Although the taxonomical composition of the cystic fibrosis (CF) lung microbiome has been largely inspected, little is still known about the overall gene content and functional profiles of the resident microbiome. To understand the dynamics of the lung microbiome in relation with patient’s disease status, a large cohort of CF subjects with moderate-severe lung disease was followed over a 15-month period. Longitudinal assessment of sputum microbiome by shotgun metagenomics revealed a patient-specific colonization of the primary and emerging CF pathogens. Even if patient genotype and exacerbation events impacted the microbiome diversity, CF microbiota rebounds to pre-treatment state. A core set of antibiotic resistance genes was found although their presence was not affected by antibiotic intake. The microbial resilience and persistence of antibiotic resistant genes support the growing consensus that the management of chronic CF infection may be improved by a more patient-specific personalization of clinical care and treatment.

Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens.

[This corrects the article DOI: 10.1371/journal.pone.0156807.].