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Background: Only a subset of enteric pathogens is under surveillance in Denmark, and knowledge on the remaining pathogens detected in acute gastroenteritis is limited. Here, we present the one-year incidence of all enteric pathogens diagnosed in Denmark, a high-income country, in 2018 and an overview of diagnostic methods used for detection.Methods: All 10 departments of clinical microbiology completed a questionnaire on test methods and provided 2018-data of persons with positive stool samples with Salmonella species, Campylobacter jejuni/coli, Yersinia enterocolitica, Aeromonas species, diarrheagenic Escherichia coli (Enteroinvasive (EIEC), Shiga toxin-producing (STEC), Enterotoxigenic (ETEC), Enteropathogenic (EPEC), and intimin-producing/attaching and effacing (AEEC)), Shigella species., Vibrio cholerae, norovirus, rotavirus, sapovirus, adenovirus, Giardia intestinalis, Cryptosporidium species, and Entamoeba histolytica.Results: Enteric bacterial infections were diagnosed with an incidence of 229.9 cases/100,000 inhabitants, virus had an incidence of 86/100,000 and enteropathogenic parasites of 12.5/100,000. Viruses constituted more than half of diagnosed enteropathogens for children below 2 years and elderly above 80 years. Diagnostic methods and algorithms differed across the country and in general PCR testing resulted in higher incidences compared to culture (bacteria), antigen-test (viruses), or microscopy (parasites) for most pathogens.Conclusions: In Denmark, the majority of detected infections are bacterial with viral agents primarily detected in the extremes of ages and with few intestinal protozoal infections. Incidence rates were affected by age, clinical setting and local test methods with PCR leading to increased detection rates. The latter needs to be taken into account when interpreting epidemiological data across the country. Background: Only a subset of enteric pathogens is under surveillance in Denmark, and knowledge on the remaining pathogens detected in acute gastroenteritis is limited. Here, we present the one-year incidence of all enteric pathogens diagnosed in Denmark, a high-income country, in 2018 and an overview of diagnostic methods used for detection. Methods: All 10 departments of clinical microbiology completed a questionnaire on test methods and provided 2018-data of persons with positive stool samples with Salmonella species, Campylobacter jejuni/coli, Yersinia enterocolitica, Aeromonas species, diarrheagenic Escherichia coli (Enteroinvasive (EIEC), Shiga toxin-producing (STEC), Enterotoxigenic (ETEC), Enteropathogenic (EPEC), and intimin-producing/attaching and effacing (AEEC)), Shigella species., Vibrio cholerae, norovirus, rotavirus, sapovirus, adenovirus, Giardia intestinalis, Cryptosporidium species, and Entamoeba histolytica. Results: Enteric bacterial infections were diagnosed with an incidence of 229.9 cases/100,000 inhabitants, virus had an incidence of 86/100,000 and enteropathogenic parasites of 12.5/100,000. Viruses constituted more than half of diagnosed enteropathogens for children below 2 years and elderly above 80 years. Diagnostic methods and algorithms differed across the country and in general PCR testing resulted in higher incidences compared to culture (bacteria), antigen-test (viruses), or microscopy (parasites) for most pathogens. Conclusions: In Denmark, the majority of detected infections are bacterial with viral agents primarily detected in the extremes of ages and with few intestinal protozoal infections. Incidence rates were affected by age, clinical setting and local test methods with PCR leading to increased detection rates. The latter needs to be taken into account when interpreting epidemiological data across the country.

Between November and December 2021, the first ever recorded outbreak of enteroinvasive Escherichia coli in Denmark occurred at national scale. We describe the investigation of this outbreak, which was initially recognised in early December 2021. A total of 88 cases (58 female; 30 male) with a median age of 52 years (range: 0–91) were detected by PCR-based diagnostic methods. Case ascertainment was complicated by current culture-free diagnostic procedures, with only 34 cases confirmed by culture, serotyping and whole genome sequencing. Isolates from cases grouped into two serotypes (O136:H7 and O96:H19), which was supported by whole-genome-sequence-phylogeny, also yielding two clusters. Interviews of 42 cases and traceback investigation pointed towards consumption of ready-to-eat salads as the outbreak cause. While the ready-to-eat salads comprised different vegetables, imported spring onions were the only common ingredient and thus the likely source. Environmental investigations failed to recover outbreak strains. This report highlights the value of fast typing (here O-typing) to confirm cases in an outbreak situation. Timely communication and data sharing are also important, and were facilitated by the national collaboration between relevant laboratories, the public health institute and the veterinary and food administration. High hygiene standards for imported fresh vegetables intended for ready-to-eat products are essential.

BackgroundStaphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes.MethodsFirst-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis.ResultsWe identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86–2.41]). No difference in mortality was observed with 0–40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83–1.37]), while with 41–365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53–.95]).ConclusionsCommunity-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality. Community-acquired Staphylococcus aureus bacteremia (SAB) was associated with twice the odds for infective endocarditis (IE), as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated S aureus IE.Background Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86-2.41]). No difference in mortality was observed with 0-40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83-1.37]), while with 41-365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53-.95]). Conclusions Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality.

Background Since 2008, Danish national surveillance of Clostridioides difficile has focused on binary toxin-positive strains in order to monitor epidemic types such as PCR ribotype (RT) 027 and 078. Additional surveillance is needed to provide a more unbiased representation of all strains from the clinical reservoir. Aim Setting up a new sentinel surveillance scheme for an improved understanding of type distribution relative to time, geography and epidemiology, here presenting data from 2016 to 2019. Methods For 2─4 weeks in spring and autumn each year between 2016 and 2019, all 10 Danish Departments of Clinical Microbiology collected faecal samples containing toxigenic C. difficile. Isolates were typed at the national reference laboratory at Statens Serum Institut. The typing method in 2016–17 used tandem-repeat-sequence typing, while the typing method in 2018–19 was whole genome sequencing. Results During the study period, the sentinel surveillance scheme included ca 14–15% of all Danish cases of C. difficile infections. Binary toxin-negative strains accounted for 75% and 16 of the 20 most prevalent types. The most common sequence types (ST) were ST2/13 (RT014/020) (19.5%), ST1 (RT027) (10.8%), ST11 (RT078) (6.7%), ST8 (RT002) (6.6%) and ST6 (RT005/117) (5.1%). The data also highlighted geographical differences, mostly related to ST1 and temporal decline of ST1 (p = 0.0008) and the increase of ST103 (p = 0.002), ST17 (p = 0.004) and ST37 (p = 0.003), the latter three binary toxin-negative. Conclusion Sentinel surveillance allowed nationwide monitoring of geographical differences and temporal changes in C. difficile infections in Denmark, including emerging types, regardless of binary toxin status.

Renal transplant recipients (RTRs) are highly susceptible to infections, and antimicrobial resistance is an increasing problem with limited treatment options. Faecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection and may be used for patients with intestinal carriage of multidrug-resistant (MDR) microorganisms. We present a RTR who suffered from recurrent urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase-producing (ESBL+) Klebsiella pneumoniae. Blood and urinary isolates revealed the same antibiotic susceptibility pattern, and whole-genome sequencing confirmed identical isolates in blood and urine. Despite several treatments with meropenem, the patient experienced recurrent infections that caused hospitalisation. ESBL+ K. pneumoniae was isolated in faeces. In an attempt to decolonise the gut, FMT was performed. A few days after nasojejunal infusion of donor faeces, the patient experienced a single relapse of UTI. During the subsequent 12 months, no further episodes of UTI occurred. Absence of ESBL+ K. pneumoniae in urine and faeces was demonstrated during follow-up. We conclude that FMT may be an effective treatment in RTRs with recurrent UTIs caused by intestinal colonisation with MDR organisms.

BACKGROUND: Intestinal failure (IF) is defined by a need for intravenous (IV) supplementation. Patients may present with multiple morbidities, and IV treatments carry a risk for catheter-related complications. Few studies described patient characteristics and clinical outcomes according to type of IF.METHODS: We consecutively included patients who were admitted to a newly established inpatient IF unit (IFU) from 2013 through 2017. We evaluated patient characteristics and clinical outcomes of all patients' first admission. Outcomes included IF classification, length of stay, central line-associated blood stream infection (CLABSI), and discharge on home parenteral support (HPS). Follow-up was conducted six months after discharge for mortality and the continued need for HPS.RESULTS: A total of 236 patients were evaluated, including 39 (17%) with type 1 IF, 123 (52%) with type 2 IF, and 74 (31%) with type 3 IF. Of 91 who had a central venous catheter (CVC) on admission, CLABSI was present in 11 (12%). The CLABSI occurrence during admission was 2 (1%) of 173 patients with a CVC. Mean length of stay declined from mean 33 days (95% confidence interval (CI): 26.2-42.5) in 2013 to 15 days (95% CI: 12.2-17.7) in 2017 (p < 0.0001). Undiagnosed comorbidity was revealed in 165 patients (70%) with unchanged frequency during the study period (p = 0.8). Sixty-seven (28%) patients were discharged with HPS.CONCLUSIONS: Inpatients with IF present with multiple morbidities. CLABSI should be investigated on admission. A low inpatient CLABSI rate may be achieved through the implementation of a specialised IFU.

As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58%) were excluded mainly due to having an allergy, being overweight, or presenting gastrointestinal complaints. Among the remaining 58 (37%) donors, complete blood and feces screenings were obtained from 46 (79%). Of these 46 donors, 15 (33%) were excluded primarily due to abnormal blood results or the presence of apathogenic intestinal parasites. Overall, 31 (20%; 95% confidence interval 14–27%) of the 155 blood donors qualified as feces donors. In conclusion, blood donors constitute a suitable and motivated population for a continuous recruitment of voluntary feces donors. We found that a stepwise recruitment procedure was feasible and that 20% of the blood donors were eligible for feces donation.

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.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center, randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin.METHODS: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark, from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n = 24), 10 days of fidaxomicin (200 mg twice daily; n = 24), or 10 days of vancomycin (125 mg 4 times daily; n = 16). Patients who had recurrence of CDI following this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a PCR test for Clostridium difficile (CD) toxin 8 weeks following the allocated treatment. Secondary endpoints included clinical resolution at week 8.RESULTS: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients with FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%) (P for FMTv vs fidaxomicin = .009; P for FMTv vs vancomycin = .001; P for fidaxomicin vs vancomycin = .31). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%) (P = .0002; P < .0001; P = .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv.CONCLUSIONS: In a randomized trial of patients with rCDI, we found the combination of vancomycin and FMT to be superior to fidaxomicin or vancomycin, based on endpoints of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov no: NCT02743234. EudraCT j.no: 2015-003004-24.

OBJECTIVES: To investigate the usefulness of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) typing as a first-line epidemiological tool in a nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VREfm).METHODS: Fifty-five VREfm isolates, previously characterized by whole-genome sequencing (WGS), were included and analysed by MALDI-TOF MS. To take peak reproducibility into account, ethanol/formic acid extraction and other steps of the protocol were conducted in triplicate. Twenty-seven spectra were generated per isolate, and spectra were visually inspected to determine discriminatory peaks. The presence or absence of these was recorded in a peak scheme.RESULTS: Nine discriminatory peaks were identified. A characteristic pattern of these could distinguish between the three major WGS groups: WGS I, WGS II and WGS III. Only one of 38 isolates belonging to WGS I, WGS II or WGS III was misclassified. However, ten of the 17 isolates not belonging to WGS I, II or III displayed peak patterns indistinguishable from those of the outbreak strain.CONCLUSIONS: Using visual inspection of spectra, MALDI-TOF MS typing proved to be useful in differentiating three VREfm outbreak clones from each other. However, as non-outbreak isolates could not be reliably differentiated from outbreak clones, the practical value of this typing method for VREfm outbreak management was limited in our setting.

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. Keywords: Candidaemia, Candida, Epidemiology, Outcome, Mortality

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.

BACKGROUND: The buttonhole cannulation technique for arteriovenous fistulas is widely used, but has been associated with an increased rate of vascular access-related infections. We describe the frequency and type of bacterial colonization of the buttonhole tract over time and associated clinical infections.STUDY DESIGN: A prospective observational cohort study with 9 months of follow-up.SETTING & PARTICIPANTS: 84 in-center hemodialysis patients using the buttonhole cannulation technique at 2 Danish dialysis centers.OUTCOMES: Bacterial growth from the buttonhole tract and dialysis cannula tip and clinically important infections during follow-up.MEASUREMENTS: On 3 occasions 1 month apart, cultures before dialysis (from the skin surrounding the buttonhole before disinfection and from the cannulation tract after disinfection and scab removal) and the cannula tip after dialysis. Patients with positive cultures from the buttonhole tract or cannula tip had repeat cultures within 1 week, along with blood cultures.RESULTS: Growth from the cannulation tract and/or cannula tip at each of the 3 monthly sets of cultures was found in 18%, 20%, and 17% of patients, respectively. 38% of patients had at least 1 positive culture from the buttonhole tract. Sustained growth was detected in 11% of patients, whereas asymptomatic bacteremia was seen in 30% of those with positive buttonhole cultures. Staphylococci species were the most common pathogens (Staphylococcus aureus, 25%; and Staphylococcus epidermidis, 41%). Colonization-positive buttonholes had more localized redness and slightly more tenderness. During follow-up, significantly more access-related infections were diagnosed among those with positive buttonhole cultures (PLIMITATIONS: No comparison to area puncture cannulation technique. Blood cultures were obtained only from patients with positive buttonhole bacteriology.CONCLUSIONS: Transient or sustained colonization of the buttonhole tract by staphylococci and asymptomatic bacteremia is common in hemodialysis patients, implying a substantial risk for access-related infections among patients using a buttonhole cannulation technique. These findings suggest the possible value of surveillance of buttonhole colonization.

Karen Rokkedal Lausch,1 Mette Søgaard,2,3 Flemming Schønning Rosenvinge,4,5 Helle Krogh Johansen,6 Trine Boysen,7 Bent Løwe Røder,8 Klaus Leth Mortensen,1,9Lene Nielsen,10 Lars Lemming,9 Bente Olesen,10 Christine Leitz,11 Lise Kristensen,9,12 Esad Dzajic,13 Lars Jørgen Østergaard,1 Henrik Carl Schønheyder,14,15 Maiken Cavling Arendrup6,16,17 1Department of Infectious Disease, Aarhus University Hospital, 8200 Aarhus, Denmark; 2Department of Cardiology, Aalborg University Hospital, 9000 Aalborg, Denmark; 3Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, 9000 Aalborg, Denmark; 4Department of Clinical Microbiology, Odense University Hospital, 5000 Odence C, Denmark; 5Department of Clinical Microbiology, Lillebaelt Hospital, 5500 Middelfart, Denmark; 6Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark; 7Department of Clinical Microbiology, Hvidovre Hospital, 2650 Hvidovre, Denmark; 8Department of Clinical Microbiology, Hospital of Slagelse, Slagelse Sygehus, 4200 Slagelse, Denmark; 9Department of Clinical Microbiology, Aarhus University Hospital, 8200 Aarhus, Denmark; 10Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, 2730 Herlev, Denmark; 11Department of Clinical Microbiology, Viborg Regionshospital, 8800 Viborg, Denmark; 12Department of Clinical Microbiology, Herning Regionshospital, 7400 Herning, Denmark; 13Department of Clinical Microbiology, Sydvestjysk Sygehus, 6700 Esbjerg, Denmark; 14Department of Clinical Microbiology, Aalborg University Hospital, 9000 Aalborg, Denmark; 15Department of Clinical Medicine, University of Aalborg, 9000 Aalborg, Denmark; 16Unit of Mycology, Statens Serum Institute, 2300 København, Denmark; 17Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark Background: In accordance with international guidelines, primary antifungal treatment (AFT) of candidemia with echinocandins has been nationally recommended in Denmark since 2009. Our nationwide cohort study describes the management of candidemia treatment focusing on the impact of prophylactic AFT on species distribution, the rate of adherence to the recommended national guidelines for AFT, and the effect of AFT on patient outcomes.Materials and methods: Incident candidemia cases from a 2-year period, 2010–2011, were included. Information on AFT was retrospectively collected from patient charts. Vital status was obtained from the Danish Civil Registration System. HRs of mortality were reported with 95% CIs using Cox regression.Results: A total of 841 candidemia patients was identified. Prior to candidemia diagnosis, 19.3% of patients received AFT (162/841). The risk of non-albicans candidemia increased after prior AFT (59.3% vs 45.5% among nontreated). Echinocandins as primary AFT were given for 44.2% (302/683) of patients. Primary treatment with echinocandins resulted in adequate treatment in a higher proportion of patients (97.7% vs 72.1%) and was associated with lower 0- to 14-day mortality compared with azole treatment (adj. HR 0.76, 95% CI: 0.55–1.06). Significantly lower 0- to 14-day mortality was observed for patients with Candida glabrata and Candida krusei with echinocandin treatment compared with azole treatment (adj. HR 0.50, 95% CI: 0.28–0.89), but not for patients with Candida albicans or Candida tropicalis.Conclusion: The association shown between prior AFT and non-albicans species underlines the importance of treatment history when selecting treatment for candidemia. Compliance with national recommendations was low, but similar to previously reported international rates. Primary treatment of candidemia with echinocandins compared with azoles yielded both a higher proportion of adequately treated patients and improved mortality rates. This real-life setting supports guidelines recommendation, and further focus on compliance with these seems warranted. Keywords: candidemia, candida, antifungal treatment, echinocandin, azole, Candida albicans, Candida glabrata

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 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 (= 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 (