Kinetics of C-Reactive Protein and Procalcitonin in the Early Identification of ICU-Acquired Infections in Critically Ill COVID-19 Patients

UNLABELLED: The SARS-CoV-2 infection is a cause of hypoxemic acute respiratory failure, leading to frequent intensive care unit (ICU) admission. Due to invasive organ support and immunosuppressive therapies, these patients are prone to nosocomial infections. Our aim was to assess the value of daily measurements of C-reactive protein (CRP) and Procalcitonin (PCT) in the early identification of ICU-acquired infections in COVID-19 patients. METHODS: We undertook a prospective observational cohort study (12 months). All adult mechanically ventilated patients admitted for ≥72 h to ICU with COVID-19 pneumonia were divided into an infected group (n = 35) and a non-infected group (n = 83). Day 0 was considered as the day of the diagnosis of infection (infected group) and Day 10 was that of ICU stay (non-infected group). The kinetics of CRP and PCT were assessed from Day -10 to Day 10 and evaluated using a general linear model, univariate, repeated-measures analysis. RESULTS: 118 patients (mean age 63 years, 74% males) were eligible for the analysis. The groups did not differ in patient age, gender, CRP and PCT serum levels at ICU admission. However, the infected group encompassed patients with a higher severity (SOFA score at ICU admission, p = 0.009) and a higher 28-day mortality (p < 0.001). Before D0, CRP kinetics showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (p < 0.001), while PCT kinetics did not appear to retain diagnostic value to predict superinfection in COVID-19 patients (p = 0.593). CONCLUSION: COVID-19 patients who developed ICU-acquired infections exhibited different biomarker kinetics before the diagnosis of those infections. Daily CRP monitoring and the recognition of the CRP kinetics could be useful in the prediction of ICU-acquired infections.publishersversionpublishe

Review of a New Biomarker in Sepsis

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Sepsis is a life-threatening syndrome characterized by a dysregulated host response to an infection that may evolve rapidly into septic shock and multiple organ failure. Management of sepsis relies on the early recognition and diagnosis of infection and the providing of adequate and prompt antibiotic therapy and organ support. A novel protein biomarker, the pancreatic stone protein (PSP), has recently been studied as a biomarker of sepsis and the available evidence suggests that it has a higher diagnostic performance for the identification of infection than the most used available biomarkers and adds prognostic value. This review summarizes the clinical evidence available for PSP in the diagnosis and prognosis of sepsis.publishersversionpublishe

Focus on infection

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Asking the same questions will not bring different answers

Funding Information: PP has an unrestricted research grant from ThermoFisher Scientific and Virogates. The other authors state that they have no competing interests.Severe sepsis is a major healthcare problem and the early initiation of antimicrobials is one of the few measures associated with improved outcomes. However, antibiotic overuse is an increasing problem in critical care. Of several potential biomarkers for antibiotic stewardship, procalcitonin represents the most widely studied and validated. In this commentary we address the current literature on the use of biomarkers to guide antimicrobial therapy in the critically ill and discuss its limitations and future directions.publishersversionpublishe

the journal's role

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one infection with two faces

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Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: a narrative review

Acute respiratory distress syndrome (ARDS) is a severe organ failure occurring mainly in critically ill patients as a result of different types of insults such as sepsis, trauma or aspiration. Sepsis is the main cause of ARDS, and it contributes to a high mortality and resources consumption both in hospital setting and in the community. ARDS develops mainly an acute respiratory failure with severe and often refractory hypoxemia. ARDS also has long term implications and sequelae. Endothelial damage plays an important role in the pathogenesis of ARDS. Understanding the mechanisms of ARDS presents opportunities for novel diagnostic and therapeutic targets. Biochemical signals can be used in concert to identify and classify patients into ARDS phenotypes allowing earlier effective treatment with personalised therapies. This is a narrative review where we aimed to flesh out the pathogenetic mechanisms and heterogeneity of ARDS. We examine the links between endothelium damage and its contribution to organ failure. We have also investigated future strategies for treatment with a special emphasis in endothelial damage

Sepsis Associated Delirium

Sepsis is a potentially life-threatening condition caused by a systemic dysregulated host response to infection. The brain is particularly susceptible to the effects of sepsis with clinical manifestations ranging from mild confusion to a deep comatose state. Sepsis-associated delirium (SAD) is a cerebral manifestation commonly occurring in patients with sepsis and is thought to occur due to a combination of neuroinflammation and disturbances in cerebral perfusion, the blood brain barrier (BBB) and neurotransmission. The neurological impairment associated with SAD can persist for months or even longer, after the initial septic episode has subsided which may impair the rehabilitation potential of sepsis survivors. Early identification and treatment of the underlying sepsis is key in the management of SAD as once present it can be difficult to control. Through the regular use of validated screening tools for delirium, cases of SAD can be identified early; this allows potentially aggravating factors to be addressed promptly. The usefulness of biomarkers, neuroimaging and electroencephalopathy (EEG) in the diagnosis of SAD remains controversial. The Society of Critical Care Medicine (SCCM) guidelines advise against the use of medications to treat delirium unless distressing symptoms are present or it is hindering the patient's ability to wean from organ support.publishersversionpublishe

a narrative review

Acute respiratory distress syndrome (ARDS) is a severe organ failure occurring mainly in critically ill patients as a result of different types of insults such as sepsis, trauma or aspiration. Sepsis is the main cause of ARDS, and it contributes to a high mortality and resources consumption both in hospital setting and in the community. ARDS develops mainly an acute respiratory failure with severe and often refractory hypoxemia. ARDS also has long term implications and sequelae. Endothelial damage plays an important role in the pathogenesis of ARDS. Understanding the mechanisms of ARDS presents opportunities for novel diagnostic and therapeutic targets. Biochemical signals can be used in concert to identify and classify patients into ARDS phenotypes allowing earlier effective treatment with personalised therapies. This is a narrative review where we aimed to flesh out the pathogenetic mechanisms and heterogeneity of ARDS. We examine the links between endothelium damage and its contribution to organ failure. We have also investigated future strategies for treatment with a special emphasis in endothelial damage.publishersversionpublishe

Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients

Background: Meropenem is a carbapenem antibiotic commonly used in critically ill patients to treat severe infections. The available pharmacokinetic (PK) data has been mostly obtained from healthy volunteers as well as from clinical studies addressing selected populations, often excluding the elderly and also patients with renal failure. Our aim was to study PK of meropenem in a broader population of septic critically ill patients. Methods: We characterized the PK of meropenem in 15 critically ill patients during the first 36 hrs of therapy. Aditionally, whenever possible, we collected a second set of late plasma samples after 5 days of therapy to evaluate PK intra-patient variability and its correlation with clinical course. Patients received meropenem (1 g every 8 hrs IV). Drug plasma profiles were determined by high-performance liquid chromatography. The PK of meropenem was characterized and compared with clinical parameters. Results: Fifteen septic critically ill patients (8 male, median age 73 yrs) were included. The geometric mean of the volume of distribution at the steady state (V-ss)/weight was 0.20 (0.15-0.27) L/kg. No correlation of Vss/weight with severity or comorbidity scores was found. However the Sequential Organ Failure Assessment score correlated with the Vss/ weight of the peripheral compartment (r(2) = 0.55, p = 0.021). The median meropenem clearance (Cl) was 73.3 (45-120) mL/min correlated with the creatinine (Cr) Cl (r(2)=0.35, p = 0.033). After 5 days (N = 7) although Vss remained stable, a decrease in the proportion of the peripheral compartment (V-ss2) was found, from 61.3 (42.5-88.5)\% to 51.7 (36.6-73.1)\%. No drug accumulation was noted. Conclusions: In this cohort of septic, unselected, critically ill patients, large meropenem PK heterogeneity was noted, although neither underdosing nor accumulation was found. However, Cr Cl correlated to meropenem Cl and the Vss2 decreased with patient's improvement.publishersversionpublishe