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Maintenance tobramycin primarily affects untargeted bacteria in the CF sputum microbiome.
- Source :
- Thorax; Sep2020, Vol. 75 Issue 9, p780-790, 11p
- Publication Year :
- 2020
-
Abstract
- <bold>Rationale: </bold>The most common antibiotic used to treat people with cystic fibrosis (PWCF) is inhaled tobramycin, administered as maintenance therapy for chronic Pseudomonas aeruginosa lung infections. While the effects of inhaled tobramycin on P. aeruginosa abundance and lung function diminish with continued therapy, this maintenance treatment is known to improve long-term outcomes, underscoring how little is known about why antibiotics work in CF infections, what their effects are on complex CF sputum microbiomes and how to improve these treatments.<bold>Objectives: </bold>To rigorously define the effect of maintenance tobramycin on CF sputum microbiome characteristics.<bold>Methods and Measurements: </bold>We collected sputum from 30 PWCF at standardised times before, during and after a single month-long course of maintenance inhaled tobramycin. We used traditional culture, quantitative PCR and metagenomic sequencing to define the dynamic effects of this treatment on sputum microbiomes, including abundance changes in both clinically targeted and untargeted bacteria, as well as functional gene categories.<bold>Main Results: </bold>CF sputum microbiota changed most markedly by 1 week of antibiotic therapy and plateaued thereafter, and this shift was largely driven by changes in non-dominant taxa. The genetically conferred functional capacities (ie, metagenomes) of subjects' sputum communities changed little with antibiotic perturbation, despite taxonomic shifts, suggesting functional redundancy within the CF sputum microbiome.<bold>Conclusions: </bold>Maintenance treatment with inhaled tobramycin, an antibiotic with demonstrated long-term mortality benefit, primarily impacted clinically untargeted bacteria in CF sputum, highlighting the importance of monitoring the non-canonical effects of antibiotics and other treatments to accurately define and improve their clinical impact. [ABSTRACT FROM AUTHOR]
- Subjects :
- RHINOVIRUSES
TOBRAMYCIN
ACHROMOBACTER
SPUTUM
CYSTIC fibrosis transmembrane conductance regulator
BRONCHIECTASIS
BACTERIAL disease prevention
SPUTUM microbiology
RESEARCH
TIME
RESEARCH methodology
EVALUATION research
MEDICAL cooperation
CYSTIC fibrosis
SEVERITY of illness index
COMPARATIVE studies
FORCED expiratory volume
GENOMES
DRUG therapy
RESEARCH funding
INHALATION administration
BACTERIA
ANTIBIOTICS
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00406376
- Volume :
- 75
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Thorax
- Publication Type :
- Academic Journal
- Accession number :
- 145222980
- Full Text :
- https://doi.org/10.1136/thoraxjnl-2019-214187