Effects of CFTR Modulators on Pseudomonas aeruginosa Infections in Cystic Fibrosis

Abstract

Background: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Modulator therapies have the ability to improve CFTR function in CF patients, but despite the clear evidence of benefits regarding CFTR modulator therapy, including improved lung function, the reduced rate of exacerbations, and an overall improved quality of life, studies focusing on the reduction rates of P. aeruginosa infections during modulator therapy expressed the need for future research on this topic. Objective: This study aimed to evaluate the impact of CFTR modulator therapies on the prevalence, density, and persistence of P. aeruginosa infection in CF patients and to explore the mechanisms involved. Methods: A systematic literature review was performed by searching five major databases (PubMed, Cochrane Library, Scopus, Google Scholar, and Web of Science), and 21 relevant articles investigating the link between CFTR therapy and P. aeruginosa infections were selected following the PRISMA guidelines. Results: The data indicated that Ivacaftor and the combination Elexacaftor/Tezacaftor/Ivacaftor (ETI) can reduce total bacterial load and markers of systemic inflammation. However, clonal lines of P. aeruginosa persist in most cases, and complete eradication is rare, mainly due to biofilm formation and antimicrobial resistance. Conclusions: Although CFTR-modulating therapies help to improve clinical condition and reduce inflammation, they do not consistently lead to the elimination of P. aeruginosa.

Keywords: Pseudomonas aeruginosa; biofilms; cystic fibrosis; lung infections; modulator therapy.

Figure 1

Flowchart of the selection process.