Maintenance tobramycin primarily affects untargeted bacteria in the CF sputum microbiome

Area of Science:

• Microbiology
• Genomics
• Clinical Medicine

Background:

• Inhaled tobramycin is a common maintenance therapy for cystic fibrosis (CF) patients with chronic *Pseudomonas aeruginosa* infections.
• While beneficial for long-term outcomes, its precise mechanisms and effects on the complex CF sputum microbiome are not fully understood.

Purpose of the Study:

• To precisely define how maintenance inhaled tobramycin therapy impacts the CF sputum microbiome's characteristics.

Main Methods:

• Sputum samples were collected from 30 CF patients before, during, and after a one-month course of inhaled tobramycin.
• Multi-omics approaches including culture, qPCR, and metagenomic sequencing were employed.
• Analysis focused on changes in bacterial abundance and functional gene categories within the sputum microbiome.

Main Results:

• The CF sputum microbiota composition shifted significantly within one week of antibiotic therapy, then stabilized.
• These shifts were mainly driven by changes in less abundant bacterial taxa.
• Despite significant taxonomic changes, the overall functional gene capacity (metagenome) of the sputum communities remained largely stable, suggesting functional redundancy.

Conclusions:

• Maintenance inhaled tobramycin, despite its mortality benefits, predominantly affects bacteria not typically targeted in CF infections.
• This underscores the critical need to monitor the broader, non-canonical impacts of antibiotic treatments.
• Understanding these effects is essential for accurately assessing and improving clinical outcomes in CF patients.