• Hadrien Winiszewski, Cyrielle Despres, Marc Puyraveau, Jennifer Lagoutte-Renosi, Damien Montange, Guillaume Besch, Sebastien Pili Floury, Claire Chaignat, Guylaine Labro, Lucie Vettoretti, Anne-Laure Clairet, Gilles Capellier, Berengère Vivet, and Gael Piton.
• Medical Intensive Care Unit, Besançon University Hospital, Besançon, France. Electronic address: hwiniszewski@chu-besancon.fr.
• J Crit Care. 2022 Feb 1; 67: 141-146.

PurposeWe hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient β-lactam concentrations.MethodsIn this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold.ResultsAmong the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient β-lactam concentrations.ConclusionDespite a fixed dose antibiotic administration protocol with prolonged infusion insufficient β-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration.Trial RegistrationNCT02820987.Copyright © 2021. Published by Elsevier Inc.

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