Brain Abscess Caused by Oral Cavity Bacteria: A Nationwide, Population-based Cohort Study.

BACKGROUND: Oral cavity bacteria are the most frequent etiology of brain abscess. Yet, data on the clinical presentation and outcome are scarce. METHODS: We performed a nationwide, population-based study comprising all adults (aged ≥18 years) with brain abscess due to oral cavity bacteria in Denmark from 2007 through 2020. Prognostic factors for unfavorable outcome (Glasgow outcome scale, 1-4) were examined using modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Among 287 identified patients, the median age was 58 years (interquartile range, 47-66), and 96 of 287 (33%) were female. Preexisting functional impairment was absent or mild in 253 of 280 (90%), and risk factors for brain abscess included immunocompromise in 95 of 287 (33%), dental infection in 68 of 287 (24%), and ear-nose-throat infection in 33 of 287 (12%). Overall, a neurological deficit was present in 246 of 276 (86%) and in combination with headache and fever in 64 of 287 (22%). Identified microorganisms were primarily the Streptococcus anginosus group, Fusobacterium, Actinomyces, and Aggregatibacter spp., and 117 of 287 (41%) were polymicrobial. Unfavorable outcome occurred in 92 of 246 (37%) at 6 months after discharge and was associated with antibiotics before neurosurgery (RR, 3.28; 95% CI, 1.53-7.04), rupture (RR, 1.89; 95% CI, 1.34-2.65), and immunocompromise (RR, 1.80; 95% CI, 1.29-2.51), but not with specific targeted antibiotic regimens. Identified dental infection was associated with favorable prognosis (RR, 0.58; 95% CI, .36-.93). CONCLUSIONS: Brain abscess due to oral cavity bacteria often occurred in previously healthy individuals without predisposing dental infections. Important risk factors for unfavorable outcome were rupture and immunocompromise. However, outcome was not associated with specific antibiotic regimens supporting carbapenem-sparing strategies.

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Clinical features and prognostic factors in adults with viral meningitis.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

Group A Streptococcus Meningitis in Adults, Denmark.

We report a 21-fold increase in group A Streptococcus meningitis in adults in Denmark during October 13, 2022-April 12, 2023, concurrent with an outbreak of invasive streptococcal disease. We describe clinical characteristics of the outbreak cases and prognosis for patients in comparison to those for previous sporadic cases.

Ramsay Hunt syndrome and concurrent varicella-zoster virus meningitis in Denmark: A nationwide cohort study.

Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.

Experience with sotrovimab treatment of SARS-CoV-2-infected patients in Denmark.

AIMS: To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in high-risk groups. METHODS: In a nationwide, population-based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high-risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti-CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors. RESULTS: Of 2933 sotrovimab-treated individuals, 83% belonged to high-risk groups (37.6% haematological malignancy, 27.4% solid organ transplantation and 17.5% treatment with anti-CD20 ≤1 year). Only 17.8% had other risks (11.8% were pregnant, 10.7% primary immunodeficiency, 21.2% other malignancy, 4.3% received anti-CD20 >1 year and 52.0% other/unknown causes). Within 90 days of infusion, 30.2% were hospitalized and 5.3% died. The main prognostic factors were the predefined high-risk groups, mainly malignant haematological disease and age ≥65 years. Number of COVID-19 vaccines (≥3) was associated with a decreased risk of hospitalization. The Delta but not the Omicron BA.2 variant was associated with a higher risk of death compared to the BA.1 variant. CONCLUSION: More than 90% of the patients treated with sotrovimab belonged to the very high-risk groups as described in the Danish guidelines. Sotrovimab-treated individuals remained at a high risk of hospitalization and death which was strongly associated with the underlying immunocompromised state and age. Having received >3 COVID-19 vaccines was association with decreased risk of death and hospitalization.

Viral lumbosacral radiculitis (Elsberg syndrome) in Denmark.

PURPOSE: To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). METHODS: Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. RESULTS: Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27-43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31-514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). CONCLUSIONS: Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.

Levels of health literacy among people living with HIV in outpatient care: a cross-sectional study from Denmark.

BACKGROUND: Low health literacy (HL) among people living with HIV (PLWHIV) encounter more disease related complications, more difficulty understanding health-related information and low adherence. Considering that, the HL levels among PLWHIV needs to be further investigated. The objective of this study was to investigate the levels of HL and patient involvement among PLWHIV in an outpatient clinic in Denmark. A second objective was to examine differences in HL levels across socio-demographic characteristics. METHODS: In 2019, a population of 682 PLWHIV from a Danish outpatient hospital clinic were enrolled in cross-sectional study. Patients who had a digital postbox received an electronic questionnaire including following domains; health literacy, patient involvement, and socio-demographic status. Health literacy was measured using the Health Literacy Questionnaire (HLQ) through scores on three subscales: social support for health (HLQ4), engaging with healthcare providers (HLQ6), and understanding health information (HLQ9). An unpaired t-test was used to investigate mean differences in the HLQ scores across socio-demographic variables. RESULTS: A total of 338 (55%) patients responded to the questionnaire. The included participants demonstrated high levels of HLQ4 (mean = 4.2) and HLQ6 (mean = 4.2), but lower for HLQ9 (mean = 2.9). In total 70-80% reported being involved in decisions about their health. We found a positive association between high level of HL (HLQ9) and living with a partner and higher levels of HL (HLQ4, HLQ6, and HLQ9) and employment. CONCLUSION: PLWHIV in a Danish out-patient care population were found to have high levels of HL despite differences in demographic characteristics. Further research is needed to examine the levels of HL among non-responders to develop HL approaches and strategies to meet the needs of individuals with different HL skills.

Oral and Anal Carriage of Streptococcus pneumoniae Among Sexually Active Men With HIV Who Have Sex With Men.

People with HIV are at increased risk of pneumococcal disease. We investigate oral and anal carriage rates of Streptococcus pneumoniae by molecular methods among 82 men with HIV who have sex with men (MSM). A questionnaire, oral wash, and anal swab samples were obtained at baseline and 12 months. Oral carriage rates were 32.9% (27/82) at baseline and 41.7% (30/72) at follow-up. Anal carriage rates were 2.4% (2/82) at baseline and 2.9% (2/70) at follow-up. Genogroup 24 was predominant. Results suggest high oral carriage rates of S. pneumoniae among MSM living with HIV. A minority were anal carriers.

Herpes Simplex Virus 2 Meningitis in Adults: A Prospective, Nationwide, Population-Based Cohort Study.

BACKGROUND: Data on the clinical presentation are scarce and prognostic factors of herpes simplex virus type 2 (HSV-2) meningitis remain unknown. METHODS: Prospective, nationwide, population-based database identifying all adults treated for HSV-2 meningitis at departments of infectious diseases in Denmark from 2015 to 2020. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) scores of 1-4 and Extended GOS scores of 1-6. Modified Poisson regression was used to compute relative risks with 95% confidence intervals for unfavorable outcome. RESULTS: HSV-2 meningitis was diagnosed in 205 patients (76% female; median age [interquartile range (IQR)], 35 [27-49] years) yielding an incidence of 0.7/100 000 population/y. Common symptoms were headache (195 of 204 patients [95%]), photophobia or phonophobia (143 of 188 [76%]), and neck stiffness (106 of 196 [54%]). The median (IQR) time to lumbar puncture was 2.0 (1-4.8) hours, and the median cerebrospinal fluid (CSF) leukocyte count was 360 (166-670) × 10 × 6/L, with a mononuclear predominance of 97% (91%-99%). Lumbar puncture was preceded by brain imaging in 61 of 205 patients (30%). Acyclovir or valacyclovir was administered in 197 of 205 patients (96%) for a median (IQR) of 10 (7-14) days. Unfavorable outcome was observed in 64 of 205 patients (31%) at discharge and 19 of 181 (11%) after 6 months and was not associated with female sex (relative risk [95% confidence interval], 1.08 [.65-1.79]), age ≥35 years (1.28 [.83-1.97]), immunocompromise (1.07 [.57-2.03]), or CSF leukocyte count >1000 × 10 × 6/L (0.78 [.33-1.84]). CONCLUSIONS: HSV-2 meningitis often presented as meningeal symptoms in younger women. Unfavorable outcome at discharge was common and was not associated with sex, age, immunocompromise, or CSF leukocyte count. Sequelae persisted beyond 6 months in one-tenth of patients.

Use of antiretroviral therapy in pregnancy and association with birth outcome among women living with HIV in Denmark: A nationwide, population-based cohort study.

OBJECTIVE: To describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes. METHODS: A population-based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes. RESULTS: In total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased odds of preterm birth, small for gestational age or low birth weight. First-trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23-11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13-9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes. CONCLUSIONS: Pregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and NRTI + PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors.

Psychosocial health in pregnancy and postpartum among women living with - and without HIV and non-pregnant women living with HIV living in the Nordic countries - Results from a longitudinal survey study.

BACKGROUND: The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. METHODS: In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019-2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. RESULTS: A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. CONCLUSIONS: A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions.

Prognostic and discriminative accuracy of the quick Sepsis-related Organ Failure Assessment compared with an early warning score: a Danish cohort study.

BACKGROUND: The clinical benefit of implementing the quick Sepsis-related Organ Failure Assessment (qSOFA) instead of early warning scores (EWS) to screen all hospitalised patients for critical illness has yet to be investigated in a large, multicentre study. METHODS: We conducted a cohort study including all hospitalised patients ≥18 years with EWS recorded at hospitals in the Central Denmark Region during the year 2016. The primary outcome was intensive care unit (ICU) admission and/or death within 2 days following an initial EWS. Prognostic accuracy was examined using sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). Discriminative accuracy was examined by the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 97 332 evaluated patients, 1714 (1.8%) experienced the primary outcome. The qSOFA ≥2 was less sensitive (11.7% (95% CI: 10.2% to 13.3%) vs 25.1% (95% CI: 23.1% to 27.3%)) and more specific (99.3% (95% CI: 99.2% to 99.3%) vs 97.5% (95% CI: 97.4% to 97.6%)) than EWS ≥5. The NPV was similar for the two scores (EWS ≥5, 98.6% (95% CI: 98.6% to 98.7%) and qSOFA ≥2, 98.4% (95% CI: 98.3% to 98.5%)), while the PPV was 15.1% (95% CI: 13.8% to 16.5%) for EWS ≥5 and 22.4% (95% CI: 19.7% to 25.3%) for qSOFA ≥2. The AUROC was 0.72 (95% CI: 0.70 to 0.73) for EWS and 0.66 (95% CI: 0.65 to 0.67) for qSOFA. CONCLUSION: The qSOFA was less sensitive (qSOFA ≥2 vs EWS ≥5) and discriminatively accurate than the EWS for predicting ICU admission and/or death within 2 days after an initial EWS. This study did not support replacing EWS with qSOFA in all hospitalised patients.

Genetic Variants and Immune Responses in a Cohort of Patients With Varicella Zoster Virus Encephalitis.

BACKGROUND: Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in which 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 peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were 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 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients. CONCLUSIONS: 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. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.

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

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.

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

BACKGROUND: There are 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. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone. METHODS: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. 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-days 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: .38-.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: .29-.46). CONCLUSIONS: 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.

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

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 10×106/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.

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

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 1 October 2014 to 30 April 2019 and from 10 March 2020 to 1 March 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 and 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.

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.

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.

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

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 ß-lactams. In an observational study, unbound piperacillin concentrations (n = 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 Pseudomonas aeruginosa (16 mg/liter), and the following PK/PD targets were evaluated: 100% free time (fT) > 1× MIC and 100% fT > 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% fT > 1× MIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT > 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% fT > 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.