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Introduction: Sepsis is a heterogeneous syndrome often misdiagnosed. Point-of-care (POC) diagnostic tests are commonly used to guide decision and include host biomarkers and molecular diagnostics. Areas covered: The diagnostic and prognostic accuracy of established and emerging biomarkers for sepsis, including procalcitonin (PCT) soluble urokinase plasminogen activator receptor (suPAR), presepsin, TRAIL/IP-10/CRP, MxA, and MxA-CRP, are analyzed in this review. The clinical utility of the two prevalent molecular techniques for pathogens identification using polymerase chain reaction (PCR) assays is also presented: FILMARRAY and QIAstat-Dx RP. Expert opinion: The rising benefits of the combined use of POC biomarkers with molecular diagnostics in daily clinical routine appear to outperform conventional practices in terms of reduced turnaround time, timely diagnosis, and prompt administration of the appropriate treatment. Yet, this must be further demonstrated in future investigations. However, the cost-effectiveness of POC tests and the high rate of false positive and negative results, indicate the need for a comprehensive clinical evaluation. [ABSTRACT FROM AUTHOR]

We assessed whether multiplex real-time PCR plus conventional microbiological testing is safe and more effective than conventional microbiological testing alone for reducing antibiotic use in community-acquired pneumonia (CAP). In this randomised trial, we recruited adults hospitalised with CAP at four Spanish hospitals. Patients were randomly assigned (1:1) to undergo either multiplex real-time PCR in non-invasive respiratory samples plus conventional microbiological testing or conventional microbiological testing alone. The primary endpoint was antibiotic use measured by days of antibiotic therapy (DOT). Between February 20, 2020, and April 24, 2023, 242 patients were enrolled; 119 were randomly assigned to multiplex real-time PCR plus conventional microbiological testing and 123 to conventional microbiological testing alone. All but one of the patients allocated to multiplex real-time PCR plus conventional microbiological testing underwent PCR, which was performed in sputum samples in 77 patients (65.2%) and in nasopharyngeal swabs in 41 (34.7%). The median DOT was 10.04 (IQR 7.98, 12.94) in the multiplex PCR plus conventional microbiological testing group and 11.33 (IQR 8.15, 16.16) in the conventional microbiological testing alone group (difference −1.04; 95% CI, −2.42 to 0.17; p = 0.093). No differences were observed in adverse events and 30-day mortality. Our findings do not support the routine implementation of multiplex real-time PCR in the initial microbiological testing in hospitalised patients with CAP. Clinicaltrials.gov registration: NCT04158492. Here, the authors report the results of a randomised trial assessing whether adding multiplex real-time PCR to conventional testing reduces antibiotic use in community-acquired pneumonia and observe no significant reduction in days of antibiotic therapy or in 30-day mortality. [ABSTRACT FROM AUTHOR]

Background: Without increasing radiation exposure, ultralow-dose computed tomography (CT) of the chest provides improved diagnostic accuracy of radiological pneumonia diagnosis compared to a chest radiograph. Yet, radiologist resources to rapidly report the chest CTs are limited. This study aimed to assess the diagnostic accuracy of emergency clinicians' assessments of chest ultralow-dose CTs for community-acquired pneumonia using a radiologist's assessments as reference standard. Methods: This was a cross-sectional diagnostic accuracy study. Ten emergency department clinicians (five junior clinicians, five consultants) assessed chest ultralow-dose CTs from acutely hospitalised patients suspected of having community-acquired pneumonia. Before assessments, the clinicians attended a focused training course on assessing ultralow-dose CTs for pneumonia. The reference standard was the assessment by an experienced emergency department radiologist. Primary outcome was the presence or absence of pulmonary opacities consistent with community-acquired pneumonia. Sensitivity, specificity, and predictive values were calculated using generalised estimating equations. Results: All clinicians assessed 128 ultralow-dose CTs. The prevalence of findings consistent with community-acquired pneumonia was 56%. Seventy-eight percent of the clinicians' CT assessments matched the reference assessment. Diagnostic accuracy estimates were: sensitivity = 83% (95%CI: 77–88), specificity = 70% (95%CI: 59–81), positive predictive value = 80% (95%CI: 74–84), negative predictive value = 78% (95%CI: 73–82). Conclusion: This study found that clinicians could assess chest ultralow-dose CTs for community-acquired pneumonia with high diagnostic accuracy. A higher level of clinical experience was not associated with better diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Community-acquired pneumonia (CAP) is an infectious disease associated with high mortality worldwide. Although Streptococcus pneumoniae remains the most frequent pathogen in CAP, data from recent studies using molecular tests have shown that respiratory viruses play a key role in adults with pneumonia. The impact of difficult-to-treat pathogens on the outcomes of pneumonia is also important even though they represent only a small proportion of overall cases. Despite improvements in the microbiological diagnosis of CAP in recent decades, the identification of the causative pathogen is often delayed because of difficulties in obtaining good-quality sputum samples, issues in transporting samples, and slow laboratory processes. Therefore, the initial treatment of CAP is usually empirical. Point-of-care testing (POCT) was introduced to avoid treatment delays and reduce reliance on empirical antibiotics. Areas covered: This review summarizes the main scientific evidence on the role of POCT in the diagnosis and management of patients with CAP. The authors searched for articles on POCT in pneumonia on PubMed from inception to 20 January 2024. The references in the identified articles were also searched. Expert opinion: POCT involves rapid diagnostic assays that can be performed at the bedside especially in cases of severe CAP and immunocompromised patients. These tests can produce results that could help guide initial therapy and management. [ABSTRACT FROM AUTHOR]

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). In this multicentre randomised controlled trial, Mariana Bichuette Cartuliares and colleagues evaluate point-of-care multiplex polymerase chain reaction in antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark. Author summary: Why was this study done?: The global rise in antimicrobial resistance fueled by the excessive use and misuse of antibiotics is a major public health concern. Fast and accurate diagnostics is important to counteract this development as it can potentially reduce the use of antibiotics/broad-spectrum antibiotics without sacrificing patient safety. Pneumonia is a common, serious condition where available point-of-care (POC) technology (polymerase chain reaction) allows clinicians to detect possible airway pathogens before treatment decisions are made. What did the researchers do and find?: In this randomised trial of 294 patients admitted with suspected pneumonia, POC did not result in the prescription of less antibiotics or less broad-spectrum antibiotics within 4 h after admission. Based on a subset of patients, the results indicated that more patients in the POC-group were treated with targeted or appropriate antibiotics 48 h and 5 days after admission. Patients in the POC-group had a non-statistically significant reduction in length of hospital stay of approximately 1 day. What do these findings mean?: The use of respiratory POC does not seem to be an effective tool for reducing the use of antibiotics in a setting with a very low level of antimicrobial resistance and already prudent use of antibiotics. The use of respiratory POC may aid to ensure a targeted and/or appropriate treatment in a setting with a restrictive use of antibiotics—and thereby may aid to sustain a restrictive strategy. The concurrent Coronavirus Disease 2019 (COVID-19) pandemic and the unusually low transmission of common respiratory viruses in the period may have affected the results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]