Jens Kjølseth Møller

National Surveillance of Fungemia in Denmark (2004 to 2009)

ABSTRACT A 6-year nationwide study of fungemia in Denmark was performed using data from an active fungemia surveillance program and from laboratory information systems in nonparticipating regions. A total of 2,820 episodes of fungemia were recorded. The incidence increased from 2004 to 2007 (7.7 to 9.6/100,000) and decreased slightly from 2008 to 2009 (8.7 to 8.6/100,000). The highest incidences were seen at the extremes of age (i.e., 11.3 and 37.1/100,000 for those <1 and 70 to 79 years old, respectively). The rate was higher for males than for females (10.1 versus 7.6/100,000, P = 0.003), with the largest difference observed for patients >50 years of age. The species distribution varied significantly by both age and gender. Candida species accounted for 98% of the pathogens, and C. albicans was predominant, although the proportion decreased (64.4% to 53.2%, P < 0.0001). C. glabrata ranked second, and the proportion increased (16.5% to 25.9%, P = 0.003). C. glabrata was more common in adults and females than in children and males, whereas C. tropicalis was more common in males (P = 0.020). C. krusei was a rare isolate (4.1%) except at one university hospital. Acquired resistance to amphotericin and echinocandins was rare. However, resistance to fluconazole (MIC of >4 μg/ml) occurred in C. albicans (7/1,183 [0.6%]), C. dubliniensis (2/65 [3.1%]), C. parapsilosis (5/83 [6.0%]), and C. tropicalis (7/104 [6.7%]). Overall, 70.8% of fungemia isolates were fully fluconazole susceptible, but the proportion decreased (79.7% to 68.9%, P = 0.02). The study confirmed an incidence rate of fungemia in Denmark three times higher than those in other Nordic countries and identified marked differences related to age and gender. Decreased susceptibility to fluconazole was frequent and increasing.

Population-Based Strategies for Outreach Screening of Urogenital Chlamydia trachomatis Infections: A Randomized, Controlled Trial

The effect of 2 population-based outreach screening strategies that used in-home sampling was compared with usual care practices for Chlamydia trachomatis infection. All 30,439 persons 21-23 years old in Aarhus County, Denmark, were divided randomly into 3 groups: group 1 (n=4500) had a home sampling kit mailed directly to their centrally registered home address; group 2 (n=4500) had a reply card mailed to their home address with which a home sampling kit could be ordered; and group 3 (n=21,439) had access to usual care. For women in groups 1 and 2, the relative risks of being tested were 4.1 (95% confidence interval [CI], 3.8-4.4) and 3.5 (95% CI, 3.2-3.9), respectively, compared with usual care. The corresponding figures for men were 19.1 (95% CI, 16.0-22.8) and 11.8 (95% CI, 9.8-14.2), respectively. Both screening strategies were highly effective, but men benefited the most from having the home sampling kit provided directly.

Mycoplasma genitalium: prevalence and behavioural risk factors in the general population

Background:Mycoplasma genitalium has been shown to cause urethritis in men and cervicitis in women and may also be a causative agent in female infertility. Objective: To estimate the prevalence of urogenital M genitalium infection and identify sexual behavioural risk factors in the general population. Methods: Participating individuals were 731 men and 921 women aged 21–23 years and not seeking the healthcare system because of symptoms. They answered questionnaires on sexual behaviour and provided samples for M genitalium testing. Results: In women aged 21–23 years, the prevalence of infection was 2.3% (21/921) and in men of the same age it was 1.1% (8/731). For both sexes, an increasing number of partners was associated with a greater chance of being infected. Among women a shorter duration of a steady relationship and having a partner with symptoms was associated with being infected, and for men younger age at first intercourse was associated with M genitalium infection. Conclusions: We conclude that the prevalence of infection in the general population is too low for population-based screening. However, the development of test algorithms based on behavioural risk factors is a promising alternative.

Species Identification of Clinical Isolates of Anaerobic Bacteria: a Comparison of Two Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems

ABSTRACT We compared two matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) systems (Shimadzu/SARAMIS and Bruker) on a collection of consecutive clinically important anaerobic bacteria (n = 290). The Bruker system had more correct identifications to the species level (67.2% versus 49.0%), but also more incorrect identifications (7.9% versus 1.4%). The system databases need to be optimized to increase identification levels. However, MALDI-TOF MS in its present version seems to be a fast and inexpensive method for identification of most clinically important anaerobic bacteria.

Diagnosis of urogenital Chlamydia trachomatis infection in women based on mailed samples obtained at home: multipractice comparative study

Abstract Objective: To compare urine and vaginal flush samples collected by women at home with endocervical and urethral swabs obtained by general practitioners for their efficacy in the diagnosis of urogenital Chlamydia trachomatis infection. Design: Multipractice comparative study. Setting: 33 general practices and a central department of clinical microbiology in Aarhus County, Denmark. Subjects: 222 women aged 18–25 years who for any reason had a gynaecological examination. Interventions: Endocervical and urethral swabs were obtained by the womens general practitioners. The same women when at home then collected a first void urine sample, a midstream urine sample, and a vaginal flush sample (using a vaginal pipette) and mailed them to the laboratory. Main outcome measures: C trachomatis detected by the polymerase chain reaction and the ligase chain reaction. Eight tests for C trachomatis were performed for every woman. When two of the eight yielded positive results the patient was considered infected. Results: The overall prevalence of C trachomatis infection was 11.2% (23/205 women). Test sensitivities in samples obtained by general practitioners, samples obtained at home subjected to polymerase chain reaction, and samples obtained at home subjected to ligase chain reaction were 91%, 96%, and 100% respectively. The corresponding specificities were 100%, 92.9%, and 99.5%. Conclusions: The diagnostic efficacy of samples obtained by women at home and mailed to the laboratory was as good as for samples obtained by a general practitioner when using the ligase chain reaction. This may have important implications for the practicability of screening for this common, often asymptomatic, and treatable infection. Key messages A combination of mailed samples obtained at home is necessary in order to obtain optimal diagnostic sensitivity; a single urine sample is not enough Mailed samples obtained at home may also be appropriate for diagnosis in young asymptomatic women with regular partners; these women have a high prevalence of urogenital C trachomatis infection The use of mailed self obtained samples in women might limit costs and increase the practicability of screening programmes for urogenital C trachomatis infection

Eight-Plex PCR and Liquid-Array Detection of Bacterial and Viral Pathogens in Cerebrospinal Fluid from Patients with Suspected Meningitis

ABSTRACT We here report on the development of a novel multiplex PCR with product detection in a Luminex 100 suspension array system. The assay covers the nine most important bacterial and viral pathogens found in Danish meningitis patients. The microorganisms include Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Streptococcus agalactiae, herpes simplex virus types 1 and 2, and varicella-zoster virus. The study was based on 1,187 samples, of which 55 were found to be positive by PCR. The assay was found to have an excellent sensitivity and an excellent specificity compared to the results of a “gold standard,” defined by routine laboratory tests, for the two most important pathogens, S. pneumoniae (95 and 99.1%, respectively) and N. meningitidis (100 and 99.7%, respectively). The method provides a valuable supplement to the traditional microscopy and culture of cerebrospinal fluid (CSF) samples in a routine diagnostic setting, and results can be available within 1 workday. The method is suitable for use for the initial screening and identification of nine important microorganisms in CSF samples from patients with suspected meningitis. Compared to microscopy and culture of CSF, this rapid and sensitive method will support physicians with the selection of the appropriate antimicrobial agents and the initiation of timely treatment in the absence of live microorganisms in the CSF.

The “true” incidence of surgically treated deep prosthetic joint infection after 32,896 primary total hip arthroplasties: A prospective cohort study

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.

Obesity, diabetes, and the risk of infections diagnosed in hospital and post‐discharge infections after cesarean section: a prospective cohort study

Objective. To assess the impact of obesity and diabetes on the risk of post‐cesarean infections. Design. Prospective cohort study. Setting. Obstetric departments at three hospitals in Denmark. Population. 2,492 consecutive women having cesarean section (CS) from February 2007 to August 2008. Methods. We collected complete data from medical records and databases on CS, body mass index, diabetes (type 1, type 2, and gestational), and post‐cesarean infections. Post‐discharge infections diagnosed by general practitioners were ascertained through positive microbiological cultures and antibiotic prescriptions. Main Outcome Measures. Cumulative incidences of infections within 30 days after CS. Results. Of 2,492 women having CS, 373 (15.2%) were obese and 123 (4.9%) had diabetes. Overall, 458 women (18.4%) had a post‐cesarean infection within 30 days and 174 (7.0%) were diagnosed in‐hospital. The risk of post‐cesarean infections was higher among obese than non‐obese women: adjusted (for diabetes and emergency/elective CS) odds ratio (OR)=1.43; 95% confidence interval (CI): 1.09–1.88, particularly for in‐hospital infections (OR=1.86; 95%CI: 1.28–2.72). After controlling for obesity and mode of CS, type 2 or gestational diabetes were weak predictors of infection risk (OR=1.18; 95%CI: 0.72–1.93), whereas the adjusted OR in women with type 1 diabetes was 1.65 (95%CI: 0.64–4.25). Among diabetic women, obesity increased the risk of post‐cesarean infections more than twofold; the adjusted ORs were 2.06 (95%CI: 1.13–3.75) for infections overall and 2.74 (95%CI: 1.25–6.01) for in‐hospital infections. Conclusion. Obesity increases the risk of post‐cesarean infections and diabetes further strengthens this association.

Impact of intensified testing for urogenital Chlamydia trachomatis infections: a randomised study with 9-year follow-up

Background DNA amplification assays are increasingly being used to facilitate the testing of asymptomatic individuals for urogenital Chlamydia trachomatis. The long-term clinical benefit in terms of avoided infertility and ectopic pregnancy is unknown. Methods In 1997, 15 459 women and 14 980 men aged 21–23 years were living in Aarhus County, Denmark. A random sample of 4000 women and 5000 men was contacted by mail and offered the opportunity to be tested for C trachomatis by means of a sample obtained at home and mailed directly to the laboratory. The remaining 11 459 women and 9980 men received usual care and constituted the control population. All men and women were subsequently followed for 9 years by the use of Danish health registers. Data were collected on pelvic inflammatory disease (PID), ectopic pregnancy (EP), infertility diagnoses, in-vitro fertilisation (IVF) treatment and births in women, and on epididymitis in men. The intervention and control groups were compared using Cox regression analyses and the intention-to-screen principle. Results Among women, no differences were found between the intervention group and the control group: HR (95% CI) for PID 1.12 (0.70 to 1.79); EP 0.97 (0.63 to 1.51); infertility 0.87 (0.71 to 1.07); IVF treatment 0.88 (0.62 to 1.26) and births 1.02 (0.95 to 1.10). In men, the HR for epididymitis was 1.25 (0.70 to 2.24). Conclusions A population-based offer to be tested for urogenital C trachomatis infection by the use of non-invasive samples and DNA amplification did not reduce the long-term risk of reproductive complications in women or of epididymitis in men. Trial registration number in www.clinicaltrials.gov NCT 00827970.

Changing etiology of bacteremia in patients with hematological malignancies in Denmark

To ascertain whether the microbiological etiology of bacteremia among patients with hematological malignancies has changed in Denmark, the species distribution of clinically relevant blood culture isolates from the Hematological Department at Rigshospitalet, Copenhagen in 1990 was compared with 2 previous studies (1970-72; 1981-85). In addition, time trends of the etiology of bacteremia among hematological patients in Copenhagen (eastern Denmark) and in Arhus (western Denmark) were compared. In contrast to many other studies, a significant increase in the proportion of Gram-negative aerobes was observed in Copenhagen (from 43% in 1981-85 to 55% in 1990; p < 0.05), whereas in Arhus the proportion of Gram-positive aerobes increased steadily during the 1980s (from 34% to 51%; p < 0.05). In Copenhagen, non-hemolytic streptococci and Xanthomonas maltophilia increased significantly and accounted for 10% (p < 0.01) and 5% (p < 0.05) respectively, of all isolates in 1990, whereas Staphylococcus aureus during the 2 decades studied decreased from 25% to 8% (p < 0.001). In both regions, a decrease was observed in the proportion of Pseudomonas aeruginosa which accounted for only about 5% of all isolates in 1990. No changes were observed in the rates of anaerobes and yeasts. Several factors may contribute to the reported differences in the etiology of bacteremia among hematological patients, e.g. criteria used to assign the clinical significance of the isolate, blood culture system used, practice of using indwelling intravenous catheters, different policies with respect to antimicrobial treatment, and the degree of immunosuppression. A local surveillance of blood culture isolates is mandatory if changes in etiology and resistance development are to be detected.