Evidence map›Paper›PMID 32460856›Full record

ArticleJournal of translational medicine2020

Influence of extracorporeal membrane oxygenation on the pharmacokinetics of ceftolozane/tazobactam: an ex vivo and in vivo study.

Camille Mané, Clément Delmas, Jean Porterie, Géraldine Jourdan, Patrick Verwaerde, Bertrand Marcheix, Didier Concordet, Bernard Georges, Stéphanie Ruiz, Peggy Gandia

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 26% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Camille ManéPharmacokinetics and Toxicology Laboratory, Toulouse University Hospital, Toulouse, France.
Clément DelmasIntensive Cardiac Care Unit, Rangueil University Hospital, Toulouse, France.
Jean PorterieInstitute of Metabolic and Cardiovascular Diseases (I2MC), UMR-1048, National Institute of Health and Medical Research (INSERM), Toulouse, France.
Géraldine JourdanCritical and Intensive Care Unit, Stomalab UMR 5273 CNRS/UPS-EFS-ENVT-INSERM U1031, Toulouse School of Veterinary Medicine, Toulouse, France.
Patrick VerwaerdeAnesthesia-Emergency-Intensive Care Department, UPEC/IMRB-Inserm U955, Alfort School of Veterinary Medicine, Maisons-Alfort, France.
Bertrand MarcheixCardiovascular Surgery Unit, Rangueil University Hospital, Toulouse, France.
Didier ConcordetINTHERES, INRAE, ENVT, Université de Toulouse, Toulouse, France.
Bernard GeorgesAnesthesia-General Intensive Care Division, Rangueil General Intensive Care Department, Toulouse University Hospital, Toulouse, France.
Stéphanie RuizAnesthesia-General Intensive Care Division, Rangueil General Intensive Care Department, Toulouse University Hospital, Toulouse, France.
Peggy GandiaPharmacokinetics and Toxicology Laboratory, Toulouse University Hospital, Toulouse, France. gandia.p@chu-toulouse.fr.ORCID 0000-0002-4385-7894
École Nationale Vétérinaire de Toulouse · FRInserm · FRCentre National de la Recherche Scientifique · FRHôpital Rangueil · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExtracorporeal membrane oxygenation (ECMO) is increasingly used in intensive care units and can modify drug pharmacokinetics and lead to under-exposure associated with treatment failure. Ceftolozane/tazobactam is an antibiotic combination used for complicated infections in critically ill patients. Launched in 2015, sparse data are available on the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam. The aim of the present study was to determine the influence of ECMO on the pharmacokinetics of ceftolozane-tazobactam.

methodsAn ex vivo model (closed-loop ECMO circuits primed with human whole blood) was used to study adsorption during 8-h inter-dose intervals over a 24-h period (for all three ceftolozane/tazobactam injections) with eight samples per inter-dose interval. Two different dosages of ceftolozane/tazobactam injection were studied and a control (whole blood spiked with ceftolozane/tazobactam in a glass tube) was performed. An in vivo porcine model was developed with a 1-h infusion of ceftolozane-tazobactam and concentration monitoring for 11 h. Pigs undergoing ECMO were compared with a control group. Pharmacokinetic analysis of in vivo data (non-compartmental analysis and non-linear mixed effects modelling) was performed to determine the influence of ECMO.

resultsWith the ex vivo model, variations in concentration ranged from - 5.73 to 1.26% and from - 12.95 to - 2.89% respectively for ceftolozane (concentrations ranging from 20 to 180 mg/l) and tazobactam (concentrations ranging from 10 to 75 mg/l) after 8 h. In vivo pharmacokinetic exploration showed that ECMO induces a significant decrease of 37% for tazobactam clearance without significant modification in the pharmacokinetics of ceftolozane, probably due to a small cohort size.

conclusionsConsidering that the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam is not clinically significant, normal ceftolozane and tazobactam dosing in critically ill patients should be effective for patients undergoing ECMO.

Indexed as

Extracorporeal Membrane OxygenationAnimalsAnti-Bacterial AgentsCephalosporinsCritical IllnessHumansSwineTazobactamAnti-Bacterial AgentsceftolozaneCephalosporinsTazobactamBeta-lactamCeftolozaneECMOPharmacokineticsTazobactam

Identifiers

PMID32460856
PMCPMC7251674
OpenAlexW3031310847

What OpenQuestion holds

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Registered trials

None linked

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.