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Although viruses are an underestimated cause of community-acquired pneumonias (CAP) and hospital-acquired pneumonias (HAP)/ventilator-associated pneumonias (VAP) in intensive care unit (ICU) patients, they have an impact on morbidity and mortality.In this perspective article, we discuss the available data regarding the management of severe influenza CAP and herpesviridae HAP/VAP. We review diagnostic and therapeutic strategies in order to give clear messages and address unsolved questions.Influenza CAP affects yearly thousands of people; however, robust data regarding antiviral treatment in the most critical forms are scarce. While efficacy of oseltamivir has been investigated in randomized controlled trials (RCT) in uncomplicated influenza, only observational data are available in ICU patients. Herpesviridae are an underestimated cause of HAP/VAP in ICU patients. Whilst incidence of herpesviridae identification in samples from lower respiratory tract of ICU patients is relatively high (from 20% to 50%), efforts should be made to differentiate local reactivation from true lung infection. Only few randomized controlled trials evaluated the efficacy of antiviral treatment in herpesviridae reactivation/infection in ICU patients and all were exploratory or negative. Further studies are needed to evaluate the impact of such treatment in specific populations.

Antibiotic resistance is a major health problem and will be probably one of the leading causes of deaths in the coming years. One of the most effective ways to fight against resistance is to decrease antibiotic consumption. Intensive care units (ICUs) are places where antibiotics are widely prescribed, and where multidrug-resistant pathogens are frequently encountered. However, ICU physicians may have opportunities to decrease antibiotics consumption and to apply antimicrobial stewardship programs. The main measures that may be implemented include refraining from immediate prescription of antibiotics when infection is suspected (except in patients with shock, where immediate administration of antibiotics is essential); limiting empiric broad-spectrum antibiotics (including anti-MRSA antibiotics) in patients without risk factors for multidrug-resistant pathogens; switching to monotherapy instead of combination therapy and narrowing spectrum when culture and susceptibility tests results are available; limiting the use of carbapenems to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and new beta-lactams to difficult-to-treat pathogen (when these news beta-lactams are the only available option); and shortening the duration of antimicrobial treatment, the use of procalcitonin being one tool to attain this goal. Antimicrobial stewardship programs should combine these measures rather than applying a single one. ICUs and ICU physicians should be at the frontline for developing antimicrobial stewardship programs.

International audience; Background: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis.Objectives: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A−).Methods: A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).Results: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A− patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A− patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A− had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A− patients (54%) but in none of the MIS-A+ patients.Conclusion: MIS-A+ and MIS-A− fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology

Several electroencephalographic (EEG) features -mainly the reactivity of background activity-have been suggested as reliable predictors of outcome for patients with post-anoxic coma (PAC). However, EEG in PAC often contains abundant EEG paroxysms (EP) that may hinder the detection of background EEG activity. We aimed to identify the features, among the different paroxysmal and non-paroxysmal EEG patterns, that may predict the outcome of patients with PAC.We retrospectively reviewed the clinical and EEG characteristics of 67 patients with PAC and selected those with abundant EP. We classified EP according to several features and assessed their prognostic value for survival at 15 days. We calculated a global regularity score, as the sum of the value (1 if regular, 0 if not) attributed to each of 4 features of EP (duration, morphology, amplitude, and frequency).The 35 patient-group with abundant EP showed a higher mortality than the group without abundant EP. Among 12 features of EP, four regularity features (regularity of EP duration, morphology, amplitude, and global regularity score) had a poor prognostic value. A global regularity score ≥ 3 showed a positive predictive value of 100 % for a poor outcome and a negative predictive value of 54 %, with good interrater consistency (Cohen's kappa = .63).The presence of EP and their regularity features in PAC patients are strongly associated with poor outcome. We propose a global regularity score, easily derived from visual EEG inspection, that may be a reliable prognostic tool for these patients. Prospective and larger studies are needed to confirm these findings.

International audience; Purpose: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).Methods: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.Results: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.Conclusions: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

We aimed to explore the relationships between specific viral mutations/mutational patterns and ventilator-associated pneumonia (VAP) occurrence in COVID-19 patients admitted in intensive care units between October 1, 2020, and May 30, 2021. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing. In this prospective multicentre cohort study, 259 patients were included. 222 patients (47%) had been infected with pre-existing ancestral variants, 116 (45%) with variant α, and 21 (8%) with other variants. 153 patients (59%) developed at least one VAP. There was no significant relationship between VAP occurrence and a specific SARS CoV-2 lineage/sublineage or mutational pattern.

Background ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare. Methods We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days. Results Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70–0.78]), junior physicians (0.78 [0.74–0.81]) and attending physicians (0.75 [0.72–0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67–0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death. Conclusions Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing. Trial registration ISRCTN ISRCTN59376582, retrospectively registered October 31st 2013.

Background Acute distress respiratory syndrome (ARDS) patients with veno-venous extra corporeal membrane oxygenation (ECMO) support are particularly exposed to ECMO-associated infection (ECMO-AI). Unfortunately, data regarding AI prophylaxis in this setting are lacking. Selective decontamination regimens decrease AI incidence, including ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in critically ill patients. We hypothesized that a multiple-site decontamination (MSD) regimen is associated with a reduction in the incidence of AI among VV-ECMO patients. Methods We conducted a retrospective observational study in three French ECMO referral centers from January 2010 to December 2021. All adult patients (> 18 years old) who received VV-ECMO support for ARDS were eligible. In addition to standard care (SC), 2 ICUs used MSD, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, once daily chlorhexidine body-wash and a 5-day nasal mupirocin course. AIs were compared between the 2 ICUs using MSD (MSD group) and the last ICU using SC. Results They were 241 patients available for the study. Sixty-nine were admitted in an ICU that applied MSD while the 172 others received standard care and constituted the SC group. There were 19 ECMO-AIs (12 VAP, 7 BSI) in the MSD group (1162 ECMO-days) compared to 143 AIs (104 VAP, 39 BSI) in the SC group (2376 ECMO-days), (p p p = 0.001). Mortality in ICU was similar in both groups (43% in the SC group vs 45% in the MSD group p = 0.90). Results were similar after propensity-score matching. Conclusion In this cohort of patients from different hospitals, MSD appeared to be safe in ECMO patients and may be associated with improved outcomes including lower ECMO-AI and MDRO acquisition incidences. Since residual confounders may persist, these promising results deserve confirmation by randomized controlled trials.

Background Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. Results We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p p p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38–1.26], p = 0.23). Conclusions In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

Background Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. Methods We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. Results Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70–0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50–86], specificity of 85% [55–98], a negative predictive value of 58% [36–93] and a positive predictive value 90% [67–96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12–0.75], p = 0.01). Conclusion In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.

Background Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in Covid-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. Methods Retrospective monocentric cohort study of 145 patients with severe Covid-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. Results Among the 145 Covid-19 patients included, 50% and 42 % had HSV and CMV lung reactivations, respectively; whereas among the 89 influenza patients, 63% and 28% had CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in Covid-19 patients (p = 0.03, see figure 1), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in Covid-19 and influenza patients (p=0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in Covid-19 patients, in influenza patients, or when all patients were grouped. Estimated cumulative incidence of herpes simplex virus (HSV) lung reactivation, extubation or death in Covid-19 and influenza patients, taking into account only the first event that occurred. p values for differences between Covid-19 and influenza patients were 0.03 for HSV reactivation, 0.53 for death and 0.87 for extubation. Conclusion HSV and CMV lung reactivations are frequent in Covid-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit (ICU) admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients. Disclosures CHARLES-EDOUARD LUYT, MD PhD, AdvanzPharma: Honoraria|Aerogen: Honoraria|Merck: Honoraria.

OBJECTIVES Postoperative mediastinitis, a feared complication after cardiac surgery, is associated with high mortality, especially of critically ill patients. Candida species infections are rare and severe, with poorly known outcomes. We conducted a case–control study to describe the characteristics, management and outcomes of patients with postoperative Candida mediastinitis. METHODS This French, monocentre, retrospective study included all patients with postoperative Candida mediastinitis (January 2003–February 2020) requiring intensive care unit admission. Candida mediastinitis patients (henceforth cases) were matched 1:1 with postoperative bacterial mediastinitis (henceforth control), based on 3 factors during mediastinitis management: age >40 years, cardiac transplantation and invasive circulatory device used. The primary end point was the probability of survival within 1 year after intensive care unit (ICU) admission. RESULTS Forty cases were matched to 40 controls. The global male/female ratio was 2.1, with mean age at admission 47.9 ± 13.8 years. Candida species were: 67.5% albicans, 17.5% glabrata, 15% parapsilosis, 5.0% tropicalis, 2.5% krusei and 2.5% lusitaniae. The median duration of mechanical ventilation was 23, 68.8% of patients received renal replacement therapy and 62.5% extracorporeal membrane oxygenation support. The probability of survival within the first year after ICU admission was 40 ± 5.5% and was significantly lower for cases than for controls (43 ± 8% vs 80 ± 6.3%, respectively; Log-rank test: P < 0.0001). The multivariable Cox proportional hazards model retained only renal replacement therapy [hazard ratio (HR) 3.7, 95% confidence interval (CI) 1.1–13.1; P = 0.04] and Candida mediastinitis (HR 2.4, 95% CI 1.1–5.6; P = 0.04) as independently associated with 1-year mortality. CONCLUSIONS Candida mediastinitis is a serious event after cardiac surgery and independently associated with 1-year mortality. Further studies are needed to determine whether deaths are directly attributable to Candida mediastinitis.

Background Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. Objective and design We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. Subjects and methods We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. Results Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of −1.99 (95% confidence interval [CI] −2.36 to −1.62), −1.98 (95% CI −2.94 to −1.02), −2.20 (95% CI −3.15 to −1.25) and − 2.10 (95% CI −3.29 to −0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). Conclusions This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Background: Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing strains. The pharmacokinetics of cefiderocol has been studied in healthy subjects and particularly in phase II and III studies. This retrospective study investigated intravenous cefiderocol population pharmacokinetics in adult patients treated by cefiderocol. Methods: We studied 55 consecutive patients hospitalized in an intensive care unit. Cefiderocol plasma samples were obtained on different occasions during treatment. Plasma concentration was assayed using mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2020R1. Results: A total of 205 plasma samples were obtained from 55 patients. Eighty percent of patients received cefiderocol for ventilator-associated pneumonia due to carbapenem-resistant Pseudomonas aeruginosa infection. Cefiderocol concentration time-courses were best fit to a two-compartment open model with first-order elimination. Elimination clearance was positively related to renal function (estimated by the CKD formula). Adding albumin plasma binding in the model significantly improved the model assuming a ~40% unbound drug fraction given a ~40 g/L albuminemia. The final model included CKD plus cefiderocol plasma binding effects. Fat-free mass was better than total body weight to influence, via the allometric rule, clearance and volume terms, but this effect was negligible. The final clearance based on free circulating drug (CLU) for a typical patient, CKD = 90, was 7.38 L/h [relative standard error, RSE, 22%] with a between-subject variability of 0.47 [RSE 10%] (exponential distribution). Conclusion: This study showed that albumin binding and CKD effects were significant predictors of unbound and total plasma cefiderocol concentrations. Our results indicate that individual adjustment of cefiderocol can be used to reach high minimum inhibitory concentrations based on an estimation of unbound drug concentration and optimize therapeutic efficacy.

Background Although rarely addressed in the literature, a key question in the care of critically pregnant women with severe acute respiratory distress syndrome (ARDS), especially at the time of extracorporeal membrane oxygenation (ECMO) decision, is whether delivery might substantially improve the mother’s and child’s conditions. This multicenter, retrospective cohort aims to report maternal and fetal short- and long-term outcomes of pregnant women with ECMO-rescued severe ARDS according to the timing of the delivery decision taken before or after ECMO cannulation. Methods We included critically ill women with ongoing pregnancy or within 15 days after a maternal/child-rescue-aimed delivery supported by ECMO for a severe ARDS between October 2009 and August 2021 in four ECMO centers. Clinical characteristics, critical care management, complications, and hospital discharge status for both mothers and children were collected. Long-term outcomes and premature birth complications were assessed. Results Among 563 women on venovenous ECMO during the study period, 11 were cannulated during an ongoing pregnancy at a median (range) of 25 (21–29) gestational weeks, and 13 after an emergency delivery performed at 32 (17–39) weeks of gestation. Pre-ECMO PaO2/FiO2 ratio was 57 (26–98) and did not differ between the two groups. Patients on ECMO after delivery reported more major bleeding (46 vs. 18%, p = 0.05) than those with ongoing pregnancy. Overall, the maternal hospital survival was 88%, which was not different between the two groups. Four (36%) of pregnant women had a spontaneous expulsion on ECMO, and fetal survival was higher when ECMO was set after delivery (92% vs. 55%, p = 0.03). Among newborns alive, no severe preterm morbidity or long-term sequelae were reported. Conclusion Continuation of the pregnancy on ECMO support carries a significant risk of fetal death while improving prematurity-related morbidity in alive newborns with no difference in maternal outcomes. Decisions regarding timing, place, and mode of delivery should be taken and regularly (re)assess by a multidisciplinary team in experienced ECMO centers.

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.

OBJECTIVES To determine the characteristics and outcomes of patients prone-positioned during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and lung CT pattern associated with improved respiratory system static compliance after that intervention. DESIGN Retrospective, single-center study over 8 years. SETTINGS Twenty-six bed ICU in a tertiary center. MEASUREMENTS AND MAIN RESULTS A propensity score-matched analysis compared patients with prone-positioning during extracorporeal membrane oxygenation and those without. An increase of the static compliance greater than or equal to 3 mL/cm H2O after 16 hours of prone-positioning defined prone-positioning responders. The primary outcome was the time to successful extracorporeal membrane oxygenation weaning within 90 days of postextracorporeal membrane oxygenation start, with death as a competing risk. Among 298 venovenous extracorporeal membrane oxygenation-treated adults with severe acute respiratory distress syndrome, 64 were prone-positioning extracorporeal membrane oxygenation. Although both propensity score-matched groups had similar extracorporeal membrane oxygenation durations, prone-positioning extracorporeal membrane oxygenation patients' 90-day probability of being weaned-off extracorporeal membrane oxygenation and alive was higher (0.75 vs 0.54, p = 0.03; subdistribution hazard ratio [95% CI], 1.54 [1.05-2.58]) and 90-day mortality was lower (20% vs 42%, p < 0.01) than that for no prone-positioning extracorporeal membrane oxygenation patients. Extracorporeal membrane oxygenation-related complications were comparable for the two groups. Patients without improved static compliance had higher percentages of nonaerated or poorly aerated ventral and medial-ventral lung regions (p = 0.047). CONCLUSIONS Prone-positioning during venovenous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Patients with greater normally aerated lung tissue in the ventral and medial-ventral regions on quantitative lung CT-scan performed before prone-positioning are more likely to improve their static compliance after that procedure during extracorporeal membrane oxygenation.

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35–56) years, with a median body mass index of 30 (27–35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8–16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin–antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p

Background Ventilator-associated lower respiratory tract infections (VA-LRTI) are common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between corticosteroid adjuvant administration and the incidence of VA-LRTI. MethodsPlanned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 hours for a SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VA-LRTI diagnosis required strict definition with clinical, radiological and microbiological documentation. We assessed the association of VA-LRTI with corticosteroid administration using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on prespecified confounders.Results 545 patients were included, of whom 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VA-LRTI was violated (p=0.018) indicating that this effect varied during the ICU stay. We found a lower risk of VA-LRTI for corticosteroid treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time dependent coefficients, the association between corticosteroids and the incidence of VA-LRTI was not significant (overall effect p=0.068), with time-dependent hazard ratios (95% confidence interval) of 0.45 (0.18 to 1.10) at day 2, 0.89 (0.62 to 1.27) at day 7, 1.38 (0.99 to 1.92) at day 14 and 1.80 (1.08 to 2.98) at day 21.Conclusions No significant association was found between corticosteroid adjuvant therapy and the incidence of VA-LRTI, although a significant time-varying effect of corticosteroids was identified along the 28-day follow-up.

L’antibiothérapie est l’un des traitements les plus prescrits en réanimation. La prescription empirique, précoce et adéquate de ces traitements conditionne le pronostic vital. Bien qu’indispensable dans notre pratique quotidienne, ces traitements sont associés à de fréquents effets secondaires et notamment à l’émergence de résistance. Ce problème de santé majeur provoquera directement le décès de plus de 300 millions de patients lors des prochaines décennies. Dans ce contexte, les réanimateurs doivent développer des stratégies afin d’optimiser l’utilisation de ces molécules. La réduction de la durée de l’antibiothérapie en réanimation est une stratégie importante dans le combat contre la résistance aux antibiotiques. En effet, plusieurs études ont mis en évidence que le risque d’émergence de résistances augmentait avec la durée d’exposition. La tendance générale est donc à la réduction de la durée de traitement. Il existe 3 opportunités pour raccourcir la durée de traitement antibiotique en réanimation : arrêter l’antibiothérapie empirique quand l’infection est infirmée ; ne traiter que 8 jours la majorité des infections ; et enfin personnaliser la durée de traitement en fonction de la cinétique de la procalcitonine.

Background Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. Methods Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. Results Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. Conclusions HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs.We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiOIn ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with a rarer occurrence of severe disease requiring intensive care. However, a substantial number of patients infected with variant Omicron still experienced severe COVID-19. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 participating intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients for whom SARS-CoV-2 variant lineage was determined, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) was different from that in those infected with variant Delta (n = 111). We observed no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% were immunocompromised, most of whom had received two doses of vaccine or more (85.9%) but displayed a poor humoral response to vaccination (mean difference in serum anti-spike IgG antibody titers between vaccinated and non-vaccinated immunocompromised patients: 1078 BAU/mL [-319.4; 2475.0]; p = 0.160). The mortality rate of immunocompromised patients infected with variant Omicron was significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there was no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms or mutational profile and the 28-day mortality.

International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2

Background Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is currently one of the first-line therapies for refractory cardiogenic shock (CS), but its applicability is undermined by the high morbidity associated with its complications, especially those related to mechanical ventilation (MV). We aimed to assess the prognostic impact of keeping patients in refractory CS awake at cannulation and during the VA-ECMO run. Methods A 7-year database of patients given peripheral VA-ECMO support was used to conduct a propensity-score (PS)-matched analysis to balance their clinical profiles. Patients were classified as ‘awake ECMO’ or ‘non-awake ECMO’, respectively, if invasive MV was used during ≤50% or >50% of the VA-ECMO run. Primary outcomes included ventilator-associated pneumonia and ECMO-related complication rates, and secondary outcomes were 60-day and 1-year mortality. A multivariate logistic-regression analysis was used to identify whether MV at cannulation was independently associated with 60-day mortality. Results Among 231 patients included, 91 (39%) were ‘awake’ and 140 (61%) ‘non-awake’. After PS-matching adjustment, the ‘awake ECMO’ group had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, and less antibiotic and sedative consumption. This strategy was also associated with reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021) compared to the ‘non-awake’ group, respectively. Lastly, MV at ECMO cannulation was independently associated with 60-day mortality. Conclusion An ‘awake ECMO’ management in VA-ECMO-supported CS patients is feasible, safe, and associated with improved short- and long-term outcomes.

Purpose To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. Methods Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. Results Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. Conclusions PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-00994-9.