Clinical trial NCT03970265: Development a Method to Extract Antibiotic Concentration From Interstitial Lung and Epithelial Lining Fluid.
Official title: Development of a Method to Extract Interstitial Lung Fluid and Epithelial Lining Fluid for Antibiotic Concentration Measurement in Explanted Lung Tissue (Feasibility Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Transplantation
Keywords: Interstitial lung fluid
Epithelial lining fluid
Antibiotic concentration in the lung
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2019-05-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Lung transplant patients at University Hospital of Munich

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Meropenem concentration in Interstitial Lung Fluid (ILF) and Epithelial Lining Fluid (ELF) in 30 explanted lungs
timeFrame: 1 year
Secondary outcomes:
measure: Correlation of blood and tissue concentrations of Meropenem
timeFrame: 1 year
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Anaesthesiology of the University Hospital of Munich
Study officials:
affiliation: Department of Anaesthesiology, University Hospital, LMU Munich
name: Michael Zoller, Dr.med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Anaesthesiology, University Hospital, LMU Munich
name: Ines Schroeder, Dr.med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Laboratory Medicine, University Hospital, LMU Munich
name: Mathias Brügel, Dr.med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Laboratory Medicine, University Hospital, LMU Munich
name: Michael Vogeser, Prof.Dr.med.
role: STUDY_CHAIR
affiliation: Department of Anaesthesiology, University Hospital, LMU Munich
name: Christina Scharf, Dr.med.
role: STUDY_CHAIR
affiliation: Department of Anaesthesiology, University Hospital, LMU Munich
name: Uwe Liebchen, Dr.med.
role: STUDY_CHAIR
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Eike Speck, Dr.med.
role: STUDY_CHAIR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Paal Michael, Dr.rer.nat.
role: STUDY_CHAIR
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Alexander Indrich, Dr.med.
role: STUDY_CHAIR
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Daniel Siegl, Dr.med.
role: STUDY_CHAIR
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Bernhard Zwissler, Prof.Dr.med
role: STUDY_DIRECTOR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Daniel Teupser, Prof.Dr.med.
role: STUDY_DIRECTOR
References:
citation: 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.