The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart ...including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown.
To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia.
This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality.
Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality.
qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.
Recently, the use of nebulized antibiotics in the intensive care unit, in particular amikacin, has been the subject of much discussion, owing to unconvincing results from the latest randomized ...clinical trials. Here, we examine and reappraise the evidence in favor and against this therapeutic strategy; we then discuss the potential factors that might have played a role in the negative findings of recent clinical trials. Also, we call attention to several factors that are seldom considered by study developers and regulatory agencies, to promote translational research in this field and improve the design of future randomized clinical trials.
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is known to present with pulmonary and extra‐pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS‐CoV‐2 ...infection is likely to lead to more severe disease, with multi‐organ effects, including cardiovascular disease. SARS‐CoV‐2 has been associated with acute and long‐term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS‐CoV‐2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS‐CoV‐2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1‐like macrophage infiltration in the cardiac tissues of COVID‐19 patients. The DNA damage present in the SARS‐CoV‐2 patient samples, were further confirmed by γ‐H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon‐stimulated genes, in particular interferon and complement pathways, when compared with COVID‐19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS‐CoV‐2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra‐pulmonary organs, including the cardiovascular system of COVID‐19 patients, to delineate the immunopathobiology of SARS‐CoV‐2 infection, and long term impact on health.
Cardiac tissues collected at rapid autopsy from COVID‐19 and pandemic H1N1 patients were profiled using digital spatial profiling technology. The transcriptional profiles were compared and contrasted in the study to understand the impact of viral infection. Host transcriptomics showed distinct transcriptional profiles, such as DNA damage and repair which were upregulated in COVID‐19. The study highlights the need to understand the pathobiology of severe acute respiratory syndrome coronavirus 2 infection and the multi‐organ effects.
Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care ...Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic.
The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort.
Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population.
AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.
Our aim was to demonstrate that biofilm formation in a clinical strain of methicillin-resistant Staphylococcus aureus (MRSA) can be enhanced by environment exposure in an endotracheal tube (ETT) and ...to determine how it is affected by systemic treatment and atmospheric conditions. Second, we aimed to assess biofilm production dynamics after extubation. We prospectively analyzed 70 ETT samples obtained from pigs randomized to be untreated (controls, n = 20), or treated with vancomycin (n = 32) or linezolid (n = 18). A clinical MRSA strain (MRSA-in) was inoculated in pigs to create a pneumonia model, before treating with antibiotics. Tracheally intubated pigs with MRSA severe pneumonia, were mechanically ventilated for 69 ± 16 hours. All MRSA isolates retrieved from ETTs (ETT-MRSA) were tested for their in vitro biofilm production by microtiter plate assay. In vitro biofilm production of MRSA isolates was sequentially studied over the next 8 days post-extubation to assess biofilm capability dynamics over time. All experiments were performed under ambient air (O
) or ambient air supplemented with 5% CO
. We collected 52 ETT-MRSA isolates (placebo N = 19, linezolid N = 11, and vancomycin N = 22) that were clonally identical to the MRSA-in. Among the ETT-MRSA isolates, biofilm production more than doubled after extubation in 40% and 50% under 5% CO
and O
, respectively. Systemic antibiotic treatment during intubation did not affect this outcome. Under both atmospheric conditions, biofilm production for MRSA-in was at least doubled for 9 ETT-MRSA isolates, and assessment of these showed that biofilm production decreased progressively over a 4-day period after extubation. In conclusion, a weak biofilm producer MRSA strain significantly enhances its biofilm production within an ETT, but it is influenced by the ETT environment rather than by the systemic treatment used during intubation or by the atmospheric conditions used for bacterial growth.
Patients with mono-lateral pneumonia and severe respiratory failure can be positioned in lateral decubitus, with the healthy lung dependent, to improve ventilation-perfusion coupling. Oxygenation ...response to this manoeuvre is heterogeneous and derecruitment of dependent lung has not been elucidated. Nine pigs (32.2 ± 1.2 kg) were sedated and mechanically ventilated. Mono-lateral right-sided pneumonia was induced with intrabronchial challenge of Pseudomonas aeruginosa. After 24 h, lungs were recruited and the animals were randomly positioned on right or left side. After 3 h of lateral positioning, the animals were placed supine; another recruitment manoeuvre was performed, and the effects of contralateral decubitus were assessed. Primary outcome was lung ultrasound score (LUS) of the dependent lung after 3-h lateral positioning. LUS of the left non-infected lung worsened while positioned in left-lateral position (from 1.33 ± 1.73 at baseline to 6.78 ± 4.49; p = 0.005). LUS of the right-infected lung improved when placed upward (9.22 ± 2.73 to 6.67 ± 3.24; p = 0.09), but worsened in right-lateral position (7.78 ± 2.86 to 13.33 ± 3.08; p < 0.001). PaO
/FiO
improved in the left-lateral position (p = 0.005). In an animal model of right-lung pneumonia, left-lateral decubitus improved oxygenation, but collapsed the healthy lung. Right-lateral orientation further collapsed the diseased lung. Our data raise potential clinical concerns for the use of lateral position in mono-lateral pneumonia.
IntroductionThere is a paucity of data that can be used to guide the management of critically ill patients with COVID-19. In response, a research and data-sharing collaborative—The COVID-19 Critical ...Care Consortium—has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights crucial to improving outcomes.Methods and analysisThis is an international, multicentre, observational study of patients with confirmed or suspected SARS-CoV-2 infection admitted to ICUs. This is an evolving, open-ended study that commenced on 1 January 2020 and currently includes >350 sites in over 48 countries. The study enrols patients at the time of ICU admission and follows them to the time of death, hospital discharge or 28 days post-ICU admission, whichever occurs last. Key data, collected via an electronic case report form devised in collaboration with the International Severe Acute Respiratory and Emerging Infection Consortium/Short Period Incidence Study of Severe Acute Respiratory Illness networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane oxygenation and associated complications, as well as data on adjunctive therapies.Ethics and disseminationLocal principal investigators will ensure that the study adheres to all relevant national regulations, and that the necessary approvals are in place before a site may contribute data. In jurisdictions where a waiver of consent is deemed insufficient, prospective, representative or retrospective consent will be obtained, as appropriate. A web-based dashboard has been developed to provide relevant data and descriptive statistics to international collaborators in real-time. It is anticipated that, following study completion, all de-identified data will be made open access.Trial registration numberACTRN12620000421932 (http://anzctr.org.au/ACTRN12620000421932.aspx).
To compare the efficacy of systemic treatment with linezolid (LNZ) versus vancomycin (VAN) on methicillin-resistant Staphylococcus aureus (MRSA) burden and eradication in endotracheal tube (ETT) ...biofilm and ETT cuff from orotracheally intubated patients with MRSA respiratory infection.
Prospective observational clinical study was carried out at four European tertiary hospitals. Plasma and endotracheal aspirate (ETA) levels of LNZ and VAN were determined 72 h after treatment initiation through high-performance liquid chromatography or bioassay. LNZ or VAN concentration in the ETT biofilm and MRSA burden and eradication was determined upon extubation. The minimum inhibitory concentration (MIC) for LNZ and VAN was assessed by E-test strips (Biomerieux®). Scanning electron microscopy images were obtained, and ETT biofilm thickness was compared between groups.
Twenty-five patients, 15 treated with LNZ and 10 with VAN, were included in the study. LNZ presented a significantly higher concentration (μg/mL) than VAN in ETT biofilm (72.8 1.3-127.1 vs 0.4 0.4-1.3, p < 0.001), although both drugs achieved therapeutic plasma levels 72 h after treatment initiation. Systemic treatment with LNZ achieved lower ETT cuff MRSA burdens than systemic treatment with VAN. Indeed, LNZ increased the MRSA eradication rate in ETT cuff compared with VAN (LNZ 75%, VAN 20%, p = 0.031).
In ICU patients with MRSA respiratory infection intubated for long periods, systemic treatment with LNZ obtains a greater beneficial effect than VAN in limiting MRSA burden in ETT cuff.
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