NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.

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.

Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication in Patients With Brain Abscess in Denmark.

BACKGROUND: It is unknown whether patients diagnosed with brain abscess have an increased risk of psychiatric disorders. METHODS: In this nationwide, population-based matched cohort study from Denmark, we compared the incidence of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medications between patients diagnosed with brain abscess and individuals from the general population, matched on date of birth, sex, and residential area. RESULTS: We included 435 patients diagnosed with brain abscess and 3909 individuals in the comparison cohort: 61% were male and median age was 54 years. Patients diagnosed with brain abscess were more likely to suffer from comorbidity. The risk of a hospital diagnosis of psychiatric disorders was increased the first 5 years of observation. In the subpopulation, who had never been in contact with psychiatric hospitals or received psychiatric medication before study inclusion, the risk of developing psychiatric disorders was close to that of the background population, especially when we excluded dementia from this outcome. There was a substantial increase in the receipt of anxiolytics and antidepressants. The difference in the proportion of individuals who received anxiolytics and antidepressants increased from 4% (95% confidence interval [CI], 0%-7%) and 2% (95% CI, -1% to 5%) 2 years before study inclusion to 17% (95% CI, 12%-21%) and 11% (95% CI, 7%-16%) in the year after study inclusion. CONCLUSIONS: Patients with brain abscess without prior psychiatric disorders or receipt of psychiatric medicine are not at increased risk psychiatric disorders diagnosed in psychiatric hospitals, but they have an increased receipt of psychiatric medication.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

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.

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.

BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci. OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination. RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively. CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

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.

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.

Cerebral abscesses with odontogenic origin: a population-based cohort study.

OBJECTIVES: Recent studies have indicated that cerebral abscess (CA) patients with odontogenic origin are on the rise. However, CA patients are often poorly characterized and with an unknown etiologic background. The purpose of this study is to identify and characterize CA patients that may have an odontogenic origin based on microbiologic, radiographic, and/or clinical findings. MATERIALS AND METHODS: This is a population-based cohort study analyzing retrospective and prospective data from CA patients. Radiographic examinations of panoramic radiographs (PRs) or computed tomography (CT) scans were conducted. CA patients characterized with odontogenic origin required the fulfilment of the following criteria on admission: (1) Oral pathologic conditions were the only bacterial infections present, (2) oral microorganisms were isolated in the purulent exudate from the brain, and (3) radiographically and/or clinical recordings of oral pathologic conditions. RESULTS: A total of 44 patients could be included in this study of which 25 (57%) were characterized as having CA with a likely odontogenic origin. Type two diabetes (T2D) (p = 0.014) and microorganisms of the Streptococcus anginosus group (SAG) (p < 0.01) were overrepresented in patients with CAs of odontogenic origin. CONCLUSIONS: Odontogenic infections may cause CAs to a greater extent than previously assumed. T2D was overrepresented among patients with odontogenic CA. When microorganisms of the SAG were isolated from the brain pus, CA patients had a predisposing odontogenic or sinus infection. CLINICAL RELEVANCE: The identification of patients with a likely odontogenic CA will contribute to understanding the etiology of the infectious disease and highlighting the importance of preserving oral health.

Dentist's Visits and Risk of Brain Abscess: A Nationwide, Population-Based Case-Control Study.

BACKGROUND: Brain abscesses are frequently caused by oral cavity bacteria, but whether dental status and invasive dental procedures are important risk factors is unknown. METHODS: A nationwide, population-based, case-control study examined the association between dentist's visits and invasive dental procedures and risk of brain abscess caused by oral cavity bacteria from 1989 through 2016. Date of brain abscess diagnosis was considered the index date. Using risk-set sampling, 10 population controls per case were individually matched by age, sex, and residential area. Conditional logistic regression was used to compute odds ratios with 95% confidence intervals (CIs), adjusted for comorbidity. RESULTS: We identified 362 patients with culture-proven brain abscess caused by oral cavity bacteria. The median age was 53 years (interquartile range, 39-65 years) and 220 (61%) were male. Invasive dental procedures within 6 months before the index date was observed in 21 of 362 (6%) patients with brain abscess and 179 of 3257 (5%) population controls (adjusted odds ratio [aOR], 1.07 [95% CI, .67-1.70]). Two hundred thirteen of 362 (59%) patients with brain abscess had visited their dentist within 1 year before the index date compared with 1944 of 3257 (60%) of population controls (aOR, 0.99 [95% CI, .77-1.26]). Using no dentist's visits as reference, we observed aORs of 0.95 (95% CI, .64-1.40) for 1-2 visits within 3 years of the index date and 1.01 (95% CI, .76-1.35) for 3 or more visits. CONCLUSIONS: Recent invasive dental procedures and number of dentist's visits were not associated with culture-verified brain abscess caused by oral cavity bacteria.

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.

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis.

BACKGROUND: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).

Self-assessed health status and associated mortality in endocarditis: secondary findings from the POET trial.

PURPOSE: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. METHODS: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. RESULTS: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p < 0.01). CONCLUSION: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. TRIAL REGISTRY: POET ClinicalTrials.gov number, NCT01375257.

Disseminated fusariosis with cerebral involvement in a patient with acute myeloid leukemia: Successful outcome with intrathecal -and systemic antifungal treatment.

The outcome of invasive fusariosis in hematological patients is usually dismal, particularly in patients with persistent neutropenia. We report a patient with acute myeloid leukemia (AML) with Fusarium dimerum sinusitis with hematogenic dissemination to the brain. Despite surgical debridements of the sinuses and liposomal amphotericin B, voriconazole and terbinafine, there was progression with cerebral involvement after recovery of neutropenia and with detection of F. dimerum in the cerebrospinal fluid. Topical antifungal treatment with amphotericin B deoxycholate (deoxy-AMB) intrathecally was initiated with administration three times a week. After 99 treatments of intrathecal deoxy-AMB, she had regression of the fusarium CNS lesions and is currently in complete remission from AML. This report supports the use of intrathecal amphotericin B for treatment of CNS fusariosis.

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.

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.

Accelerated treatment of endocarditis-The POET II trial: Rationale and design of a randomized controlled trial.

BACKGROUND: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. OBJECTIVE: The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. METHODS: The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. CONCLUSIONS: The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.