Evidence map›Paper›PMID 35377133›Full record

Observational studyClinical pharmacokinetics2022

An Integral Pharmacokinetic Analysis of Piperacillin and Tazobactam in Plasma and Urine in Critically Ill Patients.

Eveline Wallenburg, Rob Ter Heine, Jeroen A Schouten, Jelmer Raaijmakers, Jaap Ten Oever, Eva Kolwijck, David M Burger, Peter Pickkers, Tim Frenzel, Roger J M Brüggemann

Erratum issued Registry-linked trialOpen access · hybridAbstract readObservational Study
In one paragraph

Observational study in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03738683 (Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients - Finding the Best Predictor for Piperacillin-tazobactam Clearance), which is not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03738683 completednot on this map

Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients - Finding the Best Predictor for Piperacillin-tazobactam Clearance

TypeobservationalSponsorRadboud University Medical CenterRan2019 to 2019Enrolled40ConditionsBacterial InfectionsArmsPiperacillin/tazobactam
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. A Review ofInternational journal of microbiology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
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  9. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Eveline WallenburgDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 864, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. eveline.wallenburg@radboudumc.nl.ORCID http://orcid.org/0000-0002-9139-8960
Rob Ter HeineDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 864, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Jeroen A SchoutenDepartment of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands.
Jelmer RaaijmakersDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Jaap Ten OeverRadboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Eva KolwijckDepartment of Medical Microbiology, Jeroen Bosch Ziekenhuis, Den Bosch, The Netherlands.
David M BurgerDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 864, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Peter PickkersDepartment of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands.
Tim FrenzelDepartment of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands.
Roger J M BrüggemannDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 864, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Radboud University Nijmegen · NLJeroen Bosch Ziekenhuis · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesAlthough dose optimization studies have been performed for piperacillin and tazobactam separately, a combined integral analysis is not yet reported. As piperacillin and tazobactam pharmacokinetics are likely to show correlation, a combined pharmacokinetic model should be preferred to account for this correlation when predicting the exposure. Therefore, the aim of this study was to describe the pharmacokinetics and evaluate different dosing regimens of piperacillin and tazobactam in critically ill patients using an integral population pharmacokinetic model in plasma and urine.

methodsIn this observational study, a total of 39 adult intensive care unit patients receiving piperacillin-tazobactam as part of routine clinical care were included. Piperacillin and tazobactam concentrations in plasma and urine were measured and analyzed using non-linear mixed-effects modeling. Monte Carlo simulations were performed to predict the concentrations for different dosing strategies and different categories of renal function.

resultsA combined two-compartment linear pharmacokinetic model for both piperacillin and tazobactam was developed, with an output compartment for the renally excreted fraction. The addition of 24-h urine creatinine clearance significantly improved the model fit. A dose of 12/1.5 g/24 h as a continuous infusion is sufficient to reach a tazobactam concentration above the target (2.89 mg/L) and a piperacillin concentration above the target of 100% f T

conclusionsA regular dose of 12/1.5 g/24 h is sufficient in > 90% of the critically ill population to treat infections caused by Escherichia coli and Klebsiella pneumoniae with MICs ≤ 8 mg/L. In case of infections caused by Pseudomonas aeruginosa with an MIC of 16 mg/L, there is a fine line between therapeutic and toxic exposure. Dosing guided by renal function and therapeutic drug monitoring could enhance target attainment in such cases. CLINICALTRIALS: GOV IDENTIFIER: NCT03738683.

Indexed as

Critical IllnessPiperacillinAdultAnti-Bacterial AgentsHumansMicrobial Sensitivity TestsPenicillanic AcidTazobactamAnti-Bacterial AgentsPenicillanic AcidPiperacillinTazobactam

Identifiers

PMID35377133
PMCPMC9249689
OpenAlexW4226238115

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.