Influence of arterial blood gases on the renal arterial resistive index in intensive care unit.

BACKGROUND: Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting. METHODS: This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis. RESULTS: A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2 (R = 0.270, p = 0.03), age (R = 0.574, p < 0.0001), diastolic arterial pressure (DAP) (R = - 0.368, p = 0.0028), and SaO2 (R = - 0.284, p = 0.0231). Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267). CONCLUSION: The interpretation of renal arterial RI should take into account thresholds for PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70-0914, received approval from local Ethical Committee of Toulouse University Hospital.

Evolution of platelet activation parameters during septic shock in intensive care unit.

During severe sepsis, platelet activation may induce disseminate microvascular thrombosis, which play a key role in critical organ failure. Crucially, most of the studies in this field have explored platelet-leukocyte interactions in animal models, or explored platelets under the spectrum of thrombocytopenia or disseminated intravascular coagulation and have not taken into account the complex interplay that might exist between platelets and leukocytes during human septic shock nor the kinetics of platelet activation. Here, we assessed platelet activation parameters at the admission of patients with sepsis to the intensive care unit (ICU) and 48 hours later. Twenty-two patients were enrolled in the study, thirteen (59.1%) of whom were thrombocytopenic. The control group was composed of twelve infection-free patients admitted during the study period. The activation parameters studied included platelet-leukocyte interactions, assessed by flow cytometry in whole blood, as well as membrane surface and soluble platelet activation markers measured by flow cytometry and dedicated ELISA kits. We also investigated platelet aggregation and secretion responses of patients with sepsis following stimulation, compared to controls. At admission, the level of circulating monocyte-platelet and neutrophil-platelet heterotypic aggregates was significantly higher in sepsis patients compared to controls and returned to a level comparable to controls or even below 48 hours later. Basal levels of CD62P and CD63 platelet membrane exposure at admission and 48 hours later were low and similar to controls. In contrast, plasma level of soluble GPVI and soluble CD40 ligand was significantly increased in septic patients, at the two times of analysis, reflecting previous platelet activation. Platelet aggregation and secretion responses induced by specific agonists were significantly decreased in septic conditions, particularly 48 hours after admission. Hence, we have observed for the first time that critically ill septic patients compared to controls have both an early and durable platelet activation while their circulating platelets are less responsive to different agonists.

Assessment of Electrical Impedance Tomography to Set Optimal Positive End-Expiratory Pressure for Venoarterial Extracorporeal Membrane Oxygenation-Treated Patients.

OBJECTIVES: Patients on venoarterial extracorporeal membrane oxygenation have many risk factors for pulmonary complications in addition to their heart failure. Optimal positive end-expiratory pressure is unknown in these patients. The aim was to evaluate the ability of electrical impedance tomography to help the physician to select the optimal positive end-expiratory pressure in venoarterial extracorporeal membrane oxygenation treated and mechanically ventilated patients during a positive end-expiratory pressure trial. DESIGN: Observational prospective monocentric. SETTING: University hospital. PATIENTS: Patients (n = 23) older than 18 years old, on mechanical ventilation and venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: A decreasing positive end-expiratory pressure trial (20-5 cm H2O) in increments of 5 cm H2O was performed and monitored by a collection of clinical parameters, ventilatory and ultrasonographic (cardiac and pulmonary) to define an optimal positive end-expiratory pressure according to respiratory criteria (optimal positive end-expiratory pressure selected by physician with respiratory parameters), and then adjusted according to hemodynamic and cardiac tolerances (optimal positive end-expiratory pressure selected by physician with respiratory, hemodynamic, and echocardiographic parameters). At the same time, electrical impedance tomography data (regional distribution of ventilation, compliance, and overdistension collapse) were recorded and analyzed retrospectively to define the optimal positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: The median of this optimal positive end-expiratory pressure was 10 cm H2O in our population. Electrical impedance tomography showed that increasing positive end-expiratory pressure promoted overdistention of ventral lung, maximum at positive end-expiratory pressure 20 cm H20 (34% [interquartile range, 24.5-40]). Decreasing positive end-expiratory pressure resulted in collapse of dorsal lung (29% [interquartile range, 21-45.8]). The optimal positive end-expiratory pressure selected by physician with respiratory parameters was not different from the positive end-expiratory pressure chosen by the electrical impedance tomography. However, there is a negative impact of a high level of intrathoracic pressure on hemodynamic and cardiac tolerances. CONCLUSIONS: Our results support that electrical impedance tomography appears predictive to define optimal positive end-expiratory pressure on venoarterial extracorporeal membrane oxygenation, aided by echocardiography to optimize hemodynamic assessment and management.

Hydroxychloroquine in Coronavirus Disease 2019 Patients: What Still Needs to Be Known About the Kinetics.

Different dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples (n = 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations.

Influence of extracorporeal membrane oxygenation on the pharmacokinetics of ceftolozane/tazobactam: an ex vivo and in vivo study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in intensive care units and can modify drug pharmacokinetics and lead to under-exposure associated with treatment failure. Ceftolozane/tazobactam is an antibiotic combination used for complicated infections in critically ill patients. Launched in 2015, sparse data are available on the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam. The aim of the present study was to determine the influence of ECMO on the pharmacokinetics of ceftolozane-tazobactam. METHODS: An ex vivo model (closed-loop ECMO circuits primed with human whole blood) was used to study adsorption during 8-h inter-dose intervals over a 24-h period (for all three ceftolozane/tazobactam injections) with eight samples per inter-dose interval. Two different dosages of ceftolozane/tazobactam injection were studied and a control (whole blood spiked with ceftolozane/tazobactam in a glass tube) was performed. An in vivo porcine model was developed with a 1-h infusion of ceftolozane-tazobactam and concentration monitoring for 11 h. Pigs undergoing ECMO were compared with a control group. Pharmacokinetic analysis of in vivo data (non-compartmental analysis and non-linear mixed effects modelling) was performed to determine the influence of ECMO. RESULTS: With the ex vivo model, variations in concentration ranged from - 5.73 to 1.26% and from - 12.95 to - 2.89% respectively for ceftolozane (concentrations ranging from 20 to 180 mg/l) and tazobactam (concentrations ranging from 10 to 75 mg/l) after 8 h. In vivo pharmacokinetic exploration showed that ECMO induces a significant decrease of 37% for tazobactam clearance without significant modification in the pharmacokinetics of ceftolozane, probably due to a small cohort size. CONCLUSIONS: Considering that the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam is not clinically significant, normal ceftolozane and tazobactam dosing in critically ill patients should be effective for patients undergoing ECMO.

Kinin B1 receptor: a potential therapeutic target in sepsis-induced vascular hyperpermeability.

BACKGROUND: In sepsis, the endothelial barrier becomes incompetent, with the leaking of plasma into interstitial tissues. VE-cadherin, an adherens junction protein, is the gatekeeper of endothelial cohesion. Kinins, released during sepsis, induce vascular leakage and vasodilation. They act via two G-protein coupled receptors: B1 (B1R) and B2 (B2R). B1R is inducible in the presence of pro-inflammatory cytokines, endotoxins or after tissue injury. It acts at a later stage of sepsis and elicits a sustained inflammatory response. The aim of our study was to investigate the relationships between B1R and VE-cadherin destabilization in vivo in a later phase of sepsis. METHODS: Experimental, prospective study in a university research laboratory. We used a polymicrobial model of septic shock by cecal ligation and puncture in C57BL6 male mice or C57BL6 male mice that received a specific B1R antagonist (R-954). We studied the influence of B1R on sepsis-induced vascular permeability 30 h after surgery for several organs, and VE-cadherin expression in the lung and kidneys by injecting R-954 just before surgery. The 96-h survival was determined in mice without treatment or in animals receiving R-954 as a "prophylactic" regimen (a subcutaneous injection of 200 µg/kg, prior to CLP and 24 h after CLP), or as a "curative" regimen (injection of 100 µg/kg at H6, H24 and H48 post-surgery). RESULTS: B1R inactivation helps to maintain MAP above 65 mmHg but induces different permeability profiles depending on whether or not organ perfusion is autoregulated. In our model, VE-cadherin was destabilized in vivo during septic shock. At a late stage of sepsis, the B1R blockade reduced the VE-cadherin disruption by limiting eNOS activation. The survival rate for mice that received R-954 after sepsis induction was higher than in animals that received an antagonist as a prophylactic treatment. CONCLUSIONS: B1R antagonizing reduced mortality in our model of murine septic shock by limiting the vascular permeability induced by VE-cadherin destabilization through maintenance of the macrohemodynamics, consequently limiting organ dysfunctions.

Risk factor analysis for linezolid-associated thrombocytopenia in critically ill patients.

Linezolid is an antibiotic used against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Its primary adverse effect is haematotoxicity. The objective of this study was to analyse the risk factors for onset of thrombocytopenia in critically ill patients treated with linezolid. This was a retrospective, single-centre study of 72 patients. Platelets were measured from D0 to D20 after the start of treatment. The risk factors for thrombocytopenia were identified using a multivariate logistic regression analysis following a Monte Carlo simulation. Following ROC curve analysis, a baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L, with respective odds ratios of 117 (95% CI [97-206]) and 3 (95% CI [1.5-6.2]) in the simulated population, were identified as risk factors. Among the source population patients combining these 2 factors, a significantly higher number developed thrombocytopenia (66.7% vs. 33.3%, p = 0.0042). A baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L are risk factors for the onset of thrombocytopenia in critically ill patients treated with linezolid.

Outcome of community- versus hospital-acquired intra-abdominal infections in intensive care unit: a retrospective study.

BACKGROUND: To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in terms of mortality, severity and complications. METHODS: Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis. RESULTS: Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 [15-25] vs. 21 [15-24] respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 [7-36] vs. 6[3-12] days, p < 0.001 and 41 [24-66] vs. 17 [7-32] days, p = 0.001), and experienced more complications (reoperation and reintubation) than those with CA-IAI. CONCLUSION: CA-IAI group had higher 28-day mortality rate than HA-IAI group. Mortality was similar at 90 days but those with HA-IAI had a prolonged ICU and hospital stay. In addition, they developed more complications.

Risk factors for acquisition of carbapenem-resistance during treatment with carbapenem in the intensive care unit: a prospective study.

The emergence of carbapenemases in gram-negative aerobes is worrying. The aim of this prospective study was to estimate the incidence of acquisition of carbapenem-resistance during treatment in ICU and to identify the risk factors. This was a prospective, observational, cohort study. This study was conducted at intensive care unit, academic medical center, Toulouse Rangueil University Hospital. Patients were included if they received antibiotic treatment with carbapenem for more than 48 h. Biological samples were taken in accordance with current practice in the unit. The main endpoint was the occurrence of bacterial resistance to carbapenems occurring between the onset of treatment and the patient's exit from the ICU. Uni- and multi-variate analyses were carried out. Of the 364 patients admitted to the unit between May and November 2014, 78 were included in our study and 16 (20.51%) developed resistance. The two main risk factors were a length of stay in ICU of more than 29 days (HR = 3.61, p = 0.01) and the presence of Pseudomonas aeruginosa in the samples taken before the start of treatment (HR = 5.31, p = 0.002). No resistance due to carbapenemase production was observed in this study. The prescription of carbapenems in the ICU setting must adhere to the expert guidelines. In light of our results, special attention must be paid to patients whose stay in intensive care is prolonged, and those in whom Pseudomonas aeruginosa is isolated from bacteriological samples taken before the beginning of antibiotic therapy.

Neurally adjusted ventilatory assist (NAVA) versus pressure support ventilation: patient-ventilator interaction during invasive ventilation delivered by tracheostomy.

BACKGROUND: Prolonged weaning is a major issue in intensive care patients and tracheostomy is one of the last resort options. Optimized patient-ventilator interaction is essential to weaning. The purpose of this study was to compare patient-ventilator synchrony between pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA) in a selected population of tracheostomised patients. METHODS: We performed a prospective, sequential, non-randomized and single-centre study. Two recording periods of 60 min of airway pressure, flow, and electrical activity of the diaphragm during PSV and NAVA were recorded in a random assignment and eight periods of 1 min were analysed for each mode. We searched for macro-asynchronies (ineffective, double, and auto-triggering) and micro-asynchronies (inspiratory trigger delay, premature, and late cycling). The number and type of asynchrony events per minute and asynchrony index (AI) were determined. The two respiratory phases were compared using the non-parametric Wilcoxon test after testing the equality of the two variances (F-Test). RESULTS: Among the 61 patients analysed, the total AI was lower in NAVA than in PSV mode: 2.1% vs 14% (p < 0.0001). This was mainly due to a decrease in the micro-asynchronies index: 0.35% vs 9.8% (p < 0.0001). The occurrence of macro-asynchronies was similar in both ventilator modes except for double triggering, which increased in NAVA. The tidal volume (ml/kg) was lower in NAVA than in PSV (5.8 vs 6.2, p < 0.001), and the respiratory rate was higher in NAVA than in PSV (28 vs 26, p < 0.05). CONCLUSION: NAVA appears to be a promising ventilator mode in tracheotomised patients, especially for those requiring prolonged weaning due to the decrease in asynchronies.

Platelets Are Critical Key Players in Sepsis.

Host defense against infection is based on two crucial mechanisms: the inflammatory response and the activation of coagulation. Platelets are involved in both hemostasis and immune response. These mechanisms work together in a complex and synchronous manner making the contribution of platelets of major importance in sepsis. This is a summary of the pathophysiology of sepsis-induced thrombocytopenia, microvascular consequences, platelet-endothelial cells and platelet-pathogens interactions. The critical role of platelets during sepsis and the therapeutic implications are also reviewed.

A Plasma Membrane Association Module in Yeast Amino Acid Transporters.

Amino acid permeases (AAPs) in the plasma membrane (PM) of Saccharomyces cerevisiae are responsible for the uptake of amino acids and involved in regulation of their cellular levels. Here, we report on a strong and complex module for PM association found in the C-terminal tail of AAPs. Using in silico analyses and mutational studies we found that the C-terminal sequences of Gap1, Bap2, Hip1, Tat1, Tat2, Mmp1, Sam3, Agp1, and Gnp1 are about 50 residues long, associate with the PM, and have features that discriminate them from the termini of organellar amino acid transporters. We show that this sequence (named PMasseq) contains an amphipathic α-helix and the FWC signature, which is palmitoylated by palmitoyltransferase Pfa4. Variations of PMasseq, found in different AAPs, lead to different mobilities and localization patterns, whereas the disruption of the sequence has an adverse effect on cell viability. We propose that PMasseq modulates the function and localization of AAPs along the PM. PMasseq is one of the most complex protein signals for plasma membrane association across species and can be used as a delivery vehicle for the PM.

Comparing COVID-19 and influenza: Epidemiology, clinical characteristics, outcomes and mortality in the ICU.

RATIONALE: Several authors have compared COVID-19 infection with influenza in the ICU. OBJECTIVE: This study aimed to compare the baseline clinical profiles, care procedures, and mortality outcomes of patients admitted to the intensive care unit, categorized by infection status (Influenza vs. COVID-19). METHODS: Retrospective observational study. Data were extracted from the Toulouse University Hospital from March 2014 to March 2021. To compare survival curves, we plotted the survival at Day-90 using the Kaplan-Meier curve and conducted a log-rank test. Additionally, we performed propensity score matching to adjust for confounding factors between the COVID-19 and influenza groups. Furthermore, we use the CART model for multivariate analysis. RESULTS: The study included 363 patients admitted to the ICU due to severe viral pneumonia: 152 patients (41.9 %) with influenza and 211 patients (58.1 %) with COVID-19. COVID-19 patients exhibited a higher prevalence of cardiovascular risk factors, whereas influenza patients had significantly higher severity scores (SOFA: 10 [6-12] vs. 6 [3-9], p<0.01 and SAPS II: 51 [35-67] vs. 37 [29-50], p<0.001). Overall mortality rates were comparable between the two groups (27.6 % (n = 42) in the influenza group vs. 21.8 % (n = 46) in the COVID-19 group, p=NS). Mechanical ventilation was more commonly employed in the influenza group (76.3 % (n = 116) vs. 59.7 % (n = 126), p<0.001); however, COVID-19 patients required longer durations of mechanical ventilation (18 [9-29] days vs. 13 [5-24] days, p<0.006) and longer hospital stays (23 [13-34] days vs. 18.5 [9-34.5] days, p = 0.009). The CART analysis revealed that the use of extra renal replacement therapy was the most influential prognostic factor in the influenza group, while the PaO2/FiO2-PEEP ratio played a significant role in the COVID-19 group. CONCLUSIONS: Despite differences in clinical presentation and prognostic factors, the mortality rates at 90 days, after adjusting for confounding factors, were similar between COVID-19 and influenza patients.

Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations. The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases. WHAT THIS STUDY ADDS: Our results propose individual therapeutic drug monitoring taking into account: For the patient: the reason of admission in the ICU, the mechanical ventilation status and the creatinine clearance calculated by the modified diet in renal disease (MDRD). • For the antibiotics: the lung distribution, the minimal inhibitory concentration (MIC) of the strain to eradicate and the potential toxicity. AIM To predict the ceftazidime dosage regimen as a function of the glomerular filtration rate expressed by the modification of the diet in renal disease (MDRD), reason for admission and mechanical ventilation in intensive care unit (ICU) patients to treat Pseudomonas aeruginosa pneumonia. METHOD: A published and qualified population pharmacokinetic model was used to perform Monte Carlo simulations of ceftazidime concentrations. The serum target of 40-100 mg l(-1) was defined based on the minimal inhibitory concentration (MIC), the European break point (EBP), the pulmonary drug diffusion and toxicity. The recommended dosage regimens were based on the maximum percentile of the patients with simulated steady state concentrations reaching the target. RESULTS: Steady-state was reached at 72 h whatever the MDRD. The simulations of serum concentrations generated higher percentiles of the population reaching the target after continuous administration. We recommend a 4 g continuous dose after the usual 2 g loading dose for patients with MDRD from 10 to 30 ml min(-1) , 6 g for MDRD between 40 and 80 ml min(-1) , 8 g for MDRD from 90 to 110 ml min(-1) , 10 g for MDRD from 120 to 190 ml min(-1) and 12 g day(-1) for patients with MDRD higher than 200 ml min(-1) . CONCLUSION: Our study demonstrated that in ICU patients for a given MDRD, steady-state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.

Reciprocal signaling between adipose tissue depots and the central nervous system.

In humans, various dietary and social factors led to the development of increased brain sizes alongside large adipose tissue stores. Complex reciprocal signaling mechanisms allow for a fine-tuned interaction between the two organs to regulate energy homeostasis of the organism. As an endocrine organ, adipose tissue secretes various hormones, cytokines, and metabolites that signal energy availability to the central nervous system (CNS). Vice versa, the CNS is a critical regulator of adipose tissue function through neural networks that integrate information from the periphery and regulate sympathetic nerve outflow. This review discusses the various reciprocal signaling mechanisms in the CNS and adipose tissue to maintain organismal energy homeostasis. We are focusing on the integration of afferent signals from the periphery in neuronal populations of the mediobasal hypothalamus as well as the efferent signals from the CNS to adipose tissue and its implications for adipose tissue function. Furthermore, we are discussing central mechanisms that fine-tune the immune system in adipose tissue depots and contribute to organ homeostasis. Elucidating this complex signaling network that integrates peripheral signals to generate physiological outputs to maintain the optimal energy balance of the organism is crucial for understanding the pathophysiology of obesity and metabolic diseases such as type 2 diabetes.

Co-Infection and Ventilator-Associated Pneumonia in Critically Ill COVID-19 Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study.

Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2−5.2) in the H1N1 group and 7.2 (5.3−9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34−4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.

Evaluation of 4 quantification methods for monitoring 16 antibiotics and 1 beta-lactamase inhibitor in human serum by high-performance liquid chromatography with tandem mass spectrometry detection.

Antibiotic (ATB) prescription in an intensive care unit (ICU) requires continuous monitoring of serum dosages due to the patient's pathophysiological condition. Dosing adjustment is necessary to achieve effective targeted concentrations. Since ICUs routinely use a large number of ATBs, global monitoring needs to be developed. In the present study, we developed a global analytical method for extracting, separating and quantifying the most widely used ATBs in ICUs: amoxicillin, piperacillin, cefazolin, cefepime, cefotaxime, ceftazidime, ceftolozane, ceftriaxone, ertapenem, meropenem, ciprofloxacin, moxifloxacin, levofloxacin, daptomycin, dalbavancin, linezolid and a beta-lactamase inhibitor: tazobactam. To guarantee the robustness of the quantification, we differentiated the 16 ATBs and the beta lactamase inhibitor into 4 pools (ATB1 to ATB4), taking into account prescription frequency in the ICU, the physicochemical properties and the calibration ranges of the ATBs selected. The whole ATB was then separated with two LC columns in reversed phase: Kinetex Polar-C18 100 Å and Polar-RP-80 synergy, in less than 6.5 min. Detection was carried out by electrospray in positive ion mode, by tandem mass spectrometry (LC-MS/MS. The four quantification methods were validated according to the European guidelines on bioanalytical method validation (EMEA guide), after determining the extraction yields, matrix effects, recovery, precision, accuracy, within-run precision and between-run precision. For all analyses, bias is < 15% and is comparable to the literature and LOQs vary from 0.05 mg.L-1 for ciprofloxacin to 1.00 mg.L-1 for ceftriaxone and dalbavancin. The stability time of cefepime and piperacillin is 3 hrs and for the other ATBs 6 hrs in serum at room temperature. For long-term stability, freezing at - 80 °C guarantees 3 months of stability for ceftriaxone and dalbavancin and more than 6 months for the other ATBs.

A Clustered Case Series of Mucorales Detection in Respiratory Samples from COVID-19 Patients in Intensive Care, France, August to September 2021.

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) at Toulouse Hospital (Southern France). PCR screening on respiratory samples, which target Aspergillus or Mucorales DNA, were performed, and the number of fungal detections was evaluated monthly during the study period. During the 19 months of the study, 44 (20.3%) COVID-19 ICU patients had a positive PCR for Aspergillus, an overall rate in keeping with the incidence of ICU COVID-19 patients. Ten patients (7.1%) had a positive Mucorales PCR over the same period. Surprisingly, 9/10 had a positive Mucor/Rhizopus PCR in August-September 2021, during the fourth Delta SARS-CoV-2 variant wave. Epidemic investigations have identified a probable environmental cause linked to construction works in the vicinity of the ICU (high levels of airborne spores due to the mistaken interruption of preventive humidification and summer temperature). Even if CAM are apparently rare in Europe, a cluster can also develop in industrialised countries when environmental conditions (especially during construction work) are associated with a high number of COVID-19 patients in the ICU.

COCARDE Study-Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study.

BACKGROUND: The effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury. OBJECTIVE: The aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury. METHODS: This prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected. RESULTS: A total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function. CONCLUSIONS: A better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care. TRIAL REGISTRATION: Clinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24931.