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

NCT ID: NCT03970265

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-08-15
• Study Completion Date: 2020-07-15

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.

Conditions

Lung Transplantation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

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.

Interventions will only be performed on explanted lung tissue ex vivo and on supernatant of bronchoscopy and are therefore non-invasive

Intervention Type: DIAGNOSTIC_TEST

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Michael Zoller MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Zoller, Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology, University Hospital, LMU Munich

Ines Schroeder, Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology, University Hospital, LMU Munich

Mathias Brügel, Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Institute of Laboratory Medicine, University Hospital, LMU Munich

Michael Vogeser, Prof.Dr.med.

Role: STUDY_CHAIR

Institute of Laboratory Medicine, University Hospital, LMU Munich

Christina Scharf, Dr.med.

Role: STUDY_CHAIR

Department of Anaesthesiology, University Hospital, LMU Munich

Uwe Liebchen, Dr.med.

Role: STUDY_CHAIR

Department of Anaesthesiology, University Hospital, LMU Munich

Eike Speck, Dr.med.

Role: STUDY_CHAIR

Department of Anaesthesiology of the University Hospital of Munich

Paal Michael, Dr.rer.nat.

Role: STUDY_CHAIR

Institute of Laboratory Medicine of the University Hospital of Munich

Alexander Indrich, Dr.med.

Role: STUDY_CHAIR

Department of Anaesthesiology of the University Hospital of Munich

Daniel Siegl, Dr.med.

Role: STUDY_CHAIR

Department of Anaesthesiology of the University Hospital of Munich

Bernhard Zwissler, Prof.Dr.med

Role: STUDY_DIRECTOR

Department of Anaesthesiology of the University Hospital of Munich

Daniel Teupser, Prof.Dr.med.

Role: STUDY_DIRECTOR

Institute of Laboratory Medicine of the University Hospital of Munich

Locations

Department of Anaesthesiology of the University Hospital of Munich

Munich, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 34570645 (View on PubMed)

Other Identifiers

LMU 18-928

Identifier Type: -

Identifier Source: org_study_id