Universität zu Köln

Hagel, Stefan ORCID: 0000-0003-2999-6131, Bach, Friedhelm, Brenner, Thorsten, Bracht, Hendrik, Brinkmann, Alexander, Annecke, Thorsten, Hohn, Andreas, Weigand, Markus, Michels, Guido, Kluge, Stefan, Nierhaus, Axel, Jarczak, Dominik, Koenig, Christina, Weismann, Dirk, Frey, Otto, Witzke, Dominic, Mueller, Carsten, Bauer, Michael, Kiehntopf, Michael, Neugebauer, Sophie, Lehmann, Thomas, Roberts, Jason A., Pletz, Mathias W. and Investigators, The Target Trial (2022). Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial. Intensive Care Med., 48 (3). S. 311 - 322. NEW YORK: SPRINGER. ISSN 1432-1238

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Abstract

Purpose: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. Methods: Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR >= 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range +/- 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10. Results: Among 249 evaluable patients (66.3 +/- 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p= 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p= 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p= 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p= 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001). Conclusion: TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hagel, Stefan UNSPECIFIED orcid.org/0000-0003-2999-6131 UNSPECIFIED Bach, Friedhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Brenner, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Bracht, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkmann, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Annecke, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Hohn, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Weigand, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Michels, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED Kluge, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Nierhaus, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Jarczak, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Weismann, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Otto UNSPECIFIED UNSPECIFIED UNSPECIFIED Witzke, Dominic UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiehntopf, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Neugebauer, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Roberts, Jason A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pletz, Mathias W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Investigators, The Target Trial UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-694766
DOI:	10.1007/s00134-021-06609-6
Journal or Publication Title:	Intensive Care Med.
Volume:	48
Number:	3
Page Range:	S. 311 - 322
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1238
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTENSIVE-CARE; INFECTIONS; TAZOBACTAM; MEROPENEM; INFUSION; EXPOSURE Multiple languages Critical Care Medicine Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69476