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Anaesthesia Critical Care & Pain Medicine
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le dimanche 17 mars 2019
Doi : 10.1016/j.accpm.2019.02.015
PHARMECMO: Therapeutic drug monitoring and adequacy of current dosing regimens of antibiotics in patients on Extracorporeal Life Support
 

Adrien Bouglé a, , Olivier Dujardin a, Victoria Lepère a, Nora Ait Hamou a, Charles Vidal a, Guillaume Lebreton b, Joe-Elie Salem c, Najoua El-Helali d, Grégoire Petijean d, Julien Amour a
a Sorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique - Hôpitaux de Paris (AP–HP), Department of Anaesthesiology and Critical Care Medicine, Institute of Cardiology, Pitié-Salpêtrière Hospital, Paris, France 
b Sorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique - Hôpitaux de Paris (AP–HP), Department of Cardio-Vascular and Thoracic Surgery, Institute of Cardiology, Pitié-Salpêtrière Hospital, Paris, France 
c Sorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique - Hôpitaux de Paris (AP–HP), Department of Pharmacology, Pitié-Salpêtrière Hospital, Paris, France 
d Department of Clinical Microbiology and Therapeutic Monitoring of Anti-infective drugs, Hospital Group Paris Saint-Joseph, Paris, France 

Corresponding author.
Abstract
Introduction

Optimisation of antibiotic therapy for extracorporeal membrane oxygenation (ECMO) patients remains a pharmacological challenge. The objective of this study was to observe the plasma concentrations of commonly used antibiotics in intensive care for patients treated with extracorporeal membrane oxygenation.

Patients and methods

The PHARMECMO study was a pilot, prospective study, conducted in a cardiac surgery intensive care unit. Every adult patient under ECMO support, with known or suspected sepsis and receiving antibiotic therapy, was eligible for inclusion. Plasma concentrations of antibiotics were determined by a combination of liquid chromatography and mass spectrometry.

Results

Forty-four eligible patients were enrolled for 68 inclusions on a twelve-month period. For the association piperacillin-tazobactam (n=19), 68.7% of CT50 and 93.7% of Cmin reached the pharmacokinetic goals defined (64 mg.L-1 for CT50 and 16 mg.L-1 for Cmin). For cefotaxime (n=12), the pharmacokinetic goals (4 mg.L-1 for CT50 and 1 mg.L-1 for Cmin) were achieved in 100% of the cases for CT50 and in 81.8% of the cases for Cmin. Regarding imipenem (n=10), the pharmacokinetic goals were 16 mg.L-1 for CT50 and 4 mg.L-1 for Cmin. Only one CT50 was above 16 mg.L-1. For Cmin, 60% of the doses did not reach the target concentration. In our 10 patients, only one patient was considered as reaching the pharmacokinetic goals. Finally, for amikacin (n=6), four Cmax (66.7%) were infra-therapeutics for a target between 60 and 80 mg.L-1.

Conclusion

These preliminary results suggest that therapeutic drug monitoring could optimise the achievement of pharmacokinetic objectives associated with an effective antibiotic therapy. For most patients, the recommended doses of imipenem and amikacin did not achieve the pK targets

The full text of this article is available in PDF format.

Keywords : ECMO, Antibiotic plasma concentrations, Therapeutic drug monitoring




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