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J Cyst Fibros. 2019 Mar 8. pii: S1569-1993(19)30028-1. doi: 10.1016/j.jcf.2019.02.010. [Epub ahead of print]

The effects of cycled inhaled aztreonam on the cystic fibrosis (CF) lung microbiome.

Author information

1
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada.
2
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada; Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.
3
Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
4
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada; Department of Medicine, University of Calgary, Calgary, AB, Canada.
5
Departments of Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, University of Calgary, Alberta, Canada.
6
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
7
Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
8
Institut de recherches cliniques de Montreal and Department of Medicine, Universite de Montreal, QB, Canada.
9
Department of Medicine, McMaster University, Hamilton, ON, Canada.
10
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
11
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada; Department of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: mdparkin@ucalgary.ca.

Abstract

BACKGROUND:

To improve clinical outcomes, cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infections are prescribed inhaled anti-pseudomonal antibiotics. Although, a diverse microbial community exists within CF airways, little is known about how the CF microbiota influences patient outcomes. We hypothesized that organisms within the CF microbiota are affected by inhaled-antibiotics and baseline microbiome may be used to predict therapeutic response.

METHODS:

Adults with chronic P. aeruginosa infection from four clinics were observed during a single 28-day on/off inhaled-aztreonam cycle. Patients performed serial sputum collection, CF-respiratory infection symptom scores (CRISS), and spirometry. Patients achieving a decrease of ≥2 CRISS by day 28 were categorized as subjective responders (SR). The airway microbiome was defined by Illumina MiSeq analysis of the 16S rRNA gene.

RESULTS:

Thirty-seven patients (median 37.4 years and FEV1 44% predicted) were enrolled. No significant cohort-wide changes in the microbiome were observed between on/off AZLI cycles in either alpha- or beta-diversity metrics. However, at an individual level shifts were apparent. Twenty-one patients (57%) were SR and fourteen patients did not subjectively respond. While alpha-diversity metrics did not associate with response, patients who did not subjectively respond had a higher abundance of Staphylococcus and Streptococcus, and lower abundance of Haemophilus.

CONCLUSIONS:

The CF microbiome is relatively resilient to AZLI perturbations. However, associated changes were observed at the individual patient level. The relative abundance of key "off-target" organisms associated with subjective improvements suggesting that the microbiome may be used as a tool to predict patient response - potentially improving outcomes.

KEYWORDS:

AZLI; Cycled therapy; Inhaled antibiotics; Nebulized; Pseudomonas aeruginosa; Staphylococcus aureus; Streptococcus

PMID:
30857926
DOI:
10.1016/j.jcf.2019.02.010

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