Association Between Vegetation Size and Outcome in the Partial Oral Antibiotic Endocarditis Treatment Trial.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

Empiric treatment of healthcare-associated central nervous system infections in Denmark: do we need carbapenems?

BACKGROUND: Carbapenems are widely used for empiric treatment of healthcare-associated central nervous system (CNS) infections. We investigated the feasibility of a carbapenem-sparing strategy, utilising a third-generation cephalosporin (ceftriaxone or cefotaxime) (combined with vancomycin) for the empirical treatment of healthcare-associated CNS infections in Eastern Denmark. METHODS: The departments of neurosurgery and neuro-intensive care at Copenhagen University Hospital Rigshospitalet. First, we analysed local microbiological data (1st January 2020-31st August 2022) to identify microorganisms non-susceptible to third-generation cephalosporin. Subsequently, we assessed all carbapenem prescriptions over a three-month period for their indication and justification. RESULTS: In total, 25,247 bacterial cultures were identified, of which 2,563 CNS-related, were included in the analysis. The positivity rate was 10.5% (n = 257/2439) for cerebrospinal-fluid samples and 75.8% (n = 95/124) for brain parenchyma. CNS samples from five individual patients revealed bacteria non-susceptible to third generation cephalosporins (Enterobacter spp. (n = 3), Pseudomonas spp. (n = 2), Klebsiella spp. (n = 2), Citrobacter freundii (n = 1)). All five patients had been hospitalised for ≥10days at the time-point of antibiotic therapy. Out of 11,626 sets of blood cultures, a total of 10 individual patients had Gram-negative blood-stream infections with resistance to ceftriaxone and piperacillin/tazobactam. 140 days-of-therapy (32%) with carbapenem in 18 patients (36%) were definitively or possibly indicated according to guidelines, none were indicated for healthcare-associated CNS-infections. CONCLUSION: An empiric treatment strategy relying on a third-generation cephalosporin appears suitable for healthcare-associated CNS infections at our tertiary hospital, serving a population of 2.6 million. However, in patients with prolonged hospitalization (≥10 days), immunosuppression, prior broad-spectrum antibiotic use, or history of resistant Gram-negative bacteria, empirical prescription of carbapenem may be needed.

Close monitoring and early intervention: management principles for cystic fibrosis in Denmark.

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre-emptive treatment of lung disease and other CF-related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high-dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side-effects and costs.

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.

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.

Invasive Aspergillosis among Lung Transplant Recipients during Time Periods with Universal and Targeted Antifungal Prophylaxis-A Nationwide Cohort Study.

The optimal prevention strategy for invasive aspergillosis (IA) in lung transplant recipients (LTXr) is unknown. In 2016, the Danish guidelines were changed from universal to targeted IA prophylaxis. Previously, we found higher rates of adverse events in the universal prophylaxis period. In a Danish nationwide study including LTXr, for 2010-2019, we compared IA rates in time periods with universal vs. targeted prophylaxis and during person-time with vs. person-time without antifungal prophylaxis. IA hazard rates were analyzed in multivariable Cox models with adjustment for time after LTX. Among 295 LTXr, antifungal prophylaxis was initiated in 183/193 and 6/102 during the universal and targeted period, respectively. During the universal period, 62% discontinued prophylaxis prematurely. The median time on prophylaxis was 37 days (IQR 11-84). IA was diagnosed in 27/193 (14%) vs. 15/102 (15%) LTXr in the universal vs. targeted period, with an adjusted hazard ratio (aHR) of 0.94 (95% CI 0.49-1.82). The aHR of IA during person-time with vs. person-time without antifungal prophylaxis was 0.36 (95% CI 0.12-1.02). No difference in IA was found during periods with universal vs. targeted prophylaxis. Prophylaxis was protective of IA when taken. Targeted prophylaxis may be preferred over universal due to comparable IA rates and lower rates of adverse events.

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.

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.

Associations between invasive aspergillosis and cytomegalovirus in lung transplant recipients: a nationwide cohort study.

Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause morbidity among lung transplant recipients (LTXr). Early diagnosis and treatment could improve outcomes. We examined rates of CMV after IA and vice versa to assess whether screening for one infection is warranted after detecting the other. All Danish LTXr, 2010-2019, were followed for IA and CMV for 2 years after transplantation. IA was defined using ISHLT criteria. Adjusted incidence rate ratios (aIRR) were estimated by Poisson regression adjusted for time after transplantation. We included 295 LTXr, among whom CMV and IA were diagnosed in 128 (43%) and 48 (16%). The risk of CMV was high the first 3 months after IA, IR 98/100 person-years of follow-up (95% CI 47-206). The risk of IA was significantly increased in the first 3 months after CMV, aIRR 2.91 (95% CI 1.32-6.44). Numbers needed to screen to diagnose one case of CMV after IA, and one case of IA after CMV was approximately seven and eight, respectively. Systematic screening for CMV following diagnosis of IA, and vice versa, may improve timeliness of diagnosis and outcomes for LTXr.

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.

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.

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.

Invasive procedures and risk of brain abscess: a nationwide, population-based case-control study.

OBJECTIVES: It is unknown whether invasive procedures are associated with brain abscess. METHODS: Nationwide, population-based, matched case-control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0-6 months before study inclusion. RESULTS: We identified 435 patients and 3909 controls. The level of comorbidity was higher among patients with brain abscess than among controls. A total of 48 cases (11%) had one or more invasive procedures 0-6 months before study inclusion (adjusted odds ratios (aOR) of 3.6 (95% confidence interval (CI): 2.5-5.1), a population attributable fractions of 8% (95% CI: 7-9)). In primary care, ear, nose and throat (ENT) procedures were associated with brain abscess (aOR of 4.0 (95% CI: 2.0-8.0)), but gastrointestinal endoscopies were not (aOR of 1.0 (95% CI: 0.3-3.2)). No bronchoscopies were performed in primary care. In the hospital-based setting, ENT procedures, bronchoscopies and gastrointestinal endoscopies were associated with an increased risk of brain abscess (aOR of 14.5 (95% CI: 4.8-43.8), 20.3 (95% CI: 3.8-110.1) and 3.4 (95% CI: 2.0-5.6), respectively). CONCLUSIONS: The association between invasive procedures and brain abscess was more pronounced in the hospital-based setting than in primary care.

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.

Adverse Events Associated with Universal versus Targeted Antifungal Prophylaxis among Lung Transplant Recipients-A Nationwide Cohort Study 2010-2019.

Background: Invasive fungal infections in lung transplant (LTX) recipients cause substantial morbidity, but the best strategy for prevention has not yet been determined. We evaluated adherence to and rates of adverse events of universal versus targeted prophylaxis. Methods: All LTX recipients in the Danish National LTX Centre (2010−2019) were included. Before July 2016, universal voriconazole prophylaxis was used. After July 2016, only high-risk patients received targeted prophylaxis with posaconazole and inhaled amphotericin B. Proportions of triazole discontinuation, side-effects, off-target calcineurin-inhibitor (CNI) levels, and acute rejection were compared between the two periods. Results: Universal and targeted prophylaxis was initiated in 183/193 and 6/102 patients, respectively. Only 37% completed > 9 of the intended 12 weeks of voriconazole; 72% of discontinuations were due to hepatotoxicity. In the universal vs. targeted prophylaxis period, 89% vs. 72% (p < 0.001) patients had low CNI episodes, and 37% vs. 1% (p < 0.001) of these were associated with discontinuation of triazole; 40% vs. 14% (p < 0.001) had acute rejection; and 23% vs. 3% (p < 0.001) had acute rejection associated with low CNI episodes. Conclusions: Universal voriconazole prophylaxis was associated with high rates of discontinuation, mainly caused by hepatotoxicity. In comparison to the targeted posaconazole period, more patients had low CNI levels and acute rejection in the universal voriconazole period.

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.

[Infective endocarditis].

Infective endocarditis (IE) is one of the most severe infectious diseases with an in-hospital mortality of 20-25%. Several studies have shown, that the incidence of IE is increasing, and that patients now are older with a higher burden of comorbidities than previously. The diagnostic work-up is mainly based upon the presence of bacteraemia and echocardiography. The treatment is antibiotics and, in some cases, also cardiac surgery. In most cases, after clinical stabilization, it is safe to switch antibiotic treatment from intravenous to oral administration, as argued in this review.

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.