Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial

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...

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Published in:Intensive care medicine Vol. 48; no. 3; pp. 311 - 321
Main Authors: Hagel, Stefan, Bach, Friedhelm, Brenner, Thorsten, Bracht, Hendrik, Brinkmann, Alexander, Annecke, Thorsten, Hohn, Andreas, Weigand, Markus, Michels, Guido, Kluge, Stefan, Nierhaus, Axel, Jarczak, Dominik, König, Christina, Weismann, Dirk, Frey, Otto, Witzke, Dominic, Müller, Carsten, Bauer, Michael, Kiehntopf, Michael, Neugebauer, Sophie, Lehmann, Thomas, Roberts, Jason A., Pletz, Mathias W.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2022
Springer
Springer Nature B.V
Subjects:
Adult
Anesthesiology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Antiinfectives and antibacterials
Care and treatment
Clinical trials
Critical Care Medicine
Dosage
Drug dosages
Drug Monitoring
Emergency Medicine
Evaluation
Female
Health aspects
Health care industry
Humans
Infection
Intensive
Intensive care
Medicine
Medicine & Public Health
Monitoring
Multiple Organ Failure
Optimization
Original
Pain Medicine
Patients
Pediatrics
Penicillanic Acid
Piperacillin
Piperacillin - therapeutic use
Piperacillin, Tazobactam Drug Combination - therapeutic use
Pneumology/Respiratory System
Pseudomonas aeruginosa
Sepsis
Sepsis - complications
Sepsis - drug therapy
Septic shock
Tazobactam
Therapeutic drug monitoring
Therapy
Germany
Therapeutic drug monitoring
Sepsis
β-Lactams
ISSN:0342-4642, 1432-1238, 1432-1238
Online Access:Get full text
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Summary: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.
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ISSN:0342-4642
1432-1238
1432-1238
DOI:10.1007/s00134-021-06609-6