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.

Community-acquired pneumonia: use of clinical characteristics of acutely admitted patients for the development of a diagnostic model - a cross-sectional multicentre study.

OBJECTIVES: This study aimed to describe the clinical characteristics of adults with suspected acute community-acquired pneumonia (CAP) on hospitalisation, evaluate their prediction performance for CAP and compare the performance of the model to the initial assessment of the physician. DESIGN: Cross-sectional, multicentre study. SETTING: The data originated from the INfectious DisEases in Emergency Departments study and were collected prospectively from patient interviews and medical records. The study included four Danish medical emergency departments (EDs) and was conducted between 1 March 2021 and 28 February 2022. PARTICIPANTS: A total of 954 patients admitted with suspected infection were included in the study. PRIMARY AND SECONDARY OUTCOME: The primary outcome was CAP diagnosis assessed by an expert panel. RESULTS: According to expert evaluation, CAP had a 28% prevalence. 13 diagnostic predictors were identified using least absolute shrinkage and selection operator regression to build the prediction model: dyspnoea, expectoration, cough, common cold, malaise, chest pain, respiratory rate (>20 breaths/min), oxygen saturation (<96%), abnormal chest auscultation, leucocytes (<3.5×109/L or >8.8×109/L) and neutrophils (>7.5×109/L). C reactive protein (<20 mg/L) and having no previous event of CAP contributed negatively to the final model. The predictors yielded good prediction performance for CAP with an area under the receiver-operator characteristic curve (AUC) of 0.85 (CI 0.77 to 0.92). However, the initial diagnosis made by the ED physician performed better, with an AUC of 0.86 (CI 84% to 89%). CONCLUSION: Typical respiratory symptoms combined with abnormal vital signs and elevated infection biomarkers were predictors for CAP on admission to an ED. The clinical value of the prediction model is questionable in our setting as it does not outperform the clinician's assessment. Further studies that add novel diagnostic tools and use imaging or serological markers are needed to improve a model that would help diagnose CAP in an ED setting more accurately. TRIAL REGISTRATION NUMBER: NCT04681963.

Improving diagnostics using extended point-of-care testing during in-home assessments of older adults with signs of emerging acute disease: a prospective observational non-randomised pilot and feasibility study.

BACKGROUND: Delayed recognition of acute disease among older adults hinders timely management and increases the risk of hospital admission. Point-of-Care testing, including Focused Lung Ultrasound (FLUS) and in-home analysis of biological material, may support clinical decision-making in suspected acute respiratory disease. The aim of this study was to pilot test the study design for a planned randomised trial, investigate whether in-home extended use of point-of-care testing is feasible, and explore its' potential clinical impact. METHODS: A non-randomised pilot and feasibility study was conducted during September-November 2021 in Kolding Municipality, Denmark. A FLUS-trained physician accompanied an acute community nurse on home-visits to citizens aged 65 + y with signs of acute respiratory disease. The acute community nurses did a clinical assessment (vital signs, capillary C-reactive protein and haemoglobin) and gave a presumptive diagnosis. Subsequently, the physician performed FLUS, venipuncture with bedside analysis (electrolytes, creatinine, white blood cell differential count), nasopharyngeal swab (PCR for upper respiratory pathogens), and urine samples (flow-cytometry). Primary outcomes were feasibility of study design and extended point-of-care testing; secondary outcome was the potential clinical impact of extended point-of-care testing. RESULTS: One hundred consecutive individuals were included. Average age was 81.6 (SD ± 8.4). Feasibility of study design was acceptable, FLUS 100%, blood-analyses 81%, PCR for upper respiratory pathogens 79%, and urine flow-cytometry 4%. In addition to the acute community nurse's presumptive diagnosis, extended point-of-care testing identified 34 individuals with a condition in need of further evaluation by a physician. CONCLUSION: Overall, in-home assessments with extended point-of-care testing are feasible and may aid to identify and handle acute diseases in older adults.

The Diagnostic Accuracy of Procalcitonin, Soluble Urokinase-Type Plasminogen Activator Receptors, and C-Reactive Protein in Diagnosing Urinary Tract Infections in the Emergency Department-A Diagnostic Accuracy Study.

Background: Urinary tract infections (UTIs) are a leading bacterial infection in the emergency department (ED). Diagnosing UTIs in the ED can be challenging due to the heterogeneous presentation; therefore, fast and precise tests are needed. We aimed to evaluate the diagnostic precision of procalcitonin (PCT), soluble urokinase plasminogen activator receptors (suPARs), and C-reactive protein (CRP) in diagnosing UTIs, grading the severity of UTIs, and ruling out bacteremia. Methods: We recruited adults admitted to three Danish EDs with suspected UTIs. PCT, suPAR, and CRP were used in index tests, while blood cultures, expert panel diagnosis, and severity grading were used in the reference tests. Logistic regression and area under the receiver operator characteristic curves (AUROCs) were utilized to evaluate the models and determine the optimal cut-offs. Results: We enrolled 229 patients. PCT diagnosed UTI with an AUROC of 0.612, detected severe disease with an AUROC of 0.712, and ruled out bacteremia with an AUROC of 0.777. SuPAR had AUROCs of 0.480, 0.638, and 0.605, while CRP had AUROCs of 0.599, 0.778, and 0.646. Conclusions: The diagnostic performance of PCT, suPAR, or CRP for UTIs or to rule out severe disease was poor. However, PCT can safely rule out bacteremia in clinically relevant numbers in ED patients suspected of UTI.

Extended use of point-of-care technology versus usual care for in-home assessment by acute community nurses in older adults with signs of potential acute respiratory disease: an open-label randomised controlled trial protocol.

BACKGROUND: Due to ageing-related physiological changes, diagnosing older adults is challenging. Delayed disease recognition may lead to adverse health outcomes and increased hospitalisation, necessitating the development of new initiatives for timely diagnosis and treatment of older adults. Point-of-care technology, such as focused lung ultrasound scan and bedside analysis of blood samples (leucocytes with differential count, electrolytes, and creatinine) conducted in the patients' home, may support clinical decision-making, and potentially reduce acute hospital admissions. We present the protocol for a randomized controlled trial, which aims at assessing the effect of focused lung ultrasound scan and bedside blood analysis during in-home assessments among older adults with signs of potential acute respiratory disease on hospital admissions. METHOD: We will use a parallel open-label, individually randomised controlled trial design in an acute community healthcare setting. The trial will initiate on October 2022 and is expected to end one year later. The study population will include older adults (65 + year), with at least one of the following inclusion criteria: Cough, dyspnoea, fever, fall, or rapid functional decline. Expected study sample will comprise 632 participants. Participants in the control group will receive usual care, while the intervention group will undergo extended point-of-care technology (focused lung ultrasound scan and bedside venous blood analysis), in addition to usual care. The primary outcome is acute hospital admission within 30 days follow-up. Secondary outcomes include readmissions, mortality, length of hospital stay, hospital-free days, complications during hospital admission, treatment initiations or changes, functional level, re-referrals to the acute community healthcare service, and contacts to the primary care physician. A tertiary outcome is the diagnostic accuracy of Acute Community Nurses for conducting focused lung ultrasound compared with a specialist. Outcomes will be analysed as intention-to-treat. DISCUSSION: To our knowledge, this is the first randomised controlled trial examining the effect of extended use of point-of-care technology conducted in an in-home setting. We expect that the results may contribute to the development of new interventions aiming to improve timely diagnostics, treatment decisions, and reduce acute hospital admissions. TRIAL REGISTRATION: www. CLINICALTRIALS: org NCT05546073 (Date of registration: September 19th, 2022).

Urine Flow Cytometry and Dipstick Analysis in Diagnosing Bacteriuria and Urinary Tract Infections among Adults in the Emergency Department-A Diagnostic Accuracy Trial.

Urinary tract infections (UTIs) are a leading infectious cause of emergency department admission. Early UTI diagnosis is challenging, and a faster, preferably point-of-care urine analysis is necessary. We aimed to evaluate the diagnostic accuracy of urine flow cytometry (UFC) and urine dipstick analysis (UDA) in identifying bacteriuria and UTIs. This study included adults suspected of an infection admitted to three Danish emergency departments. UFC and UDA were the index tests, and urine culture and an expert panel diagnosis were the reference tests. We used logistic regression and receiver operator characteristics curves to find each test's optimal model and cut-off. We enrolled 966 patients and performed urine cultures on 786. Urine culture was positive in 337, and 200 patients were diagnosed with a UTI. The UFC model ruled out bacteriuria in 10.9% with a negative predictive value (NPV) of 94.6% and ruled out UTI in 38.6% with an NPV of 97.0%. UDA ruled out bacteriuria in 52.1% with an NPV of 79.2% and UTI in 52.8% with an NPV of 93.9%. Neither UFC nor UDA performed well in ruling out bacteriuria in our population. In contrast, both tests ruled out UTI safely and in clinically relevant numbers.

Antibiotic Guideline Adherence at the Emergency Department: A Descriptive Study from a Country with a Restrictive Antibiotic Policy.

BACKGROUND: Denmark has a low level of antimicrobial resistance (AMR). Patients hospitalized with suspected infection often present with unspecific symptoms. This challenges the physician between using narrow-spectrum antibiotics in accordance with guidelines or broad-spectrum antibiotics to compensate for diagnostic uncertainty. The aim of this study was to investigate adherence to a restrictive antibiotic guideline for the most common infection in emergency departments (EDs), namely community-acquired pneumonia (CAP). METHOD: This multicenter descriptive cross-sectional study included adults admitted to Danish EDs with a suspected infection. Data were collected prospectively from medical records. RESULTS: We included 954 patients in the analysis. The most prescribed antibiotics were penicillin with beta-lactamase inhibitor at 4 h (307 (32.2%)), 48 h (289 (30.3%)), and day 5 after admission (218 (22.9%)). The empirical antibiotic treatment guidelines for CAP were followed for 126 (31.3%) of the CAP patients. At 4 h, antibiotics were administered intravenously to 244 (60.7%) of the CAP patients. At day 5, 218 (54.4%) received oral antibiotics. CONCLUSION: Adherence to CAP guidelines was poor. In a country with a restrictive antibiotic policy, infections are commonly treated with broad-spectrum antibiotics against recommendations.

Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial.

BACKGROUND: Rapid and accurate detection of pathogens is needed in community-acquired pneumonia (CAP) to enable appropriate antibiotics and to slow the development of antibiotic resistance. We aimed to compare the effect of point-of-care (POC) polymerase chain reaction (PCR) detection of respiratory pathogens added to standard care with standard care only (SCO) on antibiotic prescriptions after acute hospital admission. METHODS AND FINDINGS: We performed a superiority, parallel-group, open-label, multicentre, randomised controlled trial (RCT) in 3 Danish medical emergency departments (EDs) from March 2021 to February 2022. Adults acutely admitted with suspected CAP during the daytime on weekdays were included and randomly assigned (1:1) to POC-PCR (The Biofire FilmArray Pneumonia Panel plus added to standard care) or SCO (routine culture and, if requested by the attending physician, target-specific PCR) analysis of respiratory samples. We randomly assigned 294 patients with successfully collected samples (tracheal secretion 78.4% or expectorated sputum 21.6%) to POC-PCR (n = 148, 50.4%) or SCO (146, 49.6%). Patients and investigators owning the data were blinded to the allocation and test results. Outcome adjudicators and clinical staff at the ED were not blinded to allocation and test results but were together with the statistician, blinded to data management and analysis. Laboratory staff performing standard care analyses was blinded to allocation. The study coordinator was not blinded. Intention-to-treat and per protocol analysis were performed using logistic regression with Huber-White clustered standard errors for the prescription of antibiotic treatment. Loss to follow-up comprises 3 patients in the POC-PCR (2%) and none in the SCO group. Intention-to-treat analysis showed no difference in the primary outcome of prescriptions of no or narrow-spectrum antibiotics at 4 h after admission for the POC-PCR (n = 91, 62.8%) odds ratio (OR) 1.13; (95% confidence interval (CI) [0.96, 1.34] p = 0.134) and SCO (n = 87, 59.6%). Secondary outcomes showed that prescriptions were significantly more targeted at 4-h OR 5.68; (95% CI [2.49, 12.94] p < 0.001) and 48-h OR 4.20; (95% CI [1.87, 9.40] p < 0.001) and more adequate at 48-h OR 2.11; (95% CI [1.23, 3.61] p = 0.006) and on day 5 in the POC-PCR group OR 1.40; (95% CI [1.18, 1.66] p < 0.001). There was no difference between the groups in relation to intensive care unit (ICU) admissions OR 0.54; (95% CI [0.10, 2.91] p = 0.475), readmission within 30 days OR 0.90; (95% CI [0.43, 1.86] p = 0.787), length of stay (LOS) IRR 0.82; (95% CI [0.63, 1.07] p = 0.164), 30 days mortality OR 1.24; (95% CI [0.32, 4.82] p = 0.749), and in-hospital mortality OR 0.98; (95% CI [0.19, 5.06] p = 0.986). CONCLUSIONS: In a setting with an already restrictive use of antibiotics, adding POC-PCR to the diagnostic setup did not increase the number of patients treated with narrow-spectrum or without antibiotics. POC-PCR may result in a more targeted and adequate use of antibiotics. A significant study limitation was the concurrent Coronavirus Disease 2019 (COVID-19) pandemic resulting in an unusually low transmission of respiratory virus. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04651712).

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.

Empirical antibiotic treatment for community-acquired pneumonia and accuracy for Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae: a descriptive cross-sectional study of adult patients in the emergency department.

BACKGROUND: Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an acute hospital visit and to determine if the current treatment algorithm provided specific and sufficient coverage against Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae (LMC). METHODS: A descriptive cross-sectional, multicenter study of all adults with an acute hospital visit in the Region of Southern Denmark between January 2016 and March 2018 was performed. Using medical records, we retrospectively identified the empirical antibiotic treatment and the microbiological etiology for CAP patients. CAP patients who were prescribed antibiotics within 24 h of admission and with an identified bacterial pathogen were included. The prescribed empirical antibiotic treatment and its ability to provide specific and sufficient coverage against LMC pneumonia were determined. RESULTS: Of the 19,133 patients diagnosed with CAP, 1590 (8.3%) patients were included in this study. Piperacillin-tazobactam and Beta-lactamase sensitive penicillins were the most commonly prescribed empirical treatments, 515 (32%) and 388 (24%), respectively. Our analysis showed that 42 (37%, 95% CI: 28-47%) of 113 patients with LMC pneumonia were prescribed antibiotics with LMC coverage, and 42 (12%, 95% CI: 8-15%) of 364 patients prescribed antibiotics with LMC coverage had LMC pneumonia. CONCLUSION: Piperacillin-tazobactam, a broad-spectrum antibiotic recommended for uncertain infectious focus, was the most frequent CAP treatment and prescribed to every third patient. In addition, the current empirical antibiotic treatment accuracy was low for LMC pneumonia. Therefore, future research should focus on faster diagnostic tools for identifying the infection focus and precise microbiological testing.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial].

INTRODUCTION: A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI. METHODS AND ANALYSIS: The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. INCLUSION CRITERIA: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future. ETHICS AND DISSEMINATION: This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05530551.

Vancomycin-sensitive Enterococcus faecium bacteraemia - hospital transmission and mortality in a Danish University Hospital.

Introduction. The emergence of vancomycin-resistant Enterococcus faecium (VREfm) has left the vancomycin-sensitive E. faecium (VSEfm) strains almost unnoticed.Hypothesis. Molecular characteristics, hospital transmission patterns and clinical impact of VSEfm have changed, and VSEfm is a predictor of VREfm introduction.Aim. We wanted to do a molecular characterization of VSEfm to identify hospital transmissions and links between VSEfm and VREfm, and to investigate the demographics, treatment and impact on mortality of VSEfm bacteraemia.Methodology. VSEfm and VREfm blood culture isolates from Odense University Hospital, Denmark, from 2015 to 2019 were characterized using whole-genome sequencing and core-genome multilocus sequence typing (cgMLST). Clonal shifts and diversity of the VREfm isolates were compared to the VSEfm isolates. Hospital records were used for clinical data and transmission investigation of VSEfm cases.Results. Six-hundred and thirty VSEfm isolates from 599 patients belonged to 42 sequence types (STs) and 131 complex types (CTs) in several clusters. Multiple types were involved in putative transmission, occurring over the entire period. Twenty-seven VREfm bacteraemia cases were included. No correlation between the VSEfm and VREfm clones was identified. The 30 day mortality was 40 %, but only in 6.3 % of the cases, VSEfm bacteraemia was the likely cause of death.Conclusion. The molecular types of VSEfm bacteraemia isolates are changing and diverse. No direct correlation between VSEfm and the introduction of VREfm was found, but widespread hospital transmission indicates a presence of risk factors that could facilitate transmission of other micro-organisms as well. VSEfm bacteraemia is rarely the cause of death, indicating that 30 day mortality does not reflect the cause of death.

Carrier prevalence of Clostridioides difficile in emergency departments and the association of prior antibiotic consumption: a combined cross-sectional and nested case-control study.

INTRODUCTION: Clostridioides difficile infection is an urgent public health threat, and the incidence has been increasing over the last decades. Knowledge of the prevalence of C. difficile in acutely admitted patients and risk factors for colonization with C. difficile assists emergency departments (EDs) in prioritizing preventive initiatives. This national study aimed to describe prevalence and risk factors for C. difficile carriers acutely admitted to EDs, focusing on the impact of earlier antibiotic prescription. METHODS: We conducted a nationwide analytic cross-sectional study with prospective data collection combined with a nested case-control study with retrospective data collection. All adults visiting one of eight Danish EDs were interviewed and examined for C. difficile. Using a national register, we collected the antibiotic history within the 2 years prior to enrolment. The primary outcome was the prevalence of C. difficile colonization, and secondary outcomes were related to risk factors and prior antibiotic prescription. Multivariate analyses examined the association between earlier antibiotic prescription and C. difficile colonization. RESULTS: Of 5019 participants, 89 were colonized with C. difficile (prevalence of 1.8%). A significant and exposure-dependent association was found for penicillins [DDD/person-year(PY) > 20; OR 4.93 (95% CI 2.22-10.97)] and fluoroquinolones [DDD/PY > 20; OR 8.81 (95% CI 2.54-30.55)], but not macrolides. Timing of the prescription did not affect the association. CONCLUSIONS: One out of 55 patients visiting a Danish ED were colonized with C. difficile. Risk factors for colonization included high age, comorbidity and prior prescription of fluoroquinolones and penicillins.

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.

Gram Stain and Culture of Sputum Samples Detect Only Few Pathogens in Community-Acquired Lower Respiratory Tract Infections: Secondary Analysis of a Randomized Controlled Trial.

Identification of the bacterial etiology of lower respiratory tract infections (LRTI) is crucial to ensure a narrow-spectrum, targeted antibiotic treatment. However, Gram stain and culture results are often difficult to interpret as they depend strongly on sputum sample quality. We aimed to investigate the diagnostic yield of Gram stain and culture from respiratory samples collected by tracheal suction and expiratory technique from adults admitted with suspected community-acquired LRTI (CA-LRTI). In this secondary analysis of a randomized controlled trial, 177 (62%) samples were collected by tracheal suction, and 108 (38%) by expiratory technique. We detected few pathogenic microorganisms, and regardless of sputum quality, there were no significant differences between the sample types. Common pathogens of CA-LRTI were identified by culture in 19 (7%) samples, with a significant difference between patients with or without prior antibiotic treatment (p = 0.007). The clinical value of sputum Gram stain and culture in CA-LRTI is therefore questionable, especially in patients treated with antibiotics.

Prevalence and Mortality of Infective Endocarditis in Community-Acquired and Healthcare-Associated Staphylococcus aureus Bacteremia: A Danish Nationwide Registry-Based Cohort Study.

Background: Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods: First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results: We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86-2.41]). No difference in mortality was observed with 0-40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83-1.37]), while with 41-365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53-.95]). Conclusions: Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality.

Chief Complaints, Underlying Diagnoses, and Mortality in Adult, Non-trauma Emergency Department Visits: A Population-based, Multicenter Cohort Study.

INTRODUCTION: Knowledge about the relationship between symptoms, diagnoses, and mortality in emergency department (ED) patients is essential for the emergency physician to optimize treatment, monitoring, and flow. In this study, we investigated the association between symptoms and discharge diagnoses; symptoms and mortality; and we then analyzed whether the association between symptoms and mortality was influenced by other risk factors. METHODS: This was a population-based, multicenter cohort study of all non-trauma ED patients ≥18 years who presented at a hospital in the Region of Southern Denmark between January 1, 2016-March 20, 2018. We used multivariable logistic regression to examine the association between symptoms and mortality adjusted for other risk factors. RESULTS: We included 223,612 ED visits with a median patient age of 63 and even distribution of females and males. The frequency of the chief complaints at presentation were as follows: non-specific symptoms (19%); abdominal pain (16%); dyspnea (12%); fever (8%); chest pain (8%); and neurologic complaints (7%). Discharge diagnoses were symptom-based (24%), observational (hospital visit for observation or examination, 17%), circulatory (12%), or respiratory (12%). The overall 30-day mortality was 3.5%, with 1.7% dead within 0-7 days and 1.8% within 8-30 days. The presenting symptom was associated with mortality at 0-7 days but not with mortality at 8-30 days. Patients whose charts were missing documentation of symptoms (adjusted odds ratio [aOR] 3.5) and dyspneic patients (aOR 2.4) had the highest mortality at 0-7 days across patients with different primary symptoms. Patients ≥80 years and patients with a higher degree of comorbidity had increased mortality from 0-7 days to 8-30 days (aOR from 24.0 to 42.7 and 1.9 to 2.8, respectively). CONCLUSION: Short-term mortality was more strongly associated with patient-related factors than with the primary presenting symptom at arrival to the hospital.

Expiratory Technique versus Tracheal Suction to Obtain Good-Quality Sputum from Patients with Suspected Lower Respiratory Tract Infection: A Randomized Controlled Trial.

Microbiological diagnostics of good-quality sputum samples are fundamental for infection control and targeted treatment of lower respiratory tract infections (LRTI). This study aims to compare the expiratory technique and tracheal suction on the quality of sputa from adults acutely hospitalized with suspected LRTI. We performed an open-label, randomized controlled trial. Patients were randomized to sputum sampling by tracheal suction (standard care) or the expiratory technique. The primary outcome was quality of sputum evaluated by microscopy and was analysed in the intention-to-treat population. The secondary outcomes were adverse events and patients experience. In total, 280 patients were assigned to tracheal suction (n = 141, 50.4%) or the expiratory technique (n = 139, 49.6%). Sputum samples were collected from 122 (86.5%) patients with tracheal suction and 67 (48.2%) patients with expiratory technique. Good-quality sputa were obtained more often with tracheal suction than with expiratory technique (odds ratio 1.83 [95% CI 1.05 to 3.19]; p = 0.035). There was no statistical difference in adverse events (IRR 1.21 [95% CI, 0.94 to 1.66]; p = 0.136), but patient experience was better in the expiratory technique group (p < 0.0001). In conclusion, tracheal suction should be considered a routine procedure in emergency departments for patients with suspected LRTI.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.