Antibiotics Distribution Study in Peripheral Compartments: Contribution of Microdialysis (Antimidis)

Cefazolin Distribution in Mediastinum After Heart Surgery in Children Using a Microdialysis Probe.

Postoperative mediastinitis is an important cause of postoperative morbidity in children. The main objective of this study is to describe the distribution of cefazolin, using as surgical antibiotic prophylaxis, in the mediastinal compartment in children after cardiac surgery for congenital heart disease. The investigators aims to build a population pharmacokinetic model of cefazolin using plasma and tissue concentrations in order to optimize and individualize cefazolin dosing regimens. Cefazolin tissue pharmacokinetics will use a microdialysis procedure.

Study Overview

• Status: Not yet recruiting
• Conditions: Children in Cardiac Intensive Care Requiring Surgery for Congenital Heart Disease
• Intervention / Treatment: Procedure: Microdialysis probe placement; Procedure: Microdialysis and Plasma samples

Detailed Description

Children with congenital heart disease are very fragile during the postoperative period and at risk of life-threatening mediastinitis due to various factors: post-extracorporeal circulation inflammation, frequent organ failure, possible delayed thorax closure. These patients are at risk of unpredictable pharmacokinetics alteration and inter-individual variability of the drug tissue: significant fluid intake, drug metabolism and elimination functions alteration, extracorporeal circulation. The effective prevention of postoperative mediastinitis in this population is therefore a major issue and challenge. Studying the distribution of cefazolin in the mediastinum and identifying the factors of inter-individual variability would improve the prevention of this pathology by optimizing the dosing.

During cardiac surgery, a microdialysis probe is placed by the surgeon in the mediastinum. The outgoing fluid will be collected every 30 minutes to every 2 hours, for approximately 28 hours. Six plasma samples will be drawn over these 28 hours to measure plasma concentrations. The probe's recovery will then be calculated and the probe will be removed up to 36 hours after insertion.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gael Plastow; Phone Number: +33 01 44 38 18 57; Email: gael.plastow@aphp.fr
• Study Contact Backup: Name: Noemie De Cacqueray, MD; Phone Number: +33 07 50 91 72 02; Email: noemie.decacquerayvalmenier@aphp.fr

Study Locations

• France
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75015
      • Hopital Necker Enfants Malades
      • Contact: Gael Plastow; Phone Number: +33 01 44 38 18 57; Email: gael.plastow@aphp.fr
      • Contact: Margaux Pontailler, MD; Phone Number: +33 01 71 39 65 72; Email: margaux.pontailler@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Child aged over 6 months and under 6 years
• Hospitalized in pediatric cardiac intensive care after cardiac surgery for congenital heart disease.
• Selected congenital heart diseases: ventricular septal defect auricular septal defect, pulmonary stenosis, tetralogy of Fallot
• Surgery with median sternotomy and intraoperative cardiopulmonary bypass
• Intraoperative antibiotic prophylaxis with cefazolin
• Patient affiliated with a social security plan or eligible
• whose two parents or legal guardians have accepted and signed the study consent

Exclusion Criteria:

• Emergency cardiac surgery
• Patient already enrolled in the study
• Patient who has previously undergone cardiac surgery
• Patient with haemostasis disorders or immune deficiency
• Patient with bacterial colonization indicating antibiotic prophylaxis other than cefazolin
• Participation in another interventional research study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefazolin measurements; Microdialysis probe placement and blood drawings to measure cefazolin concentration in mediastinum tissue and in plasma.	Procedure: Microdialysis probe placement; Microdialysis probe is placed at the end of cardiac surgery in mediastinum and used during 36 hours for tissue samples until withdrawal.; Procedure: Microdialysis and Plasma samples; 26 Cefazolin Free tissue concentrations 6 total plasma concentrations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total clearance	Pharmacokinetics of cefazolin total clearance in children after cardiac surgery and inter-individual variability.	36 hours
Distribution volume	Pharmacokinetics of cefazolin distribution volume in children after cardiac surgery and inter-individual variability.	36 hours
Inter-compartmental clearance	Pharmacokinetics of cefazolin inter-compartmental clearance in children after cardiac surgery and inter-individual variability.	36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monte Carlo simulations and dosing optimization	Monte Carlo simulations performed using the model with SimulX (version 2024R1) and R (version 4.4.2) softwares. Probability of attainment of PK/PD target (100 % ƒT > 4xCMI) with simulated dosing regimens No patient data is required for this step.	36 hours
post-operative mediastinitis occurrence	Assess the relationship between tissue exposure and clinical outcome: occurrence of post-operative mediastinitis	Month 1

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Chair: Margaux Pontailler, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Himebauch AS, Sankar WN, Flynn JM, Sisko MT, Moorthy GS, Gerber JS, Zuppa AF, Fox E, Dormans JP, Kilbaugh TJ. Skeletal muscle and plasma concentrations of cefazolin during complex paediatric spinal surgery. Br J Anaesth. 2016 Jul;117(1):87-94. doi: 10.1093/bja/aew032.
• Andreas M, Zeitlinger M, Wisser W, Jaeger W, Maier-Salamon A, Thalhammer F, Kocher A, Hiesmayr JM, Laufer G, Hutschala D. Cefazolin and linezolid penetration into sternal cancellous bone during coronary artery bypass grafting. Eur J Cardiothorac Surg. 2015 Nov;48(5):758-64. doi: 10.1093/ejcts/ezu491. Epub 2014 Dec 18.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: January 2, 2026
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 2, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Microdialysis; Cardiac surgery; Mediastinitis; Cefazolin
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Mediastinal Diseases; Thoracic Diseases; Mediastinitis; Investigative Techniques; Chemistry Techniques, Analytical; Dialysis; Microdialysis
• Other Study ID Numbers: APHP241591; 2025-521988-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No