We assessed the Pneumocystis jirovecii PCR accuracy on non-invasive oropharyngeal wash (OW) specimens for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV immunocompromised patients. In this retrospective study, 134 patients with suspected PJP undergoing both OW and deep respiratory sampling were included. PJP was defined by composite criteria. OW P. jirovecii PCR showed a sensitivity of 61.5% (95% CI 42.5-77.6) and a specificity of 97.2% (95% CI 92.2-99.1). Positive and negative predictive values were 84.2% and 91.3%, respectively. These results suggest OW P. jirovecii PCR may support non-invasive diagnosis, but cannot be used to exclude PJP.

Background: Blood cultures remain the reference standard for diagnosing bacteraemia in ICU patients with suspected sepsis, but are slow and frequently negative after antibiotic exposure. OCEAN Dx is an innovative viability-targeted, direct-from-blood assay that enriches intact bacterial cells before 16S PCR and nanopore sequencing. We evaluated its diagnostic performance compared with concomitant blood cultures. Methods: We conducted a prospective observational study in a tertiary ICU, enrolling adults undergoing blood cultures for suspected infection. The primary endpoint was diagnostic performance of OCEAN Dx versus concomitant blood cultures. Secondary endpoints were positivity, time to identification, taxonomic concordance, and adjudication of discordant episodes using infection-site cultures and/or follow-up blood cultures. Findings: 107 patients contributed 124 diagnostic episodes, yielding 246 evaluable paired tests; 91% were receiving antibiotics (78% broad-spectrum). Sensitivity was 95·2% and negative predictive value was 98·4%. OCEAN Dx was positive in 123/246 (50·0%) tests versus 45/372 (12%) positive blood-culture bottles. Mean time to identification was 5 h 45 min with OCEAN Dx versus 36 h 56 min with blood cultures (p<0·0001). Using the prespecified framework, 52/76 (68·4%) OCEAN Dx–positive episodes were supported by infection-site cultures and/or follow-up blood cultures. Interpretation: In ICU practice characterised by high antibiotic exposure, OCEAN Dx showed high sensitivity and excellent rule-out performance versus blood cultures, with substantially faster identification and higher microbiological yield, supporting its potential role in earlier bacteraemia assessment and antibiotic stewardship pathways.

OBJECTIVE:The French Society of Anesthesia and Intensive Care (SFAR), the French Society for the Study of the Liver (AFEF), and the Association for Hepato-Biliary-Pancreatic Surgery and Liver Transplantation (ACHBPT) jointly developed guidelines for the perioperative management of liver resection surgery. DESIGN:A multidisciplinary panel of French experts from the SFAR, the AFEF, and the ACHBPT was convened. All potential conflicts of interest were officially declared before initiation of the recommendation development process, which was conducted independently of any industry funding. The authors used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to assess the quality of evidence in the literature. METHODS:Three areas were defined: (1) preoperative assessment; (2) optimization of intraoperative management; and (3) optimization of postoperative management. For each domain, the objective of the recommendations was to address a series of questions formulated by experts according to the PICO model ("Population, Intervention, Comparison, Outcome"). Based on these questions, an extensive bibliographic search covering the period from 2004 to 2024 was conducted using predefined keywords in accordance with PRISMA recommendations. Data quality was analysed using the GRADE method. Recommendations were formulated according to the GRADE method and subsequently submitted to all experts for voting using the GRADE grid method. RESULTS:The experts' synthesis and application of the GRADE methodology resulted in 40 recommendations addressing 14 questions. After two rounds of voting and several revisions, strong agreement was achieved for all 40 recommendations. Among these recommendations, 7 were supported by a high level of evidence (GRADE 1), 23 by a low level of evidence (GRADE 2), and 10 corresponded to expert opinions (EO). Finally, no recommendation could be formulated for four questions. (ABS). CONCLUSION:Strong expert agreement was achieved regarding recommendations aimed at optimizing perioperative management in patients undergoing liver resection.

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ dysfunction and high mortality. Despite advances in treatment, sepsis remains difficult to manage. Historically, the concept of sepsis evolved from ancient observations of infection-related decay to the germ theory of the 19th century. The latest Sepsis-3 definition describes sepsis as life-threatening organ dysfunction due to a dysregulated host response. However, this clinical characterization may be too late for effective intervention. The concept of endotypes and the ontological data applied to sepsis highlight the substantial heterogeneity in pathophysiological pathways leading to this endpoint. We propose a focus on the "pre-sepsis" phase, where early immune dysregulation arises before significant organ damage. This phase represents the host's initial response to infection, preceding sepsis and, thus, organ failure. Currently, there is no formal definition of "pre-sepsis", but this phase could be defined on the basis of early biological pathways in host-pathogen interactions, such as those involving endogenous carbon monoxide. By focusing on "pre-sepsis" and developing tools to detect it, clinicians could intervene earlier and potentially prevent the progression to sepsis. This approach may lead to improved outcomes and more personalized treatments, targeting specific immune pathways tailored to patient profiles. Ultimately, this shift could address existing challenges in sepsis treatment, offering new directions for clinical research and therapeutic development.

BACKGROUND:Surgical site infections (SSIs) are common after liver transplantation (LT), with perioperative antibiotic strategies varying across centers. This study compared the incidence of SSIs in patients receiving perioperative antibiotic prophylaxis (PAP) versus preemptive antibiotic therapy (PAT). METHODS:This retrospective multicenter study included adult LT patients from 5 French hospitals (2019-2022). Exclusion criteria were prior antibiotic use at LT, prophylaxis extended beyond 24 h postoperatively, antibiotic allergies, fulminant hepatitis, and multiorgan transplants. The PAP group received narrow-spectrum antibiotics without extension beyond 24 h, whereas the PAT group received broad-spectrum antibiotics extended postoperatively. Propensity score-based overlap weighting was used for comparisons. RESULTS:Among 595 patients, 271 received PAP and 324 received PAT for a median of 5 (2-7) d ( P  < 0.001). Cefoxitin (24%) and amoxicillin-clavulanic acid (21%) were most used in the PAP group, whereas piperacillin (19%) and piperacillin-tazobactam (33%) dominated in the PAT group. SSIs occurred in 19% of PAP and 15% of PAT patients (odds ratio [OR] 0.81; 95% confidence interval [CI], 0.29-2.30; P  = 0.7). PAT was associated with reduced postoperative infections (OR 0.27; 95% CI, 0.12-0.63; P  = 0.002), shorter intensive care unit (-5.2 d; P  < 0.0001) and hospital stays (-5.5 d; P  = 0.002), and lower early allograft dysfunction (OR 0.12; 95% CI, 0.02-0.87; P  = 0.04) but with increased extended-spectrum beta-lactamase SSIs (47% versus 6%; P  = 0.006). CONCLUSIONS:PAP effectively prevents SSIs and antimicrobial resistance. Broad-spectrum antibiotics should be reserved for early treatment of suspected infections or prophylaxis for carefully selected high-risk patients.

Mechanisms controlling innate immune responses and coagulation are interdependent, evolutionarily entangled and make a complex network to form immuno-thrombosis axis which is an integral part of host-defence response. During infections, immunothrombosis generates intravascular scaffold enabling recognition, trap and destruction of pathogens facilitating tissue integrity. However, the accompanying dysregulation fosters into pathologies associated with thrombosis and regulates severity, morbidity and mortality in infections. Several extrinsic and intrinsic factors such as (epi)genetic mechanisms, age, metabolism and lifestyle regulate immunothrombosis during infections. Mounting evidence demonstrates that homocysteine, a metabolic intermediate of methionine synthesis pathway activate cells participating in immuno-thrombosis such as neutrophils, platelets, monocytes and endothelial cells. Interestingly, multiple infections are significantly associated with perturbed homocysteine metabolism. In the present review, we describe mechanistic insights into how homocysteine drives immuno-thrombotic crosstalk that generate a vicious cycle of inflammation and coagulation that fuels organ failure during infections with an emphasis on sepsis, COVID-19, and other infectious diseases caused by parasites, viral, and bacterial pathogens. Subsequently, we discuss therapeutic strategies targeting homocysteine metabolism that may improve clinical outcomes in infections.

L’insuffisance rénale aiguë (AKI) affecte 20 à 50% des patients cirrhotiques hospitalisés, atteignant jusqu’à 58% des patients en réanimation. L’harmonisation récente des critères diagnostiques avec ceux du KDIGO a permis une identification plus précoce et standardisée. Le syndrome hépatorénal (SHR), représentant 12 % des AKI, découle de mécanismes complexes combinant vasodilatation splanchnique liée à l’hypertension portale, hypovolémie efficace, activation des systèmes sympathique et rénine-angiotensine-aldostérone, vasoconstriction intrarénale, et diminution du débit de filtration glomérulaire. Ces processus sont exacerbés par des phénomènes inflammatoires et de translocation bactérienne. Le SHR-AKI est défini par une atteinte fonctionnelle ne s’améliorant pas après l’arrêt des diurétiques et 24 heures d’expansion volémique, en l’absence d’autres étiologies d’AKI. Cependant, son diagnostic reste difficile en réanimation en raison des nombreux facteurs d’agression rénale dans cette population. Le traitement repose sur l’administration de terlipressine et d’albumine, avec la transplantation hépatique comme seule option curative. Bien que les vasoconstricteurs améliorent temporairement la fonction rénale, leur utilisation doit être perçue comme un pont vers la transplantation hépatique ou la récupération rénale. À l’avenir, l’intégration de biomarqueurs, de critères diagnostiques affinés, et de stratégies thérapeutiques innovantes sera cruciale pour optimiser la prise en charge et le pronostic de ces patients à haut risque.

OBJECTIVE:Evaluate the role of short-course (72h) postoperative antibiotic prophylaxis (PPA) in reducing liver-specific surgical site infections (liver-SSI) incidence. SUMMARY BACKGROUND DATA:Simultaneous liver and colorectal resections (SLCR) represent a valid oncologic strategy for colorectal liver metastases, however, this approach has been reported to increase the risk of postoperative liver-SSIs. METHODS:Patients undergoing SLCR (2012-2024) in two tertiary centers were included and divided into two groups: patients receiving intraoperative antibiotic prophylaxis alone (IPA) and those receiving additional PPA. Outcomes included liver-SSI incidence, severe morbidity (Clavien-Dindo grade III-IV), and length of hospital stay. Matching (PSM) and Inverse Probability Treatment Weigthing (IPTW) on a propensity score and mixed-effects models were employed to adjust for confounders and center-level clustering. We tested for interactions with the liver resection approach (laparoscopy-laparotomy) and extend (major-minor). RESULTS:Of 250 patients (median [95%CI] age: 67.0 years [65.0-68.0], 58.0% men), 40% (n=100) received PPA. Liver-SSI was significantly less frequent in the PPA group (11% vs. 29.3%; P<0.001), with consistent results across centers and across resection approach (pinteraction=0.451) and extend (pinteraction=0.490). The PPA group experienced shorter hospital stay (8.0 days [7.0-10.0] vs. 11.0 days [9.0-12.0], P=0.045) and fewer severe complications (15% vs. 29.3%, P=0.01). PPA was independently associated with a reduced risk of liver-SSI before (OR: 0.24, 95%CI:0.09-0.57, P=0.002) and after matching (ORPSM: 0.27, 95%CI: 0.09-0.73, P=0.014) and IPTW (ORIPTW: 0.27, 95%CI: 0.15-0.47, P<0.001). CONCLUSIONS:PPA is associated with a significant liver-SSI reduction following SLCR and our findings support its use, warranting further validation in prospective randomized studies.

The weaning of critical care patients with acute kidney injury (AKI) from renal replacement therapy (RRT) lacks predictive criteria. The urinary urea excretion index (UUEI) based on the urine urea concentration and diuresis may be a relevant prognostic criterion. The aim of this study was to assess the value of utilising a UUEI-based weaning protocol from a RRT catheter. This was a multicentre before-after study including patients with non-obstructive AKI requiring RRT during their intensive care unit (ICU) stay. A before cohort (2013–2015) was compared to an after cohort (2017–2019) in the interval of which a UUEI-based weaning protocol was implemented. In the after cohort, as soon as the UUEI exceeded 1.35 mmol/kg/24 h, physicians were encouraged to stop RRT and withdraw the catheter, whereas in the before cohort the catheter was withdrawn at the physician’s discretion. The primary outcome was the number of RRT catheter-free days on day 28 after initiating RRT. In total, 179 and 130 patients were included in the before and after cohorts, respectively. The median numbers of catheter-free days in the before and after cohorts on day 28 were 13.0 (IQR 0.0–21.0) vs. 16.5 (IQR 4.3–24.0), respectively (p = 0.02). The adjusted rate ratio for the number of catheter-free days over the number of days at risk was 1.11 (95

Abstract Background Thrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19. Methods Biological samples were obtained from hospitalized patients (15 severe, 37 critical at sampling) and 93 non-severe ambulatory cases. Our aims were to compare NET biomarkers, functional DNase levels, and explore mechanisms driving any imbalance concerning disease severity. Results Functional DNase levels were diminished in the most severe patients, paralleling an imbalance between NET markers and DNase activity. DNase1 antigen levels were higher in ambulatory cases but lower in severe patients. DNase1L3 antigen levels remained consistent across subgroups, not rising alongside NET markers. DNASE1 polymorphisms correlated with reduced DNase1 antigen levels. Moreover, a quantitative deficiency in plasmacytoid dendritic cells (pDCs), which primarily express DNase1L3, was observed in critical patients. Analysis of public single-cell RNAseq data revealed reduced DNase1L3 expression in pDCs from severe COVID-19 patient. Conclusion Severe and critical COVID-19 cases exhibited an imbalance between NET and DNase functional activity and quantity. Early identification of NETosis imbalance could guide targeted therapies against thrombo-inflammation in COVID-19-related sepsis, such as DNase administration, to avert clinical deterioration. Trial registration: COVERAGE trial (NCT04356495) and COLCOV19-BX study (NCT04332016). Graphical Abstract

Importance:Before surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines. Objective:To evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery. Design, Setting, and Participants:Randomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France. Intervention:Patients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115). Main Outcomes and Measures:The primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery. Results:Of the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes. Conclusions and Relevance:Among patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy. Trial Registration:ClinicalTrials.gov Identifier: NCT03374449.

Le ceftazidime/avibactam (C/A) est l'association d'une céphalosporine et d'un inhibiteur de β-lactamase. Cette association a la particularité d'avoir une activité conservée sur certaines souches de bactéries résistantes aux carbapénèmes. L'objectif de cette étude est de décrire l'utilisation en vie réelle du C/A ainsi que la conformité des prescriptions aux recommandations. Il s'agit d'une étude monocentrique observationnelle rétrospective. L'ensemble des prescriptions de C/A réalisée entre mai 2019 à décembre 2023 ont été analysées. Les données démographiques des patients ainsi que les données portant sur l'épisode infectieux et l'indication ont été relevées. La conformité de l'indication a été évaluée selon les recommandations 2022 de la Société de Pathologie Infectieuse de Langue Française (SPILF). Une prescription était considérée comme conforme aux recommandations dans le traitement d'infections à entérobactéries résistantes aux carbapénèmes et dans le traitement des infections à Pseudomonas aeruginosa résistants aux carbapénèmes en cas de résistance à l'association ceftolozane/tazobactam. L'utilisation de C/A dans le cadre de traitement d'exacerbation de mucoviscidose chez les patients colonisés a été considéré comme ne rentrant pas dans le cadre des recommandations SPILF. 146 patients ont été traités par C/A sur la période. Les trois principales indications d'un traitement par C/A étaient les pneumopathies (n=52 ; 36 %), les bactériémies (n=33 ; 23 %) et les infections urinaires (n=21 ; 14 %). Une documentation microbiologique a été trouvée chez 125 patients (86 %). Les principales bactéries identifiées étaient P. aeruginosa (n=58, 41 %) et Klebsiella pneumoniae (n=38, 27 %). Lorsque la bactérie était identifiée, celle-ci était résistante aux carbapénèmes dans 83 % des épisodes (n=109). La part des prescriptions de C/A conforme aux recommandations était de 59 % (n=86). Une nette augmentation de la part des prescriptions conformes aux recommandations est observée entre 2019 (43 %) et 2023 (69 %). Les prescriptions non conformes aux recommandations étaient des prescriptions pour le traitement d'infections à P. aeruginosa en présence d'alternative thérapeutique (n=17 ; 12 %), d'infections à bactéries sensibles aux carbapénèmes (n=16 ; 11 %) et des prescriptions sans documentation microbiologique (n=14 ; 10 %). Entre 2019 et 2023, il est observé une diminution de la part des prescriptions de C/A dans le traitement d'infections à bactéries sensibles aux carbapénèmes (35 % en 2019 contre 4 % en 2023). Les prescriptions de C/A sont majoritairement conformes aux recommandations dans notre centre, avec une augmentation de la conformité au cours du temps, grâce notamment à une surveillance active des prescriptions de C/A par les pharmaciens cliniciens et les infectiologues. La part des prescriptions non-conformes aux recommandations est cependant non-négligeable. Une vigilance particulière devra être réalisée dans le traitement des infections à P. aeruginosa en présence d'alternative thérapeutique. Aucun lien d'intérêt

Background Acute kidney injury (AKI) in intensive care unit (ICU) patients with severe COVID-19 is common (> 50%). A specific inflammatory process has been suggested in the pathogenesis of AKI, which could be improved by dexamethasone (DXM). In a small monocenter study ( n = 100 patients), we reported a potential protective effect of DXM on the risk of AKI. This study aimed to investigate the preventive impact of DXM on AKI in a multicenter study of patients with severe COVID-19. Methods We conducted a multicenter study in three French ICUs from March 2020 to August 2021. All patients admitted to ICU for severe COVID-19 were included. Individuals with preexistent AKI or DXM administration before admission to ICU were excluded. While never used during the first wave, DXM was used subsequently at ICU entry, providing two treatment groups. Multivariate Cause-specific Cox models taking into account changes in ICU practices over time, were utilized to determine the association between DXM and occurrence of AKI. Results Seven hundred and ninety-eight patients were included. Mean age was 62.6 ± 12.1 years, 402/798 (50%) patients had hypertension, and 46/798 (6%) had previous chronic kidney disease. Median SOFA was 4 [3–6] and 420/798 (53%) required invasive mechanical ventilation. ICU mortality was 208/798 (26%). AKI was present in 598/798 (75%) patients: 266/598 (38%), 163/598 (27%), and 210/598 (35%) had, respectively, AKI KDIGO 1, 2, 3, and 61/598 (10%) patients required renal replacement therapy. Patients receiving DXM had a significantly decreased hazard of AKI occurrence compared to patients without DXM (HR 0.67; 95CI 0.55–0.81). These results were consistent in analyses that (1) excluded patients with DXM administration to AKI onset delay of less than 12 h, (2) incorporating the different ‘waves’ of the COVID-19 pandemic. Conclusions DXM was associated with a decrease in the risk of AKI in severe COVID-19 patients admitted to ICU. This supports the hypothesis that the inflammatory injury of AKI may be preventable.

L’insuffisance rénale aiguë (IRA) touche 20 % des admissions à l’hôpital. Après chirurgie lourde, elle concerne environ 30 à 40 % des cas [1]. L’IRA est un facteur indépendant de morbidité et de mortalité dans un grand nombre d’études. Le risque d’IRA dépend de nombreux facteurs, dont l’âge des patients, les comorbidités préopératoires, mais également le type de chirurgie, les complications peropératoires et l’usage de produits néphrotoxiques. La prévention de l’IRA est donc une nécessité impérieuse car malheureusement nous ne disposons toujours pas de traitement spécifique. Il faut donc identifier les patients à risque, limiter l’usage périopératoire de médicaments néphrotoxiques et préserver la stabilité de l’état hémodynamique (volumes et pressions) pendant et après la chirurgie.

Background: in COVID-19, dexamethasone (DXM) and tocilizumab are used to alleviate inflammation in patients requiring oxygen support. Several evidences support a role of increased immunothrombosis and NETosis in particular, in the pathogenesis of disease severity. Whether the use of immunomodulatory drugs has any impact on NETosis is currently unknown. The potential beneficial effect of immunomodulatory drugs as early treatment in mild patients is being investigated in the COVERAGE trial (NCT04356495). Objective: we aimed to characterize the kinetics of plasma NET markers in COVID-19 patients receiving immunomodulatory treatments. Methods: one hundred and sixty-six early (≤ 7 days) COVID-19 outpatients were randomly allocated to placebo group (79 i.e. 48%), inhaled ciclesonide (48 i.e. 29%) or inhaled IFN-β-1b (39 i.e. 23%). Fifty-nine critically ill patients were included: 8 received placebo (14%), 42 (71%) DXM (6mg i.v. for ten days) and nine (15%) DXM + tocilizumab (8mg/kg i.v.). We quantified NET markers (MPO-DNA, H3Cit, H3cit-DNA) in plasma at inclusion and Day 7 for outpatients, and at inclusion, Day 3 and Day 7 for critically ill patients Results: inhaled IFN-β-1b, but not inhaled ciclesonide nor placebo, was linked to a decrease in plasma H3Cit levels (p: 0.02). DXM, alone and in association, was not linked to a decrease in plasma NET markers levels in critically ill patients. Conclusion: use of immunomodulatory treatments is not linked to a decrease in plasma NET markers in COVID-19 patients, except for inhaled IFN-β-1b in early mild outpatients. Adjunction of treatment targeting NETosis might so be an interesting therapeutic approach in COVID-19 patients.

Background: Immunothrombosis is increased in severe COVID-19 and potentially involved in its pathogenesis but the mechanisms explaining its regulation are unknown. We hypothesized that decreased DNase activity could be associated with increased NETosis and clinical worsening in COVID-19 patients. Our objectives were to compare the balance between NETs biomarkers and DNase activity according to the severity of COVID-19 and to study the mechanisms responsible for the imbalance between NETosis and DNase activity. Methods: Biological samples were collected from the COLCOV19-BX study for inpatients and the COVERAGE trial (no treatment arm) for outpatients. We studied 93 non-severe, 15 severe and 37 critical COVID-19 patients. Results: Markers of NETs (MPO-DNA, H3Cit, H3cit-DNA) were higher in the most severe patients. DNase activity was lower and the balance between NET markers and DNase activity was impaired in the most severe patients. We observed a decrease in the amount of circulating DNase1 and DNase1L3 without mutations in the DNase1 and DNase1L3 genes and a quantitative defect of plasmacytoid dendritic cells (pDC), the main cells expressing DNase 1L3, in critical patients. Besides, analysis of public single cell RNAseq data revealed that pDC from COVID-19 patients express less DNase1L3. Conclusion: Severe and critical COVID-19 were associated with an imbalance between NETs and DNase activity with a defect in the amount of DNase 1 and DNase1L3. DNase1L3 deficiency could be explained by a quantitative defect of pDC. Early identification of patients with NETosis imbalance could allow targeted therapies to prevent clinical worsening, such as DNase administration.

La caspofungine (CFG) est indiquée dans le traitement des candidoses invasives, de l'aspergillose invasive et le traitement empirique chez le patient neutropénique fébrile. Le schéma posologique recommandé par le résumé des caractéristiques du produit (RCP) comprend une dose charge (DC) de 70mg à J1 puis une dose d'entretien (DE) adaptée au poids. Cependant des études pharmacocinétiques montrent qu'un poids >80kg et/ou une hypoalbuminémie sont 2 covariables corrélées à une sous-exposition en CFG. L'objectif de ce travail a été de faire un état des lieux des pratiques de prescription de CFG et de son adaptation posologique en fonction du poids et de l'albuminémie. Entre le 15 septembre et le 15 décembre 2022 nous avons réalisé une étude observationnelle rétrospective monocentrique des unités de soins adultes concernant les dispensations de CFG dans les unités de soins adultes. Nous avons relevé l'indication, le schéma posologique, la durée de traitement et les caractéristiques du patient (albuminémie et service de soins). Soixante-sept patients ont été traités par CFG avec un âge médian de 62,5ans [51,5;73]. Le poids était >80kg chez 21 patients (31%). L'albuminémie a été dosée chez 45patients (67%), avec une valeur médiane de 21 g/L. La durée médiane de traitement était de 8 jours [4;11,5]. Sur l'ensemble des prescriptions, 42 ont été initiées en réanimation (63%). Les principales indications étaient: traitement curatif documenté (55%) et traitement préemptif (39%). Les principaux sites infectieux étaient: fongémie isolée (45%), infections digestives (24%), fongémie sur cathéter (10%). Les prélèvements ont identifié: Candida albicans (61%), glabrata (15%), tropicalis (11%), kefyr (3%), krusei (3%), lusitaniae (3%) et Aspergillus fumigatus (4%). Les prélèvements sont restés négatifs chez 24 patients (36%). Trente et un patients (46%) ont reçu une DC de 70mg puis une DE de 70mg, 25 patients (37%) ont eu une DC de 70 mg puis une DE de 50mg. D'autres schémas posologiques ont été prescrits: 50mg/j sans DC (9%),140mg/j (4%), 120mg/j (2%) et 100mg/j (2%). Une adaptation posologique a été réalisée chez 18/21 (86%) patients >80kg et chez 11/44 (25%) patients avec une hypoalbuminémie. L'adaptation de dose de CFG au poids (mentionnée dans l'AMM) est effective chez une majorité de patient. Cependant, la posologie est encore rarement adaptée à l'albuminémie qui n'a pas été dosée chez près d'un tiers des patients. La majorité des posologies utilisées sont celles recommandées par le RCP, même si des données de plus en plus robustes tendent à montrer que les objectifs de rapport AUC/CMI peuvent ne pas être atteints avec ces posologies. Tous ces éléments concourent à la nécessité d'une discussion entre le clinicien, le microbiologiste et le pharmacien pour optimiser les posologies de CFG en fonction du terrain du patient et des résultats des examens mycologiques. Aucun lien d'intérêt