Association between selective digestive decontamination and decreased rate of acquired candidemia in mechanically ventilated ICU patients: a multicenter nationwide study.

BACKGROUND: Candidemia is a high-risk complication among intensive care unit (ICU) patients. While selective digestive decontamination (SDD) has been shown to be effective in preventing ICU-acquired bacterial secondary infection, its effects on ICU-acquired candidemia (ICAC) remain poorly explored. Therefore, we sought to assess the effects of SDD on ICAC. METHOD: Using the REA-REZO network, we included adult patients receiving mechanical ventilation for at least 48 h from January 2017 to January 2023. Non-parsimonious propensity score matching with a 1:1 ratio was performed to investigate the association between SDD and the rate of ICAC. RESULTS: A total of 94 437 patients receiving at least 48 h of mechanical ventilation were included throughout the study period. Of those, 3 001 were treated with SDD and 651 patients developed ICAC. The propensity score matching included 2 931 patients in the SDD group and in the standard care group. In the matched cohort analysis as well as in the overall population, the rate of ICAC was lower in patients receiving SDD (0.8% versus 0.3%; p = 0.012 and 0.7% versus 0.3%; p = 0.006, respectively). Patients with ICAC had higher mortality rate (48.4% versus 29.8%; p < 0.001). Finally, mortality rates as well as ICU length of stay in the matched populations did not differ according to SDD (31.0% versus 31.1%; p = 0.910 and 9 days [5-18] versus 9 days [5-17]; p = 0.513, respectively). CONCLUSION: In this study with a low prevalence of ICAC, SDD was associated with a lower rate of ICAC that did not translate to higher survival.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients presenting sepsis-induced immunosuppression: The GRID randomized controlled trial.

PURPOSE: Septic shock is associated in some patients with a profound immunosuppression. We hypothesized that GM-CSF would reduce the occurrence of ICU-acquired infections in immunosuppressed septic patients. METHODS: Randomized double-blind trial conducted between 2015 and 2018. Adult patients, admitted to ICU, with severe sepsis or septic shock presenting with sepsis-induced immunosuppression defined by mHLA-DR < 8000 ABC (antibodies bound per cell) at day 3 were included. Patients were randomized to receive GM-CSF 125 µg/m2 or placebo for 5 days at a 1:1 ratio. The primary outcome was the difference in the number of patients presenting≥1 ICU-acquired infection at day 28 or ICU discharge. RESULTS: The study was prematurely stopped because of insufficient recruitment. A total of 98 patients were included, 54 in the intervention group and 44 in the placebo group. The two groups were similar except for a higher body mass index and McCabe score in the intervention group. No significant difference was observed between groups regarding ICU-acquired infection (11% vs 11%, p = 1.000), 28-day mortality (24% vs 27%,p = 0.900), or the number or localization of the ICU infections. CONCLUSION: GM-CSF had no effect on the prevention of ICU-acquired infection in sepsis immunosuppression, but any conclusion is limited by the early termination of the study leading to low number of included patients.

Use of 1,3-Beta-D-Glucan concentration in peritoneal fluid for the diagnosis of intra-abdominal Candidiasis in Critically-ill patients.

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401.

Intra-Abdominal Candidiasis (IAC) is associated with a high mortality in Intensive Care Unit (ICU) patients. 1,3-Beta-D-Glucan (BDG), a component of Candida cell wall, was prospectively measured in peritoneal fluid from ICU patients Low peritoneal BDG concentrations may be used to rule out IAC.

Effect of SARS-CoV-2 infection and pandemic period on healthcare-associated infections acquired in intensive care units.

OBJECTIVES: To compare the occurrence of healthcare-associated infections acquired in intensive care units (HAI-ICUs) in France among patients with COVID-19 and those without it in 2020 and the latter with that in patients before the COVID-19 pandemic. METHODS: Multicentre HAI-ICU surveillance network (REA-REZO) data were used to identify 3 groups: 2019 patients (2019Control), a COVID-19 group (2020Cov), and a non-COVID-19 group (2020NonCov). The primary outcome was the occurrence of HAI-ICU (ventilator-associated pneumonia [VAP], bloodstream infections [BSIs], catheter-related bacteraemia). Standardized infection ratios of VAP were calculated for each quarter in 2020 and compared with those in 2019. RESULTS: A total of 30 105 patients were included in 2020: 23 798 in the 2020NonCov group, 4465 in 2020Cov group, and 39 635 patients in the 2019Control group. The frequency of VAP was strikingly greater in the 2020Cov group: 35.6 (33.4-37.8) episodes/1000 days of mechanical ventilation versus 18.4 (17.6-19.2) in the 2020NonCov group. VAP standardized infection ratio was high in 2020 patients, particularly during the 2 quarters corresponding to the 2 waves. BSI/1000 days were more frequent in the 2020Cov group (6.4% [6.4-6.4%] vs. 3.9% [3.8-3.9%] in the 2020NonCov group). VAP and BSI were also more frequent in the 2020NonCov group than in the 2019Control group. The microbial epidemiology was only slightly different. DISCUSSION: The data presented here indicate that HAI-ICUs were more frequent during the COVID-19 period, whether the patients were admitted for COVID-19 or, to a lesser extent, for another cause. This implies that managing patients with severe disease in a pandemic context carries risks for all patients.

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial.

BACKGROUND: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. METHODS: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. RESULTS: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) µg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 µg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. CONCLUSIONS: The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016.

Prognosis of Old Intensive Care COVID-19 Patients at a Glance: The Senior COVID Study.

OBJECTIVE: Admission in the intensive care unit of the old patient with coronavirus disease 19 raises an ethical question concerning the scarce resources and their short-term mortality. METHODS: Patients aged over 60 from 7 different intensive care units admitted between March 1, 2020 and May 6, 2020, with a diagnosis of coronavirus disease 19 were included in the cohort. Twenty variables were collected during the admission, such as age, severity (Simplified Acute Physiology Score [SAPS] II), several data on physiological status before intensive care unit comorbidities, evaluation of autonomy, frailty, and biological variables. The objective was to model the 30-day mortality with relevant variables, compute their odds ratio associated with their 95% CI, and produce a nomogram to easily estimate and communicate the 30-day mortality. The performance of the model was estimated with the area under the receiving operating curve. RESULTS: We included 231 patients, among them 60 (26.0%) patients have died on the 30th day. The relevant variables selected to explain the 30-day mortality were Instrumental Activities of Daily Living (IADL) score (0.82 [0.71-0.94]), age 1.12 (1.07-1.18), SAPS II 1.05 (1.02-1.08), and dementia 6.22 (1.00-38.58). A nomogram was computed to visually represent the final model. Area under the receiving operating curve was at 0.833 (0.776-0.889). CONCLUSIONS: Age, autonomy, dementia, and severity at admission were important predictive variables for the 30-day mortality status, and the nomogram could help the physician in the decision-making process and the communication with the family.

Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19.

Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.

Senior-COVID-Rea Cohort Study: A Geriatric Prediction Model of 30-day Mortality in Patients Aged over 60 Years in ICU for Severe COVID-19.

The SARS-COV2 pandemic induces tensions on health systems and ethical dilemmas. Practitioners need help tools to define patients not candidate for ICU admission. A multicentre observational study was performed to evaluate the impact of age and geriatric parameters on 30-day mortality in patients aged ≥60 years of age. Patients or next of kin were asked to answer a phone questionnaire assessing geriatric covariates 1 month before ICU admission. Among 290 screened patients, 231 were included between March 7 and May 7, 2020. In univariate, factors associated with lower 30-day survival were: age (per 10 years increase; OR 3.43, [95%CI: 2.13-5.53]), ≥3 CIRS-G grade ≥2 comorbidities (OR 2.49 [95%CI: 1.36-4.56]), impaired ADL, (OR 4.86 [95%CI: 2.44-9.72]), impaired IADL8 (OR 6.33 [95%CI: 3.31-12.10], p<0.001), frailty according to the Fried score (OR 4.33 [95%CI: 2.03-9.24]) or the CFS ≥5 (OR 3.79 [95%CI: 1.76-8.15]), 6-month fall history (OR 3.46 [95%CI: 1.58-7.63]). The final multivariate model included age (per 10 years increase; 2.94 [95%CI:1.78-5.04], p<0.001) and impaired IADL8 (OR 5.69 [95%CI: 2.90-11.47], p<0.001)). Considered as continuous variables, the model led to an AUC of 0.78 [95% CI: 0.72, 0.85]. Age and IADL8 provide independent prognostic factors for 30-day mortality in the considered population. Considering a risk of death exceeding 80% (82.6% [95%CI: 61.2% - 95.0%]), patients aged over 80 years with at least 1 IADL impairment appear as poor candidates for ICU admission.

Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study.

OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population. DESIGN: Cohort exposed/nonexposed study among the REA-REZO surveillance network. SETTING: Multicentric; ICUs in France. PATIENTS: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013). CONCLUSIONS: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern.

Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study.

Introduction: We analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill patients who had presented with either sepsis, burns, severe trauma, or major surgery. The aim was to identify common features related to virus and injury-associated pathologies and specific features linking one or several viruses to a particular pathological context. Methods: Overall and individual viral DNAemia were measured over a month using quantitative PCR assays from the 377 patients in the REALISM cohort. These patients were characterised by clinical outcomes [severity scores, mortality, Intensive Care Unit (ICU)-acquired infection (IAI)] and 48 parameters defining their host response after injury (cell populations, immune functional assays, and biomarkers). Association between viraemic event and clinical outcomes or immune markers was assessed using χ2-test or exact Fisher's test for qualitative variables and Wilcoxon test for continuous variables. Results: The cumulative incidence of viral DNAemia increased from below 4% at ICU admission to 35% for each herpesvirus during the first month. EBV, HSV1, HHV6, and CMV were detected in 18%, 12%, 10%, and 9% of patients, respectively. The incidence of high TTV viraemia (>10,000 copies/ml) increased from 11% to 15% during the same period. Herpesvirus viraemia was associated with severity at admission; CMV and HHV6 viraemia correlated with mortality during the first week and over the month. The presence of individual herpesvirus during the first month was significantly associated (p < 0.001) with the occurrence of IAI, whilst herpesvirus DNAemia coupled with high TTV viraemia during the very first week was associated with IAI. Herpesvirus viraemia was associated with a lasting exacerbated host immune response, with concurrent profound immune suppression and hyper inflammation, and delayed return to immune homeostasis. The percentage of patients presenting with herpesvirus DNAemia was significantly higher in sepsis than in all other groups. Primary infection in the hospital and high IL10 levels might favour EBV and CMV reactivation. Conclusion: In this cohort of ICU patients, phenotypic differences were observed between TTV and herpesviruses DNAemia. The higher prevalence of herpesvirus DNAemia in sepsis hints at further studies that may enable a better in vivo understanding of host determinants of herpesvirus viral reactivation. Furthermore, our data suggest that EBV and TTV may be useful as additional markers to predict clinical deterioration in ICU patients.

Association between mortality and highly antimicrobial-resistant bacteria in intensive care unit-acquired pneumonia.

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs ("REA-Raisin") database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45-1.70], P < 0.001). This association was confirmed in the matched sample (3006 HAMR and 5640 non-HAMR, OR 95%, CI 1.39 [1.27-1.52], P < 0.001) and after adjusting for confounding factors (OR ranged from 1.34 to 1.39, all P < 0.001). Our findings suggest that ICU-acquired pneumonia due to HAMR bacteria is associated with an increased ICU mortality rate, ICU length of stay, and mechanical ventilation duration.

Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol.

INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.

PRAISE: providing a roadmap for automated infection surveillance in Europe.

INTRODUCTION: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. METHODS: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. RESULTS: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. CONCLUSIONS: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists.

Mortality review as a tool to assess the contribution of healthcare-associated infections to death: results of a multicentre validity and reproducibility study, 11 European Union countries, 2017 to 2018.

IntroductionThe contribution of healthcare-associated infections (HAI) to mortality can be estimated using statistical methods, but mortality review (MR) is better suited for routine use in clinical settings. The European Centre for Disease Prevention and Control recently introduced MR into its HAI surveillance.AimWe evaluate validity and reproducibility of three MR measures.MethodsThe on-site investigator, usually an infection prevention and control doctor, and the clinician in charge of the patient independently reviewed records of deceased patients with bloodstream infection (BSI), pneumonia, Clostridioides difficile infection (CDI) or surgical site infection (SSI), and assessed the contribution to death using 3CAT: definitely/possibly/no contribution to death; WHOCAT: sole cause/part of causal sequence but not sufficient on its own/contributory cause but unrelated to condition causing death/no contribution, based on the World Health Organization's death certificate; QUANT: Likert scale: 0 (no contribution) to 10 (definitely cause of death). Inter-rater reliability was assessed with weighted kappa (wk) and intra-cluster correlation coefficient (ICC). Reviewers rated the fit of the measures.ResultsFrom 2017 to 2018, 24 hospitals (11 countries) recorded 291 cases: 87 BSI, 113 pneumonia , 71 CDI and 20 SSI. The inter-rater reliability was: 3CAT wk 0.68 (95% confidence interval (CI): 0.61-0.75); WHOCAT wk 0.65 (95% CI: 0.58-0.73); QUANT ICC 0.76 (95% CI: 0.71-0.81). Inter-rater reliability ranged from 0.72 for pneumonia to 0.52 for CDI. All three measures fitted 'reasonably' or 'well' in > 88%.ConclusionFeasibility, validity and reproducibility of these MR measures was acceptable for use in HAI surveillance.

Trends in the proportion of resistant bacteria involved in ventilator-associated pneumonia as the first hospital-acquired infection in intensive care units between 2003 and 2016 in Lyon, France.

The aim of this study was to describe the proportion of multidrug-resistant microorganisms (MDROs) involved in ventilator-associated pneumonia (VAP) as the first hospital-acquired infection in 536 adults with restricted risk factors for MDRO-related infection. We found a significant decrease in the percentage of MDROs involved in VAP between 2003 and 2016 and this percentage increased when VAP occurred after day 10.

Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study.

BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .

Expert consensus-based clinical practice guidelines management of intravascular catheters in the intensive care unit.

The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emergency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Intensivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheter-related infections' prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2- adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed definitions, and therapeutic strategies.

Expert consensus-based clinical practice guidelines management of intravascular catheters in the intensive care unit

The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emer­ gency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Inten­ sivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheterrelated infections' prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2− adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed defnitions, and therapeutic strategies.

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients.

BACKGROUND: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management. METHODS: We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results. RESULTS: We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features. CONCLUSION: We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.

A new simplified and accurate sa-SOFA score.

PURPOSE: Several remarks have been raised regarding the variables and cut-points used in the Sequential Organ Failure Assessment (SOFA) score. This study revisited the SOFA score and created a new simplified and accurate sa-SOFA score. METHODS: The study grouped four prospective cohorts (2005-2016) of patients with Systemic Inflammatory Response Syndrome. It collected 28-day mortality, sociodemographic characteristics, and the SOFA score with all variable values at Day 1. A logistic regression analysis was used to select the most relevant variables and a minimum p value approach with a 10-fold cross-validation were used to find the optimal partition of selected variables. The minimum number of cut-points (2, 3, or 4) was also tested by comparing the distributions of areas under receiver operating characteristic (AUROC) curves. RESULTS: Among the 1436 participants, 416 died within 28 days (28.9%). The sa-SOFA kept one variable per dimension and two cut-points per variable. The AUROC curves that investigated the abilities of the sa-SOFA and SOFA scores to predict 28-day mortality were 0.739 [0.712-0.768] and 0.687 [0.656-0.717], respectively (p-value of DeLong test <0.001). CONCLUSION: Keeping the conventional SOFA dimension variables, the new sa-SOFA proved to be simpler and more accurate in predicting 28-day mortality.