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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.

OBJECTIVE: To ascertain whether persons treated with statins experience a decreased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB) as compared with nonusers.PATIENTS AND METHODS: Using population-based medical registries, we conducted a case-control study including all adults with first-time CA-SAB and population controls matched on age, sex, and residence in Northern Denmark from January 1, 2000, through December 31, 2011. Statin users were categorized as current users (new or long-term use), former users, and nonusers. We used conditional logistic regression to compute odds ratios (ORs) for CA-SAB according to statin exposure, overall and stratified by intensity (RESULTS: We identified 2638 patients with first-time CA-SAB and 26,379 matched population controls. Compared with nonusers, current statin users experienced markedly decreased risk of CA-SAB (adjusted OR, 0.73; 95% CI, 0.63-0.84). The adjusted OR was 0.96 (95% CI, 0.60-1.51) for new users, 0.71 (95% CI, 0.62-0.82) for long-term users, and 1.12 (95% CI, 0.94-1.32) for former users as compared with nonusers. The CA-SAB risk decreased with increasing intensity of statin use; thus, compared with nonusers, the adjusted OR was 0.84 (95% CI, 0.68-1.04) for current users with daily dosages of less than 20 mg/d, 0.71 (95% CI, 0.58-0.87) for 20 to 39 mg/d, and 0.63 (95% CI, 0.49-0.81) for 40 mg/d or more. Conversely, we observed no differences in the risk of CA-SAB with successive increases in the duration of statin use.CONCLUSION: Statin use was associated with a decreased risk of CA-SAB, particularly in long-term users.

Objectives: Bacteria with common microbiological and clinical characteristics are often recognized as a particular group. The acronym HACEK stands for five fastidious genera associated with infective endocarditis (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella). Data on the epidemiology of HACEK are sparse. This article reports a 6-year nationwide study of HACEK bacteraemia in Denmark. Methods: Cases of HACEK bacteraemia occurring during the years 2010–2015 were retrieved from the national Danish microbiology database, covering an average surveillance population of 5.6 million per year. Results: A total of 147 cases of HACEK bacteraemia were identified, corresponding to an annual incidence of 0.44 per 100 000 population. The annual incidence for males was 0.56 per 100 000 and for females was 0.31 per 100 000. The median age was 56 years (range 0–97 years), with variation among the genera. One hundred and forty-three isolates were identified to the species level and six to the genus level: Haemophilus spp, n = 55; Aggregatibacter spp, n = 37; Cardiobacterium spp, n = 9; Eikenella corrodens n = 21; and Kingella spp, n = 27. Conclusions: This is the first study on the incidence of HACEK bacteraemia in a large surveillance population and may inspire further studies on the HACEK group. Haemophilus spp other than Haemophilus influenzae accounted for most cases of HACEK bacteraemia in Denmark, with Aggregatibacter spp in second place. Keywords: Epidemiology, Incidence, Age, Sex, Haemophilus, Aggregatibacter

Objectives: To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM). Methods: We conducted a chart review of all adults with proven CABM in three centres in Denmark from 1998 through to 2014. Patients were categorized as early diagnosis of CABM immediately on admission, or late diagnosis if CABM was not listed in referral or admission records and neither lumbar puncture nor antibiotic therapy for meningitis was considered immediately on admission. We used modified Poisson regression analysis to compute adjusted relative risks with 95% CIs for predictors of late diagnosis and in-hospital mortality. Results: A total of 113/358 (32%) patients were categorized as late diagnosis demonstrating a variety of tentative diagnoses of which 81/113 (72%) were non-infectious. We observed several statistically significant baseline differences (p 65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%), concomitant pneumonia (26/113, 23% versus 26/245, 11%), and meningococcal meningitis (6/113, 5% versus 52/245, 21%). These variables remained statistically significant in multivariate analysis. Moreover, late diagnosis was associated with increased in-hospital mortality (41/113, 36% versus 43/245, 18%; adjusted relative risk 1.7, 95% CI 1.2–2.5). Conclusions: Late diagnosis of CABM was common and patients were admitted with mostly non-infectious diagnoses. Absence of neck stiffness did not rule out CABM and special attention should be given to patients with pneumonia and the elderly. Late diagnosis was associated with incorrect patient management and increased mortality.

Key Clinical Message Pneumococci are predominant in respiratory tract infections but may have unusual presentations such as lactational mastitis. We report a 29‐year‐old breastfeeding woman with pneumococcal mastitis confirmed by positive blood culture and culture of milk. Previously, a few similar cases have been reported, but none was associated with bacteremia.

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

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.

Most Staphylococcus aureus isolates can cause invasive disease given the right circumstances, but it is unknown if some isolates are more likely to cause severe infections than others. S. aureus bloodstream isolates from 120 patients with definite infective endocarditis and 121 with S. aureus bacteraemia without infective endocarditis underwent whole-genome sequencing. Genome-wide association analysis was performed using a variety of bioinformatics approaches including SNP analysis, accessory genome analysis and k-mer based analysis. Core and accessory genome analyses found no association with either of the two clinical groups. In this study, the genome sequences of S. aureus bloodstream isolates did not discriminate between bacteraemia and infective endocarditis. Based on our study and the current literature, it is not convincing that a specific S. aureus genotype is clearly associated to infective endocarditis in patients with S. aureus bacteraemia.

OBJECTIVE: To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, as risk factors for ESBL E.coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with previous studies.METHODS: Population-based case-control study including 339 cases with community-onset ESBL E. coli UTI in 2007-2012, 3,390 non-ESBL E. coli UTI controls, and 3,390 population controls. We investigated potential risk factors by estimating odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for sex, age, and comorbidity.RESULTS: Comparing cases with non-ESBL E. coli UTI, PPI use yielded an OR of 1.6 (95% CI 1.2-2.0) and antibiotic exposure an OR of 1.4 (95% CI 1.1-1.8); these were driven by nitrofurantoin (OR 1.8; 95% CI 1.3-2.6) and macrolides (OR 1.7; 95% CI 1.2-2.3). Other risk factors included: prior hospitalization with 1-2 and >2 hospitalizations vs. none yielding ORs of 1.9 (95% CI 1.4-2.5) and 4.6 (95% CI 3.2-6.8), recent surgery (OR 2.0; 95% CI 1.5-2.8), renal disease (OR 2.2; 95% CI 1.4-3.4), chronic pulmonary disease (OR 1.4; 95% CI 1.0-2.0), and cancer (OR 1.5; 95% CI 1.1-2.1). Comparing cases with population controls, we found that most risk factors were also risk factors for non-ESBL UTI.CONCLUSIONS: ESBL E.coli UTI were associated with previous hospitalization and surgery. Nitrofurantoin and macrolides augmented the risk. PPIs had a moderate effect but may be important facilitators of ESBL carriage, due to their widespread use.

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.

BACKGROUND AND PURPOSE: It has been suggested that the risk of prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA) may be underestimated if based only on arthroplasty registry data. We therefore wanted to estimate the "true" incidence of PJI in THA using several data sources.PATIENTS AND METHODS: We searched the Danish Hip Arthroplasty Register (DHR) for primary THAs performed between 2005 and 2011. Using the DHR and the Danish National Register of Patients (NRP), we identified first revisions for any reason and those that were due to PJI. PJIs were also identified using an algorithm incorporating data from microbiological, prescription, and clinical biochemistry databases and clinical findings from the medical records. We calculated cumulative incidence with 95% confidence interval.RESULTS: 32,896 primary THAs were identified. Of these, 1,546 had first-time revisions reported to the DHR and/or the NRP. For the DHR only, the 1- and 5-year cumulative incidences of PJI were 0.51% (0.44-0.59) and 0.64% (0.51-0.79). For the NRP only, the 1- and 5-year cumulative incidences of PJI were 0.48% (0.41-0.56) and 0.57% (0.45-0.71). The corresponding 1- and 5-year cumulative incidences estimated with the algorithm were 0.86% (0.77-0.97) and 1.03% (0.87-1.22). The incidences of PJI based on the DHR and the NRP were consistently 40% lower than those estimated using the algorithm covering several data sources.INTERPRETATION: Using several available data sources, the "true" incidence of PJI following primary THA was estimated to be approximately 40% higher than previously reported by national registries alone.

Background Herpes zoster (HZ) is a vaccine-preventable disease caused by reactivation of the varicella-zoster virus. Unfortunately, formulation of recommendations on routine immunization is hampered by a lack of data on disease burden, since most countries do not record cases of HZ in the general population. We developed and validated an algorithm to identify HZ based on routinely collected registry data and used it to quantify HZ occurrence and risk factors in Denmark prior to marketing of the HZ vaccine. Methods We included patients aged ≥40 years with a first-time systemic Acyclovir, Valacyclovir, or Famciclovir prescription or a hospital-based HZ diagnosis in the Danish nationwide health registries during 1997–2013. In a validation substudy (n = 176), we computed the proportion of persons with HZ among patients who redeemed antiviral prescriptions. In a cohort study, we computed age-specific rates of HZ (45,297,258 person-years). In a case-control study, we then computed odds ratios (ORs) for common chronic diseases and immunosuppressive factors among HZ cases (n = 189,025) vs. matched population controls (n = 945,111). Results Medical record review confirmed HZ in 87% (95% confidence interval: 79–93%) of persons ≥40 years who dispensed antivirals at doses recommended for HZ. HZ rates increased from 2.15/1000 person-years in 40-year-olds to 9.45/1000 person-years in 95-year-olds. Rates were highest in women. HZ was diagnosed during hospitalization among 3.5%. As expected, persons with severe immunosuppressive conditions had the highest ORs of HZ (between 1.82 and 4.12), but various autoimmune diseases, asthma, chronic kidney disease, and inhaled glucocorticoids were also associated with increased ORs (between 1.06 and 1.64). Conclusion This algorithm is a valid tool for identifying HZ in routine healthcare data. It shows that HZ is common in Denmark, especially in patients with certain chronic conditions. Prioritized vaccination of such high-risk patients might be an option in countries considering alternatives to universal vaccination.

SUMMARYThe 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.

Adherence to antimicrobial guidelines is key to ensuring a correct treatment of severe infections and to lessening misuse of broad-spectrum antimicrobials. We conducted a retrospective cross-sectional study at the Emergency Department of Aalborg University Hospital, North Denmark Region. Our aim was to examine adherence to local antimicrobial guidelines in the empirical treatment of community-acquired infections and to identity any predictors of guideline non-adherence.We identified 1,555 patients who had blood cultures performed and were admitted to the medical emergency department in 2016. We reviewed the medical charts of 755 patients and included those who received at least one antibiotic prescription within the first 24 hours of admission. We excluded patients with known immunodeficiency, severe renal failure or hospitalisation within the previous month.Of the 383 included patients, 203 (53%) received guideline-concordant antibiotic treatment. The treatment was guideline-concordant in 41% of patients with suspected sepsis of unknown origin, in 44% with pneumonia and in 37% with urinary tract infections. Patients with underlying chronic obstructive pulmonary disease (25%) received guideline-concordant treatment significantly more often (83%, p0.01) than other groups.Adherence to local antimicrobial guidelines was not high. Further studies are needed to identify barriers to guideline adherence.None.The study was registered with the Danish Data Protection Agency (R. no. 2008-58-0028).

OBJECTIVES: Researchers have advocated for an increased awareness of occult cancer among herpes zoster patients, but there are no systematic reviews to support these claims. We therefore conducted a systematic review and meta-analysis of evidence on zoster and risk of occult cancer.METHODS: Through February 18, 2016, we searched PubMed, EMBASE and references of relevant papers for studies on zoster and risk of any cancer. One author screened retrieved papers by title and abstract; included papers were reviewed by two authors for eligibility, data extraction, and potential biases. Despite statistical heterogeneity, associations were consistently in the same direction and we therefore computed pooled relative risks using random-effects models.RESULTS: We identified 46 eligible studies, 10 of which considered all cancer types combined. The pooled relative risk for any cancer was 1.42 (95% confidence interval: 1.18, 1.71) overall and 1.83 (95% confidence interval: 1.17, 2.87) at one year after zoster. Considering cancer subtypes, the highest estimates were generally reported for occult hematological cancer. The absolute risk of any cancer at one year after presentation with zoster was 0.7%-1.8%.CONCLUSION: This study supports an association between zoster and occult cancer, but the low absolute risk of cancer limits the clinical implications.

Objective: To ascertain whether persons treated with statins experience a decreased risk of communityacquired Staphylococcus aureus bacteremia (CA-SAB) as compared with nonusers.Patients and Methods: Using population-based medical registries, we conducted a case-control study including all adults with first-time CA-SAB and population controls matched on age, sex, and residence in Northern Denmark from January 1, 2000, through December 31, 2011. Statin users were categorized as current users (new or long-term use), former users, and nonusers. We used conditional logistic regression to compute odds ratios (ORs) for CA-SAB according to statin exposure, overall and stratified by intensity (= 40 mg/d) and duration of use (= 1095 days).Results: We identified 2638 patients with first-time CA-SAB and 26,379 matched population controls. Compared with nonusers, current statin users experienced markedly decreased risk of CA-SAB (adjusted OR, 0.73; 95% CI, 0.63-0.84). The adjusted OR was 0.96 (95% CI, 0.60-1.51) for new users, 0.71 (95% CI, 0.62-0.82) for long-term users, and 1.12 (95% CI, 0.94-1.32) for former users as compared with nonusers. The CA-SAB risk decreased with increasing intensity of statin use; thus, compared with nonusers, the adjusted OR was 0.84 (95% CI, 0.68-1.04) for current users with daily dosages of less than 20 mg/d, 0.71 (95% CI, 0.58-0.87) for 20 to 39 mg/d, and 0.63 (95% CI, 0.49-0.81) for 40 mg/d or more. Conversely, we observed no differences in the risk of CA-SAB with successive increases in the duration of statin use.Conclusion: Statin use was associated with a decreased risk of CA-SAB, particularly in long-term users. (C) 2017 Mayo Foundation for Medical Education and Research

BACKGROUND: Bacterial infections are common complications in kidney transplant recipients (KTRs). Little is known about incidence rates of bacteremia and fungemia (BAF) in KTRs.METHODS: In this population-based cohort study, we used medical and administrative registries to identify episodes of BAF among KTRs in the Central Denmark and North Denmark Regions during 1995-2010. KTRs were followed from the date of their first transplantation to the earliest of BAF, graft loss, death, emigration or 31 December 2010. We calculated incidence rates of first BAF episode overall and stratified by time from transplantation. Potential risk factors were assessed using Cox regression analysis. The Kaplan-Meier analysis was used to estimate 30- and 90-day mortality.RESULTS: Among 612 KTRs, we identified 138 first episodes of bacteremia during 2397 person-years of follow-up (PYFU). The overall incidence rate (IR) was 5.8 BAF episodes per 100 PYFU (95% confidence interval [CI]: 4.9-6.8). The incidence rate declined from 84.0 per 100 PYFU (95% CI: 61.6-114.5) during post-transplant day 0-30 to 2.3 per 100 PYFU (95% CI: 1.7-3.0) from post-transplant day 365 and onwards. Hospital-onset BAF comprised 39% of the episodes of BAF. The most frequently isolated microorganisms were Escherichia coli and Klebsiella species causing 49 (35.5%) and 29 (21.0%) episodes of BAF, respectively. The 30-day mortality was 2.1% (95% CI: 0.7-6.6).CONCLUSIONS: While the risk of BAF in KTRs was high, thirty-day mortality was low. After the first post-transplant year, the IR of bacteremia was substantially lower than in the immediate post-transplant period.

BACKGROUNDIn 2015, Denmark launched an automated surveillance system for hospital-acquired infections, the Hospital-Acquired Infections Database (HAIBA).OBJECTIVETo describe the algorithm used in HAIBA, to determine its concordance with point prevalence surveys (PPSs), and to present trends for hospital-acquired bacteremiaSETTINGPrivate and public hospitals in DenmarkMETHODSA hospital-acquired bacteremia case was defined as at least 1 positive blood culture with at least 1 pathogen (bacterium or fungus) taken between 48 hours after admission and 48 hours after discharge, using the Danish Microbiology Database and the Danish National Patient Registry. PPSs performed in 2012 and 2013 were used for comparison.RESULTSNational trends showed an increase in HA bacteremia cases between 2010 and 2014. Incidence was higher for men than women (9.6 vs 5.4 per 10,000 risk days) and was highest for those aged 61–80 years (9.5 per 10,000 risk days). The median daily prevalence was 3.1% (range, 2.1%–4.7%). Regional incidence varied from 6.1 to 8.1 per 10,000 risk days. The microorganisms identified were typical for HA bacteremia. Comparison of HAIBA with PPS showed a sensitivity of 36% and a specificity of 99%. HAIBA was less sensitive for patients in hematology departments and intensive care units. Excluding these departments improved the sensitivity of HAIBA to 44%.CONCLUSIONSAlthough the estimated sensitivity of HAIBA compared with PPS is low, a PPS is not a gold standard. Given the many advantages of automated surveillance, HAIBA allows monitoring of HA bacteremia across the healthcare system, supports prioritizing preventive measures, and holds promise for evaluating interventions.Infect Control Hosp Epidemiol 2017;38:559–566

OBJECTIVES: Gram-negative bacteremia may be a harbinger of occult cancer. We examined the risk of cancer following hospitalization with bacteremia.METHODS: Using medical databases, we conducted a nationwide population-based cohort study of all Danes with a discharge diagnosis of Gram-negative bacteremia during 1994-2013. We calculated absolute risks and standardized incidence ratios (SIRs) of cancer, comparing the observed risk to that expected in the general population.RESULTS: We observed 1,379 cancers vs. 988 expected among 11,753 patients with Gram-negative bacteremia, corresponding to an overall SIR of 1.40 (95% confidence interval (CI): 1.32-1.47). During the first 6 months following the bacteremia diagnosis, the SIR for cancer was 3.33-fold (95% CI: 2.99-3.69) increased, corresponding to an absolute risk of 3.05%. The increased risk stemmed mainly from higher than expected occurrence of gastrointestinal cancer (3- to 13-fold higher), genitourinary cancer (4- to 10-fold higher), non-Hodgkin lymphoma (5-fold higher), non-specified metastatic cancer (5-fold higher), and breast and lung cancer (2-fold higher). The 6-12 months SIR for any cancer was 1.46 (95% CI: 1.22-1.72), and beyond 1 year of follow-up, the SIR declined to 1.13 (95% CI: 1.05-1.20).CONCLUSIONS: Gram-negative bacteremia is a clinical marker of occult cancer.

Objective: To examine the trend of Prosthetic Joint Infections (PJI) following primary total hip arthroplasty (THA) and the antimicrobial resistance of the bacteria causing these infections.Materials and methods: We identified a population-based cohort of patients in the Danish Hip Arthroplasty Register (DHR) who had primary THA and received their surgery in Jutland or Funen between 2005 and 2014. We followed the patients until revision, emigration, death, or up to 1-year of follow-up. Data from the DHR were combined with those from microbiology databases, the National Register of Patients, and the Civil Registration System. We estimated the cumulative 1-year incidence of PJI for two 5-year periods; 2005-2009 and 2010-2014. The hazard ratio of PJI as a measure of relative risk after adjusting for multiple risk factors was calculated.Results: Of 48,867 primary THAs identified, 1120 underwent revision within 1 year. Of these, 271 were due to PJI. The incidence of PJI was 0.53% (95% confidence interval (CI): 0.44; 0.63) during 2005-2009 and 0.57% (95% CI: 0.49; 0.67) during 2010-2014. The adjusted relative risk was 1.05 (95% CI: 0.82; 1.34) for the 2010-2014 period vs the 2005-2009 period.The most common micro-organisms identified in the 271 PJI were Staphylococcus aureus (36%) and coagulase-negative staphylococci (CoNS) (33%); others commonly identified included Enterobacteriaceae, enterococci, and streptococci. Antimicrobial resistance to beta-lactams and gentamicin did not change during the study period.Conclusion: The risk of PJI within 1-year after primary THA and the antimicrobial resistance of the most prevalent bacteria remained unchanged during the 2005-2014 study period. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The Danish Collaborative Bacteraemia Network (DACOBAN) research database includes microbiological data obtained from positive blood cultures from a geographically and demographically well-defined population serviced by three clinical microbiology departments (1.7 million residents, 32% of the Danish population). The database also includes data on comorbidity from the Danish National Patient Registry, vital status from the Danish Civil Registration System, and clinical data on 31% of nonselected records in the database. Use of the unique civil registration number given to all Danish residents enables linkage to additional registries for specific research projects. The DACOBAN database is continuously updated, and it currently comprises 39,292 patients with 49,951 bacteremic episodes from 2000 through 2011. The database is part of an international network of population-based bacteremia registries from five developed countries on three continents. The main purpose of the DACOBAN database is to study surveillance, risk, and prognosis. Sex- and age-specific data on background populations enables the computation of incidence rates. In addition, the high number of patients facilitates studies of rare microorganisms. Thus far, studies on Staphylococcus aureus, enterococci, computer algorithms for the classification of bacteremic episodes, and prognosis and risk in relation to socioeconomic factors have been published.

In a Danish population-based case-control study, we examined the association between socioeconomic status (SES) and risk of community-acquired bacteremia, as well as the contribution of chronic diseases and substance abuse to differences in bacteremia risk. Analyses were based on 4,117 patients aged 30-65 years who were hospitalized with first-time community-acquired bacteremia during 2000-2008 and 41,170 population controls matched by sex, age, and region of residence. Individual-level information on SES (education and income), chronic diseases, and substance abuse was retrieved from public and medical registries. Conditional logistic regression was used to compute odds ratios for bacteremia. Persons of low SES had a substantially higher risk of bacteremia than those of high SES (for short duration of education vs. long duration, odds ratio = 2.30 (95% confidence interval: 2.10, 2.52); for low income vs. high income, odds ratio = 2.77 (95% confidence interval: 2.54, 3.02)). A higher prevalence of chronic diseases and substance abuse in low-SES individuals versus high-SES individuals explained 43%-48% of the socioeconomic differences in bacteremia risk. In a country with a universal welfare system, differences in the burden of chronic diseases and substance abuse seem to have major importance in explaining inequalities in bacteremia risk.

Enterococci currently account for approximately 10% of all bacteraemias, reflecting remarkable changes in their epidemiology. However, population-based data of enterococcal bacteraemia are scarce. A population-based cohort study comprised all patients with a first episode of Enterococcus faecalis or Enterococcus faecium bacteraemia in two Danish regions during 2006–2009. We used data collected prospectively during clinical microbiological counselling and hospital registry data. We determined the incidence of mono- and polymicrobial bacteraemia and assessed clinical and microbiological characteristics as predictors of 30-day mortality in monomicrobial bacteraemia by logistic regression analysis. We identified 1145 bacteraemic patients, 700 (61%) of whom had monomicrobial bacteraemia. The incidence was 19.6/100 000 person-years (13.0/100 000 person-years for E. faecalis and 6.6/100 000 person-years for E. faecium ). The majority of bacteraemias were hospital-acquired ( E. faecalis, 45.7%; E. faecium, 85.2%). Urinary tract and intra-abdominal infections were the predominant foci for the two species, respectively. Infective endocarditis (IE) accounted for 25% of patients with community-acquired E. faecalis bacteraemia. Thirty-day mortality was 21.4% in patients with E. faecalis and 34.6% in patients with E. faecium. Predictors of 30-day mortality included age, co-morbidity and hospital-acquired bacteraemia. In addition, intra-abdominal infection, unknown focus and high-level gentamicin resistance were predictors of mortality in E. faecalis patients. E. faecium was associated with increased risk of mortality compared with E. faecalis. The study emphasizes the importance of enterococci both in terms of incidence and prognosis. The frequency of IE in patients with E. faecalis bacteraemia emphasizes the importance of echocardiography, especially in community-acquired cases.

Objectives The objective of the present study was to compare the efficacy of cefuroxime with that of dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish bacteraemia database, information on the indication for antimicrobial therapy, multivariate adjustment and propensity score (PS) matching. Methods This was a retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008 were included from a total of seven hospitals in the greater Copenhagen area and seven hospitals in the North Denmark Region. Information including demographics, antimicrobial therapy and clinical condition was obtained. The physician's note detailing the indication for starting empirical antimicrobial therapy was given special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day mortality were calculated using PS-adjusted Cox proportional hazards regression analyses. In addition, PS matching was performed. Results A total of 691 patients with MS-SAB received either dicloxacillin (n = 368) or cefuroxime (n = 323) as definitive antimicrobial therapy. Twenty-eight different indications for empirical antimicrobial therapy were identified and grouped into eight categories. There was no statistically significant difference in 30 day mortality between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial therapy with cefuroxime was associated with increased 90 day mortality in a PS-adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe infection' was independently associated with 90 day mortality (HR 1.97, 95% CI 1.19-3.28). Conclusions Definitive antimicrobial therapy with cefuroxime was associated with significantly higher 90 day mortality than was dicloxacillin therapy in patients with MS-SAB.

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.

Background Community-acquired bacterial meningitis (CABM) is a life-threatening disease and timing of antibiotic therapy remains crucial. We aimed to analyse the impact of antibiotic timing on the outcome of CABM in a contemporary cohort. Methods We conducted a population-based cohort study based on chart reviews of all adult cases (>16 years of age) of CABM in North Denmark from 1998 to 2014 excluding patients given pre-hospital parenteral antibiotics. We used modified Poisson regression analyses to compute the adjusted risk ratio (adj. RR) with 95 % confidence intervals (CIs) for in-hospital mortality and unfavourable outcome at discharge by time after arrival to hospital to adequate antibiotic therapy. Results We identified 195 adults with CABM of whom 173 patients were eligible for further analyses. The median door-to-antibiotic time was 2.0 h (interquartile range (IQR) 1.0–5.5). We observed increased adjusted risk ratios for in-hospital mortality of 1.6 (95 % CI 0.8–3.2) and an unfavourable outcome at discharge of 1.5 (95 % CI 1.0–2.2, p = 0.03) when treatment delays exceeded 6 h versus treatment within 2 h of admission. These findings corresponded to adjusted risk ratios of in-hospital mortality of 1.1 per hour of delay (95 % CI 0.8–1.5) and an unfavourable outcome at discharge of 1.1 per hour of delay (95 % CI 1.0–1.3) within the first 6 h of admission. Some patients (31 %) were diagnosed after admission and had more delays in antibiotic therapy and correspondingly increased in-hospital mortality (30 vs 14 %, p = 0.01) and unfavourable outcome (62 vs 37 %, p = 0.002). Conclusions Delay in antibiotic therapy was associated with unfavourable outcome at discharge. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1711-z) contains supplementary material, which is available to authorized users.

BACKGROUND: The Danish Hospital-Acquired Infections Database (HAIBA) is an automated surveillance system using hospital administrative, microbiological, and antibiotic medication data.AIM: To define and evaluate the case definition for hospital-acquired urinary tract infection (HA-UTI) and to describe surveillance data from 2010 to 2014.METHODS: The HA-UTI algorithm defined a laboratory-diagnosed UTI as a urine culture positive for no more than two micro-organisms with at least one at ≥10(4)cfu/mL, and a probable UTI as a negative urine culture and a relevant diagnosis code or antibiotic treatment. UTI was considered hospital-acquired if a urine sample was collected ≥48h after admission and FINDINGS: HAIBA detected a national incidence rate of 42.2 laboratory-diagnosed HA-UTI per 10,000 risk-days with an increasing trend. Compared to PPS the laboratory-diagnosed HA-UTI algorithm had a sensitivity of 50.0% (26/52) and a specificity of 94.2% (1842/1955). There were several reasons for discrepancies between HAIBA and PPS, including laboratory results being unavailable at the time of the survey, the results considered clinically irrelevant by the surveyor due to an indwelling urinary catheter or lack of clinical signs of infection, and UTIs being considered HA-UTI in PPS even though the first sample was taken within 48h of admission.CONCLUSION: The HAIBA algorithm was found to give valid and valuable information and has, among others, the advantages of covering the whole population and allowing continuous standardized monitoring of HA-UTI.

[Objectives] Female gender has been suggested to be associated with poor outcome in patients with Staphylococcus aureus bacteraemia (SAB), but existing data remain sparse and conflicting. We investigated clinical outcomes in female and male patients with community-acquired (CA-) SAB., [Methods] Population-based medical registers were used to conduct a cohort study of all adult patients with CA-SAB in northern Denmark, 2000–2011. Thirty-day mortality after CA-SAB for female and male patients was estimated by the Kaplan–Meier method. Using Cox proportional hazards regression, we computed hazard ratios (HRs) of death according to gender, overall and stratified by age groups, co-morbidity level, and selected major diseases while adjusting for potential confounders. Moreover, we estimated 30-day prevalence proportions for SAB-associated infective endocarditis and osteomyelitis by gender., [Results] Among 2638 patients with CA-SAB, 1022 (39%) were female. Thirty-day mortality was 29% (n = 297) in female patients and 22% (n = 355) in male patients, yielding an adjusted HR (aHR) of 1.30 (95% CI, 1.11–1.53). This association appeared robust across age groups, whereas no consistent pattern was observed according to co-morbidity level. Compared with male patients, the prognostic impact of gender was most pronounced among female patients with diabetes (aHR 1.52; 95% CI 1.04–2.21)), and among female patients with cancer (aHR 1.40; 95% CI 1.04–1.90). The 30-day prevalence of infective endocarditis or osteomyelitis did not differ according to gender., [Conclusion] Female patients with CA-SAB experienced increased 30-day mortality compared with male patients. Gender should be considered in the triage and risk stratification of CA-SAB patients., This study was supported by research grants from The Heinrich Kopp, Hertha Christensen and North Denmark Health Sciences Research Foundations. LELC and JRB received funding for research from the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—co-financed by the European Development Regional Fund “A way to achieve Europe” ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

Background Staphylococcus aureus gene expression has been sparsely studied in deep-sited infections in humans. Here, we characterized the staphylococcal transcriptome in vivo and the joint fluid metabolome in a prosthetic joint infection with an acute presentation using deep RNA sequencing and nuclear magnetic resonance spectroscopy, respectively. We compared our findings with the genome, transcriptome and metabolome of the S. aureus joint fluid isolate grown in vitro. Result From the transcriptome analysis we found increased expression of siderophore synthesis genes and multiple known virulence genes. The regulatory pattern of catabolic pathway genes indicated that the bacterial infection was sustained on amino acids, glycans and nucleosides. Upregulation of fermentation genes and the presence of ethanol in joint fluid indicated severe oxygen limitation in vivo. Conclusion This single case study highlights the capacity of combined transcriptome and metabolome analyses for elucidating the pathogenesis of prosthetic infections of major clinical importance. Electronic supplementary material The online version of this article (doi:10.1186/s12866-016-0695-6) contains supplementary material, which is available to authorized users.

Aims The purpose of this study was to validate the diagnosis of periprosthetic joint infection (PJI) in the Danish Hip Arthroplasty Register (DHR). Patients and Methods We identified a cohort of patients from the DHR who had undergone primary total hip arthroplasty (THA) since 1 January 2005 and followed them until first-time revision, death, emigration or until 31 December 2012. Revision for PJI, as registered in the DHR, was validated against a benchmark which included information from microbiology databases, prescription registers, clinical biochemistry registers and clinical records. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for PJI in the DHR alone and in the DHR when combined with microbiology databases. Results In total, 1382 of the 37 826 primary THAs in the DHR were registered as having been revised for any cause once 26 patients with errors in registration had been excluded: 232 of these were for PJI. For this group, the sensitivity was 67%, specificity 95%, PPV 77%, and NPV 92%. Combining the data from the DHR with those from microbiology databases increased the sensitivity to 90% and also improved specificity (100%), PPV (98%) and NPV (98%). Conclusion Only two thirds of revisions for PJI were captured in the DHR and only 77% of the PJI reported to the DHR could be confirmed to be infected. Take home message: combining the data from the DHR with those from microbiology databases substantially improved the validity of the diagnosis of PJI and should enable future register-based studies. Cite this article: Bone Joint J 2016;98-B:320–5.

We investigated whether different definitions of healthcare-associated infection influenced the prevalence, characteristics, and mortality of patients with Staphylococcus aureus bacteremia. With different definitions, the proportion of patients classified as having healthcare-associated S. aureus bacteremia varied substantially and the distribution of patient characteristics was influenced, whereas 30-day mortality remained robust.Infect. Control Hosp. Epidemiol. 2016;37(2):208–211

Introduction Staphylococcus aureus is a major cause of skin and deep-sited infections, often associated with the formation of biofilms. Early diagnosis and initiated therapy is essential to prevent disease progression and to reduce complications that can be serious. Imaging techniques are helpful combining anatomical with functional data in order to describe and characterize site, extent and activity of the disease. The purpose of the study was to identify and 68 Ga-label peptides with affinity for S. aureus biofilm and evaluate their potential as bacteria-specific positron emission tomography (PET) imaging agents. Methods Phage-displayed dodecapeptides were selected using an in vitro grown S. aureus biofilm as target. One cyclic (A8) and two linear (A9, A11) dodecapeptides were custom synthesized with 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) conjugated via a lysine linker (K), and for A11 also a glycine–serine–glycine spacer (GSG). The 68 Ga-labeling of A8-K-DOTA , A9-K-DOTA , and A11-GSGK-DOTA were optimized and in vitro bacterial binding was evaluated for 68 Ga- A9-K-DOTA and 68 Ga- A11-GSGK-DOTA . Stability of 68 Ga- A9-K-DOTA was studied in vitro in human serum, while the in vivo plasma stability was analyzed in mice and pigs. Additionally, the whole-body distribution kinetics of 68 Ga- A9-K-DOTA was measured in vivo by PET imaging of pigs and ex vivo in excised mice tissues. Results The 68 Ga- A9-K-DOTA and 68 Ga- A11-GSGK-DOTA remained stable in product formulation, whereas 68 Ga- A8-K-DOTA was unstable. The S. aureus binding of 68 Ga- A11-GSGK-DOTA and 68 Ga- A9-K-DOTA was observed in vitro , though blocking of the binding was not possible by excess of cold peptide. The 68 Ga- A9-K-DOTA was degraded slowly in vitro , while the combined in vivo evaluation in pigs and mice showed a rapid blood clearance and renal excretion of the 68 Ga- A9-K-DOTA . Conclusion The preliminary in vitro and in vivo studies of the phage-display S. aureus biofilm-selected 68 Ga- A9-K-DOTA showed desirable features for a novel bacteria-specific imaging agent, despite of relative fast blood degradation in vivo .

Background Patients with chronic heart failure (CHF) may experience higher mortality of Staphylococcus aureus bacteremia (SAB) than patients without CHF due to insufficient cardiovascular responses during systemic infection. We investigated 90-day mortality in SAB patients with and without CHF. Methods Using population-based medical databases, we conducted a cohort study of all adult patients with community-acquired SAB (CA-SAB) in Northern Denmark, 2000-2011. Ninety-day mortality after SAB for patients with and without CHF was estimated by the Kaplan-Meier method. Based on Cox regression analysis, we computed hazard ratios as estimates of mortality rate ratios (MRRs) overall and stratified by CHF-related conditions (e.g., cardiomyopathy and valvular heart disease), CHF severity (defined by daily dosage of loop-diuretics), and CHF duration while adjusting for potential confounders. Results Among 2638 SAB patients, 390 (14.8 %) had a history of CHF. Ninety-day mortality was 45 % in patients with CHF and 30 % in patients without CHF, which yielded an adjusted MRR (aMRR) of 1.24 (95 % CI, 1.04-1.48). Compared to patients without CHF, the excess risk of death was most pronounced among patients with valvular heart disease (aMRR = 1.73 (95 % CI, 1.26–2.38)), patients with daily loop-diuretic dosages of 81–159 mg/day (aMRR = 1.55 (95 % CI, 1.11–2.14)) and ≥160 mg/day (aMRR = 1.62 (95 % CI, 1.21–2.18)), and among patients with

Background: The search for the site of infection has high priority in patients with severe sepsis and septic shock. However, it is questionable whether mortality is associated with the specific site of infection in patients admitted to an intensive care unit (ICU). Therefore, the 30-day and 90-day mortalities in ICU patients admitted with suspected or confirmed community-acquired infection were studied. Methods: A retrospective cohort study was conducted, including all adult patients admitted to a multi-specialty tertiary ICU with severe sepsis or septic shock from November 2008 to October 2010. The site of infection was classified according to criteria set for healthcare associated infections and infections in the acute care setting by Centers for Disease Control and Prevention (CDC). Kaplan–Meier curves and Poisson regression analysis were used to evaluate the association between site of infection and 30- and 90-day all-cause mortality, adjusting for age, sex and comorbidities. Results: Three hundred and eighty-eight patients were included. One or more comorbidities were present in 76% of patients. Across all sites of infection, there were more patients with septic shock than patients with severe sepsis. The most frequent site of infection was pneumonia, followed by gastrointestinal infection. Urinary tract infection was found to be an independent predictor of mortality among septic ICU patients when adjusting for sex, age and comorbidities. Conclusions: The results suggest that identification of correct site of infection is important in the management of severe sepsis and septic shock.

Background Herpes zoster (HZ) may result in severe complications requiring hospital treatment, particularly in patients with comorbidity. Nevertheless, data on HZ from nationwide population-based hospital registries are sparse. Methods We conducted a cohort study describing first-time hospital-based (inpatient, outpatient, and emergency room) HZ diagnoses in the Danish National Patient Registry, 1994–2012. We computed the diagnosis rate; prevalence of demographic characteristics, comorbidities, and complications; length of hospital stay; and standardized mortality ratios (SMRs) using the Danish population as reference. We classified comorbidity using the Charlson Comorbidity Index (CCI) scoring system and categorized patients in groups of no (score 0), moderate (score 1), severe (score 2), and very severe comorbidity (score ≥3). In addition, we computed the prevalence of certain conditions associated with immune dysregulation (stem cell or bone marrow transplantation, solid organ transplantation, HIV infection, primary immunodeficiency, any cancer, and autoimmune diseases). Results The diagnosis rate increased almost exponentially from 6 to 91.9 per 100,000 person-years between age 50 and ≥90 years. The age-standardized rate was stable throughout the study period. The median length of hospital stay was 4 days (interquartile range: 1–8 days) for inpatients with HZ as the main reason for admission. According to the CCI, 44.3 % of patients had no comorbidity, 17.3 % moderate comorbidity, 17.4 % severe comorbidity, and 21.0 % very severe comorbidity. Comorbidities involving immune dysregulation, such as malignant (21 %) and autoimmune diseases (17 %), were particularly prevalent. Thirty percent had neurological, ophthalmic, or other complications. HZ was associated with increased all-cause mortality overall (SMR 1.8, 95 % CI: 1.7–1.8), but not in analyses restricted to patients without comorbidity (SMR 1.0, 95 % CI: 0.9–1.0). Conclusions This study provides estimates of the epidemiology of hospital-based (severe) HZ. The diagnosis rate increased substantially with age. Complications and comorbidities were prevalent, likely resulting in increased mortality. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1369-6) contains supplementary material, which is available to authorized users.

BACKGROUND: Patients with diabetes (DM) experience increased risk of Staphylococcus aureus bacteraemia (SAB), but the prognostic impact of diabetes in patients with SAB remain unclear. Therefore, we investigated 30-day all-cause mortality in patients with and without DM.METHODS: Population-based medical databases were used to conduct a cohort study of all adult patients with community-acquired SAB in Northern Denmark, 2000-2011. Using Cox proportional hazards regression, we computed hazard ratios as estimates of 30-day mortality rate ratios (MRRs) among patients with and without DM. We further investigated whether the prognostic impact of DM differed among patients with and without recent preadmission healthcare contacts (within 30 days of the current hospitalization) and by age, sex, marital status, level of comorbidity, and DM-related characteristics (e.g., duration of DM and presence of DM complications).RESULTS: Among 2638 SAB patients, 713 (27.0%) had DM. Thirty-day cumulative mortality was 25.8% in patients with DM and 24.3% in patients without DM, for an adjusted MRR (aMRR) of 1.01 (95% confidence interval (CI), 0.84-1.20). In analyses with and without recent healthcare contacts, the corresponding aMRRs were 0.84 (95% CI, 0.62-1.14) and 1.13 (95% CI, 0.91-1.41), respectively. Compared to patients without DM, the aMRR was 0.94 (95% CI, 0.74-1.20) for male patients with DM and 1.13 (95% CI, 0.87-1.47) for female patients with DM. The prognostic influence of DM on mortality did not differ notably with age, level of comorbidity, or characteristics of patients with DM.CONCLUSION: Patients with DM and community-acquired SAB did not experience higher 30-day mortality than patients without DM.

We have previously developed a model of localized osteomyelitis by injecting Staphylococcus aureus (S. aureus) unilaterally into the femoral artery of juvenile domestic pigs (Johansen et al., 2012; Nielsen et al., 2015). We used this model for the evaluation of bone-infection tracers applicable for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) (Nielsen et al., 2015). However, several of the 40 kg pigs were euthanized prior to PET and SPECT scanning due to lameness, shallow respiration, fever and anorexia; the last three clinical signs indicating dissemination of S. aureus to the lungs and other internal organs. We therefore decided to refine our model in order to improve the success rate. We speculated that younger pigs might respond differently to inoculations. A total of ten female domestic pigs were included in our study, three with a body weight of 40 kg (± 1 kg) and seven with a body weight of 20 kg (± 1 kg). The pigs were born in a SPF facility and were raised in the same herd. Pigs were scored daily for pain, including lameness. From the onset of the first clinical signs we treated seven of the pigs (one 40 kg and six 20 kg) with procaine benzylpenicillin to which the bacterial strain was susceptible. Further treatment (analgesia by buprenorphine) or euthanasia depended on disease severity and took place due to fever and shallow respiration in the 40 kg pig-group and due to lameness and pain in hind limbs in the 20 kg pig-group. After two weeks, the remaining pigs were euthanized; necropsy was performed on all ten pigs. One of the 40 kg and five of the 20 kg pigs were euthanized before day 14. The necropsy results showed osteomyelitis caused by S. aureus in six of the seven 20 kg pigs and additionally arthritis caused by S. aureus in three of the 20 kg pigs, whereas none of the 40 kg pigs had developed osteomyelitis or arthritis. Spreading of S. aureus to the lungs was seen in two of three 40 kg pigs but only in two of seven 20 kg pigs. As most of the 20 kg pigs were given penicillin, we cannot know whether the favorable results in the 20 kg pig-group were purely related to their body weight and younger age, or whether the pattern of infection also was modified by penicillin treatment. However, we are convinced that the health status and success rate can be improved by using 20 kg pigs treated with penicillin.

We report Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus) causing recurrent prosthetic valve endocarditis. The fungus was the sole agent detected during replacement of a mechanical aortic valve conduit due to abscess formation. Despite extensive surgery and anti-fungal treatment, the patient had a cerebral hemorrhage 4 months post-surgery prompting a diagnosis of recurrent prosthetic valve endocarditis and fungemia.

Larsen IK, Pedersen G, Schonheyder HC. Bacteraemia with an unknown focus: is the focus de facto absent or merely unreported? A one-year hospital-based cohort study. APMIS 2011; 119: 275–9. An unknown focus of infection is associated with an increased risk of death in patients with bacteraemia. However, the implications for patient management remain uncertain, and to our knowledge, the validity of an unknown focus has not been evaluated. Therefore, we conducted a retrospective record review of bacteraemias with an unknown focus recorded in a regional bacteraemia database. The study cohort comprised 645 cases of bacteraemia diagnosed in 537 hospitalized patients at Aalborg Hospital, Denmark, in 2003. The focus was unknown in 184 (29%) bacteraemia episodes (162 patients). The record review pointed conclusively to a focus in 39 episodes. The positive predictive value of an unknown focus was 79% and the proportion of bacteraemias with a focus increased from 71% to 78%. Among the 145 cases of bacteraemia with a de facto unknown focus, there were 36 incidents of febrile neutropenia and 20 additional incidents of early death which precluded a search for a focus. The study confirmed the focus to be de facto absent in most patients classified with an unknown focus. The distribution of foci changed only marginally by the disclosure of a focus in one of five patients in the ‘unknown’ group.

The objective of this study was to characterize extended-spectrum cephalosporinase (ESC)-producing isolates of Salmonella enterica serovar Choleraesuis recovered from patients in Thailand and Denmark. Twenty-four blood culture isolates from 22 patients were included in the study, of which 23 isolates were recovered from 21 Thai patients during 2003, 2007, or 2008 and one isolate was recovered from a Danish traveler to Thailand. ESC production was confirmed in 13 out of the 24 isolates by MIC testing. Microarray and plasmid profiling (replicon typing and restriction fragment length polymorphism [RFLP]) were used to characterize the genetic mechanisms of antimicrobial resistance in the 13 ESC-producing isolates. Pulsed-field gel electrophoresis (PFGE) and MIC testing were used to compare the clonality between the 13 ESC-producing isolates and the 11 non-ESC-producing isolates. Based on susceptibility patterns, the ESC-producing isolates were more closely related than non-ESC-producing isolates. Microarray, PCR, plasmid profiling, and replicon typing revealed that the 13 ESC-producing isolates harbored either bla CMY-2 containing incA/C or bla CTX-M-14 containing incFIIA , incFrepB , and an unknown replicon located on plasmids ranging in size from 75 to 200 kb. The RFLP and replicon typing clustered the isolates into four distinct groups. PFGE revealed 16 unique patterns and five clusters; each cluster contained two or three of the 24 isolates. The isolate from the Danish patient was indistinguishable from two Thai clinical isolates by PFGE. This study revealed the emergence of the bla CTX-M-14 gene among several clones of Salmonella serovar Choleraesuis. Numerous plasmids were identified containing up to two different ESC genes and four distinct replicons. A “travel-associated” spread was confirmed. Overall, a high degree of clonal diversity between isolates resistant and susceptible to cephalosporins was observed. The findings represent a serious threat to public health for the Thai people and tourists.

Complement-binding antibodies against Aspergillus fumigatus were determined by a fluorescent antibody technique with purified human Clq as the source of complement. Clq binding aspergillus antibodies were found in 8 (67%) of 12 patients with pulmonary aspergillosis, in 4 (57%) of 7 patients with suspected pulmonary aspergillosis, in one (14%) of 7 patients with precipitating antibodies to A. fumigatus of undetermined clinical significance, and in 4 (7%) of 54 healthy blood donors. Sera from patients with definite or probable aspergillosis produced an immunofluorescent staining of hyphal cytoplasm, whereas the staining obtained with positive donor sera was confined to hyphal walls. A positive correlation was found between the frequency and titres of Clq binding antibodies and titres of IgG and IgM aspergillus antibodies. Clq binding antibodies were found only in sera with an IgG aspergillus antibody titre greater than or equal to 640. The frequency of Clq binding antibodies in sera with IgG titres greater than or equal to 640 was significantly higher in patients with aspergillosis (67%) than in blood donors (16%) (p = 0.0036). The Clq binding antibody test may provide diagnostic information as well as clues to the pathogenesis of aspergillus lung disease.

The frequency of Aspergillus fumigatus isolates from sputum was assessed prospectively during a 22-month period in 156 patients with cystic fibrosis (CF) from one center, and findings were compared to a cross-sectional evaluation of specific IgG and IgA antibodies, occurrence of chronic Pseudomonas aeruginosa infection, and pulmonary function. The prevalence rate for the 22-month period was 40%. Positive A. fumigatus cultures appeared to be independent of the presence or duration of chronic bronchopulmonary Ps. aeruginosa infection, but isolation of A. fumigatus in patients with pseudomonas infection for more than 5 years was associated with notably decreased pulmonary function. Levels of IgG antibodies to a 470,000 daltons A. fumigatus antigen fraction were higher in patients with positive cultures in the observation period than in those without. IgG antibodies to a 25,000-50,000 daltons antigen fraction were directly correlated to A. fumigatus frequency in patients with positive cultures both prior to and during the survey. On the other hand, levels of IgA antibodies to the 470,000 daltons fraction were inversely related to A. fumigatus frequency, suggesting a role of IgA antibodies in the bronchial clearance of aspergilli. Decreased pulmonary function was found to be associated with elevated levels of A. fumigatus antibodies. It is concluded that immune reactions elicited by A. fumigatus may play a role in clearance of the fungus from the airways but also may contribute to lung morbidity in some patients.

Antibodies to Aspergillus fumigatus were investigated by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) in bronchial secretions (BS) and sera from 40 patients with neoplasia, lung infiltrates of non-fungal aetiology or chronic bronchitis. By IIF, IgG aspergillus antibodies were found in 23 samples of BS (58%) (titre range 10-40) and in all 40 sera (titre range 10-1280). IgA aspergillus antibodies were detected in 33 samples of BS (83%) (titre range 10-160) and in 33 sera (83%) (titre range 10-40). IgM aspergillus antibodies occurred in 2 samples of BS (5%) (titre 10 and 40) compared with 35 sera (88%) (titre range 10-40). Antibodies with secretory component (SC) were detected in 20 of 39 BS samples tested (51%) (titre range 10-160). Significantly higher levels of IgA antibodies were detected by ELISA in BS than in serum (2p less than 0.05) and, conversely, significantly higher levels of IgG antibodies were found in serum than in BS (2p less than 0.001). Low levels of antibodies with SC were also detected in BS by ELISA. These results suggest that aspergillus antibodies are produced within the bronchopulmonary system in patients without aspergillosis.

Zusammenfassung: Seit Februar 1978 wurden 2 Patienten wegen Cryptococcus-Meningitis am Marselisborg Hospital behandelt: Eine 50jahrige Frau und ein 22jahriger Mann, die beide keine Anzeichen eines Grundleidens zeigten. Die Patienten wurden mit intravenosen Gaben von Amphotericin B in einer Kombination mit peroralen Gaben von Flucytosin behandelt. Der Zustand des jungen Mannes besserte sich problemfrei. Die Frau mittleren Alters wurde von Anfang an auserdem mit intrathekalen Gaben von Amphotericin B behandelt, welches durch einen Ventrikelkatheter verabreicht wurde, der mit einem Rickham Reservoir verbunden war. Unter der Behandlung wurden Cryptococcen wiederholt bei der Kultur aus Liquor gefunden. Nach 3monatiger Behandlung fanden sich Cryptococcen in Liquor, welcher von Rickham Reservoir aspiriert wurde, aber nicht bei der Lumbalpunktion. Man entfernte den Katheter, worauf sich der Zustand der Patientin unter systematischer Behandlung schnell besserte. Bei einem dritten Patienten mit Hodgkin's Syndrom hatte man ursprunglich wegen Fieber und neurologischer Symptome den Verdacht auf eine Cryptococcose. Aber man wich spater von dieser Diagnose wieder ab, da der einzige Anhaltspunkt dafur der Nachweis von freiem Cryptococcus-Antigen in einer einzelnen Liquorprobe war. Summary: Since February 1978 a woman aged 50 and a man aged 22 have been treated for cryptococcal meningitis with apparent success at Marselisborg Hospital, Aarhus. There were no signs of underlying disease, but immunological investigations seem to indicate that the resistance to cryptococcal infection is permanently reduced. The patients were treated with a combination of amphotericin B intravenously and flucytosin per os, and the recovery of the young man was rather uneventful. The woman was from the beginning also given injections of amphotericin B intrathecally through a Rickham reservoir. Cryptococci were, however, repeatedly cultured from CSF and ultimately growth was found in relation to the intraventricular katheter of the Rickham reservoir. The patient recovered under systemic treatment after removal of the Rickham reservoir and intrathecal injections stopped. A third patient, with Hodgkin's disease, was suspected to have cryptococcal meningitis because of neurological symptoms and fever, but the diagnosis was not confirmed as the only basis was a titer of free cryptococcal antigen (1:40) in CSF that could not be reproduced.

Summary: The oral yeast flora and circulating IgG and IgA antibodies to Candida albicans were investigated in 76 Danish homosexual men C.albicans was isolated from 45 (65%) of 69 subjects by enrichment broth culture, but primary plate cultures were positive in 11 (16%). The frequency of yeast recovery on primary plates increased with decreasing T-lymphocyte helper-to-suppressor ratio (ratio ≤1.0: 33%; 1.1–1.4: 19%; and >1.4: 8%), whereas the frequency of positive enrichment broth cultures did not change (range 64–67%). Demographic or lifestyle parameters did not correlate significantly with oral yeast colonization as did neither IgG nor IgA antibodies to C. albicans. High levels of IgA antibodies to C. albicans were found to be associated with a Th/Ts ratio >1.0 whereas IgG candida antibody levels correlated inversely with the number of sexual partners in the past year. Zusammenfassung: Bei 76 danischen homosexuellen Mannern wurden die orale Hefeflora und IgG- und IgA-Antikorper gegen Candida albicans untersucht. Von 69 Personen konnte C. albicans 45mal (65%) in einem flussigen Anreicherungsmedium aber nur 11mal (16%) durch primare Plattenkulturen isoliert werden. Die Haufigkeit des Nachweises auf primaren Plattenkulturen steigerte sich mit abnehmender Ratio zwischen Helfer-T-Zellen und Suppressor-T-Zellen (Ratio ≤ 1,0: 33%, 1,1–1,4: 19% und >1,4: 8%). Dagegen war keine Anderung bei den positiven Anreicherungskulturen festzustellen (64 bis 67%). Es zeigten sich keine Korrelationen zwischen der oralen Hefebesiedlung einerseits und demographischen Parametern, der Lebensweise oder der Hohe der IgG- oder IgA-Antikorper gegen C. albicans andererseits. Hohe IgA-Titer gegen C. albicans traten vor allem auf, wenn die Th/Ts-Ratio >1,0 war, wahrend die IgG-AntikorperKonzentrationen zur Anzahl der sexuellen Partner des letzten Jahres vor der Untersuchung umgekehrt proportional waren.

Summary: The mucosal yeast flora and the serum levels of IgG and IgA antibodies to Candida albicans were studied weekly in 38 patients with malignant haematological disorders prophylactically treated with 400 mg ketoconazole daily during induction chemotherapy. All patients developed granulocytopenia and 30 (79%) were colonized by yeasts. IgG C. albicans antibody levels were higher in carriers of C. albicans, or other yeast species, than in non-carriers throughout the survey, and a statistically significant increase was observed in the first 4 weeks (p < 0.05). IgA C. albicans antibodies followed the same trend. It appears that even severely immunocompromized patients receiving ketoconazole retain a serological response to yeast colonization. Zusammenfassung: An 38 Patienten mit malignen Hamatopathien, die 400 mg Ketoconazol taglich als Fruhtherapie erhielten, wurden die Hefeflora der Schleimhaute und die IgG- und IgA-Antikorpertiter gegen Candida albicans untersucht. Alle Patienten entwickelten eine Granulocytopenie, und 30 (79 Prozent) waren mit Sprospilzen besiedelt Die IgG-Antikorpertiter gegen C. albicans waren wahrend der Untersuchungsperiode bei Patienten, die mit C. albicans oder anderen Hefearten besiedelt waren, hoher als bei nicht-hefebesiedelten Patienten, und in den ersten vier Wochen war ein statistisch signifikanter Titeranstieg (p < 0,05) zu beobachten. Die IgA-Antikorpertiter gegen C. albicans folgten dem gleichen Trend. Offensichtlich kommt es auch bei schwer immunkompromittierten Patienten zu einer ausgepragten Seroantwort auf die Hefebesiedlung; dies wird durch Ketoconazol nicht unterdruckt.

Udgivelsesdato: 2009-Mar Abstract We hypothesized that patients coinfected with zoonotic Salmonella and Campylobacter were frailer than monoinfected Salmonella or Campylobacter patients. The study cohort included all first-time Salmonella/Campylobacter infections in Aarhus and North Jutland counties, Denmark, from 1991 through 2003. Data on comorbidity, hospitalization in relation to the Salmonella/Campylobacter infection, and 1-year mortality were obtained from electronic registries. Among 13,449 individuals, 114 (0.85%) had Salmonella/Campylobacter coinfection, 6567 (48.8%) had Salmonella monoinfection, and 6768 (50.3%) had Campylobacter monoinfection. There were no major differences in age, gender, comorbidity, hospitalization rates, 1-year mortality, or seasonal variation between coinfected patients on the one hand and each of the monoinfected patient groups on the other. The main difference was encountered between the Salmonella serotype distribution as 49.1% of coinfected patients versus 20.3% of monoinfected Salmonella patients had Salmonella serotypes other than Salmonella Enteritidis and Salmonella Typhimurium (odds ratio [95% confidence interval]: 4.07 [2.73-6.06]). In conclusion, Salmonella/Campylobacter coinfected patients were not frailer than monoinfected patients. The difference in Salmonella serotype distribution was compatible with a higher proportion of coinfections acquired during foreign travel.