Treatment of positive catheter tip culture without bloodstream infections in critically ill patients. A case-cohort study from the OUTCOMEREA network.

PURPOSE: This study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture. METHODS: We performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality. RESULTS: We included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73). CONCLUSIONS: Antimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures.

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study.

PURPOSE: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). METHODS: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). RESULTS: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. CONCLUSIONS: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study.

BACKGROUND: Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality. METHODS: Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model. RESULTS: Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045). CONCLUSIONS: Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium.

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database.

BACKGROUND: Current guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM. METHODS: We conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, "Direct ICU" corresponding to a direct ICU admission and "Delayed ICU" corresponding to a secondary ICU admission. RESULTS: We identified 4052 patients hospitalized for a first episode of PM, including 2006 "Direct ICU" patients (50%) and 2046 "delayed ICU" patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50-71] and a median Charlson index of 1 [0-3]. Among them, median SAPS II on admission was 46 [33-62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2-14] and 21 days [13-38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56-0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU. CONCLUSIONS: Among patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission.

Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study.

KEY MESSAGES: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy. BACKGROUND: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria. METHODS: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock. RESULTS: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results. CONCLUSIONS: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.

High incidence of immune-mediated inflammatory diseases in sepsis survivors: A nationwide exposed-nonexposed epidemiological study.

OBJECTIVE: Sepsis is characterized by an excessive release of inflammatory cytokines. Cytokine dysregulation is pivotal to the pathophysiology of immune-mediated inflammatory diseases (IMIDs). We aimed to analyze the incidence of IMIDs in patients who survived sepsis. METHODS: We performed a matched-cohort study using the National Medico-Administrative Hospital database in order to analyze the association between sepsis and incident IMIDs in 2020 in France. Sepsis was defined by the combination of at least one infection diagnosis code and one organ failure code. Patients with a first sepsis diagnosed in 2020 were randomly matched with patients admitted during the same period for acute myocardial infarction (AMI) with an exact matching procedure using age, gender, and comorbidities as matching variables. The main outcome was an IMID diagnosis in a 9-month follow-up period starting the first day of hospitalization for sepsis or AMI. RESULTS: In France, the incidence rate of IMIDs after a sepsis in 2020-analyzed in 62,257 patients-was of 7956 (95% confidence interval [95% CI] 7392-8520) per 100,000 patient-years. As compared to the AMI population, we observed an increased risk for IMIDs of 2.80 (hazard ratio [HR]; 95% CI [2.22-3.54]) starting from day 16 after admission in the sepsis population. The risk of IMIDs onset in sepsis survivors depended on the type of IMIDs and was higher for immune thrombocytopenia (5.51 [1.97-15.4]), autoimmune hemolytic anemia (HR 4.83 [1.45-16.1]), and antineutrophil cytoplasmic antibody-associated vasculitis (4.66 [2.05-10.6]). Association between sepsis and IMIDs onset appeared well balanced across pathogen categories. CONCLUSION: Our study shows a high incidence of IMIDs among sepsis survivors.

Mortality, incidence, and microbiological documentation of ventilated acquired pneumonia (VAP) in critically ill patients with COVID-19 or influenza.

BACKGROUND: Data on ventilator associated pneumonia (VAP) in COVID-19 and influenza patients admitted to intensive care units (ICU) are scarce. This study aimed to estimate day-60 mortality related to VAP in ICU patients ventilated for at least 48 h, either for COVID-19 or for influenza, and to describe the epidemiological characteristics in each group of VAP. DESIGN: Multicentre retrospective observational study. SETTING: Eleven ICUs of the French OutcomeRea™ network. PATIENTS: Patients treated with invasive mechanical ventilation (IMV) for at least 48 h for either COVID-19 or for flu. RESULTS: Of the 585 patients included, 503 had COVID-19 and 82 had influenza between January 2008 and June 2021. A total of 232 patients, 209 (41.6%) with COVID-19 and 23 (28%) with influenza, developed 375 VAP episodes. Among the COVID-19 and flu patients, VAP incidences for the first VAP episode were, respectively, 99.2 and 56.4 per 1000 IMV days (p < 0.01), and incidences for all VAP episodes were 32.8 and 17.8 per 1000 IMV days (p < 0.01). Microorganisms of VAP were Gram-positive cocci in 29.6% and 23.5% of episodes of VAP (p < 0.01), respectively, including Staphylococcus aureus in 19.9% and 11.8% (p = 0.25), and Gram-negative bacilli in 84.2% and 79.4% (p = 0.47). In the overall cohort, VAP was associated with an increased risk of day-60 mortality (aHR = 1.77 [1.36; 2.30], p < 0.01), and COVID-19 had a higher mortality risk than influenza (aHR = 2.22 [CI 95%, 1.34; 3.66], p < 0.01). VAP was associated with increased day-60 mortality among COVID-19 patients (aHR = 1.75 [CI 95%, 1.32; 2.33], p < 0.01), but not among influenza patients (aHR = 1.75 [CI 95%, 0.48; 6.33], p = 0.35). CONCLUSION: The incidence of VAP was higher in patients ventilated for at least 48 h for COVID-19 than for influenza. In both groups, Gram-negative bacilli were the most frequently detected microorganisms. In patients ventilated for either COVID-19 or influenza VAP and COVID-19 were associated with a higher risk of mortality.

Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP) in patients with acute exacerbation of COPD: From the French OUTCOMEREA cohort.

BACKGROUND: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. METHODS: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. RESULTS: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01). CONCLUSION: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD.

One-Year Outcomes in Patients With Acute Stroke Requiring Mechanical Ventilation.

BACKGROUND: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU). METHODS: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors. RESULTS: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors. CONCLUSIONS: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03335995.

Epidemiology and risk factors of 28-day mortality of hospital-acquired bloodstream infection in Turkish intensive care units: a prospective observational cohort study.

OBJECTIVES: To uncover clinical epidemiology, microbiological characteristics and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs) in Turkish ICU patients. METHODS: The EUROBACT II was a prospective observational multicontinental cohort study. We performed a subanalysis of patients from 24 Turkish ICUs included in this study. Risk factors for mortality were identified using multivariable Cox frailty models. RESULTS: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78]. Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599), 67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp. and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329), SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI 1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08), COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality. However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI 1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality, whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with survival. CONCLUSIONS: Considering high antimicrobial resistance rate, importance of source control and availability of clinical pharmacists, a multifaceted management programme should be adopted in Turkish ICUs.

Risk of infections in intravascular catheters in situ for more than 10 days: a post hoc analysis of randomized controlled trials.

OBJECTIVES: We aimed to describe the infectious risk during the dwell time for different catheter types. Furthermore, we wanted to identify risk factors for infections from catheters in place for >10 days. METHODS: We performed a post hoc analysis using prospectively collected data from four randomized controlled trials. First, we evaluated the infectious risk after 10 days of analysing the significance of the interaction between dwell time and catheter type in a Cox model. Second, we investigated risk factors for infection in catheters in place for >10 days using multivariable marginal Cox models. RESULTS: We included 15 036 intravascular catheters from 24 intensive care units. Infections occurred in 46 (0.7%) of 6298 arterial catheters (ACs), 62 (1.0%) of 6036 central venous catheters (CVCs) and 47 (1.7%) of 2702 short-term dialysis catheters (DCs). The interaction between dwell time beyond 10 days and catheter type was significant for CVCs (p 0.008) and DCs (p < 0.001), thus indicating an increased risk of infection after 10 days. The interaction was not significant for ACs (p 0.98). Therefore, we selected 1405 CVCs and 454 DCs in place for >10 days for further analyses. In the multivariable marginal Cox model, we observed an increased hazard ratio (HR) for infection for femoral CVC (HR, 6.33; 95% CI, 1.99-20.09), jugular CVC (HR, 2.82; 95% CI, 1.13-7.07), femoral DC (HR, 4.53; 95% CI, 1.54-13.33) and jugular DC (HR, 4.50; 95% CI, 1.42-14.21) compared with subclavian insertions. DISCUSSION: We showed that the risk of catheter infection for CVCs and DCs increased 10 days after insertion, thus suggesting routine replacement for nonsubclavian catheters in situ for >10 days.

Clinical features, etiologies, and outcomes in adult patients with meningoencephalitis requiring intensive care (EURECA): an international prospective multicenter cohort study.

PURPOSE: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. METHODS: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. RESULTS: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective. CONCLUSION: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.

Corticosteroids for severe acute exacerbations of chronic obstructive pulmonary disease in intensive care: From the French OUTCOMEREA cohort.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission. METHODS: In the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting. RESULTS: Between January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders. CONCLUSION: Using systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.

Incidence and risk factors of prolonged grief in relatives of patients with terminal cancer in French palliative care units: The Fami-Life multicenter cohort study.

OBJECTIVES: Psychological consequences of grief among relatives are insufficiently known. We reported incidence of prolonged grief among relatives of deceased patients with cancer. METHODS: Prospective cohort study of 611 relatives of 531 patients with cancer hospitalized for more than 72 hours and who died in 26 palliative care units was conducted. The primary outcome was prolonged grief in relatives 6 months after patient death, measured with the Inventory Complicated Grief (ICG > 25, range 0-76, a higher score indicates more severe symptoms) score. Secondary outcomes in relatives 6 months after patient death were anxiety and depression symptoms based on Hospital Anxiety and Depression Scale (HADS) score (range 0 [best]-42 [worst]), higher scores indicate more severe symptoms, minimally important difference 2.5. Post-traumatic stress disorder symptoms were defined by an Impact Event Scale-Revised score >22 (range 0-88, a higher score indicates more severe symptoms). RESULTS: Among 611 included relatives, 608 (99.5%) completed the trial. At 6 months, significant ICG scores were reported by 32.7% relatives (199/608, 95% CI, 29.0-36.4). The median (interquartile range ICG score) was 20.0 (11.5-29.0). The incidence of HADS symptoms was 87.5% (95% CI, 84.8-90.2%) at Days 3-5 and 68.7% (95% CI, 65.0-72.4) 6 months after patient's death, with a median (interquartile range) difference of -4 (-10 to 0) between these 2 time points. Improvement in HADS anxiety and depression scores were reported by 62.5% (362/579) relatives. SIGNIFICANCE OF RESULTS: These findings support the importance of screening relatives having risk factors of developing prolonged grief in the palliative unit and 6 months after patient's death.

Outcomes in critically Ill HIV-infected patients between 1997 and 2020: analysis of the OUTCOMEREA multicenter cohort.

PURPOSE: Despite antiviral therapy (ART), 800,000 deaths still occur yearly and globally due to HIV infection. In parallel with the good virological control and the aging of this population, multiple comorbidities [HIV-associated-non-AIDS (HANA) conditions] may now be observed. METHODS: HIV adult patients hospitalized in intensive care unit (ICU) from all the French region from university and non-university hospital who participate to the OutcomeRea™ database on a voluntary basis over a 24-year period. RESULTS: Of the 24,298 stays registered, 630 (2.6%) were a first ICU stay for HIV patients. Over time, the mean age and number of comorbidities (diabetes, renal and respiratory history, solid neoplasia) of patients increased. The proportion of HIV diagnosed on ICU admission decreased significantly, while the median duration of HIV disease as well as the percentage of ART-treated patients increased. The distribution of main reasons for admission remained stable over time (acute respiratory distress > shock > coma). We observed a significant drop in the rate of active opportunistic infection on admission, while the rate of active hemopathy (newly diagnosed or relapsed within the last 6 months prior to admission to ICU) qualifying for AIDS increased-nonsignificantly-with a significant increase in the anticancer chemotherapy administration in ICU. Admissions for HANA or non-HIV reasons were stable over time. In multivariate analysis, predictors of 60-day mortality were advanced age, chronic liver disease, past chemotherapy, sepsis-related organ failure assessment score > 4 at admission, hospitalization duration before ICU admission > 24 h, AIDS status, but not the period of admission. CONCLUSION: Whereas the profile of ICU-admitted HIV patients has evolved over time (HIV better controlled but more associated comorbidities), mortality risk factors remain stable, including AIDS status.

Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the ICU: An Observational Study From the OUTCOMEREA Database, 1997-2018.

OBJECTIVES: Our aim was to describe changes in the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by ICUs and patient outcomes. DESIGN: We extracted data from the OutcomeRea database concerning patients admitted for AECOPD between 1997 and 2018. We analyzed trends in the use of ventilatory support, corticosteroid therapy, antibiotic therapy, and patient survival. SETTING: ICUs at 32 French sites. PATIENTS: One thousand eight hundred sixteen patients in the database had a diagnosis of AECOPD. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over time, there was a reduction in the prescription of corticosteroids and antibiotics. In a time-series analysis, these changes in practice were not linked with ICU mortality. The proportion of patients treated with invasive mechanical ventilation (IMV) also gradually declined (from 51% between 1997 and 2002 to 35% between 2013 and 2018) with an association between decrease in IMV use and reduction in ICU mortality in a time series analysis. Rates of noninvasive ventilation (NIV) failure decreased with an increase in NIV use to support weaning from IMV. There was a reduction in the median ICU length of stay (from 8 d in 1997-2002 to 4 d in 2013-2018) and in the median total duration of hospitalization (from 23 d in 1997-2002 to 14 d in 2013-2018). We observed an improvement in prognosis, with decreases in overall hospital mortality (from 24% between 1997 and 2002 to 15% between 2013 and 2018), ICU mortality (from 14% between 1997 and 2002 to 10% between 2013 and 2018), and 90-day mortality (from 41% between 1997 and 2002 to 22% between 2013 and 2018). CONCLUSIONS: The length of stay and mortality of patients with AECOPD admitted to ICUs has decreased over the last 20 years, with a wider use of NIV and a reduction in antibiotic and corticosteroid prescriptions.