in the throat (45%) than in the nose (40%). The use of an enrichment broth increased the proportion of S. aureus colonization. Conclusion We describe a large and growing cohort of healthy individuals established to investigate predictors for S. aureus carriage and the health consequences of carriage. Multiple projects using data from DBDSaCS linked with Danish health registers, biomarkers, and genetic markers are ongoing. Results will be published in the coming years.

BackgroundNational data on the spread of SARS-CoV-2 infection and knowledge on associated risk factors are important for understanding the course of the pandemic. “Testing Denmark” is a national large-scale epidemiological surveillance study of SARS-CoV-2 in the Danish population.MethodsBetween September and October 2020, approximately 1.3 million of 5.8 million Danish citizens (age > 15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by Point-of Care rapid Test (POCT) distributed to participants home addresses.FindingsIn total 318,552 participants (24.5% invitees) completed the questionnaire and provided the result of the POCT. Of these, 2,519 (0.79%) were seropositive (median age 55 years) and women were more often seropositive than men, interquartile range (IQR) 42-64, 40.2% males. Of participants with a prior positive Polymerase Chain Reaction (PCR) test (n=1,828), 29.1% were seropositive in the POCT. Seropositivity increased with age irrespective of sex. Elderly participants (>61 years) reported less symptoms and had less frequently been tested for SARS-CoV-2 compared to younger participants. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (Risk ratio (RR) 7.43, 95% CI: 6.57-8.41) and in particular household members (RR 17.70, 95% CI: 15.60-20.10). Home care workers had a higher risk of seropositivity (RR 2.09 (95% CI: 1.58-2.78) as compared to office workers. Geographic population density was not associated to seropositivity. A high degree of compliance with national preventive recommendations was reported (e.g., > 80% use of face masks), but no difference was found between seropositive and seronegative participants.InterpretationThis study provides insight into the immunity of the Danish population seven to eight months after the first COVID-19 case in Denmark. The seroprevalence was lower than expected probably due to a low sensitivity of the POCT used or due to challenges relating to the reading of test results. Occupation or exposure in local communities were major routes of infection. As elderly participants were more often seropositive despite fewer symptoms and less PCR tests performed, more emphasis should be placed on testing this age group.

BackgroundPeople experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with “Severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark.Design and methodsIn November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay.ResultsWe included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p=0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p InterpretationsThe prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. The subset of the study participants who were also sex workers were at particularly high risk of COVID-19 infection.FundingTrygFonden and HelseFonden.

BackgroundCOVID-19 is suggested to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas.MethodsAs part of “Testing Denmark”, a nationwide sero-epidemiological surveillance survey, we conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas in Denmark. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning previous testing (viral throat- and nasopharyngeal swab or antibody test), test results for COVID-19, demographics, household characteristics, employment, risk factors for SARS-CoV-2 infection and history of symptoms associated with COVID-19. Data on seroprevalence from Danish blood donors in same period using a total Ig ELISA assay were used as a proxy for the general Danish population.FindingsOf the 13,279 included participants, 2,296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p>0.001). Seropositivity was higher among males than females (RR 1.1, 95% CI 1.05-1.22%, p=0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p=0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among members of the same households (OR 5.0, 95% CI 4.1-6.2 pInterpretationDanish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased with age. Living in multiple generations or more than four persons in a household was an independent risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.

AimThe objective of this nationwide study was to investigate the association between SARS-CoV-2 transmissibility, viral load, and age of primary cases in Danish households.BackgroundSpread in households represents a major mode of transmission of SARS-CoV-2. In order to take proper action against the spread of the disease, it is important to have a better understanding of transmission in the household domain—including the role of viral load of primary cases.MethodsThe study was designed as an observational cohort study, using detailed administrative register data. We included the full population of Denmark and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021) to estimate transmissibility in house-holds comprising 2-6 people. RT-PCR Cycle threshold (Ct) values were used as a proxy for viral load.ResultsWe identified 63,657 primary cases and 139,882 household members of which 21% tested positive by RT-PCR within a 1-14 day period after the primary case. There was an approximately linear association between Ct value of the sample and transmissibility, implying that cases with samples having a higher viral load were more transmissible than cases with samples having a lower viral load. However, even for primary cases with relatively high sample Ct values, the transmissibility was not negligible, e.g., for primary cases with a sample Ct value of 38, we found that 13% of the primary cases had at least one secondary household case. Moreover, 34% of all secondary cases were found in households with primary cases having sample Ct values >30. An increasing transmissibility with age of the primary cases for adults (≥20 years) and a decreasing transmissibility with age for children (ConclusionsAlthough primary cases with sample high viral loads (low Ct values) were associated with higher SARS-CoV-2 transmissibility, we found no obvious cut-off for sample Ct values to eliminate transmissibility and a substantial amount of household transmission occurred in households where the primary cases had high sample Ct values (low viral load), The study further showed that transmissibility increases with age. These results have important public health implications, as they suggest that contact tracing should prioritize cases according to Ct values and age, and underline the importance of quick identification and isolation of cases. Furthermore, the study highlights that households can serve as a transmission bridge by creating connections between otherwise separate domains.

BackgroundThe pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and also to calculate the infection fatality rate (IFR). These measures may help the authorities to make informed decisions and adjust the current societal interventions. Blood donors comprise approximately 4.7% of the similarly aged population of Denmark and blood is donated in all areas of the country. The objective of this study was to perform real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population based IFR.MethodsAll Danish blood donors aged 17-69 years giving blood April 6 to 17 were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between areas and an estimate of the IFR was calculated. The seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CI).ResultsThe first 9,496 blood donors were tested and a combined adjusted seroprevalence of 1.7% (CI: 0.9-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers a combined IFR in patients younger than 70 is estimated at 82 per 100,000 (CI: 59-154) infections.ConclusionsThe IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR, including only individuals with no comorbidity, is likely several fold lower than the current estimate. This may have implications for risk mitigation. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.

Background: The more infectious SARS-CoV-2 virus lineage B.1.1.7, rapidly spread in Europe after December 2020, and a concern of B.1.1.7 causing more severe disease has been raised. Denmark has one of Europe´s highest capacities per capita of SARS-CoV-2 reverse transcription polymerase chain reaction (RT PCR) test and whole genome sequencing (WGS). We used national health register-data to explore whether B.1.1.7 increases the risk of COVID-19 hospitalisation. Methods and Findings: In an observational cohort study we included all SARS-CoV-2 RT PCR test-positive individuals in Denmark sampled between the 1st January and until the 9th February, 2021, identified in the national COVID-19 surveillance system. The surveillance system includes national individual RT PCR test results and viral WGS analyses and data from national health registers including COVID-19 related hospital admissions defined as first admission within 14 days of the test-positive swab. The odds ratio (OR) of admission according to infection with B.1.1.7, vs other co-existing lineages, was calculated in a logistic regression model adjusted for sex, age, period, follow-up time less than 14 days, region, and comorbidities. A total of 35,887 test-positive individuals were identified, 23,057 (64%) had WGS performed, of whom 18,499 (80%) resulted in a viral genome and a total of 2,155 of these were lineage B.1.1.7. The proportion of individuals with B.1.1.7 increased from 4% in early January to 45% in early February. Among the individuals with viral genome data, B.1.1.7 was associated with a crude OR of admission of 0.87 (95%CI, 0.72-1.05) and an adjusted OR of 1.64 (95%CI, 1.32-2.04) based on 128 admissions after B.1.1.7 infection and 1,107 admissions after infection with other lineages. The adjusted OR was increased in all strata of age and calendar time - the two most important confounders of the crude OR. Conclusions: Infection with lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with other lineages. This finding may have serious public health impact in countries with spread of B.1.1.7 and can support hospital preparedness and modelling of projected impact of the epidemic. Funding Statement: The authors received no specific funding for this work. Declaration of Interests: The authors declare that they have no competing interest. Ethics Approval Statement: This study was conducted on administrative register data. According to Danish law, ethics approval is not needed for such research.

BackgroundThe Covid-19 pandemic is one of the most serious global public health threats in recent times. Understanding transmission of SARS-CoV-2 is of utmost importance to be able to respond to outbreaks and take action against spread of the disease. Transmission within the household is a concern, especially because infection control is difficult to apply within the household domain.MethodsWe used comprehensive administrative register data from Denmark, comprising the full population and all COVID-19 tests, to estimate household transmission risk and attack rate.ResultsWe studied the testing dynamics for COVID-19 and found that the day after receiving a positive test result within the household, 35% of potential secondary cases were tested and 13% of these were positive. After a primary case in 6,782 households, 82% of potential secondary cases were tested within 14 days, of which 17% tested positive as secondary cases, implying an attack rate of 17%. Among primary cases, those aged 0-24 were underrepresented when compared with the total population. We found an approximately linearly increasing relationship between attack rate and age. We investigated the transmission risk from primary cases by age, and found an increasing risk with age of primary cases for adults, while the risk seems to decrease with age for children.ConclusionsAlthough there is an increasing attack rate and transmission risk of SARS-CoV-2 with age, children are also able to transmit SARS-CoV-2 within the household.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is increasingly related to human infections. Farmers and veterinarians have the highest risk, but infections have also occurred in individuals without prior contact to livestock. Clonal complex (CC) 398 is the predominant LA-MRSA lineage causing human infections, and although pigs are the major source of CC398 worldwide, poultry and other animals are also reservoirs. This raises concern for transmission of MRSA via meat. In this study, the occurrence and characteristics of S. aureus isolated from Danish retail meat were examined with main focus on chicken meat. A total of 145 meat samples from Danish supermarkets were examined, including chicken (Danish, n=102), turkey (non-Danish origin; n=23), and pork (Danish, n=20). S. aureus was detected in 69% of the meat samples. MRSA was detected in 19 meat samples (13%), resulting in MRSA prevalence of 4% of chicken, 52% of turkey, and 15% of pork. Three MRSA positive samples were obtained by direct plating (Brilliance MRSA2), whereas 16 MRSA positive samples were detected only after enrichment (TSB+6.5% NaCl and Brilliance MRSA2). Based on spa typing, 68% of MRSA isolates belonged to CC398 (spa t034, t011, t2582, t108), and hereof one isolate derived from chicken (1%). Further findings were spa type t1430 (CC9) in turkey samples (16%) and the human-associated t008 (CC8) in chicken samples (16%). In conclusion, S. aureus was readily detected in Danish retail meat, but presence of MRSA in chicken meat is rare and it is unlikely to be an important transmission factor of MRSA to humans.

Background: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSI). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. Methods: By crosslinking nationwide registries from 2010-2016, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. Findings: In total 60,119, distributed with 15,407, 16,790, and 27,922 BSIs were identified in the periods of 2010-2011, 2012-2013, and 2014-2016, respectively. Patients with E. faecalis had the highest prevalence of IE (16.3%) followed by S. aureus (10.2%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis increased significantly (p=0.003). Male patients had a higher prevalence of IE for all microorganisms investigated compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age. Interpretation: For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI. Funding Statement: The authors state: "No funding." Declaration of Interests: Lauge Ostergaard: no competing interest. Niels Eske Bruun: no competing interest. Marianne Voldstedlund: no competing interest. Magnus Arpi: no competing interest. Christian Ostergaard Andersen: no competing interest. Henrik C Schonheyder: no competing interest. Lars Lemming: reports grants from Merck Sharp & Dohme (MSD) outside the submitted work. Flemming Rosenvinge: no competing interest. Nana Valeur: no competing interest. Peter Sogaard: no competing interest. Paal Skytt Andersen: no competing interest. Robert Skov: no competing interest. Ming Chen: no competing interest. Kasper Iversen: no competing interest. Sabine Gill: no competing interest. Trine Kiilerich Lauridsen: no competing interest. Anders Dahl: no competing interest. Louise Bruun Oestergaard: no competing interest. Jonas Agerlund Povlsen: no competing interest. Claus Moser: no competing interest. Henning Bundgaard: no competing interest. Lars Kober: no competing interest. Emil Loldrup Fosbol: no competing interest. Ethics Approval Statement: This study was approved by the Danish Data Protection Agency. Register-based studies do not require ethical approval in Denmark.

Background Increasing attention has been given to patients with blood stream infection (BSI) and the concurrent prevalence of infective endocarditis (IE). However, there exist a gap in knowledge on the prevalence of IE among patients with a left-sided heart valve prosthesis and BSI. Purpose To examine the prevalence between different BSI and IE in patients with a left-sided heart valve prosthesis. Methods By linking Danish nationwide registries, we were able to identify patients with a left-sided prosthetic heart valve and first-time BSI of interest (Enterococcus faecalis, Staphylococcsus aureus, streptococci species (spp.), and coagulase negative staphylococci [CoNS]) in the period of 2010–2016. Concurrent admission for IE was identified from the Danish National Patient Registry in a period of up to 14 days after the BSI. Results A total of 1,465 patients with BSI were included (1,319 patients with an aortic valve prosthesis [82.6% bioprosthetic] and 146 patients with a mitral valve prosthesis [48.6% bioprosthetic]). Among the included patients, 244 had E. faecalis (median age: 78.3 years, 77.0% male), 301 had S. aureus (median age: 76.9 years, 69.1% male), 401 had streptococci spp. (median age: 78.0 years, 69.1% male) and 519 had CoNS (median age: 76.4 years, 64.2% male). The percentage of patients with a diagnosis of IE in relation to the BSI was 44.3%, 33.6%, 34.4%, and 7.9% for E. faecalis, S. aureus, streptococci spp., and CoNS, respectively. No difference in the overall results was seen by type of valve prosthesis, sex, or age group. Percentage of patients with endocarditis Conclusion In patients with a left-sided heart valve prosthesis, IE was diagnosed in almost half of the patients with E. faecalis, in 1/3 with S. aureus or streptococci spp. and in 1 in 12 with CoNS BSI. Future studies may try to explain why some microbes are more likely to cause prosthetic heart valve endocarditis, than others are.

Currently, surveillance of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in humans in Europe is not systematic but mainly event-based. In September 2014, the European Centre for Disease Prevention and Control (ECDC) initiated a questionnaire to collect data on the number of LA-MRSA from human samples (one isolate per patient) from national/regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. Identification of LA-MRSA as clonal complex (CC) 398 by multilocus sequence typing (MLST) was preferred, although surrogate methods such as spa-typing were also accepted. The questionnaire was returned by 28 laboratories in 27 EU/EEA countries. Overall, LA-MRSA represented 3.9% of 13,756 typed MRSA human isolates, but it represented ≥ 10% in five countries (Belgium, Denmark, Spain, the Netherlands and Slovenia). Seven of the reference laboratories did not type MRSA isolates in 2013. To monitor the dispersion of LA-MRSA and facilitate targeted control measures, we advocate periodic systematic surveys or integrated multi-sectorial surveillance., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

The impact of antibiotic prophylaxis on fecal carriage of ESBL-/AmpC-/carbapenemase-producing Enterobacteriaceae (CPE) was investigated. Patients admitted for elective surgery or diagnostic procedure in a Department of Surgical Gastroenterology (SG) (n= 450) and Orthopedic Surgery (OS) (n= 300) provided a fecal swab at admission and responded to a questionnaire on possible exposures. SG patients received gentamicin/penicillin G (±metronidazole); OS patients received cefuroxime. Two days after surgery a second swab was taken. From SG patients, 6% of first swabs and 9% of second swabs were positive for ESBL-/AmpC-producers. A similar carriage rate was observed in OS patients (6% and 8%, respectively). No CPE were detected. Escherichia coli was the predominant species and blaCTX-M-15 (29% and 22%) and blaCTX-M-14 (11% and 17%) were the most prevalent ESBL genotypes among SG and OS patients. Two different prophylactic antibiotic regimens had no impact on carriage rates. Previous hospitalization and antimicrobial treatment were associated with carriage for SG patients.

We investigated the evolution and epidemiology of a novel livestock-associated methicillin-resistant Staphylococcus aureus strain, which colonizes and infects urban-dwelling Danes even without a Danish animal reservoir. Genetic evidence suggests both poultry and human adaptation, with poultry meat implicated as a probable source.

Enterococci are commensals of the intestinal tract of many animals and humans. Of the various known and still unnamed new enterococcal species, only isolates of Enterococcus faecium and Enterococcus faecalis have received increased medical and public health attention. According to textbook knowledge, the majority of infections are caused by E. faecalis. In recent decades, the number of enterococcal infections has increased, with the increase being exclusively associated with a rising number of nosocomial E. faecium infections. This increase has been accompanied by the dissemination of certain hospital-acquired strain variants and an alarming progress in the development of antibiotic resistance namely vancomycin resistance. With this review we focus on a description of the specific situation of vancomycin resistance among clinical E. faecium isolates in Germany over the past 30 years. The present review describes three VRE episodes in Germany, each of which is framed by the beginning and end of the respective decade. The first episode is specified by the first appearance of VRE in 1990 and a country-wide spread of specific vanA-type VRE strains (ST117/CT24) until the late 1990s. The second decade was initially marked by regional clusters and VRE outbreaks in hospitals in South-Western Germany in 2004 and 2005, mainly caused by vanA-type VRE of ST203. Against the background of a certain "basic level" of VRE prevalence throughout Germany, an early shift from the vanA genotype to the vanB genotype in clinical isolates already occurred at the end of the 2000s without much notice. With the beginning of the third decade in 2010, VRE rates in Germany have permanently increased, first in some federal states and soon after country-wide. Besides an increase in VRE prevalence, this decade was marked by a sharp increase in vanB-type resistance and a dominance of a few, novel strain variants like ST192 and later on ST117 (CT71, CT469) and ST80 (CT1065). The largest VRE outbreak, which involved about 2,900 patients and lasted over three years, was caused by a novel and until that time, unknown strain type of ST80/CT1013 (vanB). Across all periods, VRE outbreaks were mainly oligoclonal and strain types varied over space (hospital wards) and time. The spread of VRE strains obviously respects political borders; for instance, both vancomycin-variable enterococci which were highly prevalent in Denmark and ST796 VRE which successfully disseminated in Australia and Switzerland, were still completely absent among German hospital patients, until to date.

Evaluating trends in antibiotic resistance and communicating the results to a broad audience are important for dealing with this global threat. The Drug Resistance Index (DRI), which combines use and resistance into a single measure, was developed as an easy-to-understand measure of the effectiveness of antibiotic therapy. We demonstrate its utility in communicating differences in the effectiveness of antibiotic therapy across countries.We calculated the DRI for countries with data on antibiotic use and resistance for the disease-causing organisms considered by the WHO as priority pathogens:41 countries had the requisite data and were included in the study. Resistance and use rates were highly variable across countries, butThe DRI is a useful indicator of the problem of resistance. By combining data on antibiotic use with resistance, it captures a snapshot of how the antibiotics a country typically uses match their resistance profiles. This single measure of the effectiveness of antibiotic therapy provides a means of benchmarking against other countries and can, over time, indicate changes in drug effectiveness that can be easily communicated.

Background Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of ‘classical' S. aureus, while as yet no S. schweitzeri infections have been reported. Aim To provide decision support on whether and how to distinguish and report both species. Sources PubMed, searched for S. argenteus and S. schweitzeri. Content This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures. Implications We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. ‘member of the S.aureus complex') to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates.

Livestock-associated methicillin-resistant Staphylococcus aureus clonal complex CC398 (LA-MRSA CC398) is resistant to nearly all β-lactams and several non-β-lactam antimicrobials. Over the last decade, it has become widespread in pig farms across Europe and is now an important cause of human infections in countries with previously low levels of MRSA, such as the Netherlands and Denmark. The hitherto uncontrolled spread of LA-MRSA CC398 underscores an urgent need to understand its epidemiology in order to develop evidence-based interventions. This study demonstrates that pig movements between farms in combination with increased bacterial resistance to specific antibiotics and heavy metals were important drivers of the rapid spread of LA-MRSA CC398 in the Danish pig production system. These findings should be taken into consideration when researchers and policy makers evaluate and decide on actions and policies to limit the spread of LA-MRSA CC398 and other pathogens in food animals., The spread of livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) within the Danish pig production system has been linked to an increased number of human infections. Yet, the population structure and transmission dynamics of this important pathogen remain poorly understood. In this study, whole-genome sequences from 371 LA-MRSA CC398 isolates collected between 2004 and 2015 were subjected to bioinformatic analyses. The isolates originated from Danish pig farms (n = 209) and people having livestock contact (n = 79). In addition, whole-genome sequence data from 82 isolates representing an international reference collection and 83 isolates from Danish patients were included in the analysis. The results demonstrated that the increasing prevalence of LA-MRSA CC398 in Danish pigs and patients was caused by clonal expansion of three dominant lineages. The results also showed that these lineages were enriched for the tetracycline resistance gene tet(K) and other determinants conferring resistance to some of the most frequently used antimicrobials in Danish pigs. The association between pig movements and the spread of LA-MRSA CC398 was assessed in a Poisson regression analysis of 17,009 pig movements into 273 farms with known LA-MRSA CC398 status. The results demonstrated that animal movements have played a critical role in the dissemination of LA-MRSA CC398 within the Danish pig production system, although other transmission routes may also have contributed. Consistent with this scenario, the genetic relatedness of isolates from different farms was positively correlated with the number of animal movements between the farms.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is a high-risk infection and feared complication related to hemodialysis. This study aimed to investigate incidence and risk factors for SAB depending on hemodialysis access type.METHODS: The Danish National Registry on Regular Dialysis and Transplantation was used to identify patients from January 1, 1996 to December 31, 2011 with end-stage kidney disease. Patients were followed until death, the first episode of SAB, or end of study (December 31, 2011). Independent risk factors were assessed by multivariable Poisson regression with time-updated exposure variables.FINDINGS: Total of 9997 patients were included. The initial modality of renal replacement therapy was hemodialysis in 6826 patients and peritoneal dialysis in 2882 patients; 289 patients had preemptive kidney transplantation. SAB occurred in 1278 patients (12.8%). The incidence rate of SAB declined after 90 days and leveled off after 270 days in hemodialysis, peritoneal dialysis, and kidney transplanted. As compared to peritoneal dialysis, the adjusted rate ratio (RR) for SAB was 7.42 (95% CI 5.63-9.79) in uncuffed central venous catheter (CVC), 5.68 (95% CI 4.39-7.36) in cuffed CVC, 4.43 (95% CI 2.10-9.53) in arteriovenous graft, and 3.40 (95% CI 2.79-4.15) in arteriovenous fistula. SAB risk did not differ between uncuffed and cuffed CVC. The risk of SAB was increased during the first three months of renal replacement therapy especially for CVC (RR 11.37 [95% CI7.09-18.22]) compared with peritoneal dialysis. Diabetes mellitus (RR 1.35 [95% CI 1.20-1.51]) and male sex (RR 1.15 [95% CI 1.03-1.29]) were also associated with SAB.DISCUSSION: Patients on hemodialysis had a high incidence rate of SAB, particularly those undergoing hemodialysis via CVC. SAB risk was comparable for cuffed and uncuffed CVC. Diabetes mellitus, male sex, and the first three months in renal replacement therapy were independently associated with SAB.

Until recently, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommended the cefoxitin disc to screen for mecA-mediated β-lactam resistance in Staphylococcus pseudintermedius. A recent study indicated that cefoxitin was inferior to oxacillin in this respect. We have re-evaluated cefoxitin and oxacillin discs for screening for methicillin resistance in S. pseudintermedius.We included 224 animal and human S. pseudintermedius isolates from Europe (n = 108) and North America (n = 116), of which 109 were mecA-positive. Disc diffusion was performed per EUCAST recommendations using 30-μg cefoxitin and 1-μg oxacillin discs from three manufacturers and Mueller-Hinton agar from two manufacturers.Cefoxitin inhibition zones ranged from 6 to 33 mm for mecA-positive S. pseudintermedius (MRSP) and from 29 to 41 mm for mecA-negative S. pseudintermedius (MSSP). The corresponding oxacillin zone intervals were 6-20 mm and 19-30 mm. For cefoxitin 16% (95% CI 14.8-18.0%) of the isolates were in the area where positive and negative results overlapped. For oxacillin the corresponding number was 2% (1.6-2.9%). For oxacillin a breakpoint of susceptible (S) ≥ 20 mm and resistant (R) 20 mm resulted in only 0.4% and 1.1% very major error and major error rates respectively.This investigation confirms that the 1-μg oxacillin disc predicts mecA-mediated methicillin resistance in S. pseudintermedius better than the 30-μg cefoxitin disc. For a 1-μg oxacillin disc we propose that 20 mm should be used as cut off for resistance, i.e. isolates with a zone diameter20 mm are resistant to all β-lactam antibiotics except those with activity against methicillin-resistant staphylococci.

Background The recommended duration of antibiotic treatment for uncomplicated Staphylococcus aureus bloodstream infections is 14 days. We compared the outcomes of patients receiving short-course (6–10 days) vs. prolonged-course (11–16 days) antibiotic therapy for S. aureus bacteremia (SAB). Methods 30-day outcome of patients with penicillin (PSSAB, n = 202)) or methicillin-susceptible SAB (MSSAB, n = 203) treated with in vitro active therapy in the range of 6–16 days was analyzed using pooled data from two previously published, observational studies. Individuals were matched 1:1 by nearest neighbor propensity score matching without replacement. Regression analysis was performed to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment. Eligible individuals had to have >1 day of follow-up after discontinuation of antimicrobials. Individuals with a diagnosis of endocarditis, bone infection, meningitis or pneumonia were excluded. Results There were 107 well-balanced matched pairs; 58 in the PSSAB and 39 in the MSSAB cohort. For PSSAB, the median duration of therapy was 8 (interquartile range [IQR], 7–10) in the short-course group and 12 days (IQR, 10–13) in the prolonged-course group. For the MSSAB cohort, these numbers were 9 days (IQR, 7–10) and 14 days (IQR, 13–16 days), respectively. No difference in mortality between short-course and prolonged-course treatment was observed (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], .23–2.41) and 1.14; 95% CI, 0.31–4.20), respectively for PSSAB and MSSAB. Conclusion Short courses of antibiotic therapy yielded similar clinical outcomes as prolonged courses of antibiotic therapy for S. aureus bacteremia. The findings warrant a randomized clinical trial to study the safety and efficacy of shortened antimicrobial therapy for the treatment of uncomplicated SAB. Disclosures All authors: No reported disclosures.

OBJECTIVES: An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB).METHODS: Danish register-based nation-wide observational cohort study between 1995 and 2008 with matched control subjects from the general population.RESULTS: Within a year, 278 of 15669 SAB patients and 2570 of 156690 controls developed MI, stroke or another ATE. The incidence rates among SAB patients were highest within the first 30 days and decreased over a year. The adjusted relative risk of MI, stroke and other ATE during the first 30 days after SAB in patients compared to controls were 2.2 (95% CI: 1.6-3.1), 5.5 (95% CI: 3.8-8.3) and 15.5 (95% CI: 6.9-35), respectively. Compared to controls, the increased adjusted relative risk persisted for 30 days for MI, 180 days for stroke and one year for other ATE. Increasing age, hypertension, atrial flutter/fibrillation, prior ATE and endocarditis in SAB patients were associated with an increased risk of ATE.CONCLUSIONS: SAB was associated with a short-term increased risk of ATE that persisted longer dependent on type of event. Studies are warranted to investigate treatment strategies to diminish ATE after SAB.

The authors regret that the author name Silvano Esposito was published incorrectly. The authors would like to apologise for any inconvenience caused.

Background: In recent years, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) multi locus sequence type CC398 has spread widely in the livestock production in Europe. The rates of LA-MRSA in hospitals have been found to be largely determined by contact to and density of livestock in the area.Methods: This is a cross sectional study of the prevalence of LA-MRSA among hospital staff in a Danish hospital situated in a livestock production region. We analysed nasal swabs, air and dust samples for the presence of MRSA using PCR and mass spectrometry.Results: Of 1745 employees, 545 (31%) contributed nasal swabs. MRSA was not detected in any participant, nor was it detected in air or dust at the hospital or in houses of employees living on farms. Four percent of the participants had contact to pigs either directly or through household members. LA-MRSA was detected in two of 26 samples from animal sheds, both of them from pig farms. The participation rate was relatively low, but participants were representative for the source population with regards to animal contact and job titles.Conclusions: The study suggests a low point prevalence of LA-MRSA carriage in Danish hospital staff even in regions where livestock production is dense. Should more studies confirm our findings we see no need for additional hospital precautions towards LA-MRSA in Denmark at the moment. We think that our data might reduce potential stigmatization of hospital workers with contact to LA-MRSA positive farms at their work places and in their communities.

Background Staphylococcus aureus bacteremia (SAB) is the leading cause of infective endocarditis in several countries. Since socioeconomic status (SES) is known to influence the risk of infectious diseases in general, we aimed to investigate the association between SES and SAB, and risk of subsequent endocarditis in a nationwide adult population. Methods All Danish residents were consecutively included at age ≥ 30 years during 1996–2010. We obtained information on SES (highest attained educational level), comorbidities, and microbiologically verified SAB by cross-linking nationwide registries. The incidence rate ratios (IRRs) of SAB and later endocarditis were investigated using Poisson regression models adjusted for sex, age and year (reference = highest SES). Results Our study population comprised 3,394,936 individuals (median age = 43.2 years). Over a median follow-up of 15.9 years, 13,181 individuals acquired SAB. SES was inversely associated with SAB acquisition, which declined with increasing age, e.g. in individuals with lowest SES, IRRs were 3.78 (95% confidence interval [CI] = 2.89–4.95) in age 30–50 years, 1.87 (CI = 1.60–2.18) in age > 50–70 years and 1.31 (CI = 1.11–1.54) in age > 70 years (interaction-p

International audience; In this study, the performances of four methicillin-resistant Staphylococcus aureus (MRSA) chromogenic screening media were compared for detecting mecC-positive MRSA. Using 111 clinical isolates representative of the various mecC-MRSA clones in Europe, chromID\textregistered MRSA (bioMérieux) and BrillianceTM MRSA 2 (Oxoid Ltd.) showed higher sensitivity (99.1% and 97.3%, respectively) than BBLTM CHROMagar\textregistered MRSA II (BD Diagnostics) and MRSASelectTM (Bio-Rad) (79.3% and 63.1%, respectively) (P \textless0.0001). These findings have important implications for effective public health diagnostics and epidemiological surveillance of MRSA.

Transmission of methicillin-resistant Staphylococcus aureus (MRSA) from animals to humans is of great concern due to the implications for human health and the health care system. The objective was to investigate the frequency and duration of MRSA carriage in human volunteers after a short-term exposure in a swine farm. The experimental study included 34 human volunteers staying 1 h in a MRSA-positive swine farm in four trials. In two of the trials, the influence of farm work involving pig contact was studied using a crossover design. The quantities of MRSA in nasal swabs, throat swabs, and air samples were measured at different time points and analyzed in relation to relevant covariates. This investigation showed that, overall, 94% of the volunteers acquired MRSA during the farm visit. Two hours after the volunteers left the stable, the nasal MRSA count had declined to unquantifiable levels in 95% of the samples. After 48 h, 94% of the volunteers were MRSA-negative. Nasal MRSA carriage was positively correlated to personal exposure to airborne MRSA and farm work involving pig contact and negatively correlated to smoking. No association was observed between MRSA carriage and face touching behavior, nasal methicillin-susceptible Staphylococcus aureus (MSSA) carriage, age, or gender. The increase in human MRSA carriage among the volunteers with pig contact seems to be dependent on the increased concentration of airborne MRSA of the surrounding air and not directly on physical contact with pigs. MRSA was not detected in any of the throat samples. IMPORTANCE The experimental approach made it possible to elucidate the contributions of airborne MRSA levels and farm work to nasal MRSA carriage in a swine farm. Short-term exposure to airborne MRSA poses a substantial risk for farm visitors to become nasal carriers, but the carriage is typically cleared within hours to a few days. The risk for short-term visitors to cause secondary transmissions of MRSA is most likely negligible due to the observed decline to unquantifiable levels in 95% of the nasal samples after only 2 h. The MRSA load in the nose was highly correlated to the amount of MRSA in the air and interventions to reduce the level of airborne MRSA or the use of face masks might consequently reduce nasal contamination.

Summary Background Data on risk factors and rates of reinfection associated with Staphylococcus aureus bacteraemia (SAB) are sparse. Methods We conducted a nationwide cohort study of cases of SAB diagnosed between 1995 and 2008. Reinfection was defined as an episode of SAB more than 90 days after the initial episode of SAB. Comorbidity was evaluated by the Charlson Comorbidity Index (CCI). Cox proportional hazards modelling was used to estimate hazard rates (HR). Results Of 10,891 eligible patients, 774 (7.1%) experienced reinfection a median of 458 days (range 90–5021 days) after their primary SAB episode corresponding to a reinfection rate of 1459 (95% confidence interval (CI): 1357–1562) per 100,000 personyears. In multivariate analysis, sex, origin, a vascular or peritoneal device, endocarditis and comorbidity were associated with reinfection. The association was more than two-fold higher among patients in dialysis and for patients with severe comorbidity (CCI≥2). HIV infection (Hazard ratio (HR) 6.18, 95% CI: 4.17–9.16), renal disease (HR 3.92, 95% CI: 3.22–4.78), diabetes with complications (HR 2.11, 95% CI: 1.69–2.62), diabetes without complications (HR 1.61, 95% CI: 1.34–1.93), mild (HR: 1.94, 95% CI: 1.36–2.76) and severe liver disease (HR 2.08, 95% CI: 1.08–4.03), peptic ulcer (HR 1.33, 95% CI: 1.03–1.72), and paraplegia (HR 2.15, 95% CI: 1.02–4.54) were each associated with an increased risk of reinfection. Conclusions Patients with previous SAB have a 60-fold higher risk of SAB compared to the general population. Patients with HIV infection, renal disease, diabetes, liver disease, peptic ulcer and paraplegia had the highest rates of reinfection.

Selective reporting of antibiotic susceptibility test (AST) results is one possible laboratory-based antibiotic stewardship intervention. The primary aim of this study was to identify where and how selective reporting of AST results is implemented in Europe both in inpatient and in outpatient settings. An ESCMID cross-sectional, self-administered, internet-based survey was conducted among all EUCIC (European Committee on Infection Control) or EUCAST (European Committee on Antimicrobial Susceptibility Testing) national representatives in Europe and Israel. Of 38 countries, 36 chose to participate in the survey. Selective reporting of AST results was implemented in 11/36 countries (31%), was partially implemented in 4/36 (11%) and was limited to local initiatives or was not adopted in 21/36 (58%). It was endorsed as standard of care by health authorities in only three countries. The organisation of selective reporting was everywhere discretionally managed by each laboratory, with a pronounced intra-and inter-country variability. The most frequent application was in uncomplicated community-acquired infections, particularly urinary tract and skin and soft-tissue infections. The list of reported antibiotics ranged from a few first-line options, to longer reports where only last-resort antibiotics were hidden. Several barriers to implementation were reported, mainly lack of guidelines, poor system support, insufficient resources, and lack of professionals' capability. In conclusion, selective reporting of AST results is poorly implemented in Europe and is applied with a huge heterogeneity of practices. Development of an international framework, based on existing initiatives and identified barriers, could favour its dissemination as one important element of antibiotic stewardship programmes. KEYWORDS: Antibiotic prescription; Antibiotic resistance; Antibiotic stewardship; Antibiotic susceptibility testing; Questionnaire; Selective reporting PMID: 28093208 DOI: 10.1016/j.ijantimicag.2016.11.014, Selective reporting of antibiotic susceptibility test (AST) results is one possible laboratory-based antibiotic stewardship intervention. The primary aim of this study was to identify where and how selective reporting of AST results is implemented in Europe both in inpatient and in outpatient settings. An ESCMID cross-sectional, self-administered, internet-based survey was conducted among all EUCIC (European Committee on Infection Control) or EUCAST (European Committee on Antimicrobial Susceptibility Testing) national representatives in Europe and Israel. Of 38 countries, 36 chose to participate in the survey. Selective reporting of AST results was implemented in 11/36 countries (31%), was partially implemented in 4/36 (11%) and was limited to local initiatives or was not adopted in 21/36 (58%). It was endorsed as standard of care by health authorities in only three countries. The organisation of selective reporting was everywhere discretionally managed by each laboratory, with a pronounced intra- and inter-country variability. The most frequent application was in uncomplicated community-acquired infections, particularly urinary tract and skin and soft-tissue infections. The list of reported antibiotics ranged from a few first-line options, to longer reports where only last-resort antibiotics were hidden. Several barriers to implementation were reported, mainly lack of guidelines, poor system support, insufficient resources, and lack of professionals' capability. In conclusion, selective reporting of AST results is poorly implemented in Europe and is applied with a huge heterogeneity of practices. Development of an international framework, based on existing initiatives and identified barriers, could favour its dissemination as one important element of antibiotic stewardship programmes.

BACKGROUND: Point-of-care testing (POCT) in primary care may improve rational antibiotic prescribing. We examined use of POCT in Denmark, including patient- and general practitioner (GP)-related predictors.METHODS: We linked nationwide health care databases to assess POCT use (C-reactive protein (CRP), group A streptococcal (GAS) antigen swabs, bacteriological cultures, and urine test strips) per 1,000 overall GP consultations, 2004-2013. We computed odds ratios (OR) of POCT in patients prescribed antibiotics according to patient and GP age and sex, GP practice type, location, and workload.RESULTS: The overall use of POCT in Denmark increased by 45.8% during 2004-2013, from 147.2 per 1,000 overall consultations to 214.8. CRP tests increased by 132%, bacteriological cultures by 101.7% while GAS swabs decreased by 8.6%. POCT preceded 28% of antibiotic prescriptions in 2004 increasing to 44% in 2013. The use of POCT varied more than 5-fold among individual practices, from 54.9 to 394.7 per 1,000 consultations in 2013. POCT use varied substantially with patient age, and males were less likely to receive POCT than females (adjusted OR = 0.75, 95% CI 0.74-0.75) driven by usage of urine test strips among females (18% vs. 7%). Odds of POCT were higher among female GPs and decreased with higher GP age, with lowest usage among male GPs >60 years. GP urban/rural location and workload had little impact.CONCLUSION: GPs use POCT increasingly with the highest use among young female GPs. In 2013, 44% of all antibiotic prescriptions were preceded by POCT but testing rates vary greatly across individual GPs.

Denmark is a country with high prevalence of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 in pigs. Even though pig farming is regarded as the main source of human infection or colonization with MRSA CC398, 10-15% of the human cases appear not to be linked to pigs. Following the recent reports of MRSA CC398 in horses in other European countries and the lack of knowledge on S. aureus carriage in this animal species, we carried out a study to investigate whether horses constitute a reservoir of MRSA CC398 in Denmark, and to gain knowledge on the frequency and genetic diversity of S. aureus in horses, including bothmethicillin-resistant and -susceptible S. aureus (MSSA). Nasal swabs were collected from 401 horses originating from 74 farms, either at their farms or prior to admission to veterinary clinics. Following culture on selectivemedia, species identification by MALDI-TOF MS and MRSA confirmation by standard PCR-based methods, S. aureus and MRSA were detected in 54 (13%) and 17 (4%) horses originating from 30 (40%) and 7 (9%) farms, respectively. Based on spa typing, MSSA differed genetically from MRSA isolates. The spa type prevalent among MSSA isolates was t127 (CC1), which was detected in 12 horses from 11 farms and represents the most common S. aureus clone isolated from human bacteremia cases in Denmark. Among the 17 MRSA carriers, 10 horses from three farms carried CC398 t011 harboring the immune evasion cluster (IEC), four horses from two farms carried IEC-negative CC398 t034, and three horses from two farms carried a mecC-positive MRSA lineage previously associated with wildlife and domestic ruminants (CC130 t528). Based on whole-genome phylogenetic analysis of the 14 MRSA CC398, t011 isolates belonged to the recently identified horse-adapted clone in Europe and were closely related to human t011 isolates fromthree Danish equine veterinarians, whereas t034 isolates belonged to pig-adapted clones. Our study confirms that horses carry an equine-specific clone of MRSA CC398 that can be transmitted to veterinary personnel, and reveals that these animals are exposed to MRSA and MSSA clones that are likely to originate from livestock and humans, respectively.

Clin Microbiol Infect ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated (HA), community-associated (CA) and livestock-associated (LA) infections. Recently, the discovery of human and bovine MRSA isolates carrying a new mecA gene homologue, mecA(LGA251) (now designated mecC), has caused concern because they are not detected by conventional, confirmatory tests for MRSA. Very little is known about their frequency, epidemiology and possible transmission between livestock and humans. In this study, the epidemiology of the mecC isolates in Denmark was investigated by screening the national collections of MRSA cases (from 1988 onwards) and S. aureus bacteraemia cases (from 1958 onwards). Isolates carrying mecC were only recovered infrequently before 2003 (n = 2) but now seem to be increasing, with 110 cases in 2003-2011. Clinical data on mecC-carrying MRSA demonstrated that mecC-MRSA were primarily community-acquired (CA-MRSA) and affected persons typically living in rural areas, being older than other CA-MRSA patients. Among 22 cases in Region Zealand, four reported contact with cattle and sheep. Two of these persons lived on farms with livestock positive for mecC-carrying MRSA, sharing spa type (t843), MLVA (MT429) and PFGE pattern with the human isolates. These observations indicate that mecC-carrying MRSA can be exchanged between humans and ruminants.

International audience; The evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification. © 2016 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Background: A genetic predisposition to Staphylococcus aureus bacteremia has been demonstrated in animals, suggesting that genetic differences might influence susceptibility to S aureus in humans.Objective: To determine whether a history of S aureus bacteremia in first-degree relatives increases the rate of the disease, and whether this rate is affected by the type of family relationship (that is, parent or sibling) or by how the relative acquired the infection.Design: Register-based nationwide cohort study (1992 to 2011).Setting: Denmark.Participants: First-degree relatives (children or siblings) of patients previously hospitalized with S aureus bacteremia.Measurements: Poisson regression models were used to calculate standardized incidence ratios (SIRs) of S aureus bacteremia, with the incidence rate in the population as a reference.Results: 34 774 individuals (the exposed cohort) with a first-degree relative (index case patient) previously hospitalized with S aureus bacteremia were followed up for a median of 7.8 years (interquartile range, 3.6 to 13.0). A higher rate of S aureus bacteremia was observed among these first-degree relatives (SIR, 2.49 [95% CI, 1.95 to 3.19]) than in the background population. The estimate was significantly higher if the index case patient was a sibling (SIR, 5.01 [CI, 3.30 to 7.62]) than a parent (SIR, 1.96 [CI, 1.45 to 2.67]; interaction P < 0.0001). No interaction was observed regarding the sex of the first-degree relative (interaction P for parents = 0.85; interaction P for siblings = 0.92). Stratifying by disease acquisition revealed the highest rates in individuals exposed to index case patients with non-hospital-acquired infection. Few were infected with genetically identical bacteremia isolates.Limitation: The rarity of the outcome limited the number of variables in the multiple regression analysis, and whether nonsignificant interactions were true or caused by insufficient statistical power remains uncertain.Conclusion: A significant familial clustering of S aureus bacteremia was found, with the greatest relative rate of disease observed in individuals exposed to siblings with a history of the disease.Primary Funding Source: The Danish Heart Foundation and the Christian Larsen and Judge Ellen Larsen Foundation.

This study provides strong, novel evidence that humans may introduce methicillin-resistant Staphylococcus aureus CC398 into closed pig populations; it also demonstrates that stringent control and eradication measures were effective and prevented dissemination from pig farms to the general human population., Background. Emerging livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) persist in livestock populations and represent a reservoir for transmission to humans. Understanding the routes of introduction and further transmission is crucial to control this threat to human health. Methods. All reported cases of livestock-associated MRSA (CC398) in humans and pigs in Norway between 2008 and 2014 were included. Data were collected during an extensive outbreak investigation, including contact tracing and stringent surveillance. Whole-genome sequencing of isolates from all human cases and pig farms was performed to support and expand the epidemiological findings. The national strategy furthermore included a “search-and-destroy” policy at the pig farm level. Results. Three outbreak clusters were identified, including 26 pig farms, 2 slaughterhouses, and 36 humans. Primary introductions likely occurred by human transmission to 3 sow farms with secondary transmission to other pig farms, mainly through animal trade and to a lesser extent via humans or livestock trucks. All MRSA CC398 isolated from humans without an epidemiological link to the outbreaks were genetically distinct from isolates within the outbreak clusters indicating limited dissemination to the general population. Conclusions. This study identified preventable routes of MRSA CC398 introduction and transmission: human occupational exposure, trade of pigs and livestock transport vehicles. These findings are essential for keeping pig populations MRSA free and, from a “One Health” perspective, preventing pig farms from becoming reservoirs for MRSA transmission to humans.

Summary Objectives Data describing long-term mortality in patients with Staphylococcus aureus bacteremia (SAB) is scarce. This study investigated risk factors, causes of death and temporal trends in long-term mortality associated with SAB. Methods Nationwide population-based matched cohort study. Mortality rates and ratios for 25,855 cases and 258,547 controls were analyzed by Poisson regression. Hazard ratio of death was computed by Cox proportional hazards regression analysis. Results The majority of deaths occurred within the first year of SAB (44.6%) and a further 15% occurred within the following 2–5 years. The mortality rate was 14-fold higher in the first year after SAB and 4.5-fold higher overall for cases compared to controls. Increasing age, comorbidity and hospital contact within 90 days of SAB was associated with an increased risk of death. The overall relative risk of death decreased gradually by 38% from 1992–1995 to 2012–2014. Compared to controls, SAB patients were more likely to die from congenital malformation, musculoskeletal/skin disease, digestive system disease, genitourinary disease, infectious disease, endocrine disease, injury and cancer and less likely to die from respiratory disease, nervous system disease, unknown causes, psychiatric disorders, cardiovascular disease and senility. Over time, rates of death decreased or were stable for all disease categories except for musculoskeletal and skin disease where a trend towards an increase was seen. Conclusion Long-term mortality after SAB was high but decreased over time. SAB cases were more likely to die of eight specific causes of death and less likely to die of five other causes of death compared to controls. Causes of death decreased for most disease categories. Risk factors associated with long-term mortality were similar to those found for short-term mortality. To improve long-term survival after SAB, patients should be screened for comorbidity associated with SAB.

The rapid dissemination of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) since the early 2000s and the appearance of new successful lineages is a matter of concern. The burden of these infections varies widely between different groups of individuals and in different regions of the world. Estimating the total burden of disease is therefore problematic. Skin and soft-tissue infections, often in otherwise healthy young individuals, are the most common clinical manifestation of these infections. The antibiotic susceptibilities of these strains also vary, although they are often more susceptible to 'traditional' antibiotics than related hospital-acquired strains. Preventing the dissemination of these organisms throughout the general population requires a multifaceted approach, including screening and decolonisation, general hygiene and cleaning measures, antibiotic stewardship programmes and, in the future, vaccination. The current evidence on the prevention and control of CA-MRSA is appraised and summarised in this review.

SUMMARYThe prevalence and risk factors associated with livestock-associated MRSA (LA-MRSA) carriage was examined in Danish and Belgian veterinarians. The MRSA and LA-MRSA carriage rates were 9·5% (95% CI 5·3–15·6) and 7·5% (95% CI 3·8–13·1) for MRSA and LA-MRSA, respectively, in Belgium and 1·4% (95% CI: 0·17–5·05) in Denmark (all Danish MRSA isolates belonged to the LA-MRSA genotype). All LA-MRSA isolates were resistant to tetracycline and 53·4% (7/13) showed a multi-resistant phenotype. LA-MRSA was significantly associated with veterinarians in contact with livestock (P=0·046). In the multivariable analysis, working with small animals in a veterinary clinic seems to be negatively associated (OR 0·15, 95% CI 0–1·0,P=0·05) and a strong direct association was found for LA-MRSA acquisition and exposure to live pigs (OR 12·1, 95% CI 1·6–548·5,P=0·01). Since carriage of MRSA ST398 may increase the risk of complications during hospitalization, our results underline that preventive measures may need to be developed for veterinary professionals, particularly for livestock veterinarians.

OBJECTIVES: To assess the association between comorbidities and Staphylococcus aureus bacteremia in children aged 5-18 years, thus, in children with a matured immune system. Further, we aimed to identify presumably healthy children acquiring bacteremia.STUDY DESIGN: By cross-linking nationwide registries, we consecutively included all children born from 1995 onward at their 5-year birthday or date of immigration during 2000-2015. We examined incidence rate ratios (IRR) between preselected exposures and microbiologically verified S aureus bacteremia (reference = children without exposure) using Poisson regression models.RESULTS: We followed 1 109 169 children in 2000-2015 during which 307 children (incidence rate: 3.7 per 100 000 person-years) acquired S aureus bacteremia (methicillin-resistant S aureus = 8; 2.6%). Children without known comorbidities or recent contact with the healthcare system comprised 37.1% of infected children. The highest IRRs were observed in children undergoing dialysis or plasmapheresis (IRR = 367.2 [95% CI) = 188.5-715.3]), children with organ transplantation (IRR = 149.5 [95% CI = 73.9-302.2]), and children with cancer (IRR = 102.9 [95% CI = 74.4-142.2]). Positive associations also were observed in children with chromosomal anomalies (IRR = 7.16 [95% CI = 2.96-17.34]), atopic dermatitis (IRR = 4.89 [95% CI = 3.11-7.69]), congenital heart disease (IRR = 3.14 [95% CI = 1.92-5.11]), and in children undergoing surgery (IRR = 3.34 [95% CI = 2.59-4.28]). Neither premature birth nor parental socioeconomic status was associated with increased disease rates.CONCLUSIONS: S aureus bacteremia is uncommon in children between 5 and 18 years of age. Risk factors known from the adult population, such as dialysis, plasmapheresis, organ transplantation, and cancer, were associated with the highest relative rates. However, prematurity and parental socioeconomic status were not associated with increased rates. Approximately one-third of infected children were presumably healthy.

The worldwide emergence of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) during the last decade represents a significant change in the biology of MRSA strains and is changing the epidemiology of MRSA infections. CA-MRSA infections are caused by strains belonging to lineages distinct from HA-MRSA. In the community, CA-MRSA strains typically cause skin and soft tissue infections in children and younger adults. However, CA-MRSA strains increasingly cause healthcare-acquired infections including surgical site infections, ventilator-associated pneumonia and bacteraemia. A mathematical model showing the influence of MRSA transmission in the community on the prevalence of MRSA in hospitals is presented. The increasing prevalence of MRSA in the community also results in an increase in community-onset MRSA (CO-MRSA) among S. aureus bacteraemia and other invasive infections. These patients do not have typical risk factors for MRSA. Such changes may have profound implications for the choice of empirical therapy for serious infections where S. aureus is a possible cause. The new and potentially very large reservoir of MRSA in production animals with subsequent transmission to humans represents an additional serious threat to the control of MRSA both in general and as a cause of healthcare-acquired infections. CA-MRSA is thus a matter of serious concern and should be suppressed.

Three latex agglutination kits for rapid identification of Staphylococcus aureus were compared by testing a selection of isolates, which included methicillin resistant S. aureus, methicillin sensitive S. aureus and a diverse selection of coagulase-negative staphylococci. The sensitivities of Monostaph Plus (Bionor Laboratories, Skien, Norway), Pastorex Plus (Bio-Rad Laboratories, Hercules, CA) and Staphaurex Plus (Oxoid, Cambridge, UK) were 98.5, 98.3 and 98.3% respectively, and the specificities were 97.5, 97.0 and 96.5%, respectively. None of the kits detected Staphylococcus lugdunensis correctly. This evaluation shows that the Monostaph Plus agglutination kit performs well and comparable to Pastorex Staph-Plus and Staphaurex Plus. PRACTICAL APPLICATIONS Latex agglutination kits are very useful in the routine identification of Staphylococcus aureus, but can occasionally give false-positive or false-negative results. Knowledge of how the various available kits are performing is, therefore, very important when selecting a kit for use. Correct identification of S. aureus is important, especially in relation to methicillin-resistant S. aureus, since other staphylococci species are known to carry the methicillin-resistance determinant mecA, but are of less clinical importance. This study is the first study comparing an improved version of the Monstaph-Plus kit with other latex agglutination kits, and provides new data about this kit.

Contains fulltext : 71394.pdf (Publisher’s version ) (Closed access) Pig farmers and veterinarians in contact with livestock in The Netherlands have a higher risk of methicillin-resistant Staphylococcus aureus (MRSA) carriage than the general population. The objective of this study was to investigate whether this is also true for other professionals in contact with pigs in an international setting. A convenience sample of 272 participants at an international conference on pig health in Denmark was screened for MRSA carriage using combined nose/throat swabs and were asked to complete a questionnaire concerning animal contacts, exposure to known MRSA risk-factors, and the protective measures taken when entering pig farms. In total, 34 (12.5%) participants from nine countries carried MRSA. Thirty-one of these isolates were non-typeable by pulsed-field gel electrophoresis following SmaI digestion of chromosomal DNA. All of the non-typeable isolates belonged to spa types (t011, t034, t108, t571, t567 and t899) that correspond to multilocus sequence type 398. All of the above-mentioned spa types, with the exception of t899, have been isolated previously from either Dutch pigs, pig farmers and/or veterinarians. Protective measures, e.g., masks, gowns and gloves, did not protect against MRSA acquisition. Transmission of MRSA from pigs to staff tending to these animals appears to be an international problem, creating a new reservoir for community-acquired MRSA (CA-MRSA) in humans in Europe, and possibly worldwide. The rise of a new zoonotic source of MRSA could have a severe impact on the epidemiology of CA-MRSA, and may have consequences for the control of MRSA, especially in those countries that maintain a low prevalence by means of search-and-destroy policies.

Persons living or working on farms, particularly pig farms, are at increased risk for infection., An emerging subtype of methicillin-resistant Staphylococcus aureus (MRSA), clonal complex (CC) 398, is associated with animals, particularly pigs. We conducted a matched case–control and a case–case study comparing 21 CC398 case-patients with 2 controls randomly selected from the Danish Civil Registry and 2 case-patients infected with MRSA other than CC398. On farms of case-patients, animals were examined for MRSA. Thirteen case-patients reported pig exposure. Living or working on farms with animals was an independent risk factor for CC398 in the case–control (matched odds ratio [MOR] 35.4, 95% confidence interval [CI] 2.7–469.8) and the case–case study (MOR 14.5, 95%CI 2.7–76.7). History of hospitalization was associated with an increased risk only in the case–control study (MOR 11.4, 95% CI 1.4–94.8). A total of 23 of 50 pigs on 4 of 5 farms were positive for CC398. Our results, corroborated by microbiologic testing, demonstrate that pigs are a source of CC398 in Denmark.

The implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http:// www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show that in silico predictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) communityoriented database infrastructure and analysis tools. IMPORTANCE The spread of antibiotic-resistant bacteria is a public health emergency of global concern, threatening medical intervention at every level of health care delivery. Several recent studies have demonstrated the promise of routine wholegenome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control. However, as this technology becomes more widely adopted, the key challenges of generating representative national and international data sets and the development of bioinformatic tools to manage and interpret the data become increasingly pertinent. This study provides a road map for the integration of WGS data into routine pathogen surveillance. We emphasize the importance of large-scale routine surveys to provide the population context for more targeted or localized investigation and the development of open-access bioinformatic tools to provide the means to combine and compare independently generated data with publicly available data sets., 0, SCOPUS: ar.j, info:eu-repo/semantics/published