The prevalence of non-tuberculous mycobacteria (NTM) infections is increasing worldwide especially among people with cystic fibrosis (CF). The most common NTM species are Mycobacterium abscessus complex and Mycobacterium avium complex. To date no single drug has been developed targeting these pathogens.
Thanks to three previous FFC Ricerca projects (FFC#19/2018, FFC#14/2020, FFC#18/2021), the molecule named VOMG was discovered with in vitro and in vivo bactericidal activity against Mycobacterium abscessus (Mab) and other pathogens.
Kaftrio is a CFTR modulator drug that addresses the basic defect in CF. Little information is known on its contribution to novel antimicrobial therapies against non-tuberculous mycobacteria in CF and its potential role in antimicrobial combination therapy.
The aims of the project are: i) to evaluate the possible Kaftrio interaction with other antimicrobials used in therapy (or under development) and its antimicrobial activity against NTM drug-resistant clinical isolates; ii) to study the pharmacokinetic/pharmacodynamic properties of VOMG against M. abscessus. An innovative methodology, called hollow fiber system, will be used: the system, established at the University of Zaragoza, allows the reproduction of selected drug exposures to infer PK/PD parameters.
VOMG and Kaftrio could be a novel combined therapy with dual activity: CFTR modulator and enhanced antimicrobial activity. In addition, understanding how Kaftrio might influence (and being influenced) the efficacy of other currently used antibiotics in CF therapy could contribute to treatment improvement of people with CF.