Augmented renal clearance, low ß-lactam concentrations and clinical outcomes in the critically ill: An observational prospective cohort study

Article Article scientifique Article Augmented renal clearance, low ß-lactam concentrations and clinical outcomes in the critically ill: An observational prospective cohort study eng 2015 author Csaki Huttner Angela 788122 author Von Dach Elodie 591850 Elodie Von Dach-Saouter author Renzoni Adriana Maria 134435 author Huttner Benedikt 0000-0002-1749-9464 666500 author Affaticati Mathieu Robert 652830 author Pagani Léonardo 743265 author Daali Youssef 46042 author Pugin Jérôme 69624 author Karmime Abderrahim 29133 author Fathi Marc 565078 author Lew Daniel Pablo 26516 author Harbarth Stéphan Juergen 0000-0002-3551-1025 93885 385-392 10.1016/j.ijantimicag.2014.12.017 25656151 0924-8579 Whilst augmented renal clearance (ARC) is associated with reduced ß-lactam plasma concentrations, its impact on clinical outcomes is unclear. This single-centre prospective, observational, cohort study included non-pregnant, critically ill patients aged 18-60 years with presumed severe infection treated with imipenem, meropenem, piperacillin/tazobactam or cefepime and with creatinine clearance (CLCr) =60mL/min. Peak, intermediate and trough levels of ß-lactams were drawn on Days 1-3 and 5. Concentrations were deemed 'subthreshold' if they did not meet EUCAST-defined non-species-related breakpoints. Primary and secondary endpoints were clinical response 28 days after inclusion, and ARC prevalence (CLCr=130mL/min) and subthreshold and undetectable concentrations, respectively. Logistic regression was used to evaluate associations between ARC, antibiotic concentrations and clinical failure. From 2010 to 2013, 100 patients were enrolled (mean age, 45 years; median CLCr at inclusion, 144.1mL/min). ARC was present in 64 (64%) of the patients. Most patients received imipenem/cilastatin (54%). Moreover, 86% and 27% of patients had at least one subthreshold or undetectable trough level, respectively. Among imipenem and piperacillin trough levels, 77% and 61% were subthreshold, respectively, but intermediate levels of both antibiotics were largely above threshold. ARC strongly predicted undetectable trough concentrations (OR=3.3, 95% CI 1.11-9.94). A link between ARC and clinical failure (18/98; 18%) was not observed. ARC and subthreshold ß-lactam antibiotic concentrations were widespread but were not associated with clinical failure. Larger studies are necessary to determine whether standard dosing regimens in the presence of ARC impact negatively on clinical outcome and antibiotic resistance. Dewey 615 Dewey 616 31 Section des sciences pharmaceutiques 17 54 Département de microbiologie et médecine moléculaire 21B 56 Département de médecine 221 false 526 Résistance aux antibiotiques 866 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 321 Groupe Pugin Jérôme (Soins intensifs) 587 1280 Pharmaco-omiques et médecine de précision 1003 International journal of antimicrobial agents 45 4 d4dcc842-f465-4550-8c7b-376b8d3f504f Article (Published version) Restricted 1-s2.0-S0924857915000114-main.pdf 550216 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département de médecine

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Augmented renal clearance, low ß-lactam concentrations and clinical outcomes in the critically ill: An observational prospective cohort study	International journal of antimicrobial agents			2015	840	3

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Affaticati, Mathieu Robert