Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study).

BACKGROUND: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients' characteristics, and determine ICU mortality associated factors. METHODS: We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate. RESULTS: Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality. CONCLUSION: The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.

Development and validation of a clinico-biological score to predict outcomes in patients with drowning-associated cardiac arrest.

BACKGROUND: While several scoring systems have been developed to predict short-term outcome in out-of-hospital cardiac arrest patients, there is currently no dedicated prognostic tool for drowning-associated cardiac arrest (DACA) patients. METHODS: Patients experiencing DACA from two retrospective multicenter cohorts of drowning patients were included in the present study. Among the patients from the development cohort, risk-factors for day-28 mortality were assessed by logistic regression. A prediction score was conceived and assessed in patients from the validation cohort. RESULTS: Among the 103 included patients from the development cohort, the day-28 mortality rate reached 51% (53/103). Identified independent early risk-factors for day-28 mortality included cardiopulmonary resuscitation duration longer than 20 min (OR 6.40 [95% CI 1.88-23.32]; p = 0.003), temperature at Intensive Care Unit admission <34 °C (OR 8.84 [95% CI 2.66-32.92]; p < 0.001), need for invasive mechanical ventilation (OR 6.83 [95% CI 1.47-40.87]; p = 0.02) and lactate concentration > 7 mmol/L (OR 3.56 [95% CI 1.01-13.07]; p = 0.04). The Area Under the ROC Curve (AUC) of the developed score based on those variables reached 0.91 (95% CI, 0.86-0.97). The optimal cut-off for predicting poor outcomes was 4 points with a sensitivity of 92% (95% CI, 82-98%), a specificity of 82% (95% CI, 67-91%), a positive predictive value (PPV) of 84% (95% CI, 72-95%) and a negative predictive value (NPV) of 91% (95% CI, 79-96%). The assessment of this score on the validation cohort of 81 patients exhibited an AUC of 0.82. Using the same 4 points threshold, sensitivity, specificity, PPV and NPV values of the validation cohort were: 81%, 67%, 72% and 77%, respectively. CONCLUSION: In patients suffering from drowning induced initial cardiac arrest admitted to ICU with a DACA score ≥ 4, the likelihood of survival at day-28 is significantly lower. Prospective validation of the DACA score and assessment of its usefulness are warranted in the future.

Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS. DESIGN: Retrospective analysis of a multicenter cohort. PATIENTS: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients. CONCLUSIONS: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

Prevention of ICU-acquired infection with decontamination regimen in immunocompromised patients: a pre/post observational study.

PURPOSE: Although the proportion of immunocompromised patients admitted to the ICU is increasing, data regarding specific management, including acquired infection (ICU-AI) prophylaxis, in this setting are lacking. We aim to investigate the effect of multiple-site decontamination regimens (MSD) in immunocompromised patients. METHODS: We conducted a prospective pre-/post-observational study in 2 ICUs in Bretagne, western France. Adults who required mechanical ventilation for 24 h or more were eligible. During the study period, MSD was implemented in participating ICUs in addition to standard care. It consists of the administration of topical antibiotics (gentamicin, colistin sulfate, and amphotericin B), four times daily in the oropharynx and the gastric tube, 4% chlorhexidine bodywash once daily, and a 5-day nasal mupirocin course. RESULTS: Overall, 295 immunocompromised patients were available for analysis (151 in the post-implementation group vs 143 in the pre-implementation group). Solid organ cancer was present in 77/295 patients while immunomodulatory treatments were noticed in 135/295. They were 35 ICU-AI in 29/143 patients in the standard-care group as compared with 10 ICU-AI in 9/151 patients in the post-implementation group (p < 0.001). In a multivariable Poisson regression model, MSD was independently associated with a decreased incidence of ICU-AI (incidence rate ratio = 0.39; 95%CI [0.20-0.87] p = 0.008). There were 35/143 deaths in the standard-care group as compared with 22/151 in the post-implementation group (p = 0.046), this difference remained in a multivariable Cox model (HR = 0.58; 95CI [0.34-0.95] p = 0.048). CONCLUSION: In conclusion, MSD appeared to be associated with improved outcomes in critically ill immunocompromised patients.

Infectious encephalitis in elderly patients: a prospective multicentre observational study in France 2016-2019.

PURPOSE: Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. METHODS: We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years. RESULTS: Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥ 65 years, including 74 (15%) ≥ 80 years. Patients ≥ 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm3[13-220] in 65-79 years, 62 [17-180] in ≥ 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥ 80 years (P < 0.001). Age ≥ 80 years, coma on admission, CSF protein ≥ 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality. CONCLUSION: Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.

Attributable mortality of ICU acquired bloodstream infections: a propensity-score matched analysis.

The mortality attributable to ICU-acquired bloodstream infection (BSI) differs between studies due to statistical methods used for cohort matching. Propensity-score matching has never been used to avoid eventual bias when studying BSI attributable mortality in the ICU. We conducted an observational prospective study over a 4-year period, on patients admitted for at least 48 h in 2 intensive care units. Based on risk factors for death in the ICU and for BSI, each patient with BSI was matched with 3 patients without BSI using propensity-score matching. We performed a competitive risk analysis to study BSI mortality attributable fraction. Of 2464 included patients, 71 (2.9%) had a BSI. Propensity-score matching was highly effective and group characteristics were fully balanced. Crude mortality was 36.6% in patients with BSI and 21.6% in propensity-score matched patients (p=0.018). Attributable mortality of BSI was 2.3% [1.2-4.0] and number needed to harm was 6.7. With Fine and Gray model, a higher risk for death was observed in patients with BSI than in propensity-score matched patients (sub distribution Hazard Ratio (sdHR) = 2.11; 95% CI [1.32-3.37] p = 0.002). Patients with BSI had a higher risk for death and BSI attributable mortality fraction was 2.3%.

Clinical spectrum and risk factors for mortality among seawater and freshwater critically ill drowning patients: a French multicenter study.

BACKGROUND: Drowning is a global threat and one of the leading causes of injury around the world. The impact of drowning conditions including water salinity on patients' prognosis remains poorly explored in Intensive Care Units (ICUs) patients. METHODS: We conducted a retrospective multicenter study on patients admitted to 14 ICUs in the west of France from January 2013 to January 2020. We first compared demographic and clinical characteristics at admission as well as clinical courses of these patients according to the salinity of drowning water. Then, we aimed to identify variables associated with 28-day survival using a Cox proportional hazard model. RESULTS: Of the 270 consecutive included patients, drowning occurred in seawater in 199 patients (73.7%) and in freshwater in 71 patients (26.3%). Day-28 mortality was observed in 55 patients (20.4%). Freshwater was independently associated with 28-day mortality (Adjusted Hazard Ratio (aHR) 1.84 [95% Confidence Interval (CI) 1.03-3.29], p = 0.04). A higher proportion of freshwater patients presented psychiatric comorbidities (47.9 vs. 19.1%; p < 0.0001) and the etiology of drowning appeared more frequently to be a suicide attempt in this population (25.7 vs. 4.2%; p < 0.0001). The other factors independently associated with 28-day mortality were the occurrence of a drowning-related cardiac arrest (aHR 11.5 [95% CI 2.51-52.43], p = 0.0017), duration of cardiopulmonary resuscitation (aHR 1.05 [95% CI 1.03-1.07], p < 0.0001) and SOFA score at day 1 (aHR 1.2 [95% CI 1.11-1.3], p < 0.0001). CONCLUSIONS: In this large multicenter cohort, freshwater drowning patients had a poorer prognosis than saltwater drowning patients. Reasons for such discrepancies include differences in underlying psychiatric comorbidity, drowning circumstances and severities. Patients with initial cardiac arrest secondary to drowning remain with a very poor prognosis.

Thyroid Storm in the ICU: A Retrospective Multicenter Study.

OBJECTIVES: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. DESIGN: Retrospective, multicenter, national study over an 18-year period (2000-2017). SETTING: Thirty-one French ICUs. PATIENTS: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. CONCLUSIONS: Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.

Incidence and risk factors for acquired colonization and infection due to extended-spectrum beta-lactamase-producing Gram-negative bacilli: a retrospective analysis in three ICUs with low multidrug resistance rate.

The purpose of this study is to assess risk factors for the acquisition of extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5-2.5%]), and 15 (0.5%; 95% CI [0.3-0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5-95.1%] and 95.2% [93.5-97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86-32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem ß-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI.

Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase.

BACKGROUND: A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety. METHODS: Single doses (0.25 to 100 mg) and repeated oral doses (2.5 to 20 mg for 10 days) of BIA 10-2474 had been administered to 84 healthy volunteers in sequential cohorts; no severe adverse events had been reported. Another cohort of participants was then assigned to placebo (2 participants) or 50 mg of BIA 10-2474 per day (6 participants). This report focuses on neurologic adverse events in participants in this final cohort. A total of 4 of the 6 participants who received active treatment consented to have their clinical and radiologic data included in this report. RESULTS: An acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging showed bilateral and symmetric cerebral lesions, including microhemorrhages and hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging sequences predominantly involving the pons and hippocampi. One patient became brain dead; the condition of two patients subsequently improved, but one patient had residual memory impairment, and the other patient had a residual cerebellar syndrome. One patient remained asymptomatic. CONCLUSIONS: An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.

Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics.

BACKGROUND: As a consequence of drug sequestration, increase in volume of distribution, or alteration of elimination, extracorporeal membrane oxygenation (ECMO) might lead to inadequate plasma concentrations of vital drugs. The aim of this experimental study was to develop an ex vivo model to better characterize the impact of ECMO procedure on beta-lactam antibiotics pharmacokinetics. METHODS: Plasma concentrations of cefotaxime, ceftazidime, cefepime, piperacillin, oxacillin, amoxicillin, and ceftriaxone were measured in an ex vivo ECMO circuit primed with whole human blood and compared with controls stored in glass tubes and polyvinyl chloride tubing. Serial blood samples were collected over 48 hours, and the concentrations of beta-lactam antibiotics were quantified using a validated high-performance liquid chromatography assay. The concentrations' decay rate over time was compared between the ECMO circuits and controls using nonlinear mixed-effect modeling. RESULTS: Cefotaxime concentrations decreased markedly: 86% of the initial concentration remained after 4 hours and only 21% after 48 hours (P < 0.05 for the comparison in rate of decrease with both glass and polyvinyl chloride controls). There was no difference in the rate of decrease between ECMO circuit and controls for the other beta-lactam antibiotics. The average drug recoveries from the ECMO circuits at 48 hours were as follows: ceftazidime, 73%; cefepime, 67%; piperacillin, 71%; oxacillin, 46%; and amoxicillin, 72%. Concentrations of ceftriaxone remained stable throughout the 48-hour study both in ECMO circuits and in controls. CONCLUSIONS: Significant losses of cefotaxime were observed, whereas ceftazidime, cefepime, piperacillin, oxacillin, and amoxicillin decrease was moderate and similar to that of the control group, and ceftriaxone concentrations remained unchanged. These results are reassuring for the use of beta-lactam antibiotics in critically ill patients treated with ECMO.

Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood.

INTRODUCTION: As a result of drug sequestration and increased volume of distribution, the extracorporeal membrane oxygenation (ECMO) procedure might lead to a decrease in drug concentrations during a patient's treatment. The aim of this study was to evaluate sedative, antibiotic and immunosuppressive drug loss in ECMO circuit using ex-vivo and in-vitro experiments. METHODS: Blood concentrations of propofol, midazolam, cyclosporine and vancomycin were measured in an ex-vivo ECMO circuit primed with whole human blood, and compared to controls stored in polypropylene tubes. In vitro experiments were also conducted to further explore the role of temperature, oxygen exposure and polyvinylchloride surfaces on propofol loss in the ECMO circuit. RESULTS: Propofol concentration decreased rapidly; 70% of its baseline concentration was lost after only 30 minutes, and only 11% remained after five hours (P <0.001 for the comparison with control polypropylene tube propofol concentration). Further experiments demonstrated that oxygen exposure and contact with polyvinylchloride tubing were respectively responsible for 70% and 85% of propofol loss after 45 minutes. Midazolam concentration also rapidly decreased in the ECMO circuit, with only 54% and 11% of baseline concentration being detected at 30 minutes and 24 hours respectively (P = 0.01 versus control). Alternatively, cyclosporine concentration remained stable for the five first hours, then decreased to 78% and 73% of the baseline value after 24 hours and 48 hours, (P = 0.35 versus control). Lastly, vancomycin concentration remained stable in the ECMO circuit for the 48-hour experimental protocol. CONCLUSIONS: We observed important losses of propofol and midazolam, while cyclosporine concentration decreased slowly and moderately, and vancomycin concentration remained unchanged in the ex-vivo ECMO circuit primed with whole human blood. These data might help intensive care unit physicians planning clinical trials with a final objective to better adapt doses of these drugs while treating critically ill ECMO patients.

At-risk drinking is independently associated with ICU and one-year mortality in critically ill nontrauma patients*.

OBJECTIVES: The impact of at-risk drinking on the outcomes of nontrauma patients is not well characterized. The aim of this study was to determine whether at-risk drinking is independently associated with the survival of nontrauma patients in an ICU and within 1 year following ICU discharge. DESIGN: Observational cohort study. SETTING: A 21-bed mixed ICU in a university hospital. PATIENTS: A total of 662 patients who experienced an ICU stay of 3 days or more and for whom alcohol consumption could be assessed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU-related variables were collected prospectively, and a 1-year follow-up was determined retrospectively. Analyses were adjusted based on prognostic determinants of short- and long-term outcomes, as previously described in ICU patients and alcohol abusers. Two hundred and eight patients (33%) were identified as at-risk drinkers according to the National Institute on Alcohol Abuse and Alcoholism criteria. Additionally, 111 patients (17%) died in the ICU, and 97 (15%) died after ICU discharge. From the ICU admission until the end of the 1-year follow-up period, the at-risk drinkers exhibited poorer survival than the non-at-risk drinkers (p = 0.0004, as determined by the log-rank test). More specifically, 50 at-risk drinkers (24%) versus 61 non-at-risk drinkers (13%) died in the ICU (p = 0.0009 for the comparison). After adjustment, at-risk drinking remained independently associated with mortality in the ICU (adjusted odds ratio of 1.83; 95% CI of 1.16-2.89; p = 0.01) and with mortality within the year following ICU discharge (adjusted hazard ratio of 1.70; 95% CI of 1.15-2.52; p = 0.008). The causes of death in the at-risk and non-at-risk drinkers were similar. CONCLUSIONS: In this population of critically ill nontrauma patients, at-risk drinking was independently associated with death in the ICU and within the year following ICU discharge.

Characteristics, management and outcome of Herpes Simplex and Varicella-Zoster virus encephalitis: a multicentre prospective cohort study.

OBJECTIVE: To characterize differences between Herpes Simplex virus encephalitis and Varicella-Zoster virus encephalitis (HSVE and VZVE) and other aetiologies of infectious encephalitis (IE), and to investigate the impact of time-to-aciclovir (ACV) start, ACV dose and duration on outcome. METHODS: We compared 132 HSVE, 65 VZVE and 297 other IE enrolled in a prospective cohort (ENCEIF). We estimated associations between time-to-ACV start, dose or duration and outcome through adjusted odds ratio (aOR) using logistic regression analysis. RESULTS: Prevalence of immunodepression differed among aetiologies: 15/65 (23%) for VZVE, 13/132 (10%) for HSVE and 30/297 (10%) for other IE (p <0.05), as was presence of seizure at admission: 27/132 (20%) for HSVE, 4/65 (6%) for VZVE and 43/297 (14%) for other IE (p <0.05). Poor outcome at hospital discharge (Glasgow outcome scale ≤3) differed among the three groups: 40/127 (31%) for HSVE, 12/65 (18%) for VZVE and 38/290 (13%) for other IE (p <0.05). Time-to-ACV start was associated with outcome in HSVE (aOR 3.61 [1.25-10.40]), but not in VZVE (aOR 0.84 [0.18-3.85]). Increased ACV dose was not associated with outcome among HSVE (aOR 1.25 [0.44-3.64]) nor VZVE (aOR 1.16 [0.24-5.73]). DISCUSSION: HSVE and VZVE are distinct in clinical presentation, outcome and prognostic factors. The impact of early ACV initiation was more apparent for HSVE than for VZVE; however, this could be because of VZVE's smaller sample size and lower outcome rate leading to low statistical power or because of potential distinct IE pathophysiology.

The depth of neuromuscular blockade is not related to chest wall elastance and respiratory mechanics in moderate to severe acute respiratory distress syndrome patients. A prospective cohort study.

BACKGROUND: Data concerning the depth of neuromuscular blockade (NMB) required for effective relaxation of the respiratory muscles in ARDS are scarce. We hypothesised that complete versus partial NMB can modify respiratory mechanics. METHOD: Prospective study to compare the respiratory mechanics of ARDS patients according to the NMB depth. Each patient was analysed at two times: deep NMB (facial train of four count (TOFC) = 0) and intermediate NMB (TOFC >0). The primary endpoint was the comparison of chest wall elastance (ELCW) according to the NMB level. RESULTS: 33 ARDS patients were analysed. There was no statistical difference between the ELCW at TOFC = 0 compared to TOFC >0: 7 cmH2O/l [5.7-9.5] versus 7 cmH2O/l [5.3-10.8] (p = 0.36). The depth of NMB did not modify the expiratory nor inspiratory oesophageal pressure (Pesexp = 8 cmH2O [5-9.5] at TOFC = 0 versus 7 cmH2O [5-10] at TOFC >0; (p = 0.16) and Pesinsp = 10 cmH2O [8.2-13] at TOFC = 0 versus 10 cmH2O [8-13] at TOFC >0; (p = 0.12)). CONCLUSION: In ARDS, the relaxation of the respiratory muscles seems to be independent of the NMB level.

Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study.

PURPOSE: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. METHODS: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. RESULTS: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048). CONCLUSION: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.