Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible Enterococcus faecium: a nationwide cohort study in Denmark, 2010-2019.

The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with Enterococcus faecium-positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge among VRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients with E. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010-13, 2.6%; 2014-16, 6.3%; 2017-19; 9.4%). Mortality (HR 1.08, 95%CI 0.90-1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75-1.06; 126 VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18-2.96). There was no interaction between time from admission to BSI (1-2, 3-14, and >14 days) and HR of death (P = 0.14) or discharge (P = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P < 0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014 only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time to appropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study.

Evaluating the OH-EpiCap tool using the Danish integrated surveillance program for AMU and AMR as a case study.

Antimicrobial resistance (AMR) is considered a One Health (OH) challenge, ideally demanding concerted efforts from the animal, human and environmental side. DANMAP, the Danish Integrated Antimicrobial Resistance Monitoring and Research Program, is monitoring AMR and antimicrobial use in animals and humans. OH-EpiCap is an evaluation tool, developed to address essential elements in OH surveillance systems, such as the dimensions of the organization, operational activities and the impact of the surveillance activities. We aimed to evaluate DANMAP using OH-EpiCap and hereby assessed the suitability of OH-EpiCap to evaluate integrated AMR surveillance systems. During the evaluation, the strengths and weaknesses of DANMAP concerning the "OH-ness" of the program were discussed. Furthermore, possible adaptations of the standard operating procedures and governance structure were addressed. Attention was paid to the ability and easiness of DANMAP to cope with current and future challenges connected to integrated AMR surveillance. It was concluded that DANMAP has a strong OH approach covering relevant aspects for humans and animals, whereas environmental aspects are missing. OH-EpiCap proved to be straightforward to use and provided valuable insights. The authors recommend OH-EpiCap to be used by health authorities and stakeholders. It is not suitable for the technical evaluation of a surveillance program.

A global analysis of One Health Networks and the proliferation of One Health collaborations.

There has been a renewed focus on threats to the human-animal-environment interface as a result of the COVID-19 pandemic, and investments in One Health collaborations are expected to increase. Efforts to monitor the development of One Health Networks (OHNs) are essential to avoid duplication or misalignment of investments. This Series paper shows the global distribution of existing OHNs and assesses their collective characteristics to identify potential deficits in the ways OHNs have formed and to help increase the effectiveness of investments. We searched PubMed, Google, Google Scholar, and relevant conference websites for potential OHNs and identified 184 worldwide for further analysis. We developed four case studies to show important findings from our research and exemplify best practices in One Health operationalisation. Our findings show that, although more OHNs were formed in the past 10 years than in the preceding decade, investment in OHNs has not been equitably distributed; more OHNs are formed and headquartered in Europe than in any other region, and emerging infections and novel pathogens were the priority focus area for most OHNs, with fewer OHNs focusing on other important hazards and pressing threats to health security. We found substantial deficits in the OHNs collaboration model regarding the diversity of stakeholder and sector representation, which we argue impedes effective and equitable OHN formation and contributes to other imbalances in OHN distribution and priorities. These findings are supported by previous evidence that shows the skewed investment in One Health thus far. The increased attention to One Health after the COVID-19 pandemic is an opportunity to focus efforts and resources to areas that need them most. Analyses, such as this Series paper, should be used to establish databases and repositories of OHNs worldwide. Increased attention should then be given to understanding existing resource allocation and distribution patterns, establish more egalitarian networks that encompass the breadth of One Health issues, and serve communities most affected by emerging, re-emerging, or endemic threats at the human-animal-environment interface.

Seroprevalence of SARS-CoV-2 Antibodies in Denmark: Results of Two Nationwide Population-Based Surveys, February and May 2021.

Background: Seroprevalence studies can be used to measure the progression of national COVID-19 epidemics. The Danish National Seroprevalence Survey of SARS-CoV-2 infections (DSS) was conducted as five separate surveys between May 2020 and May 2021. Here, we present results from the two last surveys conducted in February and May 2021. Methods: Persons aged 12 or older were randomly selected from the Danish Population Register and those having received COVID-19 vaccination subsequently excluded. Invitations to have blood drawn in local test centers were sent by mail. Samples were analyzed for whole Immunoglobulin by ELISA. Seroprevalence was estimated by sex, age and geography. Comparisons to vaccination uptake and RT-PCR test results were made. Results: In February 2021, we found detectable antibodies in 7.2% (95% CI: 6.3-7.9%) of the invited participants (participation rate 25%) and in May 2021 in 8.6% (95% CI: 7.6-9.5%) of the invited (participation rate: 14%). Seroprevalence did not differ by sex, but by age group, generally being higher among the <50 than 50+ year-olds. In May 2021, levels of seroprevalence varied from an estimated 13% (95% CI: 12-15%) in the capital to 5.2% (95% CI: 3.4-7.4%) in rural areas. Combining seroprevalence results with vaccine coverage, estimates of protection against infection in May 2021 varied from 95% among 65+ year-olds down to 10-20% among 12-40 year-olds. In March-May 2021, an estimated 80% of all community SARS-CoV-2 infections were diagnosed by RT-PCR and captured by surveillance. Conclusion: Seroprevalence estimates doubled during the 2020-21 winter wave of SARS-CoV-2 infections and then stabilized as vaccinations were rolled out. The epidemic affected large cities and younger people the most. Denmark saw comparatively low infections rates, but high test coverage; an estimated four out of five infections were detected by RT-PCR in March-May 2021.

Trends in Antibiotic Use in Danish, Finnish, Norwegian and Swedish Children.

Objective: To compare the use of antibiotics in children in four Northern European countries. Methods: We conducted a register-based study based on individual-level prescription data from national prescription registers. We identified all redeemed outpatient prescriptions for systemic antibiotics in children aged 0-14 years from July 2006 to June 2017 in Denmark, Finland, Norway, and Sweden. We computed incidence rates and incidence rate ratios of treatment episodes with any antibiotic and different antibiotic classes. Results: In 2016/2017, the rates of antibiotic treatment episodes per 1000 person-years in children aged 0-14 years were 429, 284, 219, and 184 in Finland, Denmark, Sweden, and Norway, respectively, and the rate ratios (95% confidence intervals) compared with Norway were 2.33 (2.33-2.34), 1.54 (1.54-1.55), and 1.19 (1.19-1.20) in Finland, Denmark, and Sweden, respectively. The rate of antibiotic treatment episodes declined over time in all countries. The relative reductions in 2016/2017 compared with 2006/2007 were 36% in Finland, 40% in Denmark, 49% in Sweden, and 29% in Norway. Treatment episodes peaked between age 12 and 18 months. The most used antibiotic class was beta-lactamase sensitive penicillins among all children in Norway and Sweden and among children above two years in Denmark, while penicillins with extended spectrum were most used in Finland and among the youngest children in Denmark. Conclusion: In all countries, the use of antibiotics in children declined between 2006 and 2017. However, there were still considerable differences in antibiotic use between otherwise quite similar Nordic countries, with a more than 2-fold difference between the countries with the lowest and highest rates. Interventions to reduce the number of antibiotic treatment episodes in the countries with higher rates could reduce the total antibiotic use.

Testing Denmark: a Danish Nationwide Surveillance Study of COVID-19.

"Testing Denmark" is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (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. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57-8.41), particular in household members (RR 17.70, 95% CI: 15.60-20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58-2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants' homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.

Measuring Antimicrobial Use Needs Global Harmonization.

Global health and global economies are predicted to be severely affected by antimicrobial resistance (AMR). The three organizations World Health Organization/World Organisation for Animal Health/Food and Agriculture Organization (WHO/OIE/FAO) are working in their domains to prevent any future AMR crisis. Antimicrobial use (AMU), especially in food animals, is contributing to the development and dissemination of AMR bacteria and genes. AMU monitoring is a strategic objective of the global and national action plans on AMR. However, the AMU reporting metrics at different levels are not harmonized yet, posing difficulties in comparisons among AMU data from different sources. A tripartite WHO/OIE/FAO collaboration is urgently required to develop and implement a globally accepted AMU metric system to ensure reliable comparisons among various data sets.

Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010-2018.

BACKGROUND: The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010-2018. METHODS: Antibiotic resistance among invasive isolates from 2010-2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. RESULTS: Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0-2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (<10%) except in Finland and Iceland (<15%), but benzylpenicillin was recommended for community-acquired pneumonia in all countries. CONCLUSION: Despite similar resistance rates among Enterobacteriaceae there were differences in practice guidelines for pyelonephritis and sepsis. National surveillance of antibiotic resistance can be used for comparison and optimization of guidelines and stewardship interventions to preserve the low levels of antibiotic resistance in Nordic countries.

Prevalence and Clinical Manifestations of Giardia intestinalis and Other Intestinal Parasites in Children and Adults in Algeria.

Giardia intestinalis is one of the most common causes of parasite-induced diarrhea, abdominal pain, flatulence, and malabsorption. Yet, data on the epidemiology of G. intestinalis infections in North Africa are limited. The purpose of this study was to carry out a retrospective survey on the level of intestinal parasitism with a particular emphasis on G. intestinalis in children and adults in Algiers, Algeria. A total of 2,054 individuals from outpatient clinics or hospitalized at Beni-Messous University Hospital of Algiers undergoing stool microscopy for ova and parasites were included. The overall parasite infection rate was 28%. In the 567 parasite-positive samples, Blastocystis was found most frequently (57.3%), followed in frequency by Endolimax nana (41.0%), Entamoeba histolytica/dispar (19.6%), G. intestinalis (17.1%), Entamoeba coli (13.9%), Chilomastix mesnili (1.0%), Iodamoeba bütschlii (0.7%), Entamoeba hartmanni (0.5%), and Cryptosporidium spp. (0.2%). Intestinal parasites were generally more common in adults than in children, except for Giardia, which was more common in children (P = 0.0001). Giardia infection was independent of gender (P = 0.94). Compared with other intestinal parasitic infections, clinical manifestations, such as abdominal pain (P = 0.28) and diarrhea (P = 0.82), were found not to be significantly linked to Giardia infection. In conclusion, G. intestinalis is common in individuals referred to the University Hospital of Beni-Messous with digestive symptoms, particularly so in children. However, in our study, intestinal symptoms appeared not to be more linked to Giardia than to other intestinal parasites.

Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020.

In June-November 2020, SARS-CoV-2-infected mink were detected in 290 of 1,147 Danish mink farms. In North Denmark Region, 30% (324/1,092) of people found connected to mink farms tested SARS-CoV-2-PCR-positive and approximately 27% (95% confidence interval (CI): 25-30) of SARS-CoV-2-strains from humans in the community were mink-associated. Measures proved insufficient to mitigate spread. On 4 November, the government ordered culling of all Danish mink. Farmed mink constitute a potential virus reservoir challenging pandemic control.

Novel mcr-3 variant, encoding mobile colistin resistance, in an ST131 Escherichia coli isolate from bloodstream infection, Denmark, 2014.

A novel variant of the plasmid-borne colistin resistance gene mcr-3 was detected on an IncHI2 plasmid in an ST131 CTX-M-55-producing Escherichia coli isolate from a Danish patient with bloodstream infection in 2014. The discovery of novel plasmid-borne genes conferring resistance to colistin is of special interest since colistin has reemerged as an important drug in the treatment of infections with multidrug-resistant Gram-negative bacteria.

[Epidemic increase in the incidence of carbapenemase-producing Enterobacteriaceae in Denmark].

Carbapenemase-producing Enterobacteriaceae (CPE) are extremely multiresistant bacteria with few or no treatment options. Infections with CPE are associated with a mortality of 40-50%. In Denmark, CPE were first detected in 2008. Prior to 2013 the CPE incidence was low, but since then the incidence has increased significantly. Seven outbreaks have occurred, and at least 25 patients have been infected or colonized. The rise in CPE incidence emphasizes the need for a national intervention to reduce the spread. This can be obtained through systematic surveillance, infection control and reduction of antibiotic consumption.

Fastidious Gram-Negatives: Identification by the Vitek 2 Neisseria-Haemophilus Card and by Partial 16S rRNA Gene Sequencing Analysis.

Taxonomy and identification of fastidious Gram negatives are evolving and challenging. We compared identifications achieved with the Vitek 2 Neisseria-Haemophilus (NH) card and partial 16S rRNA gene sequence (526 bp stretch) analysis with identifications obtained with extensive phenotypic characterization using 100 fastidious Gram negative bacteria. Seventy-five strains represented 21 of the 26 taxa included in the Vitek 2 NH database and 25 strains represented related species not included in the database. Of the 100 strains, 31 were the type strains of the species. Vitek 2 NH identification results: 48 of 75 database strains were correctly identified, 11 strains gave `low discrimination´, seven strains were unidentified, and nine strains were misidentified. Identification of 25 non-database strains resulted in 14 strains incorrectly identified as belonging to species in the database. Partial 16S rRNA gene sequence analysis results: For 76 strains phenotypic and sequencing identifications were identical, for 23 strains the sequencing identifications were either probable or possible, and for one strain only the genus was confirmed. Thus, the Vitek 2 NH system identifies most of the commonly occurring species included in the database. Some strains of rarely occurring species and strains of non-database species closely related to database species cause problems. Partial 16S rRNA gene sequence analysis performs well, but does not always suffice, additional phenotypical characterization being useful for final identification.

Six cases of Aerococcus sanguinicola infection: clinical relevance and bacterial identification.

Aerococcus sanguinicola is a Gram-positive coccus first described in 2001. Infections in humans are rare but the use of 16S rRNA gene sequencing and improved phenotypic methods has facilitated the identification of A. sanguinicola. We report here 6 cases of A. sanguinicola bacteraemia, 2 of which were associated with infective endocarditis. Most patients were elderly (median age 70 y) and had underlying neurological disorders including dementia, cerebral degeneration, and myelomeningocele. The primary focus of infection was the urinary tract in 3 cases and the gallbladder in 1; no focus was detected in 2 cases. Long-term prognosis was poor reflecting the frailty of the patients. All strains were susceptible to penicillin, ampicillin, cefuroxime, vancomycin, erythromycin, and rifampicin. The optimal treatment of infection with A. sanguinicola has yet to be determined.

Granulicatella elegans bacteraemia in patients with abdominal infections.

Bloodstream infections with Granulicatella (previous Abiotrophia) elegans are rare. A few reported cases were associated with infective endocarditis. Three cases of bacteraemia with G. elegans in patients who were operated for acute abdominal diseases are described. Abdominal foci should be considered when G. elegans is recovered from blood.

Case of bacteraemic cellulitis by a non-haemolytic strain of Streptococcus pyogenes.

Erysipelas and bacteraemia with what initially was diagnosed as a non-haemolytic streptococcus is reported. As neither colony morphology nor clinical picture was characteristic of non-haemolytic streptococci, the isolate was sent to a reference laboratory. 16S rRNA sequencing and phenotypic characterization identified the strain as a streptolysin S-deficient S. pyogenes..