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Prolonged Infusion of β-Lactams Decreases Mortality in Patients with Septic Shock: A Retrospective before-and-after Study

Septic shock substantially alters the pharmacokinetic properties of β-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 β-lactams extend the time that...

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Main Authors: Daniel Christoph Richter (Author), Maximilian Dietrich (Author), Lazar Detelinov Lalev (Author), Felix C. F. Schmitt (Author), Mascha Onida Fiedler (Author), Thomas Bruckner (Author), Dominic Stoerzinger (Author), Ute Chiriac (Author), Sabrina Klein (Author), Thilo Hackert (Author), Thorsten Brenner (Author), Alexander Brinkmann (Author), Markus A. Weigand (Author)
Format: Book
Published: MDPI AG, 2021-06-01T00:00:00Z.
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Summary:Septic shock substantially alters the pharmacokinetic properties of β-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 β-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (<i>f</i>t <sub>>MIC</sub>) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with β-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017-2020 received PI of β-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%, <i>n</i> = 119/290 vs. IB: 54.8%, <i>n</i> = 68/114; <i>p</i> = 0.0097) and day 90 (PI: 47.9%, <i>n</i> = 139/290 vs. IB: 62.9%, <i>n</i> = 78/124; <i>p</i> = 0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (−10%, <i>p</i> = 0.14). PI was further associated with a reduction in the duration of invasive ventilation and a stronger decrease in SOFA scores within a 14 day-observation period. PI of β-lactams was associated with a significant reduction of mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.
Item Description:10.3390/antibiotics10060687
2079-6382

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