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

• Published in: Journal of cystic fibrosis Vol. 18; no. 6; pp. 829 - 837
• Main Authors: Heirali, Alya A., Acosta, Nicole, Storey, Douglas G., Workentine, Matthew L., Somayaji, Ranjani, Laforest-Lapointe, Isabelle, Leung, Winnie, Quon, Bradley S., Berthiaume, Yves, Rabin, Harvey R., Waddell, Barbara J., Rossi, Laura, Surette, Michael G., Parkins, Michael D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2019
• Subjects: AZLI; Cycled therapy; Inhaled antibiotics; Nebulized; Pseudomonas aeruginosa; Staphylococcus aureus; Streptococcus; BC; NSAID; DIOS; CRISS; PERMANOVA; TIS/P (TOBI); Inhaled antibiotics; Nebulized; CSAA; OTU; CFU; Non-SR; Pseudomonas aeruginosa; SDI; Staphylococcus aureus; BMI; SR; COL; Bcc; CF; OR; rRNA; AZLI; IQR; Non-OR; TID; CFRSD; Streptococcus; Cycled therapy; DNA; FEV1; FEV6
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2019.02.010

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. 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. 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. 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. •The CF microbiome was assessed during a 56-day cycle of inhaled aztreonam (AZLI).•No major changes in the microbiome were observed with AZLI usage.•Clinical response was tested for associations with changes in the microbiome.•Organisms known to resist AZLI were found in higher abundance in non-responders.•This study suggests that the microbiome may serve to personalize therapies in CF.