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BMC Microbiol. 2021 Mar 30;21(1):96. doi: 10.1186/s12866-021-02159-5.

Azithromycin and the microbiota of cystic fibrosis sputum.

BMC microbiology

Nicole Acosta, Christina S Thornton, Michael G Surette, Ranjani Somayaji, Laura Rossi, Harvey R Rabin, Michael D Parkins

Affiliations

  1. Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta, Canada.
  2. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
  3. Department of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta, Canada.
  4. Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta, Canada. [email protected].
  5. Department of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta, Canada. [email protected].

PMID: 33784986 PMCID: PMC8008652 DOI: 10.1186/s12866-021-02159-5

Abstract

BACKGROUND: Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis - we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure.

RESULTS: Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders - demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas.

CONCLUSIONS: Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.

Keywords: Azithromycin; Cystic fibrosis; Macrolides; Microbiome; Stenotrophomonas

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