scholarly journals A Metabolomics approach for the diagnosis Of SecondAry InfeCtions in COVID-19 (MOSAIC): a study protocol

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gordan McCreath ◽  
Phillip D. Whitfield ◽  
Andrew J. Roe ◽  
Malcolm J. Watson ◽  
Malcolm A. B. Sim
Keyword(s):  
Critically Ill ◽  
Antimicrobial Therapy ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Secondary Infection ◽  
Data Sets ◽  
Critical Care Units ◽  
Secondary Infections ◽  
Increased Risk ◽  
Additional Sample

Abstract Background Critically ill patients with COVID-19 are at an increased risk of developing secondary bacterial infections. These are both difficult to diagnose and are associated with an increased mortality. Metabolomics may aid clinicians in diagnosing secondary bacterial infections in COVID-19 through identification and quantification of disease specific biomarkers, with the aim of identifying underlying causative microorganisms and directing antimicrobial therapy. Methods This is a multi-centre prospective diagnostic observational study. Patients with COVID-19 will be recruited from critical care units in three Scottish hospitals. Three serial blood samples will be taken from patients, and an additional sample taken if a patient shows clinical or microbiological evidence of secondary infection. Samples will be analysed using LC–MS and subjected to bioinformatic processing and statistical analysis to explore the metabolite changes associated with bacterial infections in COVID-19 patients. Comparisons of the data sets will be made with standard microbiological and biochemical methods of diagnosing infection. Discussion Metabolomics analyses may provide additional strategies for identifying secondary infections, which might permit faster initiation of specific tailored antimicrobial therapy to critically ill patients with COVID-19.

scholarly journals Multi-Drug Resistance Bacterial Infections in Critically Ill Patients Admitted with COVID-19

2021 ◽  
Vol 9 (8) ◽  
pp. 1773
Author(s):  
Daniela Pasero ◽  
Andrea Pasquale Cossu ◽  
Pierpaolo Terragni
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Invasive Mechanical Ventilation ◽  
Multi Drug Resistance ◽  
Icu Admission ◽  
Risk Of Death ◽  
Stewardship Program ◽  
Secondary Infections ◽  
Tract Infections

Introduction. It is known that bacterial infections represent a common complication during viral respiratory tract infections such as influenza, with a concomitant increase in morbidity and mortality. Nevertheless, the prevalence of bacterial co-infections and secondary infections in critically ill patients affected by coronavirus disease 2019 (COVID-19) is not well understood yet. We performed a review of the literature currently available to examine the incidence of bacterial secondary infections acquired during hospital stay and the risk factors associated with multidrug resistance. Most of the studies, mainly retrospective and single-centered, highlighted that the incidence of co-infections is low, affecting about 3.5% of hospitalized patients, while the majority are hospital acquired infections, developed later, generally 10–15 days after ICU admission. The prolonged ICU hospitalization and the extensive use of broad-spectrum antimicrobial drugs during the COVID-19 outbreak might have contributed to the selection of pathogens with different profiles of resistance. Consequently, the reported incidence of MDR bacterial infections in critically ill COVID-19 patients is high, ranging between 32% to 50%. MDR infections are linked to a higher length of stay in ICU but not to a higher risk of death. The only risk factor independently associated with MDR secondary infections reported was invasive mechanical ventilation (OR 1.062; 95% CI 1.012–1.114), but also steroid therapy and prolonged length of ICU stay may play a pivotal role. The empiric antimicrobial therapy for a ventilated patient with suspected or proven bacterial co-infection at ICU admission should be prescribed judiciously and managed according to a stewardship program in order to interrupt or adjust it on the basis of culture results.

scholarly journals Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Emma J. Kooistra ◽  
Miranda van Berkel ◽  
Noortje F. van Kempen ◽  
Celine R. M. van Latum ◽  
Niklas Bruse ◽  
...  
Keyword(s):  
Critically Ill ◽  
Bacterial Infections ◽  
Secondary Infection ◽  
Receiver Operating Curve ◽  
Detection Accuracy ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Receiver Operating Curve Analysis ◽  
Secondary Infections ◽  
Rebound Increase

Abstract Background Procalcitonin (PCT) and C-reactive protein (CRP) were previously shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, since the introduction of immunomodulatory therapy, the value of these biomarkers is unclear. We investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections. Methods In this prospective study, 190 critically ill COVID-19 patients were divided into three treatment groups: no dexamethasone, no tocilizumab (D−T−), dexamethasone, no tocilizumab (D+T−), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards. Furthermore, the D+T− and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection. Results Following cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T− group. Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T− group (p = 0.052 and p = 0.08, respectively). Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection (p = 0.0003), this rise was only apparent from day 2 post-infection onwards. CRP levels remained suppressed in the D+T+ group. Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs (0.80 and 0.76, respectively, with p values for differences between groups of 0.001 and 0.02, respectively). Conclusions Cessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections. Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients.

scholarly journals Secondary infections in mechanically ventilated patients with COVID-19: An overlooked matter?

2021 ◽  
Author(s):  
Alejandro Suarez-de-la-Rica ◽  
◽  
Patricia Serrano ◽  
Rodrigo de-la-Oliva ◽  
Pedro Sánchez-Díaz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Secondary Infection ◽  
Demographic Data ◽  
Rank Test ◽  
Mechanically Ventilated ◽  
Log Rank Test ◽  
Secondary Infections ◽  
Nosocomial Bacteremia

Introduction. The susceptibility to infection probably increases in COVID-19 patients due to a combination of virusand drug-induced immunosuppression. The reported rate of secondary infections was quite low in previous studies. The objectives of our study were to investigate the rate of secondary infections, risk factors for secondary infections and risk factors for mortality in COVID-19 critically ill patients. Material and methods. We performed a single-center retrospective study in mechanically ventilated critically ill COVID-19 patients admitted to our Critical Care Unit (CCU). We recorded the patients’ demographic data; clinical data; microbiology data and incidence of secondary infection during CCU stay, including ventilator-associated pneumonia (VAP) and nosocomial bacteremia (primary and secondary). Results. A total of 107 patients with a mean age 62.2 ± 10.6 years were included. Incidence of secondary infection during CCU stay was 43.0% (46 patients), including nosocomial bacteremia (34 patients) and VAP (35 patients). Age was related to development of secondary infection (65.2 ± 7.3 vs. 59.9 ± 12.2 years, p=0.007). Age ≥ 65 years and secondary infection were independent predictors of mortality (OR=2.692, 95% CI 1.068-6.782, p<0.036; and OR=3.658, 95% CI 1.385- 9.660, p=0.009, respectively). The hazard ratio for death within 90 days in the ≥ 65 years group and in patients infected by antimicrobial resistant pathogens was 1.901 (95% CI 1.198- 3.018; p= 0.005 by log-rank test) and 1.787 (95% CI 1.023-3.122; p= 0.036 by log-rank test), respectively. Conclusions. Our data suggest that the incidence of secondary infection and infection by antimicrobial resistant pathogens is very high in critically ill patients with COVID-19 with a significant impact on prognosis.

scholarly journals Immune profiling demonstrates a common immune signature of delayed acquired immunodeficiency in patients with various etiologies of severe injury

2021 ◽  
Author(s):  
Fabienne Venet ◽  
Julien Textoris ◽  
Sophie Blein ◽  
Mary-Luz Rol ◽  
Maxime Bodinier ◽  
...  
Keyword(s):  
Immune Responses ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Secondary Infections ◽  
Increased Risk ◽  
Acquired Immunodeficiency ◽  
Anti Inflammatory ◽  
Immune Profiling

AbstractBackground and Research QuestionThe host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies.Study Design and Methods353 septic, trauma and surgical patients and 175 healthy volunteers were prospectively included in the REAnimation Low Immune Status Marker (REALISM) study. Extensive immune profiling was performed by assessing cellular phenotypes and functions, protein and mRNA levels at days 1-2, 3-4 and 5-7 after inclusion using a panel of 30 standardized immune markers.ResultsUsing REALISM immunomonitoring panel, no specificity in the immune profile was observed between septic, trauma and surgical patients. This common injury-induced immune response was characterized by an initial adaptive (i.e. physiologic) response engaging all constituents of the immune system (pro- and anti-inflammatory cytokine release, innate and adaptive immune responses) but not associated with increased risk of secondary infections. In contrary, the persistence in a subgroup of patients of profound immune alterations at the end of the first week after admission was associated with increased risk of secondary infections independently of exposure to invasive devices. The combined monitoring of markers of pro/anti-inflammatory, innate and adaptive immune responses allowed a better enrichment of patients with risk of secondary infections in the selected population.InterpretationThese results illustrate the delayed development of a common maladaptive injury-acquired immunodeficiency in a subgroup of severely injured patients independently of initial etiologies. Critically ill patients’ immune status could be captured through the combined monitoring a common panel of complementary markers of pro/anti-inflammatory, innate and adaptive immune responses. Such immune monitoring panel will help clinicians to identify critically ill patients who could benefit from tailored immunoadjuvant therapies.Clinical Trial Registrationclinicaltrials.gov: NCT02638779Summary conflict of interest statementsJT, SB, VM and AP are employees of bioMérieux SA, an in vitro diagnostic company. FV, TR, YB, BD, OM, TG, CT and GM are employees of Hospices Civils de Lyon. JT, TR, SB, VM, AP, FV and GM work in a joint research unit, co funded by the Hospices Civils de Lyon and bioMérieux. JT, AP, GM and FV are co-inventors in patent applications covering the following markers: CX3CR1, CD127, IL10 and S100A9. LKT and CT are employees of and hold stock and shares in GlaxoSmithKline. LQU is an employee of Sanofi Pasteur. PC was employee of Sanofi, Inc. and declares no other competing interests.Funding informationThis study received funding from the Agence Nationale de la Recherche through a grant awarded to BIOASTER (Grant number #ANR-10-AIRT-03) and from bioMérieux, Sanofi and GSK.

scholarly journals Clinical Features and Risk Factors for Secondary Infection in Critically Ill Patients With COVID-19

2020 ◽  
Author(s):  
Tongtong Pan ◽  
Dazhi Chen ◽  
Yi Chen ◽  
Chenwei Pan ◽  
Feifei Su ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Clinical Features ◽  
Critically Ill Patients ◽  
Trigger Point ◽  
Secondary Infection ◽  
Infected Group ◽  
Effective Control ◽  
Utilization Rate ◽  
Secondary Infections

Abstract Background: To analyze the clinical features and the possible risk factors of secondary infection, and explore their impact on prognosis of COVID-19. Methods: A total of 165 severe and critical hospitalized patients diagnosed with COVID-19 were included. The clinical characteristics, laboratory tests, imaging data, secondary infections and outcomes were analyzed. Results: The mean age of total patients was (57.3±15.2) years, of which 111 were males (67.3%). 108 cases were with basic diseases (65.5%), and 1 death (0.6%). The secondary infection rate in critical patients was significantly higher than in severe patients (P <0.05). The secondary infections were mainly lung infections. The pathogens were principally Burkholderia multivorans, Stenotrophomonas maltophilia, Acinetobacter baumannii and Klebsiella pneumoniae. The recovery rate of 28 days in the infected group was significantly lower than that in the non-infected group (p < 0.001).The utilization rate and usage time of invasive ventilator, and deep vein catheterization, catheter indwelling and ECMO were the risk factors for the secondary infected patients.Conclusion: Secondary infection is an extremely common complication in critically ill patients and a trigger point for exacerbation of the disease. An effective control on the secondary infection will do good to the prognosis of COVID-19 patients.

scholarly journals Serum Procalcitonin Level and Mortality Risk in Critically ill Patients with Ventilator-Associated Pneumonia

2015 ◽  
Vol 37 (5) ◽  
pp. 1967-1972 ◽  
Author(s):  
Bo Li ◽  
Xin Zhao ◽  
Shumei Li
Keyword(s):  
Critically Ill ◽  
Mortality Risk ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
High Serum ◽  
Ventilator Associated Pneumonia ◽  
Prognostic Role ◽  
Procalcitonin Level ◽  
Increased Risk

Background/Aims: The prognostic role of serum procalcitonin level in critically ill patients with ventilator-associated pneumonia was unclear. The aim of our study was to investigate the relationship between serum procalcitonin level and mortality risk in critically ill patients with ventilator-associated pneumonia. Methods: Data of critically ill patients with ventilator-associated pneumonia were retrospectively collected. Demographics, comorbidities, and serum procalcitonin level were extracted from electronic medical records. The primary outcome was mortality within two months after diagnosis. Multivariable Cox regression analyses were performed to assess the prognostic role of serum procalcitonin level in those patients. Results: A total of 115 critically ill patients with ventilator-associated pneumonia were enrolled in our study. Serum procalcitonin level was not associated with age, gender, or other comorbidities. Univariate Cox regression model showed that high serum procalcitonin level was associated increased risk of morality within 2 months after diagnosis (OR = 2.32, 95% CI 1.25-4.31, P = 0.008). Multivariable Cox regression model showed that high serum procalcitonin level was independently associated increased risk of morality within 2 months after diagnosis (OR = 2.38, 95% CI 1.26-4.50, P = 0.008). Conclusion: High serum procalcitonin level is an independent prognostic biomarker of mortality risk in critically ill patients with ventilator-associated pneumonia, and it's a promising biomarker of prognosis in critically ill patients.

scholarly journals Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 918-925 ◽  
Author(s):  
Emma M Pinder ◽  
Anthony J Rostron ◽  
Thomas P Hellyer ◽  
Marie-Helene Ruchaud-Sparagano ◽  
Jonathan Scott ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Ex Vivo ◽  
Controlled Trial ◽  
Personalised Medicine ◽  
Common Adverse Event ◽  
Controlled Clinical Trial ◽  
Gm Csf ◽  
Hla Dr ◽  
Increased Risk

BackgroundCritically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired.MethodsThis was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 μg/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression and safety.ResultsThirty-eight patients were recruited from five intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis≥50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was fever.ConclusionsGM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.

scholarly journals Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients

2018 ◽  
Vol 4 (5) ◽  
pp. 166-174
Author(s):  
Nora J mabelis ◽  
Kimberly N. Shudofsky ◽  
Joost J. van Raaij ◽  
Sjoerd D. Meenks ◽  
Thomas Havenith ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Therapeutic Drug

scholarly journals Risk Potential for Organ Dysfunction Associated with Sodium Bicarbonate Therapy (SBT) in Critically Ill Patients with Hemodynamic Worsening

2021 ◽  
Author(s):  
Tiehua Wang ◽  
Lingxian Yi ◽  
Hua Zhang ◽  
Tianhao Wang ◽  
Jingjing Xi ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Critically Ill ◽  
Organ Dysfunction ◽  
Critically Ill Patients ◽  
Control Group ◽  
Increased Risk ◽  
Bicarbonate Therapy ◽  
Risk Potential

Abstract Background: The role of sodium bicarbonate therapy (SBT) remains controversial. This study aimed to investigate whether hemodynamic status before SBT contributed to the heterogeneous outcomes associated with SBT in acute critically ill patients.Methods: We obtained data from patients with metabolic acidosis from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score matching (PSM) was applied to match the SBT group with the control group. Logistic regression and Cox regression were used to analyze a composite of newly “developed or exacerbated organ dysfunction” (d/eOD) within 7 days of ICU admission and 28-day mortality associated with SBT for metabolic acidosis.Results: A total of 1765 patients with metabolic acidosis were enrolled, and 332 pairs obtained by PSM were applied to the final analyses in the study. An increased incidence of newly d/eOD was observed in the SB group compared with the control group (54.8% vs 44.6%, p<0.01). Multivariable logistic regression indicated that the adjusted OR of SBT for this composite outcome was no longer significant [OR (95% CI): 1.39 (0.9, 1.85); p=0.164]. This effect of SBT did not change with the quintiles stratified by pH. Interestingly, SBT was associated with an increased risk of the composite of newly d/eOD in the subgroup of patients with worsening hemodynamics before SBT [adjusted OR (95% CI): 3.6 (1.84, 7.22), p< 0.001]. Moreover, the risk potential for this composite of outcomes was significantly increased in patients characterized by both worsening [adjusted OR (95% CI): 2.91 (1.54, 5.47), p< 0.001] and unchanged hemodynamics [adjusted OR (95% CI): 1.94 (1.01, 3.72), p=0.046) compared to patients with improved hemodynamics before SBT. Our study failed to demonstrate an association between SBT and 28-day mortality in acute critically ill patients with metabolic acidosis.Conclusions: Our findings suggested that SBT for metabolic acidosis was associated with an increased risk potential for subsequent d/eOD, while the hemodynamic status remained unstable during the acute phase of critical illness.

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