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

J Cyst Fibros. 2019 Nov;18(6):829-837. doi: 10.1016/j.jcf.2019.02.010. Epub 2019 Mar 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Aztreonam / administration & dosage*
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / physiopathology
  • Cystic Fibrosis* / psychology
  • Cystic Fibrosis* / therapy
  • Diagnostic Self Evaluation*
  • Female
  • Humans
  • Lung* / microbiology
  • Lung* / physiopathology
  • Male
  • Microbiota / drug effects*
  • Outcome Assessment, Health Care / methods
  • Patient Outcome Assessment
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa* / drug effects
  • Pseudomonas aeruginosa* / isolation & purification
  • Respiratory Function Tests
  • Sputum / microbiology


  • Anti-Bacterial Agents
  • Aztreonam