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).

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.

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.

Point-of-Care Lung Ultrasound in Emergency Medicine: A Scoping Review With an Interactive Database.

BACKGROUND: This scoping review was conducted to provide an overview of the evidence of point-of-care lung ultrasound (LUS) in emergency medicine. By emphasizing clinical topics, time trends, study designs, and the scope of the primary outcomes, a map is provided for physicians and researchers to guide their future initiatives. RESEARCH QUESTION: Which study designs and primary outcomes are reported in published studies of LUS in emergency medicine? STUDY DESIGN AND METHODS: We performed a systematic search in the PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library databases for LUS studies published prior to May 13, 2023. Study characteristics were synthesized quantitatively. The primary outcomes in all papers were categorized into the hierarchical Fryback and Thornbury levels. RESULTS: A total of 4,076 papers were screened and, following selection and handsearching, 406 papers were included. The number of publications doubled from January 2020 to May 2023 (204 to 406 papers). The study designs were primarily observational (n = 375 [92%]), followed by randomized (n = 18 [4%]) and case series (n = 13 [3%]). The primary outcome measure concerned diagnostic accuracy in 319 papers (79%), diagnostic thinking in 32 (8%), therapeutic changes in 4 (1%), and patient outcomes in 14 (3%). No increase in the proportions of randomized controlled trials or the scope of primary outcome measures was observed with time. A freely available interactive database was created to enable readers to search for any given interest (https://public.tableau.com/app/profile/blinded/viz/LUSinEM_240216/INFO). INTERPRETATION: Observational diagnostic studies have been produced in abundance, leaving a paucity of research exploring clinical utility. Notably, research exploring whether LUS causes changes to clinical decisions is imperative prior to any further research being made into patient benefits.

Effectiveness of expiratory technique and induced sputum in obtaining good quality sputum from patients acutely hospitalized with suspected lower respiratory tract infection: a statistical analysis plan for a randomized controlled trial.

BACKGROUND: Targeted antimicrobial treatment is essential to avoid unnecessary use of broad-spectrum antibiotics and antimicrobial resistance. Targeted treatment relies on a precise microbiological diagnosis - in pneumonia, this poses a challenge as the usefulness of Gram stains and cultures is highly dependent on the quality of the sputum sample. This study aims to examine adverse effects and quality of sputum samples obtained by expiratory techniques (forced expiratory technique and sputum induction) compared with tracheal suction. The hypothesis is that expiratory techniques are non-inferior to tracheal suction in obtaining samples from the lower respiratory tract. This statistical analysis plan (SAP) describes the study design, method, and data analysis of the trial to increase transparency, avoid reporting bias or data-driven analysis and increase the study's reproducibility. METHOD: The design is a pragmatic, non-inferiority, parallel-arm randomized controlled trial including 280 patients admitted with suspected lower respiratory infection to two emergency departments. Patients are randomized to a usual care group, where sputum samples are collected by tracheal suction or to an intervention group where sputum samples are collected by forced expiratory technique and sputum induction. The statistical analysis will follow an intention-to-treat protocol. This SAP is developed and submitted before the end of recruitment, database closure, and statistical analyses. DISCUSSION: The results of this study will provide valuable knowledge to clinical practice by comparing adverse effects and sputum sample quality associated with different sample methods. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04595526 . Submitted on October 19, 2020.

Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study.

BACKGROUND: The major obstacle in prescribing an appropriate and targeted antibiotic treatment is insufficient knowledge concerning whether the patient has a bacterial infection, where the focus of infection is and which bacteria are the agents of the infection. A prerequisite for the appropriate use of antibiotics is timely access to accurate diagnostics such as point-of-care (POC) testing.The study aims to evaluate diagnostic tools and working methods that support a prompt and accurate diagnosis of hospitalised patients suspected of an acute infection. We will focus on the most common acute infections: community-acquired pneumonia (CAP) and acute pyelonephritis (APN). The objectives are to investigate (1) patient characteristics and treatment trajectory of the different acute infections, (2) diagnostic and prognostic accuracy of infection markers, (3) diagnostic accuracy of POC urine flow cytometry on diagnosing and excluding bacteriuria, (4) how effective the addition of POC analysis of sputum to the diagnostic set-up for CAP is on antibiotic prescriptions, (5) diagnostic accuracy of POC ultrasound and ultralow dose (ULD) computerized tomography (CT) on diagnosing CAP, (6) diagnostic accuracy of specialist ultrasound on diagnosing APN, (7) diagnostic accuracy of POC ultrasound in diagnosing hydronephrosis in patients suspected of APN. METHODS AND ANALYSIS: It is a multifaceted multicentre diagnostic study, including 1000 adults admitted with suspicion of an acute infection. Participants will, within the first 24 hours of admission, undergo additional diagnostic tests including infection markers, POC urine flow cytometry, POC analysis of sputum, POC and specialist ultrasound, and ULDCT. The primary reference standard is an assigned diagnosis determined by a panel of experts. ETHICS, DISSEMINATION AND REGISTRATION: Approved by Regional Committees on Health Research Ethics for Southern Denmark, Danish Data Protection Agency and clinicaltrials.gov. Results will be presented in peer-reviewed journals, and positive, negative and inconclusive results will be published. TRIAL REGISTRATION NUMBERS: NCT04661085, NCT04681963, NCT04667195, NCT04652167, NCT04686318, NCT04686292, NCT04651712, NCT04645030, NCT04651244.

Limited value of sputum culture to guide antibiotic treatment in a Danish emergency department.

INTRODUCTION: Antibiotics resistance is increasing worldwide. The Region of Southern Denmark developed an antibiotic stewardship to reduce the use of broad-spectrum antibiotics in hospitals including microbiological diagnostics of sputum samples. The aim of this study was to evaluate the implementation of the stewardship in the emergency department (ED) concerning management of pulmonary infections. The objectives were: 1) to investigate whether the empirical therapy was prescribed correctly, 2) to identify the quality and results of pre-antibiotic sputum collection and 3) to investigate whether the antibiotic treatment was revised based on the microbiological results. METHODS: This was a quality assessment study. Patient files from patients discharged with either pneumonia or acute exacerbation of chronic pulmonary disease were reviewed, and written feedback was provided to the doctors, focusing on the regional guideline. RESULTS: Among the 257 medical records audited, the guideline was followed in 89% of the cases. Pre-antibiotic sputum samples were collected from 47% of the patients and 79% of these had sufficient quality for cultivation. None of the empirical antibiotic treatments were revised based on the microbiological results but some were revised based on other clinical parameters. CONCLUSIONS: Sputum samples had no clinical value for adjustment of the antibiotic treatment. Improvements of sputum sample collection and faster microbiological diagnostics are needed for sputum analysis to have any impact on the antibiotic treatment of patients with a pulmonary infection in the ED. FUNDING: none. TRIAL REGISTRATION: not relevant.