Summary of project PR002321
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002321. The data can be accessed directly via it's Project DOI: 10.21228/M8MJ9D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002321 |
| Project DOI: | doi: 10.21228/M8MJ9D |
| Project Title: | Evaluation of in vitro pharmacodynamic drug interactions of ceftazidime-avibactam with tigecycline in ESBL- (extended spectrum beta-lactamase) and carbapenemase producing Escherichia coli |
| Project Summary: | Background: Combination therapy offers a promising option to enhance efficacy and prevent resistance. A comprehensive and quantitative assessment of the last-resort combination of ceftazidime/avibactam and tigecycline is not available. Objective: This study systematically investigated the pharmacodynamic interaction between ceftazidime/avibactam and tigecycline in clinical and isogenic Escherichia coli strains harbouring genes that encode various carbapenemases or ESBLs (extended spectrum beta-lactamases). Methods: An adaptive in vitro 'dynamic' checkerboard design and pharmacometric modelling were employed for the evaluation of pharmacodynamic interactions in fifteen bacterial isolates. Additionally, time-kill assays and metabolomic analyses were used to provide mechanistic insights. Metabolomic analysis: Mechanistical investigation of the PD interaction between ceftazidime/avibactam-tigecycline was studied in a selected clinical isolate of E. coli (strain JUM_JEA) using metabolomic analyses in mono- and combination treatment scenarios. Time-kill assays were conducted for ceftazidime/avibactam and tigecycline concentrations of 4 x MIC (minimum inhibitory concentration) as well as combinations of both antibiotics at 4 x MIC CZA – 4 x MIC TGC and growth controls as four replicates over 4 h with samples at 0, 2 and 4 h. Results: Antagonistic drug interactions between ceftazidime/avibactam and tigecycline were identified in the majority of tested strains. Time-kill assays confirmed antagonistic interactions, with tigecycline limiting ceftazidime/avibactam total killing. Metabolomic analyses of mono and combined drug exposure to bacteria revealed matching metabolomes in tigecycline alone and the combination with ceftazidime/avibactam, corroborating the identified antagonism between these drugs. |
| Institute: | European Molecular Biology Laboratory |
| Department: | EMBL Heidelberg |
| Last Name: | Drotleff |
| First Name: | Bernhard |
| Address: | Meyerhofstr. 1, Heidelberg, BW, 69117, Germany |
| Email: | bernhard.drotleff@embl.de |
| Phone: | none |
| Publications: | https://doi.org/10.1016/j.ijantimicag.2025.107457 |
| Contributors: | Aneeq Farooq, Bernhard Drotleff, Niklas Kroemer, Mei-Ling Han, Jian Li, Jean Winoc Decousser, David Schrey, Julien Buyck, Nicolas Grégoire, Patrice Nordmann, Sebastian G. Wicha |
Summary of all studies in project PR002321
| Study ID | Study Title | Species | Institute | Analysis (* : Contains Untargted data) |
Release Date | Version | Samples | Download (* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003735 | Evaluation of in vitro pharmacodynamic drug interactions of ceftazidime-avibactam with tigecycline in ESBL- (extended spectrum beta-lactamase) and carbapenemase producing Escherichia coli | Escherichia coli | European Molecular Biology Laboratory | MS | 2025-03-13 | 1 | 256 | Uploaded data (23G)* |
