Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Prolonged Infusion of ß-lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-after Study

Version 1 : Received: 26 May 2021 / Approved: 27 May 2021 / Online: 27 May 2021 (13:13:52 CEST)

A peer-reviewed article of this Preprint also exists.

Richter, D.C.; Dietrich, M.; Lalev, L.D.; Schmitt, F.C.; Fiedler, M.O.; Bruckner, T.; Stoerzinger, D.; Chiriac, U.; Klein, S.; Hackert, T.; Brenner, T.; Brinkmann, A.; Weigand, M.A. Prolonged Infusion of β-Lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-After Study. Antibiotics 2021, 10, 687. Richter, D.C.; Dietrich, M.; Lalev, L.D.; Schmitt, F.C.; Fiedler, M.O.; Bruckner, T.; Stoerzinger, D.; Chiriac, U.; Klein, S.; Hackert, T.; Brenner, T.; Brinkmann, A.; Weigand, M.A. Prolonged Infusion of β-Lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-After Study. Antibiotics 2021, 10, 687.

Abstract

Septic shock substantially alters the pharmacokinetic properties of ß-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of ß-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with ß-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017-2020 received PI of ß-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n=119/290 vs. IB: 54.8%, n=68/114; p=0.0097) and day 90 (PI: 47.9%, n=139/290 vs. IB: 62.9%, n=78/124; p=0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (-10%). PI further reduced duration of invasive ventilation. PI of β-lactam antibiotics led to a stronger decrease in SOFA scores within a 14d-observation period. PI of ß-lactams significantly reduces mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

Keywords

prolonged infusion; ß-lactams; septic shock; mortality; antibiotic therapy; critical care

Subject

Medicine and Pharmacology, Immunology and Allergy

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