Project: Optimization of Antibiotic Combinations using Organoids for treatment of Mycobacterium abscessus infections.

Acronym	ACOMa (Reference Number: JPIAMR2022-050)
Duration	29/05/2023 - 28/05/2026
Project Topic	Mycobacterium abscessus (Mabs) is an emerging opportunistic pathogen responsible for lung infections particularly in cystic fibrosis patients. These infections are challenging worldwide due to their increasing incidence, their extreme resistance to available antimicrobial agents and the lack of new antibiotics in the pipeline. Antibiotic therapies are generally based on pharmacokinetic/pharmacodynamic (PK/PD) indices related to Minimal Inhibitory Concentration (MIC). Although useful for clinicians, MIC-based PK/PD is of little value with antibiotic combinations. In this context, pre-clinical in vitro investigations and semi-mechanistic PK/PD modelling for dosing regimen optimization of the antibiotic combinations appears to be the most promising approach. However, the accuracy of these PK/PD models is highly dependent of the quality of the in vitro data that generally raised a number of issues. Consequently, to improve the treatments of lung infections by Mabs, the objective of the ACOMa project is to implement a strong pre-clinical approach coupling a wide screening of new antibiotic combinations in vitro, the use of innovative lung organoids to consider the CF lung environment and semi-mechanistic PK/PD modelling to optimize antibiotic combinations. Finally, the most promising antibiotic combination-dosing regimen will be evaluated in vivo.
Website	visit project website
Network	JPIAMR-ACTION
Call	2nd JPIAMR-ACTION Joint Call 2022

Project partner

Number	Name	Role	Country
1	INSERM U1070 “Pharmacology of Antimicrobial Agents and antibioResistance”	Coordinator	France
2	Universität Zürich	Partner	Switzerland
3	Institute of Pharmacology and Structural Biology	Partner	France
4	Ospedale San Raffaele	Partner	Italy
5	Basel university	Observer	Switzerland