Hospital-based antimicrobial stewardship in Denmark, Greenland and the Faroe Islands - current landscape and barriers.

OBJECTIVES: To describe the current organization and implementation of formalized, multi-disciplinary hospital-based antimicrobial stewardship (AMS) structures in Denmark, the Faroe Islands and Greenland. METHODS: A structured electronic questionnaire was sent to all trainees and specialists in clinical microbiology (N=207) and infectious diseases (N=260), as well as clinical pharmacists (N=20) and paediatricians (N=10) with expertise in infectious diseases. The survey had 30 multiple-choice, rating-scale, and open-ended questions based on an international consensus checklist for hospital AMS, adapted to a Danish context. RESULTS: Overall, 145 individual responses representing 20 hospitals were received. Nine hospitals (45%) reported a formal AMS strategy, eight (40%) a formal organizational multi-disciplinary structure and a multi-disciplinary AMS team, and six (30%) a designated professional as a leader of the AMS team. A majority of hospitals reported access to updated guidelines (80%) and regularly monitored and reported the quantity of antibiotics prescribed (70% and 65%, respectively). Only one hospital (5%) reported a dedicated, sustainable and sufficient AMS budget, three hospitals (15%) audited courses of therapy for specific agents/clinical conditions and four hospitals (20%) had a document clearly defining roles, procedures of collaboration and responsibilities for AMS. A total of 42% of all individual respondents had received formal AMS training. Main barriers were a lack of financial resources (52%), a lack of mandate from the hospital management (30%) and AMS not being a priority (18%). CONCLUSIONS: Core elements important for multi-disciplinary hospital-based AMS can be strengthened in Danish hospitals. Funding, clear mandates, prioritization from the hospital management and the implementation of multi-disciplinary AMS structures may help close the identified gaps.

Interobserver agreement on landmark and flexure identification in colon capsule endoscopy.

PURPOSE: When an optical colonoscopy is carried out, Scope Guide can assist the endoscopist in determining the localization. In colon capsule endoscopy (CCE), this support is not available. To our knowledge, the interobserver agreement on landmark identification has never been studied. This study aims to investigate the interobserver agreement on landmark identification in CCE. METHODS: An interobserver study was carried out comparing the landmark identification (the ileocecal valve, hepatic flexure, splenic flexure, and anus) in CCE investigations between an external private contractor and three in-house CCE readers with different levels of experience. All CCE investigations analyzed in this study were carried out as a part of the Danish screening program for colorectal cancer. Patients were between 50 and 74 years old with a positive fecal immunochemical test (FIT). A random sample of 20 CCE investigations was taken from the total sample of more than 800 videos. RESULTS: Overall interobserver agreement on all landmarks was 51%. Interobserver agreement on the first cecal image (ileocecal valve), hepatic flexure, splenic flexure, and last rectal image (anus) was 72%, 29%, 22%, and 83%, respectively. The overall interobserver agreement, including only examinations with adequate bowel preparation (n = 16), was 54%, and for individual landmarks, 73%, 32%, 24%, and 85%. CONCLUSION: Overall interobserver agreement on all four landmarks from CCE was poor. Measures are needed to improve landmark identification in CCE investigations. Artificial intelligence could be a possible solution to this problem.

High incidence of candidaemia in a nationwide cohort: Underlying diseases, risk factors and mortality.

BACKGROUND: Denmark has a high incidence rate of candidaemia. A Nordic study suggested a higher Danish prevalence of haematological malignancies as an underlying reason. This nationwide study ascertained clinical characteristics of Danish candidaemia patients and investigated potential factors contributing to the high incidence and mortality. METHODS: Microbiological and clinical data for candidaemia patients in 2010-2011 were retrieved. 30-day mortality was estimated by hazard ratios (HR) with 95% confidence intervals (CI, Cox regression). RESULTS: Data were available for 912/973 candidaemia episodes (93.7%). Intensive care unit (ICU) held the largest share of patients (43.2%). Prevalent host factors were multi-morbidity (≥2 underlying diseases, 74.2%) and gastrointestinal disease (52.5%). Haematological disease was infrequent (7.8%). Risk factors included antibiotic exposure (90.5%), CVC (71.9%) and Candida colonisation (66.7%). 30-day mortality was 43.4%, and 53.6% in ICU. Mortality was lower for patients with recent abdominal surgery (HR 0.70, 95% CI: 0.54-0.92). CONCLUSION: A substantial prevalence of multi-morbidity and a high 30-day mortality was found. We hypothesise, that an increasing population of severely ill patients with prolonged supportive treatment and microbiological testing may in part explain the high candidaemia incidence in Denmark. Nationwide studies are warranted to clarify this issue.

Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and Acquired Resistance Causes Concern.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of Candida albicans isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001), and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively, P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

Description and validation of a new automated surveillance system for Clostridium difficile in Denmark.

The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010-2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.

Posttreatment Antifungal Resistance among Colonizing Candida Isolates in Candidemia Patients: Results from a Systematic Multicenter Study.

The prevalence of intrinsic and acquired resistance among colonizing Candida isolates from patients after candidemia was investigated systematically in a 1-year nationwide study. Patients were treated at the discretion of the treating physician. Oral swabs were obtained after treatment. Species distributions and MIC data were investigated for blood and posttreatment oral isolates from patients exposed to either azoles or echinocandins for <7 or ≥ 7 days. Species identification was confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS) sequencing, susceptibility was examined by EUCAST EDef 7.2 methodology, echinocandin resistance was examined by FKS sequencing, and genetic relatedness was examined by multilocus sequence typing (MLST). One hundred ninety-three episodes provided 205 blood and 220 oral isolates. MLST analysis demonstrated a genetic relationship for 90% of all paired blood and oral isolates. Patients exposed to azoles for ≥ 7 days (n = 93) had a significantly larger proportion of species intrinsically less susceptible to azoles (particularly Candida glabrata) among oral isolates than among initial blood isolates (36.6% versus 12.9%; P < 0.001). A similar shift toward species less susceptible to echinocandins among 85 patients exposed to echinocandins for ≥ 7 days was not observed (4.8% of oral isolates versus 3.2% of blood isolates; P > 0.5). Acquired resistance in Candida albicans was rare (<5%). However, acquired resistance to fluconazole (29.4%; P < 0.05) and anidulafungin (21.6%; P < 0.05) was common in C. glabrata isolates from patients exposed to either azoles or echinocandins. Our findings suggest that the colonizing mucosal microbiota may be an unrecognized reservoir of resistant Candida species, especially C. glabrata, following treatment for candidemia. The resistance rates were high, raising concern in general for patients exposed to antifungal drugs.

Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme.

Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes.

Adaptations to aerobic interval training: interactive effects of exercise intensity and total work duration.

To compare the effects of three 7-week interval training programs varying in work period duration but matched for effort in trained recreational cyclists. Thirty-five cyclists (29 male, 6 female, VO(2peak) 52 ± 6 mL kg/min) were randomized to four training groups with equivalent training the previous 2 months (∼6 h/wk, ∼1.5 int. session/wk). Low only (n=8) trained 4-6 sessions/wk at a low-intensity. Three groups (n=9 each) trained 2 sessions/wk × 7 wk: 4 × 4 min, 4 × 8 min, or 4 × 16 min, plus 2-3 weekly low-intensity bouts. Interval sessions were prescribed at the maximal tolerable intensity. Interval training was performed at 88 ± 2, 90 ± 2, and 94 ± 2% of HR(peak) and 4.9, 9.6, and 13.2 mmol/L blood lactate in 4 × 16, 4 × 8, and 4 × 4 min groups, respectively (both P<0.001). 4 × 8 min training induced greater overall gains in VO(2) peak, power@VO(2) peak, and power@4 mM bLa- (Mean ± 95%CI): 11.4 (8.0-14.9), vs 4.2 (0.4-8.0), 5.6 (2.1-9.1), and 5.5% (2.0-9.0) in Low, 4 × 16, and 4 × 4 min groups, respectively (P<0.02 for 4 × 8 min vs all other groups). Interval training intensity and accumulated duration interact to influence the adaptive response. Accumulating 32 min of work at 90% HR max induces greater adaptive gains than accumulating 16 min of work at ∼95% HR max despite lower RPE.

The influence of local effects on thermal sensation under non-uniform environmental conditions--gender differences in thermophysiology, thermal comfort and productivity during convective and radiant cooling.

Applying high temperature cooling concepts, i.e. high temperature cooling (T(supply) is 16-20°C) HVAC systems, in the built environment allows the reduction in the use of (high quality) energy. However, application of high temperature cooling systems can result in whole body and local discomfort of the occupants. Non-uniform thermal conditions, which may occur due to application of high temperature cooling systems, can be responsible for discomfort. Contradictions in literature exist regarding the validity of the often used predicted mean vote (PMV) index for both genders, and the index is not intended for evaluating the discomfort due to non-uniform environmental conditions. In some cases, however, combinations of local and general discomfort factors, for example draught under warm conditions, may not be uncomfortable. The objective of this study was to investigate gender differences in thermophysiology, thermal comfort and productivity in response to thermal non-uniform environmental conditions. Twenty healthy subjects (10 males and 10 females, age 20-29 years) were exposed to two different experimental conditions: a convective cooling situation (CC) and a radiant cooling situation (RC). During the experiments physiological responses, thermal comfort and productivity were measured. The results show that under both experimental conditions the actual mean thermal sensation votes significantly differ from the PMV-index; the subjects are feeling colder than predicted. Furthermore, the females are more uncomfortable and dissatisfied compared to the males. For females, the local sensations and skin temperatures of the extremities have a significant influence on whole body thermal sensation and are therefore important to consider under non-uniform environmental conditions.

Reflections on the state of research: indoor environmental quality.

UNLABELLED: More than 30 years after the First International Indoor Climate Symposium, ten researchers from the USA, Slovakia, Sweden, and Denmark gathered to review the current status of indoor environmental research. We initiated our review with discussions during the 1-day meeting and followed that with parallel research and writing efforts culminating with internal review and revision cycles. In this paper, we present our choices for the most important research findings on indoor environmental quality from the past three decades followed by a discussion of the most important research questions in our field today. We then continue with a discussion on whether there are research areas for which we can 'close the book' and say that we already know what is needed. Finally, we discuss whether we can maintain our identity in the future or it is time to team up with new partners. PRACTICAL IMPLICATIONS: In the early years of this field, the accumulated knowledge was small and it was possible for any researcher to acquire a complete understanding. To do so has become impossible today as what we know has grown to exceed the learning capacity of any person. These circumstances challenge us to work collectively to synthesize what we do know and to define clearly what remains to be learned. If we fail to do these things well, we risk repeating research without memory, an inefficiency that we cannot afford.

Outbreak of Clostridium difficile 027 in North Zealand, Denmark, 2008-2009.

We report an outbreak of Clostridium difficile PCR ribotype 027 in Denmark. The outbreak includes to date 73 cases from the area north of Copenhagen, but there may be related cases elsewhere in Zealand. Most infections are healthcare-associated and in patients who previously received antibiotic treatment. The strain is resistant to moxifloxacin, erythromycin, and clindamycin, and carries genes for toxin A, toxin B, and for the binary toxin. The antimicrobial pattern differs from that of the strain involved in a small cluster in Denmark in 2006-2007. Because of this outbreak, hygienic measures in the involved hospitals have been reinforced. Nationwide, microbiological laboratories were alerted to the outbreak and encouraged to send isolates for toxin profiling and PCR ribotyping.

In situ detection of bacteria involved in cathodic depolarization and stainless steel surface corrosion using microautoradiography.

AIMS: To examine the activity of bacteria involved in cathodic depolarization and surface corrosion on stainless steel in an in situ model system. METHODS AND RESULTS: The microautoradiographic technique (MAR) was used to evaluate the activity of bacterial populations on stainless steel surfaces with a single cell resolution. Anaerobic uptake and fixation of (14)C-labelled bicarbonate occurred within corrosion sites in the absence of atmospheric hydrogen or other external electron donors, whereas it was taken up and fixed by bacteria at all other stainless steel surfaces in the presence of atmospheric hydrogen. This indicates that the bacteria utilized electrons originating from the corrosion sites due to the ongoing corrosion (cathodic depolarization). CONCLUSION: Under in situ conditions, bacteria were fixating (14)C-labelled bicarbonate at corrosion sites in the absence of atmospheric hydrogen. This indicates that electrons transferred to the bacteria provided energy for bicarbonate fixation due to cathodic depolarization. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of the MAR method showed ongoing biocorrosion in the applied in situ model system and allowed in situ examination of bacterial activity on a single cell level directly on a metal surface providing information about potential corrosion mechanisms. Furthermore, application of fluorescence in situ hybridization in combination with MAR allows for identification of the active bacteria.