Efecto de la terapia antimicrobiana frente a biofilms duales de Mycobacterium abscessus y Pseudomonas aeruginosa

Résumé

Chronic lung infection is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. Bacteria in the CF lung are arranged as polymicrobial biofilms, which are aggregated structures of sessile microorganisms highly tolerant to antimicrobial therapy. Pseudomonas aeruginosa is the most prevalent species causing acute and chronic respiratory infection among CF patients. However, the CF lung microbiota also comprises other microorganisms, such as Non- Tuberculous Mycobacteria (NTM), which are presumed to be acquired from environmental reservoirs. Mycobacterium abscessus is a microorganism that can cause biofilm-related pulmonary infections in patients with preexisting lung disease and is increasingly being isolated from respiratory samples of CF patients. Some studies suggest that antimicrobial therapy, to which CF patients are exposed since childhood, may favor the colonization of the lung environment by M. abscessus, given its intrinsic resistance to antibiotics. The treatment against M. abscessus lung disease is based on a multidrug regimen guided by the in vitro susceptibility testing results of the isolates. However, the rates of therapeutic failure and recurrence are high, suggesting a poor correlation between the in vitro result and the in vivo outcome. This study aims to determine if the incorporation of factors that mimic the host microenvironment, such as lung epithelial cells, and microorganisms that share niche with M. abscessus, such as P. aeruginosa, can influence M. abscessus response to antimicrobial treatment. Furthermore, we aim to evaluate if the treatment directed at other classic pathogens often co-isolated with M. abscessus, like P. aeruginosa, could give an adaptive advantage to M. abscessus...