Publications by authors named "Merete Storgaard"

67 Publications

Improved survival among hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. A nationwide population-based cohort study.

Clin Infect Dis 2021 Jun 10. Epub 2021 Jun 10.

Department of Medicine, Zealand University Hospital, Roskilde, Denmark.

Background: There is limited data on outcomes of moderate to severe Coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting.

Objective: To compare the effectiveness of standard of care (SOC) alone vs SOC plus remdesivir and dexamethasone.

Methods: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI).

Results: The 30-d mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI, 0.38-0.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36 (95% CI, 0.29-0.46)).

Conclusions And Relevance: Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.
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http://dx.doi.org/10.1093/cid/ciab536DOI Listing
June 2021

Enterovirus Meningitis in Adults: A Prospective Nationwide Population-Based Cohort Study.

Neurology 2021 Jun 4. Epub 2021 Jun 4.

Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus N, Denmark.

Objective: To test the hypothesis that enterovirus meningitis (EM) is a frequent and self-limiting condition, the epidemiology of enterovirus meningitis (EM) in adults was examined.

Methods: Using a prospective, nationwide, population-based database, all adults with EM confirmed by PCR of the cerebrospinal fluid (CSF) from 2015-2019 were included. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) scores of 1-4 at discharge. Modified Poisson regression was used to compute adjusted relative risks (RRs).

Results: 419 cases of EM in 418 adults (46% female, median age 31 years [IQR 27-35]) yielded an incidence of 1.80/100,000/year. Admission diagnoses included CNS infection 247/397 (62%), other neurological conditions 89/397 (22%), and cerebrovascular diseases 33/397 (8%). Genotype was available for 271 cases, of which Echovirus 30 accounted for 155 (57%).Patients presented with headache 412/415 (99%), history of fever 303/372 (81%), photophobia 292/379 (77%), and neck stiffness 159/407 (39%). Fever (≥38.0 °C) was observed in 192/399 (48%) at admission. The median CSF leukocyte count was 130 10/L (range 0-2,100) with polymorphonuclear predominance (>50%) in 110/396 (28%). Cranial imaging preceded lumbar puncture in 127/417 (30%) and was associated with non-CNS infection admission diagnoses and delayed lumbar puncture (median 4.8 hours [IQR 3.4-7.9] vs. 1.5 [IQR 0.8-2.8], p<0.001). Unfavorable outcome occurred in 99/419 (24%) at discharge; more often in females (RR 2.30 [1.58-3.33]) and less frequent in Echovirus 30 (RR 0.67 [0.46-1.00]) in adjusted analyses. Outcome remained unfavorable in 22/379 (6%) after six months.

Conclusions: EM is common among young, healthy adults. Although the long-term prognosis remains reassuring, a substantial proportion have moderate disability at discharge, especially females.
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http://dx.doi.org/10.1212/WNL.0000000000012294DOI Listing
June 2021

COVID-19 vs influenza A/B supeRInfectionS in the IntenSive care unit (CRISIS): Protocol for a Danish nationwide cohort study.

Acta Anaesthesiol Scand 2021 Jun 4. Epub 2021 Jun 4.

Dept. Of Intensive Care, 4131, Rigshospitalet, University of Copenhagen, Capital Region of Denmark, Blegdamsvej 9, 2100, Copenhagen Ø.

Background: Superinfection following viral infection is a known complication, which may lead to longer hospitalisation and worse outcome. Empirical antibiotic therapy may prevent bacterial superinfections, but may also lead to overuse, adverse effects and development of resistant pathogens. Knowledge about the incidence of superinfections in intensive care unit (ICU) patients with severe Coronavirus Disease 2019 (COVID-19) is limited.

Methods: We will conduct a nationwide cohort study comparing the incidence of superinfections in patients with severe COVID-19 admitted to the ICU compared with ICU patients with influenza A/B in Denmark. We will include approximately 1000 patients in each group from the time period of October 1 , 2014 to April 30 , 2019 and from March 10 , 2020 to March 1 , 2021 for patients with influenza and COVID-19, respectively. The primary outcome is any superinfection within 90 days of admission to the ICU. We will use logistic regression analysis comparing COVID-19 with influenza A/B after adjustment for relevant predefined confounders. Secondarily, we will use unadjusted and adjusted logistic regression analyses to assess six potential risk factors (sex, age, cancer (including haematological), immunosuppression, use of life support on day 1 in the ICU) for superinfections, and compare outcomes in patients with COVID-19 with/without superinfections, and present descriptive data regarding the superinfections.

Conclusion: This study will provide important knowledge about superinfections in ICU patients with severe COVID-19.
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http://dx.doi.org/10.1111/aas.13934DOI Listing
June 2021

Genetic variants and immune responses in a cohort of patients with varicella zoster virus encephalitis.

J Infect Dis 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Background: Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases where otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection.

Methods: We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient PBMCs were infected with VZV and innate antiviral interferon and cytokine responses as well as viral replication was evaluated. Data were analyzed by Mann Whitney U test.

Results: We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within two major functional clusters: i) innate viral sensors and immune pathways and ii) autophagy pathways. Antiviral interferon (IFN) and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2/17.

Conclusion: This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. Collectively, these data suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.
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http://dx.doi.org/10.1093/infdis/jiab254DOI Listing
May 2021

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

EClinicalMedicine 2021 May 22;35:100849. Epub 2021 Apr 22.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.

Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load.

Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group ( = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79;  = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log copies/mL ( <0·05) and -0·82 log in the placebo group ( <0·05).

Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.
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http://dx.doi.org/10.1016/j.eclinm.2021.100849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060682PMC
May 2021

Persistent Symptoms in Patients Recovering From COVID-19 in Denmark.

Open Forum Infect Dis 2021 Apr 29;8(4):ofab042. Epub 2021 Jan 29.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Background: Although persistent symptoms after coronavirus disease 2019 (COVID-19) are emerging as a major complication to the infection, data on the diversity and duration of symptoms are needed.

Methods: Patients aged ≥18 years with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 who were hospitalized at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, in the period from March 11 to May 15 were offered follow-up after hospitalization. On admission, a comprehensive symptom and medical history was collected, including demographic characteristics, duration of symptoms, comorbidities, and concomitant medications. At discharge, patients were offered follow-up consultations-either by telephone or at an in-person visit-at 6 and 12 weeks at our post-COVID-19 outpatient clinic to assess whether symptoms present at admission had resolved.

Results: During the inclusion period, 71 patients were admitted with COVID-19. Of these, 10 patients died, 3 were transferred to another region, 4 declined to participate, and 5 were lost to follow-up before the 12-week evaluation. Thus, 49 patients were included. Overall, 96% reported 1 or more persisting symptoms at 12-week follow-up. The main symptoms were fatigue, dyspnea, cough, chemosensory dysfunction, and headache.

Conclusions: A wide range of persistent symptoms in patients recovering from COVID-19 were present 12 weeks after hospitalization, calling for larger descriptive studies and interdisciplinary research collaborations.
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http://dx.doi.org/10.1093/ofid/ofab042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928683PMC
April 2021

Prevalence and association with birth outcomes of low Vitamin D levels among pregnant women living with HIV.

AIDS 2021 Mar 31. Epub 2021 Mar 31.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet Research Unit for infectious Diseases, Odense University Hospital, University of Southern Denmark Department of Infectious Diseases, Aarhus University Hospital, Skejby Department of Infectious Diseases, Aalborg University Hospital, Aalborg Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.

Objectives: To evaluate the prevalence of low vitamin D levels among well-treated pregnant women living with HIV (WLWH) on combination antiretroviral therapy in Denmark, to identify risk factors of low vitamin D levels, and to assess the association between vitamin D status and birth outcomes.

Design: Nationwide cohort study.

Methods: All WLWH in Denmark giving birth from 2000-2018 with a vitamin D measurement during pregnancy were identified. Risk factors for low vitamin D (deficiency or insufficiency) were assessed using log-binomial regression models, both univariate and adjusted for maternal and HIV factors. The association between vitamin D status and birth outcomes was assessed using linear regression models for continues outcomes and log-binomial models for binary outcomes.

Results: Among 208 WLWH, the prevalence of vitamin D deficiency was 13%, insufficiency 34%, and sufficiency 53%. Being of African origin (RR 2.68, p = 0.01), Asian origin (RR 3.38, p = < 0.01), or having HIV RNA levels >50 copies/mL (RR 1.43, p = 0.04) was associated with an increased risk of low vitamin D level. WLWH with vitamin D deficiency had an increased risk of preterm birth (RR 2.66, p = 0.03) and giving birth to small for gestational age (SGA) children (RR 6.83, p = 0.02) compared to WLWH with sufficient vitamin D level.

Conclusion: Low vitamin D level was prevalent among well-treated pregnant WLWH in Denmark, especially among women of African or Asian origin, and women with detectable viral loads. Vitamin D deficiency was associated with an increased risk of preterm birth and SGA.
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http://dx.doi.org/10.1097/QAD.0000000000002899DOI Listing
March 2021

Reactive arthritis after COVID-19.

BMJ Case Rep 2021 Mar 2;14(3). Epub 2021 Mar 2.

Intensive Care, Aarhus Universitetshospital, Aarhus, Denmark.

A previously healthy 53-year-old man was hospitalised for 12 days due to COVID-19 with shortness of breath. A few days after discharge from hospital, the patient developed fever and severe pain in several joints in the lower extremities. The pain was so severe that the patient was unable to stand on his feet. Synovial fluid from the right-side knee contained a high number of polynuclear cells and a few mononuclear cells. Microscopy, culture and PCR tests for bacterial infection were all negative. Furthermore, the patient tested negative for rheumatoid factor, anti-cyclic citrullinated peptide and human leukocyte antigen (HLA)-B27. Thus, the condition was compatible with reactive arthritis. The condition improved markedly after a few days' treatment with non-steroid anti-inflammatory drugs and prednisolone.
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http://dx.doi.org/10.1136/bcr-2020-241375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929821PMC
March 2021

Oral and anal carriage of Neisseria meningitidis among sexually active HIV-infected men who have sex with men in Denmark 2014-15.

Int J Infect Dis 2021 Apr 18;105:337-344. Epub 2021 Feb 18.

Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Amager, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Introduction: Outbreaks of invasive meningococcal disease (IMD) among men who have sex with men (MSM) caused by a hypervirulent, non-encapsulated Neisseria meningitidis (Nm) clone belonging to genogroup C have been described. We aimed to determine the oral and anal carriage rates and genogroups of Nm among MSM living with HIV.

Methods: Sexually active MSM living with HIV were included. A questionnaire, an oral wash sample and an anal swab were collected at baseline and 12 months follow-up. Identification of Nm and genogrouping was performed using real-time polymerase chain reaction analysis.

Results: Among 82 MSM, the Nm carriage rate was 31.7% (95% CI 21.9-42.9) at baseline. The oral carriage rate was 24.4% (95% CI 15.6-35.1) and the anal rate was 11.0% (95% CI 5.1-19.8). Non-groupable Nm were most prevalent followed by genogroup B and genogroup Y. Rates were similar at follow-up.

Conclusion: Strains of Nm were detected in both oral washes and anal samples in our study. Our results suggest that Nm may be transmitted sexually among MSM. Non-groupable Nm were predominant in our population and no genogroup C Nm were detected.
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http://dx.doi.org/10.1016/j.ijid.2021.02.062DOI Listing
April 2021

Poor compliance with an antibiotic directive-A call for intensified monitoring.

Int J Infect Dis 2021 Mar 16;104:474-478. Epub 2021 Jan 16.

Department of Infectious Diseases, Aarhus University Hospital, Skejby, Aarhus, Denmark. Electronic address:

Background: In April 2017, the Central Denmark Region Antibiotic Stewardship Committee issued a directive to reduce the general use of piperacillin-tazobactam and prescribe narrow-spectrum antibiotics for mild and moderate pneumonia. The directive was distributed to all regional hospital clinicians.

Methods: Electronic medical records were used to obtain de-identified details of all antibiotics administered (together with diagnosis codes) to all in-hospital patients (pre-directive and post-directive) in the nine regional hospitals. Average moving range statistical process control charts were used to analyze pre-directive and post-directive variation in antibiotic usage patterns.

Results: Upon the distribution of the directive, a period of decline of the overall usage of piperacillin-tazobactam ensued. Rather than benzylpenicillin, as recommended for pneumonia, the initial decline in piperacillin/tazobactam usage was accompanied by increased use of cefuroxime.

Conclusions: A steward-directed reduction in piperacillin-tazobactam usage was accompanied by less desirable usage of a broad-spectrum alternative. Future antibiotic stewardship initiatives will hopefully benefit from close monitoring and timely feedback to clinicians. A dialogue with clinicians based on near real-time data is predicted to improve antibiotic stewardship actions.
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http://dx.doi.org/10.1016/j.ijid.2021.01.029DOI Listing
March 2021

CT and MR neuroimaging findings in patients with Lyme neuroborreliosis: A national prospective cohort study.

J Neurol Sci 2020 Dec 10;419:117176. Epub 2020 Oct 10.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.

Background: We aimed to describe the use and findings of cranial computerized tomography (CT-head), spine and brain magnetic resonance imaging (MRI-spine/MRI-brain) in Lyme neuroborreliose (LNB).

Methods: Patients with LNB were identified using a nationwide, population-based prospective cohort of all adults treated for neuroinfections at departments of infectious diseases in Denmark from 2015 to 2019. Multivariate logistic regression analyses assessed associations between clinical characteristics and MRI-findings consistent with LNB.

Results: We included 368 patients (272 definite LNB and 96 probable LNB), 280 scans were performed in 198 patients. Neuroimaging was associated with older age (59 vs. 57, p = 0.03), suspicion of other diseases (77% vs. 37%, p < 0.0001), no history of tick bites (58% vs. 43%, p = 0.01), physical/cognitive deficits prior to admission (15% vs 5%, p = 0.006), peripheral palsy (10% vs. 2%, p = 0.0008), encephalitis (8% vs. 1%, p = 0.0007) and cognitive impairment (8% vs. 2%, p = 0.03) compared with those without neuroimaging. Normal or incidental findings were common (93/98 CT-head and 154/182 MRI). 1/98 CT-head, 19/131 MRI-brain and 6/51 MRI-spine had findings consistent with LNB. Symptoms ≥45 days was associated with MRI-findings consistent with LNB (adjusted odds ratio (aOR) 4.2, 95%confidence interval 1.2-14.4, p = 0.02).

Conclusion: In this Danish cohort including 368 LNB-patients, use of neuroimaging was common and often performed in older comorbid patients without previous tick-bite intended to investigate alternative diagnoses. The results were in general without pathology and neuroimaging cannot exclude LNB or replace lumbar puncture. MRI is of value when investigating alternative neurological diseases and may support suspicion of LNB in cases with meningeal/leptomeningeal/neural enhancement.
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http://dx.doi.org/10.1016/j.jns.2020.117176DOI Listing
December 2020

Normocellular Community-Acquired Bacterial Meningitis in Adults: A Nationwide Population-Based Case Series.

Ann Emerg Med 2021 01 1;77(1):11-18. Epub 2020 Aug 1.

Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark. Electronic address:

Study Objective: This study sought to describe the clinical presentation of normocellular community-acquired bacterial meningitis in adults.

Methods: Using the prospective, nationwide, population-based database of the Danish Study Group of Infections of the Brain, the study identified all adults with normocellular community-acquired bacterial meningitis who were treated at departments of infectious diseases in Denmark from 2015 through 2018. Normocellular community-acquired bacterial meningitis was defined as a cerebrospinal fluid leukocyte count of up to 10×10/L combined with detection of bacteria in the cerebrospinal fluid. Outcome was categorized according to the Glasgow Outcome Scale at discharge.

Results: Normocellular cerebrospinal fluid was observed in 12 of 696 (2%) patients with community-acquired bacterial meningitis. The median age was 70 years (range 17 to 92 years), and 8 of 12 (67%) patients were male. All patients had symptoms suggestive of community-acquired bacterial meningitis and pathogens identified by culture (Streptococcus pneumoniae, n=10; Staphylococcus aureus, n=1) or polymerase chain reaction (Neisseria meningitidis; n=1) of the cerebrospinal fluid. Bacteremia was found in 9 of 12 (75%) patients, and 1 of 12 (8%) presented with septic shock. None of the patients had serious underlying immunocompromising conditions. The median times from admission to lumbar puncture and meningitis treatment were 2.5 hours (interquartile range 1.1 to 3.9 hours) and 2.6 hours (interquartile range 0.9 to 22.8 hours). In 3 of 11 (27%) patients, empiric treatment for community-acquired bacterial meningitis was interrupted by a normal cerebrospinal fluid cell count. The overall case-fatality rate was 3 of 12 (25%); meningitis treatment was interrupted in 1 of these patients, and 8 of 12 (67%) had a Glasgow Outcome Scale score of 1 to 4 at discharge.

Conclusion: Normocellular community-acquired bacterial meningitis is not very common, but it is important to consider and may be associated with a pneumococcal cause.
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http://dx.doi.org/10.1016/j.annemergmed.2020.05.041DOI Listing
January 2021

Fatal pulmonary fibrosis: a post-COVID-19 autopsy case.

J Clin Pathol 2020 Jul 28. Epub 2020 Jul 28.

Department of Histopathology, Aarhus University Hospital, Aarhus N, Denmark.

There is growing evidence of histopathological changes in autopsied individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, data on histopathological changes in autopsied patients with eradicated COVID-19 are limited. We performed an autopsy on a Caucasian female in her 80s, who died due to severe, bilateral pulmonary fibrosis after eliminated SARS-CoV-2 infection. In addition, CT scans from 2 months before infection and from 6 days prior to death were compared. Comparison of the CT scans showed bilateral development of widespread fibrosis in previously healthy lungs. Microscopic examination showed different areas with acute and organising diffuse alveolar damage and fibrosis with honeycomb-like remodelling and bronchial metaplasia. We here report a unique autopsy case with development of widespread pulmonary fibrosis in a woman in her 80s with previous COVID-19 and no history of pulmonary illnesses.
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http://dx.doi.org/10.1136/jclinpath-2020-206879DOI Listing
July 2020

Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics.

Lancet Infect Dis 2020 09 3;20(9):e238-e244. Epub 2020 Jul 3.

Department of Science and Environment, Roskilde University, Roskilde, Denmark; Department of Global Health, George Washington University, Washington, DC, USA.

The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R) for SARS-CoV-2 is estimated to be 2·5 (range 1·8-3·6) compared with 2·0-3·0 for SARS-CoV and the 1918 influenza pandemic, 0·9 for MERS-CoV, and 1·5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100 000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R and associated mortality and could in part explain the geographical differences.
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http://dx.doi.org/10.1016/S1473-3099(20)30484-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333991PMC
September 2020

Successful use of extracorporeal membrane oxygenation in respiratory failure due to influenza and acute myeloid leukemia.

Int J Infect Dis 2020 Jul 26;96:570-572. Epub 2020 May 26.

Department of Infectious Diseases, Aarhus University Hospital, Skejby, Aarhus, Denmark.

We report the use of extracorporeal membrane oxygenation (ECMO) in a 28-year-old woman who had an influenza infection complicated with severe acute respiratory distress syndrome (ARDS) during treatment for acute myeloid leukemia. Despite ventilator management with positive end-expiratory pressure, nitrogen oxide inhalation, and prone positioning, there was severe hypoxemia. ECMO led to improvement in gas exchange and lung mechanics. This case shows that ECMO can be lifesaving in the treatment of immunocompromised patients who have hypoxemia that is refractory to conventional treatment.
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http://dx.doi.org/10.1016/j.ijid.2020.05.074DOI Listing
July 2020

Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment.

Antimicrob Agents Chemother 2020 06 23;64(7). Epub 2020 Jun 23.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations ( = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The initial dose of 8, 12, or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for (16 mg/liter), and the following PK/PD targets were evaluated: 100% free time (T) > 1× MIC and 100% T > 4× MIC. A population pharmacokinetic model was developed using NONMEM 7.4.3 consisting of a one-compartment disposition model with linear elimination separated into nonrenal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% T > 1× MIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% T > 4× MIC. Probability of target attainment for a simulated cohort of patients showed that increasing the daily dose by 4-g increments (piperacillin component) did not result in substantially improved target attainment for the 100% T > 4× MIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a continuous infusion (CI) regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.
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http://dx.doi.org/10.1128/AAC.02556-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318020PMC
June 2020

Lyme neuroborreliosis in adults: A nationwide prospective cohort study.

Ticks Tick Borne Dis 2020 07 24;11(4):101411. Epub 2020 Feb 24.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address:

The goal of this paper is to characterize the clinical presentation, serological results, current antibiotic treatment practice, including compliance with current European guidelines, and outcome in adults with Lyme neuroborreliosis (LNB) diagnosed at departments of infectious diseases in Denmark. Using a nationwide prospective cohort of patients with central nervous system infections, we identified all adults (≥ 18 years of age) treated for LNB at departments of infectious diseases in Denmark from 2015 through 2017. The database contains information on baseline demographics, history of tick bite, erythema migrans, clinical presentation, laboratory results of blood samples, and cerebrospinal (CSF) biochemistry (e.g. specific Borrelia burgdorferi sensu lato (s.l.) antibodies in serum, B. burgdorferi s.l. intrathecal antibody index) as well as antibiotic therapy. Outcome was assessed by the Glasgow Outcome Scale (GOS) and the presence of residual symptoms at follow-up one month after discharge. We included 194 LNB patients with a median age of 59 years (range 18-85 years, interquartile range [IQR] 47-69 years). The female-to-male ratio was 0.8. A total of 177 of 191 (93 %) of patients had early (second stage) LNB. A history of tick bite or erythema migrans was registered in 75 (39 %) and 49 (25 %) patients, respectively. The median duration of neurological symptoms before first hospital contact was 21 days (range 0-600 days, IQR 10-42 days). Predominant symptoms consisted of radicular pain in 135 of 194 (70 %), cranial nerve paresis in 88 of 194 (45 %), headache in 71 of 185 (38 %), and extremity paresis in 33 of 194 (17 %) patients. Serum-B. burgdorferi s.l. IgM and/or IgG antibodies were detectable in 166 of 181 (92 %) patients at the time of first CSF investigation. Median duration of antibiotic treatment was 14 days (range 10-35 days, IQR 14-21 days) and 59 (39 %) of the patients received intravenous ceftriaxone and/or benzylpenicillin G throughout treatment. At the 1-month follow-up, GOS was unfavorable (< 5) in 54 of 193 (28 %) patients. An unfavorable GOS score was more often registered in patients with ≥ 45 days of symptom duration (20 of 45 (44 %) vs. 34 of 145 (23 %); P = 0.006). In conclusion, a European cohort of adult patients with LNB diagnosed between 2015-2017 presented with classic symptoms and CSF findings. However, a substantial diagnostic delay was still observed. In disagreement with current guidelines, a substantial part of LNB patients were treated with antibiotics longer than 14 days and/or intravenously as route of administration.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101411DOI Listing
July 2020

Varicella Zoster Virus Encephalitis in Denmark From 2015 to 2019-A Nationwide Prospective Cohort Study.

Clin Infect Dis 2021 04;72(7):1192-1199

Department of Infectious Diseases, Aarhus University Hospital, Aarhus N, Denmark.

Background: Knowledge of the epidemiology and clinical characteristics of varicella zoster virus (VZV) encephalitis remains limited.

Methods: Nationwide prospective cohort study of adults treated for microbiologically confirmed VZV encephalitis at Danish departments of infectious diseases from 2015 to 2019. Modified Poisson regression analysis was used to compute adjusted relative risks (RRs) of unfavorable outcome.

Results: We identified 92 adults (49% female) with VZV encephalitis, yielding an incidence of 5.3/1 000 000 per year (95% CI, 4.2-6.6). Median age was 75 years (IQR, 67-83) and immunocompromising conditions were frequent (39%). Predominant symptoms were confusion (76%), headache (56%), nausea (45%), gait disturbance (42%), and personality changes (41%). Cranial imaging showed cerebral vasculitis (including infarction and hemorrhage) in 14 (16%) patients and encephalitic abnormalities in 11 (13%) with predilection for the brainstem and deep brain structures. Intravenous acyclovir treatment was initiated a median (IQR) of 13.4 hours (5.2-46.3) since admission, while cranial imaging and lumbar puncture were performed after 6.3 hours (2.5-31.0) and 18.5 hours (4.9-42.0). In-hospital, 1-month, and 3-month mortalities were 4%, 9%, and 11%, respectively. Unfavorable outcome (Glasgow Outcome Score of 1-4) was found in 69% at discharge, with age (adjusted RR [aRR], 1.02; 95% CI, 1.01-1.03), vasculitis (aRR, 1.38; 95% CI, 1.02-1.86), and Glasgow Coma Scale (GCS) <15 (aRR, 1.32; 95% CI, 1.01-1.73) identified as independent risk factors.

Conclusions: VZV encephalitis occurs primarily in elderly or immunocompromised patients with a higher incidence than previously estimated. The diagnosis is often delayed; risk factors for unfavorable outcome are age, cerebral vasculitis, and GCS <15.
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http://dx.doi.org/10.1093/cid/ciaa185DOI Listing
April 2021

Management of Osteoporosis in Patients Living With HIV-A Systematic Review and Meta-analysis.

J Acquir Immune Defic Syndr 2020 01;83(1):1-8

Departments of Endocrinology and Internal Medicine; and.

Objective: Osteoporosis is reported as a common comorbidity in patients living with HIV (PLHIV). The aim of this systematic review and meta-analysis is to assess the evidence on fracture risk in PLHIV, bone mineral density (BMD) in PLHIV compared with controls, longitudinal changes in BMD in PLHIV, and effect of antiosteoporosis treatment in PLHIV.

Methods: A systematic literature search was conducted using the databases Medline at PubMed and EMBASE using the search terms: "HIV" and "fracture" or "bone turnover," or "bone mineral density." Eligibility criteria followed the aim of the study and include randomized controlled trials and observational studies. Two reviewers extracted the data independently. Meta-analysis was performed using random-effects model assessing fracture risk, BMD compared with controls, and changes in BMD.

Results: One hundred forty-two of 2397 papers identified were included in the systematic review, and subsequently, 84 were included in the meta-analysis. The risks of a fragility fracture [1.51, 95% confidence interval (CI): 1.41 to 1.63] and hip fracture (4.05, 95% CI: 2.99 to 5.49) were increased. PLHIV have lower BMD at the hip (z-score -0.31, 95% CI: -0.46 to -0.27) and lumbar spine (z-score -0.36, 95% CI: -0.39 to -0.15) compared with controls. The reduced BMD did not fully explain the increased fracture risk in PLHIV.

Conclusions: Current management of osteoporosis in PLHIV follows general osteoporosis guidelines; however, the increased fracture risk is not fully explained by lower BMD, and thus, antiosteoporosis intervention may be beneficial at a higher BMD in PLHIV.
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http://dx.doi.org/10.1097/QAI.0000000000002207DOI Listing
January 2020

Study protocol: becoming and being a mother living with HIV - a multicentre longitudinal mixed methods study among pregnant women living with HIV, non-pregnant women living with HIV and pregnant women not living with HIV in a high-income setting (the 2B MOM study).

BMJ Open 2019 10 15;9(10):e027761. Epub 2019 Oct 15.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Introduction: The success of combination antiretroviral therapy has decreased the risk of perinatal HIV transmission and normalised pregnancy in women living with HIV (WLWH). Despite these advances, WLWH still face complex medical and psychosocial issues during pregnancy and postpartum, and there is a gap of knowledge on the experiences of becoming and being a mother living with HIV in today's context. The overall aim of this study is to investigate psychosocial outcomes and experiences of WLWH in Scandinavia during pregnancy and early motherhood.

Methods And Analysis: This is a multicentre longitudinal convergent mixed methods study consisting of a quantitative survey study, a qualitative interview study and a mixed methods analysis. The survey study aims to examine psychosocial outcomes of WLWH across the pregnancy - postpartum trajectory. Participants are pregnant WLWH living in Scandinavia. Two control groups of HIV-negative pregnant women and non-pregnant WLWH are also included. Data is collected in the third trimester, 3 and 6 months postpartum using standardised questionnaires. Statistical analysis will assess changes over time and identify predictors of adverse outcomes. The interview study seeks to understand experiences of pregnancy and becoming a mother while living with HIV. Pregnant WLWH who are enrolled in the survey study will be asked to participate in individual interviews in the third trimester and 6 months postpartum. Data will be analysed using narrative analysis. The survey and interview results will be merged in a mixed methods analysis to assess confirmation, expansion or discordance between the data sets.

Ethics And Dissemination: Approval from the Danish Data Protection Agency (VD-2018-253), and the Finnish and Swedish Ethics Committees have been obtained (HUS/1330/2019 and Dnr: 2019-04451, respectively). Study results will be disseminated to patient organisations, through publications in peer-reviewed journals and at scientific conferences.
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http://dx.doi.org/10.1136/bmjopen-2018-027761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797316PMC
October 2019

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark - the SHADE.

BMC Infect Dis 2019 Aug 22;19(1):740. Epub 2019 Aug 22.

Molecular Pathology Laboratory, Department of Pathology, Copenhagen University Hospital, Hvidovre, Denmark.

Background: Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark.

Methods: From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011-2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL.

Results: Of 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 < 350 cells/μL predicted genotype-specific hrHPV persistence (adjusted OR 4.36 (95%CI: 1.18-16.04)) and ≥ HSIL was predicted by prior AIDS (adjusted OR 8.55 (95% CI 1.21-60.28)).

Conclusions: This prospective cohort study of well-treated WLWH in Denmark found a high rate of persistent hrHPV infections with predominantly non-16/18 hrHPV genotypes. CD4 count < 350 cells/μL predicted hrHPV persistence, while prior AIDS predicted ≥HSIL.
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http://dx.doi.org/10.1186/s12879-019-4377-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706931PMC
August 2019

Children Exposed or Unexposed to Human Immunodeficiency Virus: Weight, Height, and Body Mass Index During the First 5 Years of Life-A Danish Nationwide Cohort.

Clin Infect Dis 2020 05;70(10):2168-2177

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre.

Background: Exposures to human immunodeficiency (HIV) and antiretroviral therapy in utero may have adverse effects on infant growth. Among children born in Denmark and aged 0-5 years, we aimed to compare anthropometric outcomes in HIV-exposed but uninfected (HEU) children with those in children not exposed to HIV.

Methods: In a nationwide register-based study we included all singleton HEU children born in Denmark in 2000-2016. HEU children were individually matched by child sex, parity, and maternal place of birth to 5 singleton controls born to mothers without HIV. Weight-for-age z (WAZ) scores, length-for-age z (LAZ) scores, and weight-for-length or body mass index-for-age z scores were generated according to the World Health Organization standards and the Fenton growth chart for premature infants. Differences in mean z scores were analyzed using linear mixed models, both univariate and adjusted for social and maternal factors.

Results: In total, 485 HEU children and 2495 HIV-unexposed controls were included. Compared with controls, HEU children were smaller at birth, with an adjusted difference in mean WAZ and LAZ scores of -0.29 (95% confidence interval [CI], -.46 to -.12) and -0.51 (95% CI, -.71 to -.31), respectively (both P ≤ .001). Over time, there was a trend toward increasing WAZ and LAZ scores in HEU children, and there was no significant difference in adjusted WAZ scores after age 14 days (-0.13 [95% CI, -.27 to .01]; P = .07) and LAZ scores after age 6 months (-0.15 [95% CI, -.32 to .02]; P = .08).

Conclusion: Compared with a matched control group, HEU children were smaller at birth, but this difference decreased with time and is not considered to have a negative effect on the health and well-being of HEU children during early childhood.
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http://dx.doi.org/10.1093/cid/ciz605DOI Listing
May 2020

Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza.

Med Microbiol Immunol 2019 Dec 6;208(6):869-876. Epub 2019 Jun 6.

Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

Influenza infection is common worldwide with many individuals affected each year during epidemics and occasionally pandemics. Previous studies in animal models and a few human cases have established an important role of innate type I and III interferon (IFN) for viral elimination and mounting of antiviral responses. However, genetic and immunological determinants of very severe disseminated influenza virus infection in humans remain incompletely understood. Here, we describe an adult patient with severe influenza virus A (IAV) infection, in whom we identified a rare variant E331V in IFN regulatory factor (IRF)7 by whole-exome sequencing. Examination of patient cells demonstrated a cellular phenotype suggesting functional IRF7 impairment, since priming with IFN was almost abolished and IFN responses to IAV were significantly impaired in patient cells. Moreover, IAV replication was significantly higher in patient cells than in controls. Finally, expression of IRF7 E331V in HEK293 cells demonstrated significantly reduced activation of both IFNA7 and IFNB promoters in a luciferase reporter gene expression assay compared to IRF7 wild type. These findings provide further support for the essential role of IRF7 in amplifying antiviral IFN responses to ensure potent and sustained IFN responses during influenza virus infection in humans.
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http://dx.doi.org/10.1007/s00430-019-00623-8DOI Listing
December 2019

Fecal Microbiota Transplantation Is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection.

Gastroenterology 2019 Apr 2;156(5):1324-1332.e3. Epub 2019 Jan 2.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Background & Aims: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin.

Methods: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube, after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n = 24), 10 days of fidaxomicin (200 mg twice daily; n = 24), or 10 days of vancomycin (125 mg 4 times daily; n = 16). Patients who had rCDI after this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a polymerase chain reaction test for Clostridium difficile (CD) toxin 8 weeks after the allocated treatment. Secondary end points included clinical resolution at week 8.

Results: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients given FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%; P = .009 for FMTv vs fidaxomicin; P = .001 for FMTv vs vancomycin; P = .31 for fidaxomicin vs vancomycin). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%; P = .0002; P < .0001; P = .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv.

Conclusions: In a randomized trial of patients with rCDI, we found the FMTv combination superior to fidaxomicin or vancomycin based on end points of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov, number NCT02743234; EudraCT, j.no 2015-003004-24.
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http://dx.doi.org/10.1053/j.gastro.2018.12.019DOI Listing
April 2019

Do probiotics prevent colonization with multi-resistant Enterobacteriaceae during travel? A randomized controlled trial.

Travel Med Infect Dis 2019 Jan - Feb;27:81-86. Epub 2018 Nov 30.

Aarhus University Hospital, Department of Infectious Diseases, Aarhus, Denmark.

Background: Travelers to India are often colonized with extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) or Carbapenemase-producing Enterobacteriaceae (CPE). The aim of this study was to investigate if the probiotic species Lactobacillus Rhamnosus GG (LGG) could prevent the colonization of the gut with multi-drug resistant bacteria.

Methods: Adult Danish travelers traveling to India for 10-28 days were randomized to receive either LGG or no probiotics during travel. Rectal swabs and questionnaires were obtained before travel, immediately after and six months after return. Swaps were screened for the presence of ESBL-E and CPE.

Results: 31 travelers were randomized to the LGG group and 30 to the control group. Before traveling, 6/50 (12.0%) were colonized with ESBL-E. After return, 41/44 (93.2%) of those not colonized before travel were colonized and 11/36 (30.6%) were still colonized after six months. There was no statistically significant difference in the colonization rate between the group receiving LGG and the control group. No CPE was detected in any cases.

Conclusions: The study confirms the very high incidence of colonization with ESBL-E associated with travel to India with >90% colonized upon return and one third were intestinal carriers for at least six months. Use of LGG did not have any effect on the risk of colonization with ESBL-E.
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http://dx.doi.org/10.1016/j.tmaid.2018.11.013DOI Listing
April 2019

Pediatric Candidemia Epidemiology and Morbidities: A Nationwide Cohort.

Pediatr Infect Dis J 2019 05;38(5):464-469

Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital.

Background: Candidemia is the most frequent pediatric fungal infection, but incompletely elucidated in population-based settings. We performed a nationwide cohort study including all pediatric patients with candidemia in Denmark from 2004 to 2014 to determine age, incidence, species distribution, underlying diseases, patient management and outcomes.

Methods: All candidemia episodes were identified through the active nationwide fungemia surveillance program. Susceptibility testing followed the EUCAST E.Def 7 (European Committee on Antifungal Susceptibility Testing, Edition Definitive) reference method. χ test, Fisher exact test and Venn diagrams were used for statistical analyses.

Results: One hundred fifty-three pediatric patients (≤ 15 years) with 158 candidemia episodes were identified. The overall annual incidence rate was 1.3/100,000 population, higher for neonates (5.7/100,000 live births) and low birth weight neonates (103.8/100,000 live births). From 2004 to 2009 to 2010 to 2014, the proportion of Candida albicans decreased from 74.4% to 64.7%, whereas fluconazole resistance increased from 7.8% to 17.7%. Virtually all patients had at least 1 underlying disease (98.6%) and multimorbidity was common (43.5%, ≥2 underlying diseases). Underlying diseases differed by age with heart malformations and gastrointestinal disease prevalent in children younger than 3 years. The overall 30-days mortality was 10.2% and highest for neonates (17.1%). Mortality increased from 2004 to 2010 to 2014, driven by an increase among older children.

Conclusion: This first nationwide epidemiologic study of pediatric candidemia confirmed a high incidence among neonates and a substantial burden of comorbidities. Moreover, an increasing proportion of fluconazole resistant nonalbicans species was observed. Our findings underline the importance of choosing correct treatment and continuous surveillance of pediatric candidemia.
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http://dx.doi.org/10.1097/INF.0000000000002207DOI Listing
May 2019

Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark - The SHADE cohort study.

J Clin Virol 2018 08 25;105:64-71. Epub 2018 May 25.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark.

Background: Women living with HIV (WLWH) have elevated risk of human papillomavirus (HPV) related cancers.

Objectives: To assess prevalence, distribution and concordance of cervical, oral, and anal HPV infection, and predictors of oral and anal HPV in WLWH in Denmark.

Study Design: WLWH followed in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) were enrolled and examined for cervical, oral, and anal HPV infection. Logistic regression models were used to identify predictors of anal and oral HPV.

Results: A total of 214 of 334 WLWH had sufficient DNA for analysis at all three anatomical sites and were included in analyses. Cervical, oral, and anal high-risk (hr) HPV prevalence were 28.0%, 3.7% and 39.3%. Most frequent i) cervical, ii) oral and iii) anal hrHPV genotypes were i) hrHPV58 (8.4%), 52 (5.1%), 16 (5.1%) and 51 (5.1%); ii) 52 (1.4%) and iii) 51 (9.3%), 58 (8.9%), 16 (7.0%) and 18 (7.0%). Among present cervical, oral, and anal hrHPV genotypes, 6.7%, 12.5% and 17.9% were targeted by the 2-or 4-valent HPV vaccines, whereas 50.0%, 50.0% and 42.9% of hrHPV genotypes were covered by the 9-valent HPV vaccine. Anal HPV infection was predicted by cervical HPV infection (adjusted OR 4.47 (95%CI 2.25-8.89)).

Conclusion: Cervical and anal HPV infection were highly prevalent in WLWH. Non-16/18 hrHPV genotypes were predominant at all anatomical sites. Almost half of all hrHPV infections at the three anatomical sites could have been prevented by childhood/adolescent vaccination with the 9-valent HPV vaccine.
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http://dx.doi.org/10.1016/j.jcv.2018.05.010DOI Listing
August 2018

[Disease burden and definition of sepsis in adults].

Ugeskr Laeger 2018 Apr;180(15)

Sepsis is the terminal event for most infectious diseases and is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is frequent, deathly and associated with high burden for patients, relatives and societies. Sepsis is underreported in diagnostic coding, making estimation difficult of the true burden of the disease in Denmark. It is likely, however, that sepsis contributes to 15% of all deaths in Denmark.
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April 2018

Population Pharmacokinetics of Piperacillin in Sepsis Patients: Should Alternative Dosing Strategies Be Considered?

Antimicrob Agents Chemother 2018 05 26;62(5). Epub 2018 Apr 26.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Sufficient antibiotic dosing in septic patients is essential for reducing mortality. Piperacillin-tazobactam is often used for empirical treatment, but due to the pharmacokinetic (PK) variability seen in septic patients, optimal dosing may be a challenge. We determined the PK profile for piperacillin given at 4 g every 8 h in 22 septic patients admitted to a medical ward. Piperacillin concentrations were compared to the clinical breakpoint MIC for (16 mg/liter), and the following PK/pharmacodynamic (PD) targets were evaluated: the percentage of the dosing interval that the free drug concentration is maintained above the MIC () of 50% and 100%. A two-compartment population PK model described the data well, with clearance being divided into renal and nonrenal components. The renal component was proportional to the estimated creatinine clearance (eCL) and constituted 74% of the total clearance in a typical individual (eCL, 83.9 ml/min). Patients with a high eCL (>130 ml/min) were at risk of subtherapeutic concentrations for the current regimen, with a 90% probability of target attainment being reached at MICs of 2.0 (50% ) and 0.125 mg/liter (100% ). Simulations of alternative dosing regimens and modes of administration showed that dose increment and prolonged infusion increased the chance of achieving predefined PK/PD targets. Alternative dosing strategies may therefore be needed to optimize piperacillin exposure in septic patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02569086.).
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http://dx.doi.org/10.1128/AAC.02306-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923116PMC
May 2018