Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on respiratory microbiota composition

Anton Y. Peleg, Jocelyn M. Choo, Katherine M. Langan, Deirdre Edgeworth, Dominic Keating, John Wilson, Geraint B. Rogers, Tom Kotsimbos

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

BACKGROUND: G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised.

METHODS: Twenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing.

RESULTS: No significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P=0.95, square root ECV=-4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time (P<0.0001, Mann Whitney U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P=0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered (P=0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor (P=0.004, two-tailed paired Student's t-test).

CONCLUSIONS: The short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalJournal of Cystic Fibrosis
Volume17
Issue number1
Early online date14 Oct 2017
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Antibiotics
  • Ivacaftor
  • Respiratory microbiome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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