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Treatment of resistant bacteria such as meticillin-resistant Staphylococcus aureus (MRSA) relies on achieving adequate antibiotic concentrations at the site of infection. Strategies to attain such targets in septic critically ill patients receiving renal replacement therapy (RRT) are uncommon but could be useful for increasing the likelihood of therapeutic dosing. The aim of this study was to conduct a population pharmacokinetic (PK) analysis in septic patients undergoing continuous RRT and to determine which parameters were associated with inadequate vancomycin concentrations. In total, 81 patients with 199 blood samples were included in the study. All patients received vancomycin dosing according to the local protocol, which included a weight-based loading dose followed by continuous infusion. The vancomycin concentration-time points were adequately described with a one-compartment model with zero order input. The median population PK estimate for vancomycin clearance (CL) was 2.9 L/h [interquartile range (IQR) 2.4-3.4 L/h] and for volume of distribution (Vd) was 0.8 L/kg (IQR 0.6-1.1 L/kg). The goodness-of-fit plots for the model were adequate. When covariates were tested, none were found to adequately explain changing vancomycin CL or Vd in the population PK model. In particular, the lack of correlation between CL and RRT settings was likely due to the multiple confounders known to influence antibiotic prescription in this setting. These data provide a cautionary tale of the challenges of describing pharmacokinetics in critically ill patients receiving RRT and highlights the need for a detailed, prospective, multicentre study to better inform dosing practice., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction - Le sepsis représente la prémière cause de mortalité chez les patients critiques. La protéine C reactive (C-Reactive Protein-CRP) et la procalcitonine (PCT) sont les marqueurs biologiques plus utilisés dans la pratique clinique. Le forme soluble du recepteur du plasminogène type-urokinase (soluble urokinase-type plasminogen receptor -suPAR) est un nouveau biomarqueur, présent dans les liquides humains et participant à différents moments de la réponse immunitaire. Des taux sériques élevés de suPAR ont été associés à une mortalité accrue chez différentes populations de patients non critiques. Son utilité chez les patients critiques n’a pas encore été definie. Le but de cette etude était d’évaluer le role diagnostique et prognostique de suPAR aux Soins Intensifs (SI).Patients et Méthodes - Nous avons étudié tous les patients adults admis dans notre service de Décembre 2010 à Mai 2011 (6 mois), excepté les patients mineurs (moins de 18 ans), ceux supposés rester aux SI moins de 24 H, les entrants du week-end (pour raisons pratiques) et ceux qui ont refusé leur participation. Nous avons défini le sepsis, le sepsis sévère et le choc septique selon les critères standards. Les concentrations de suPAR ont été mesurées à l’admission et ensuite quotidiennement pendant le séjour aux SI (pour un maximum de 15 jours) utilisant un kit ELISA (ViroGates A/S Copenhagen, Danemark).Résultats - Nous avons étudié 31 volontaires sains et 258 patients (161 hommes). Les patients avaient un âge moyen de 58 ±17 ans, un score APACHE II et un score SOFA à l’admission de 17 (9-23) et 6 (3-9), respectivement. L’admission aux SI était due à des raisons médicales (n = 133, dont 87 avec sepsis), traumatisme (n = 23), chirurgie programmée (n = 78) et chirurgie d’urgence (n = 24, dont 7 avec sepsis). Le sepsis était présent à l’admission chez 94 patients (36,4%) ;dont 23 sepsis sévère (24,5% des septiques) et 49 un choc septique (52.1% des septiques). La mortalité globale était de 13.6%, info:eu-repo/semantics/published

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis., Journal Article, Review, SCOPUS: sh.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published, Communication at the 41st SCCM Congress (4-8 February 2012 – Houston, USA).

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