Development a Method to Extract Antibiotic Concentration From Interstitial Lung and Epithelial Lining Fluid. (ALF)

Development of a Method to Extract Interstitial Lung Fluid and Epithelial Lining Fluid for Antibiotic Concentration Measurement in Explanted Lung Tissue (Feasibility Study)

Infections are critical factors for the survival of critically ill patients. A serious problem is the high variability of antibiotic concentrations in critically ill patients. This may result in the risk of underdosage with possible ineffective therapeutic levels as well as in the risk of overdosage with possible adverse and toxic effects. Essential for the effectiveness of antibiotic therapy is the antibiotic concentration at target site. The goal of this study is to establish a method to extract Interstitial Lung Fluid (ILF) and Epithelial Lining Fluid (ELF) for antibiotic concentration measurements in patients following lung Transplantation and to calculate a tissue/serum concentration ratio. Improved knowledge regarding tissue penetration of Antibiotics may help to optimize drug dosing and management.

Study Overview

• Status: Completed
• Conditions: Lung Transplantation
• Intervention / Treatment: Diagnostic test: extraction of ELF and ILF from explanted lung tissue; meropenem concentration in ELF and ILF; ELF on postoperative day 1-5 when bronchoscopy is performed within clinical routine.

Detailed Description

Informed consent will be obtained prior to inclusion. 30 patients following lung Transplantation at the University Hospital of Munich will be included in this study. Intravenous Meropenem will be administered as perioperative antibiotic prophylaxis for lung transplantation. Interstitial Lung Fluid and Epithelial Lining Fluid will be extracted immediately after explantation of the lung from explanted lung tissue. Concentrations of antibiotics will be determined by liquid chromatography-mass spectrometry (LC-MS/MS) in ILF and ELF. Serum samples will be collected according to our in clinical routine established therapeutic drug monitoring. Tissue/Serum concentration ratio will be calculated. ELF will be collected on postoperative day 1-5 when bronchoscopy is performed during clinical routine. Numerous clinical and laboratory parameters will be determined. The investigators expect that correlations between antibiotic target site and blood concentrations and clinical and laboratory parameters will be found.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81377
    • Department of Anaesthesiology of the University Hospital of Munich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Lung transplant patients at University Hospital of Munich

Description

Inclusion Criteria:

1. Lung Transplantation at University Hospital of Munich
2. Administration of Meropenem as perioperative antibiotic prophylaxis
3. Valid informed consent subscribed by the patient prior to inclusion

Exclusion Criteria:

1. missing informed consent
2. subsequent withdrawal of the participation in the study by the patient or the guardian

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meropenem concentration in Interstitial Lung Fluid (ILF) and Epithelial Lining Fluid (ELF) in 30 explanted lungs	The primary goal of this study is to measure Meropenem concentration by LC-MS/MS in ELF and ILF from 30 explanted lung tissue.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of blood and tissue concentrations of Meropenem	Calculation of tissue/serum concentration ratio will be calculated	1 year

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Investigators: Study Chair: Paal Michael, Dr.rer.nat., Institute of Laboratory Medicine of the University Hospital of Munich; Principal Investigator: Michael Zoller, Dr.med., Department of Anaesthesiology, University Hospital, LMU Munich; Principal Investigator: Ines Schroeder, Dr.med., Department of Anaesthesiology, University Hospital, LMU Munich; Principal Investigator: Mathias Brügel, Dr.med., Institute of Laboratory Medicine, University Hospital, LMU Munich; Study Chair: Michael Vogeser, Prof.Dr.med., Institute of Laboratory Medicine, University Hospital, LMU Munich; Study Chair: Christina Scharf, Dr.med., Department of Anaesthesiology, University Hospital, LMU Munich; Study Chair: Uwe Liebchen, Dr.med., Department of Anaesthesiology, University Hospital, LMU Munich; Study Chair: Eike Speck, Dr.med., Department of Anaesthesiology of the University Hospital of Munich; Study Chair: Alexander Indrich, Dr.med., Department of Anaesthesiology of the University Hospital of Munich; Study Chair: Daniel Siegl, Dr.med., Department of Anaesthesiology of the University Hospital of Munich; Study Director: Bernhard Zwissler, Prof.Dr.med, Department of Anaesthesiology of the University Hospital of Munich

Publications and helpful links

General Publications

• Paal M, Scharf C, Denninger AK, Ilia L, Kloft C, Kneidinger N, Liebchen U, Michel S, Schneider C, Schropf S, Schuster C, Vogeser M, Weinelt F, Zander J, Zoller M, Schroeder I. Target Site Pharmacokinetics of Meropenem: Measurement in Human Explanted Lung Tissue by Bronchoalveolar Lavage, Microdialysis, and Homogenized Lung Tissue. Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0156421. doi: 10.1128/AAC.01564-21. Epub 2021 Sep 27.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Actual): July 15, 2020
• Study Completion (Actual): July 15, 2020

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Interstitial lung fluid; Epithelial lining fluid; Antibiotic concentration in the lung
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Meropenem
• Other Study ID Numbers: LMU 18-928

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