The role of rapid multiplex molecular syndromic panels in the clinical management of infections in critically ill patients: an experts-opinion document. Critical care (London, England) Rapid multiplex molecular syndromic panels (RMMSP) (3 or more pathogens and time-to-results < 6 h) allow simultaneous detection of multiple pathogens and genotypic resistance markers. Their implementation has revolutionized the clinical landscape by significantly enhancing diagnostic accuracy and reducing time-to-results in different critical conditions. The current revision is a comprehensive but not systematic review of the literature. We conducted electronic searches of the PubMed, Medline, Embase, and Google Scholar databases to identify studies assessing the clinical performance of RMMSP in critically ill patients until July 30, 2024. A multidisciplinary group of 11 Spanish specialists developed clinical questions pertaining to the indications and limitations of these diagnostic tools in daily practice in different clinical scenarios. The topics covered included pneumonia, sepsis/septic shock, candidemia, meningitis/encephalitis, and off-label uses of these RMMSP. These tools reduced the time-to-diagnosis (and therefore the time-to-appropriate treatment), reduced inappropriate empiric treatment and the length of antibiotic therapy (which has a positive impact on antimicrobial stewardship and might be associated with lower in-hospital mortality), may reduce the length of hospital stay, which could potentially lead to cost savings. Despite their advantages, these RMMSP have limitations that should be known, including limited availability, missed diagnoses if the causative agent or resistance determinants are not included in the panel, false positives, and codetections. Overall, the implementation of RMMSP represents a significant advancement in infectious disease diagnostics, enabling more precise and timely interventions. This document addresses relevant issues related to the use of RMMSP on different critically ill patient profiles, to standardize procedures, assist in making management decisions and help specialists to obtain optimal outcomes. 10.1186/s13054-024-05224-3

Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesthesia and analgesia Physiological hemostasis is a balance between pro- and anticoagulant pathways, and in sepsis, this equilibrium is disturbed, resulting in systemic thrombin generation, impaired anticoagulant activity, and suppression of fibrinolysis, a condition termed sepsis-induced coagulopathy (SIC). SIC is a common complication, being present in 24% of patients with sepsis and 66% of patients with septic shock, and is often associated with poor clinical outcomes and high mortality. 1 , 2 Recent preclinical and clinical studies have generated new insights into the molecular pathogenesis of SIC. In this article, we analyze the complex pathophysiology of SIC with a focus on the role of procoagulant innate immune signaling in hemostatic activation--tissue factor production, thrombin generation, endotheliopathy, and impaired antithrombotic functions. We also review clinical presentations of SIC, the diagnostic scoring system and laboratory tests, the current standard of care, and clinical trials evaluating the efficacies of anticoagulant therapies. 10.1213/ANE.0000000000006888

Sepsis-induced cardiogenic shock: controversies and evidence gaps in diagnosis and management. Journal of intensive care Sepsis often leads to vasoplegia and a hyperdynamic cardiac state, with treatment focused on restoring vascular tone. However, sepsis can also cause reversible myocardial dysfunction, particularly in the elderly with pre-existing heart conditions. The Surviving Sepsis Campaign Guidelines recommend using dobutamine with norepinephrine or epinephrine alone for patients with septic shock with cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and stable blood pressure. However, the definition of cardiac dysfunction and hypoperfusion in these guidelines remains controversial, leading to varied clinical interpretations. Cardiac dysfunction with persistent hypoperfusion despite restoring adequate preload and afterload is often considered a cardiogenic shock. Therefore, sepsis complicated by new-onset myocardial dysfunction or worsening of underlying myocardial dysfunction due to sepsis-induced cardiomyopathy, resulting in cardiogenic shock, can be defined as "Sepsis-induced cardiogenic shock (SICS)". SICS is known to be associated with significantly higher mortality. A history of cardiac dysfunction is a strong predictor of SICS, highlighting the need for precise diagnosis and management given the aging population and rising cardiovascular disease prevalence. Therefore, SICS might benefit from early invasive hemodynamic monitoring with a pulmonary artery catheter (PAC), unlike those with septic shock alone. While routine PAC monitoring for all septic patients is impractical, echocardiography could be a useful screening tool for high-risk individuals. If echocardiography indicates cardiogenic shock, PAC might be warranted for continuous monitoring. The role of inotropes in SICS remains uncertain. Mechanical circulatory support (MCS) might be considered for severe cases, as high-dose vasopressors and inotropes are associated with worse outcomes. Correct patient selection is the key to improving outcomes with MCS. Engaging a cardiogenic shock team for a multidisciplinary approach can be beneficial. In summary, addressing the evidence gaps in SICS diagnosis and management is crucial. Echocardiography for screening, advanced monitoring with PAC, and careful patient selection for MCS are important for optimal patient care. 10.1186/s40560-024-00770-y

Penetration of linezolid into the pleural cavity in critically ill patients with proven or suspected Gram-positive bacterial infections: a retrospective pharmacokinetic study. The Journal of antimicrobial chemotherapy OBJECTIVES:To describe the pharmacokinetics (PK) of linezolid in plasma and pleural fluid (PF) in critically ill patients with proven or suspected Gram-positive bacterial infections. PATIENTS AND METHODS:Observational PK study in 14 critically ill patients treated with linezolid at standard doses. Blood and PF samples were collected and analysed by HPLC. The ratio between PF and plasma concentrations was calculated. The PK/pharmacodynamic (PD) target of linezolid in plasma was defined as 100% of the duration of the dosing interval in which concentrations were above the MIC (%100 T > MIC). RESULTS:The median (5th and 95th percentiles) linezolid concentration values for plasma pre-dose at steady state (Cmin,ss) and at the end of the 1-h infusion at steady state (Cmax,ss) were 1.1 (0.02-28.3) and 13.8 mg/L (2.9-38.1), respectively, and the PF pre-dose concentration (PF0 h) and PF concentration at the end of the 1-h intravenous infusion (PF1 h) were 2.8 (0.1-31.6) and 4.2 mg/L (0.1-45.2), respectively. At both times (pre-dose and post-infusion), a strong positive correlation was observed between PF and plasma linezolid concentrations (Spearman's rho coefficients = 0.8 and 0.9, with P < 0.001 for both). The defined PK/PD target in plasma was achieved in 8 (57.1%), 4 (28.6%) and 3 (21.4%) patients assuming an MIC of 1, 2 and 4 mg/L, respectively. CONCLUSIONS:Linezolid seems to penetrate well into the PF, with concentrations exceeding those in plasma. However, high inter-individual variability, both in plasma and PF concentrations, was observed. A high proportion of patients did not achieve the PK/PD target in plasma, especially in the presence of high MIC strains. 10.1093/jac/dkae444