Protein and transcriptional biomarker profiling may inform treatment strategies in lower respiratory tract infections by indicating bacterial-viral differentiation.

Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (n = 36), viral (n = 27; excluding SARS-CoV-2), SARS-CoV-2 (n = 22), and mixed bacterial-viral (n = 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial, n = 8; viral, n = 8; and SARS-CoV-2, n = 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1ß, and TNFα) that discriminated between patients with bacterial (n = 36) vs viral (n = 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial-viral infections (antibiotics clinically justified; n = 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified; n = 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1ß, IL7, IP10, MIP1α, MIP1ß, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (n = 8) from viral and SARS-CoV-2 (n = 16) etiology. Protein-protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial-viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs. IMPORTANCE: Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Patient influx to emergency departments at two Norwegian university hospitals from 2012-21. / Pasienttilstrøyming til akuttmottak ved to norske universitetssjukehus i 2012­21.

Background: The increase in patient visits to emergency departments is a global challenge. We wished to survey patient inflow and patient composition over time at two Norwegian university hospitals. Material and method: A retrospective, descriptive study of patient contacts (patients ≥ 16 years of age) in the emergency departments of Haukeland University Hospital, Bergen, and St Olav's Hospital, Trondheim University Hospital in the period 2012-21. Data were retrieved from patient records and the patient administration system. Result: A total of 585 780 patient contacts were included. The number of patient contacts in the emergency departments was 30 696 in 2012 and 40 396 in 2021 at Haukeland University Hospital, and 18 967 in 2012 and 28 822 in 2021 at St Olav's Hospital. The largest increase during the study period appeared to be in the age group 67-79 years, with an increase of 57 % (from 6 190 to 9 691) at Haukeland University Hospital, and 77 % (from 3 849 to 6 817) at St Olav's Hospital. The proportion of patient contacts that ended in hospitalisation was 82 % in 2012 and 74 % in 2021 at Haukeland University Hospital, and 87 % in 2012 and 61 % in 2021 at St Olav's Hospital. Of the patients that were admitted, the median age was 65 years, while the median age of those who were discharged from the emergency department was 48 years at Haukeland University Hospital and 52 years at St Olav's Hospital. Interpretation: The study showed an increase in patient contacts in the emergency departments at Haukeland University Hospital and St Olav's Hospital over a period of ten years. The number of older adults in the population will continue to increase in the years ahead, and the need for urgent care assessments will correspondingly increase. It is important that the health services are aware of changes in patient influx and patient composition in order to ensure patient safety and the working environment of emergency departments in the future.

Microbial aetiology of community-acquired pneumonia in hospitalised adults: A prospective study utilising comprehensive molecular testing.

OBJECTIVES: This study aimed to describe the microbial aetiology of community-acquired pneumonia (CAP) in adults admitted to a tertiary care hospital and assess the impact of syndromic polymerase chain reaction (PCR) panels on pathogen detection. METHODS: Conducted at Haukeland University Hospital, Norway, from September 2020 to April 2023, this prospective study enrolled adults with suspected CAP. We analysed lower respiratory tract samples using both standard-of-care tests and the BIOFIRE® FILMARRAY® Pneumonia Plus Panel (FAP plus). The added value of FAP Plus in enhancing the detection of clinically relevant pathogens, alongside standard-of-care diagnostics, was assessed. RESULTS: Of the 3238 patients screened, 640 met the inclusion criteria, with 384 confirmed to have CAP at discharge. In these patients, pathogens with proven or probable clinical significance were identified in 312 (81.3%) patients. Haemophilus influenzae was the most prevalent pathogen, found in 118 patients (30.7%), followed by SARS-CoV-2 in 74 (19.3%), and Streptococcus pneumoniae in 64 (16.7%). Respiratory viruses were detected in 186 (48.4%) patients. The use of FAP plus improved the pathogen detection rate from 62.8% with standard-of-care methods to 81.3%. CONCLUSIONS: Pathogens were identified in 81% of CAP patients, with Haemophilus influenzae and respiratory viruses being the most frequently detected pathogens. The addition of the FAP plus panel, markedly improved pathogen detection rates compared to standard-of-care diagnostics alone.

The diagnostic utility of microscopic quality assessment of sputum samples in the era of rapid syndromic PCR testing.

This prospective study assessed the value of initial microscopy evaluation of sputum samples submitted for rapid syndromic PCR-based testing. Bacterial detections by the BioFire FilmArray Pneumonia Panel plus in 126 high- and 108 low-quality sputum samples, based on initial microscopy evaluation in samples from patients with lower respiratory tract infections were compared. We found that high-quality samples had a higher proportion of bacterial detections compared to low-quality samples (P = 0.013). This included a higher proportion of detections of bacteria deemed clinically relevant by predefined criteria (70% and 55%, P = 0.016), as well as a higher proportion of detections of Haemophilus influenzae (36% and 20%, P = 0.010). High-quality samples also had more detections of bacteria with high semi-quantitative values. The study found no significant difference between high- and low-quality samples in the proportions of samples with a single species of bacteria detected, samples with a bacteria treated by the clinician, samples with detection of a proven etiology of community-acquired pneumonia by predefined criteria, the number of bacterial species detected, or the detection of Streptococcus pneumoniae, Moraxella catarrhalis, or Staphylococcus aureus. The results showed that 40% (95% CI 35%-47%) of the bacterial detections would have been missed if only high-quality samples were analyzed. This included 41% (27%-56%) of detections of S. pneumoniae, 33% (23%-45%) of detections of H. influenzae, 42% (28%-58%) of detections of S. aureus, and 37% (23%-54%) of detections of M. catarrhalis. These findings suggest that all sputum samples submitted for rapid syndromic PCR testing should be analyzed, regardless of initial microscopy quality assessment. (This study has been registered at ClinicalTrials.gov under registration no. NCT04660084.) IMPORTANCE Microscopic quality assessment of sputum samples was originally designed for sputum culture, and its applicability in today's workflow, which includes syndromic PCR testing, may differ. Addressing this crucial gap, our study emphasizes the need to optimize the use and workflow of syndromic PCR panels, like the BioFire FilmArray Pneumonia plus (FAP plus), in microbiology laboratories. These advanced PCR-based tests offer rapid and comprehensive pathogen detection for respiratory infections, yet their full potential remains uncertain. By comparing bacterial detections in high- and low-quality sputum samples, we underscore the importance of including low-quality samples in testing. Our findings reveal a significant proportion of potentially clinically relevant bacterial detections that would have been missed if only high-quality samples were analyzed. These insights support the efficient implementation of syndromic PCR panels, ultimately enhancing patient care and outcomes.

Validation of a modified South African triage scale in a high-resource setting: a retrospective cohort study.

BACKGROUND: Triage systems are widely used in emergency departments, but are not always validated. The South African Triage Scale (SATS) has mainly been studied in resource-limited settings. The aim of this study was to determine the validity of a modified version of the SATS for the general population of patients admitted to an ED at a tertiary hospital in a high-income country. The secondary objective was to study the triage performance according to age and patient categories. METHODS: We conducted a retrospective cohort study of patients presenting to the Emergency Department of Haukeland University Hospital in Norway during a four-year period. We used short-term mortality, ICU admission, and the need for immediate surgery and other interventions as the primary endpoints. RESULTS: A total of 162,034 emergency department visits were included in the analysis. The negative predictive value of a low triage level to exclude severe illness was 99.1% (95% confidence interval: 99.0-99.2%). The level of overtriage, defined as the proportion of patients assigned to a high triage level who were not admitted to the hospital, was 4.1% (3.9-4.2%). Receiver operating characteristic (ROC) curves showed an area under the ROC for the detection of severe illness of 0.874 (95% confidence interval: 0.870-0.879) for all patients and 0.856 (0.837-0.875), 0.884 (0.878-0.890) and 0.869 (0.862-0.876) for children, adults and elderly individuals respectively. CONCLUSION: We found that the modified SATS had a good sensitivity to identify short-term mortality, ICU admission, and the need for rapid surgery and other interventions. The sensitivity was higher in adults than in children and higher in medical patients than in surgical patients. The over- and undertriage rates were acceptable.

Comparison of rapid molecular testing methods for detecting respiratory viruses in emergency care: a prospective study.

BACKGROUND: Respiratory tract infections (RTIs) caused by contagious viruses are common among patients presenting to the emergency department (ED). Early detection of these viruses can help prevent nosocomial transmission. AIM: To investigate the efficacy of three rapid molecular methods, namely FilmArray® Pneumonia Panel plus (FAP plus), ID NOW™ Influenza A and B 2 (ID NOW2) point-of-care test, and an in-house real-time polymerase chain reaction (RT-PCR) test, to identify patients with viral RTIs requiring isolation in an emergency setting. METHODS: We included a FilmArray® Pneumonia Panel plus in the initial workup of patients with suspected RTIs during a flu season. The RT-PCR and the influenza point-of-care test were performed as part of routine diagnostics, on demand from the treating physicians. We compared viral detections and compared time to positive test results for each method. FINDINGS: The FAP plus significantly reduced the turnaround time and was able to identify 95% patients with potential contagious viral RTI. Routine diagnostics ordered by the treating physician had a turnaround time of a median 22 h and detected 87% of patients with potential contagious viral RTI. In patients that had all three tests, the ID NOW2 detected 62% of patients with influenza. CONCLUSIONS: The FAP plus was able to rapidly and reliably identify patients with potential contagious viral RTIs; its use was feasible in the ED setting. Failing to test patients with viral RTI and using tests with long turnaround time may lead to nosocomial transmission of viral infections and adverse patient outcomes.

Epistaxis after testing for COVID-19. / Neseblødning etter testing for covid-19.

BACKGROUND: Testing for airway microbes has increased during the current COVID-19 pandemic. This case report demonstrates that testing can lead to complications. CASE PRESENTATION: A man in his seventies was transferred to our hospital for coronary angiography. On admission he underwent testing with nasopharyngeal swab for COVID-19. He started bleeding profusely from the nostril insertion site. The haemorrhage was controlled by bilateral anterior and posterior balloon tamponade, the coronary angiography was postponed, he was given a transfusion of packed red blood cells and had to spend a total of nine days in hospital. INTERPRETATION: The World Health Organization recommends screening of all patients for COVID-19 upon admission to hospital. The risk of every procedure must be carefully considered in relation to the benefits, especially when large numbers of patients are affected. For our patient, the likelihood of COVID-19 infection was low, and the risk of complications was high.

Inflammatory Mediator Profiles Differ in Sepsis Patients With and Without Bacteremia.

Systemic levels of cytokines are altered during infection and sepsis. This prospective observational study aimed to investigate whether plasma levels of multiple inflammatory mediators differed between sepsis patients with and those without bacteremia during the initial phase of hospitalization. A total of 80 sepsis patients with proven bacterial infection and no immunosuppression were included in the study. Plasma samples were collected within 24 h of hospitalization, and Luminex® analysis was performed on 35 mediators: 16 cytokines, six growth factors, four adhesion molecules, and nine matrix metalloproteases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs). Forty-two patients (52.5%) and 38 (47.5%) patients showed positive and negative blood cultures, respectively. There were significant differences in plasma levels of six soluble mediators between the two "bacteremia" and "non-bacteremia" groups, using Mann-Whitney U test (p < 0.0014): tumor necrosis factor alpha (TNFα), CCL4, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and TIMP-1. Ten soluble mediators also significantly differed in plasma levels between the two groups, with p-values ranging between 0.05 and 0.0014: interleukin (IL)-1ra, IL-10, CCL2, CCL5, CXCL8, CXCL11, hepatocyte growth factor, MMP-8, TIMP-2, and TIMP-4. VCAM-1 showed the most robust results using univariate and multivariate logistic regression. Using unsupervised hierarchical clustering, we found that TNFα, CCL4, E-selectin, VCAM-1, ICAM-1, and TIMP-1 could be used to discriminate between patients with and those without bacteremia. Patients with bacteremia were mainly clustered in two separate groups (two upper clusters, 41/42, 98%), with higher levels of the mediators. One (2%) patient with bacteremia was clustered in the lower cluster, which compromised most of the patients without bacteremia (23/38, 61%) (χ2 test, p < 0.0001). Our study showed that analysis of the plasma inflammatory mediator profile could represent a potential strategy for early identification of patients with bacteremia.