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.

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).

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.

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.

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.

Colonization with multiresistant bacteria in acute hospital care: the association of prior antibiotic consumption as a risk factor.

BACKGROUND: Antibiotic resistance poses a worldwide threat and knowledge concerning risk factors for colonization with multiresistant bacteria (MRB) is limited. OBJECTIVES: To examine the impact of prior antibiotic consumption on MRB colonization, with focus on type of antibiotic and timeline between antibiotic prescription and MRB colonization. METHODS: A nationwide case-control study was conducted and adults visiting emergency departments were invited to participate. All patients were swabbed in the throat, nose and rectum, and analysed for colonization with ESBL-producing Enterobacteriaceae (ESBL-E), MRSA, carbapenemase-producing enterobacteria and VRE. Antibiotic history 2 years prior to enrolment was collected at an individual level through a national register. Multivariate analyses were performed to examine the association between antibiotic consumption and MRB status. A subgroup analysis of ESBL-E-colonized cases was made. RESULTS: We included 256 patients colonized with MRB and 4763 controls. In the 2 years prior to study inclusion, 77% of cases and 68% of controls had at least one antibiotic prescription (P = 0.002). We found a significant increase in risk of colonization with ESBL-E if penicillins (OR = 1.58-1.65) or fluoroquinolones (OR = 2.25-6.15) were prescribed. The analysis of all MRB-colonized patients showed similar results. An assessment of the timeline showed a significant increase in risk of colonization up to 2 years after exposure to penicillins, fluoroquinolones and macrolides. CONCLUSIONS: The prevalence of ESBL-E colonization was related to fluoroquinolone, macrolide and penicillin consumption for at least 2 years after antibiotic treatment.

Clinical value of FDG-PET/CT in bacteremia of unknown origin with catalase-negative gram-positive cocci or Staphylococcus aureus.

INTRODUCTION: Bacteremia is associated with high mortality, especially when the site of infection is unknown. While conventional imaging usually focus on specific body parts, FDG-PET/CT visualizes hypermetabolic foci throughout the body. PURPOSE: To investigate the ability of FDG/PET-CT to detect the site of infection and its clinical impact in bacteremia of unknown origin with catalase-negative Gram-positive cocci (excluding pneumococci and enterococci) or Staphylococcus aureus (BUOCSA). METHODS: We retrospectively identified 157 patients with 165 episodes of BUOCSA, who subsequently underwent FDG-PET/CT. Data were collected from medical records. Decision regarding important sites of infection in patients with bacteremia was based on the entire patient course and served as reference diagnosis for comparison with FDG-PET/CT findings. FDG-PET/CT was considered to have high clinical impact if it correctly revealed site(s) of infection in areas not assessed by other imaging modalities or if other imaging modalities were negative/equivocal in these areas, or if it established a new clinically relevant diagnosis, and/or led to change in antimicrobial treatment. RESULTS: FDG-PET/CT detected sites of infection in 56.4% of cases and had high clinical impact in 47.3%. It was the first imaging modality to identify sites of infection in 41.1% bacteremia cases, led to change of antimicrobial therapy in 14.7%, and established a new diagnosis unrelated to bacteremia in 9.8%. Detection rate and clinical impact were not significantly influenced by duration of antimicrobial treatment preceding FDG-PET/CT, days from suspicion of bacteremia to FDG-PET/CT-scan, type of bacteremia, or cancer. CONCLUSION: FDG-PET/CT appears clinically useful in BUOCSA. Prospective studies are warranted for confirmation.

Cross sectional study of multiresistant bacteria in Danish emergency departments: prevalence, patterns and risk factors for colonization (AB-RED project).

BACKGROUND: Multiresistant bacteria (MRB) is an increasing problem. Early identification of patients with MRB is mandatory to avoid transmission and to target the antibiotic treatment. The emergency department (ED) is a key player in the early identification of patients who are colonized with MRB. There is currently sparse knowledge of both prevalence and risk factors for colonization with MRSA, ESBL, VRE, CPE and CD in acutely admitted patients in Western European countries including Denmark. To develop evidence-based screening tools for identifying carriers of resistant bacteria among acutely admitted patients, systematic collection of information on risk factors and exposures is required. Since a geographical variation is suspected, it is desirable to include emergency departments across the country. The aim of this project is to provide a comprehensive overview of prevalence and risk factors for MRSA, ESBL, VRE, CPE and CD colonization in patients admitted to Danish ED's. The objectives are to describe the prevalence and demography of resistance, co-infections, to identify risk factors for carrier state and to develop and validate a screening tool for identification of carriers. METHODS: Multicenter descriptive and analytic cross-sectional survey from January-May 2018 of around 10.000 acutely admitted patients > 18 years in 8 EDs for carrier state and risk factors for antibiotic resistant bacteria. Information about the background and possible risk factors for carrier status together with swabs from the nose, throat and rectum is collected and analyzed for MRSA, ESBL, VRE, CPE and CD. The prevalence of the resistant bacteria are calculated at hospital level, regional level and national level and described with relation to residency, sex, age and risk factors. A screening model for identification of carrier stage of resistant bacteria is developed and validated. DISCUSSION: The study will provide the prevalence of colonized patients with resistant bacteria on arrival to the ED and variation in demographic patterns, and will develop a clinical tool to identify certain risk groups. This will enable the clinician to target antibiotic treatments and to reduce the in-hospital spreading of resistant bacteria. This knowledge is important for implementing and evaluating antimicrobial stewardships, screening and infection control strategies. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03352167 (registration date: 20. November 2017).

Automated image analysis for quantification of filamentous bacteria.

BACKGROUND: Antibiotics of the ß-lactam group are able to alter the shape of the bacterial cell wall, e.g. filamentation or a spheroplast formation. Early determination of antimicrobial susceptibility may be complicated by filamentation of bacteria as this can be falsely interpreted as growth in systems relying on colorimetry or turbidometry (such as Vitek-2, Phoenix, MicroScan WalkAway). The objective was to examine an automated image analysis algorithm for quantification of filamentous bacteria using the 3D digital microscopy imaging system, oCelloScope. RESULTS: Three E. coli strains displaying different resistant profiles and differences in filamentation kinetics were used to study a novel image analysis algorithm to quantify length of bacteria and bacterial filamentation. A total of 12 ß-lactam antibiotics or ß-lactam-ß-lactamase inhibitor combinations were analyzed for their ability to induce filamentation. Filamentation peaked at approximately 120 min with an average cell length of 30 µm. CONCLUSION: The automated image analysis algorithm showed a clear ability to rapidly detect and quantify ß-lactam-induced filamentation in E. coli. This rapid determination of ß-lactam-mediated morphological alterations may facilitate future development of fast and accurate AST systems, which in turn will enable early targeted antimicrobial therapy. Therefore, rapid detection of ß-lactam-mediated morphological changes may have important clinical implications.

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.

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.

Clinical characteristics, factors associated with urinary tract infection and outcome in acutely admitted patients with infection; an exploratory cross-sectional cohort study.

Background: Urinary tract infections (UTIs) remain a leading infectious disease cause of admission to the emergency department (ED) and antibiotic prescription. Heterogeneity of disease presentation challenges early diagnostics, leading to improper antibiotic prescription and delayed diagnosis. Prior studies have relied on positive urine cultures for diagnosis, but its performance suffers from false positives and false negatives. This study aimed to identify factors associated with UTIs and describe patient characteristics and outcomes while not using positive urine culture as an obligatory part of diagnosis. Methods: Adult patients admitted to the ED suspected of infection were prospectively included in an exploratory cross-sectional cohort study. An expert panel retrospectively determined the final diagnosis. Factors associated with a UTI were identified using univariate and multivariate logistic regression analysis, outcomes were evaluated with adjusted Cox regression analysis, and length of stay was compared with a zero-inflated negative binomial logistic regression model. Results: Of 966 patients who were enrolled, 200 were diagnosed with a UTI by the expert panel. We found a significant association between a UTI diagnosis and the typical UTI symptoms: dysuria (OR 7.8), change of urine appearance (OR 3.9), suprapubic or flank pain (OR 3.7), and increased urinary frequency (OR 3.2). Urinary dipstick analysis for white blood cells (WBCs) (OR 6.0-24.0), nitrite (OR 4.7), and blood (OR 3.6-12.0) was also significantly associated. Subgroup analysis of urinary dipstick analysis of men and women still showed significance in both groups. No significant difference in outcome or length of stay was found. Conclusion: Typical UTI symptoms are associated with a UTI diagnosis, which underlines the importance of exploring a patient's medical history. Urinary dipstick analysis for WBC, nitrite, and blood is also strongly associated and should be considered when evaluating patients admitted to the ED with suspicion of infection.

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.

Real-time optical antimicrobial susceptibility testing.

Rapid antibiotic susceptibility testing is in high demand in health care fields as antimicrobial-resistant bacterial strains emerge and spread. Here, we describe an optical screening system (oCelloScope) which, based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time, introduces real-time detection of bacterial growth and antimicrobial susceptibility with imaging material to support the automatically generated graphs. Automated antibiotic susceptibility tests of a monoculture showed statistically significant antibiotic effects within 6 min and within 30 min in complex samples from pigs suffering from catheter-associated urinary tract infections. The oCelloScope system provides a fast high-throughput screening method for detecting bacterial susceptibility that might entail an earlier diagnosis and introduction of appropriate targeted therapy and thus combat the threat from multidrug-resistant pathogenic bacteria. The oCelloScope system can be employed for a broad range of applications within bacteriology and might present new vistas as a point-of-care instrument in clinical and veterinary settings.

Performance of matrix-assisted laser desorption-time of flight mass spectrometry for identification of clinical yeast isolates.

Accurate and fast yeast identification is important when treating patients with invasive fungal disease as susceptibility to antifungal agents is highly species related. Matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF-MS) provides a powerful tool with a clear potential to improve current diagnostic practice. Two MALDI-TOF-MS-systems (BioTyper/Bruker and Saramis/AXIMA) were evaluated using: (i) A collection of 102 archived, well characterised yeast isolates representing 14 different species and (ii) Prospectively collected isolates obtained from clinical samples at two participating laboratories. Of the 102 archived isolates, 81 (79%) and 92 (90%) were correctly identified by Saramis/AXIMA and BioTyper/Bruker respectively. Saramis/AXIMA was unable to separate Candida albicans, C. africana and C. dubliniensis in 13 of 32 isolates. After manual interpretation of the mass spectra output, all 13 isolates were correctly identified, resulting in an overall identification performance of 92%. No misidentifications occurred with the two systems. Of the routine isolates one laboratory identified 99/99 (100%) and 90/99 (91%) to species level by Saramis/Axima and conventional identification, respectively, whereas the other laboratory identified 83/98 (85%) to species level by both BioTyper/Bruker and conventional identification. Both MALDI-TOF-MS systems are fast, have built-in databases that cover the majority of clinically relevant Candida species, and have an accuracy that outperforms our conventional identification systems.

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.

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.

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.

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.

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.