Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection

D. R. VanDevanter (Lead / Corresponding author), I. Gonda, J. Dahms, D. Cipolla, A. M. Davis, J. D. Chalmers, J. Froehlich

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213–26].

Methods: Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied.

Results: Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13–1.40) versus 0.54 (95% CI 0.89–0.19) log 10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45–1.69) versus 0.70 (95% CI 1.11–0.29) log 10 CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC 50 increased from 0.5 to 1 mg/L, MIC 90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected.

Conclusion: Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.

Original languageEnglish
Pages (from-to)1532-1538
Number of pages7
JournalClinical Microbiology and Infection
Volume25
Issue number12
Early online date26 Apr 2019
DOIs
Publication statusPublished - Dec 2019

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Keywords

  • ARD-3150
  • Inhaled antibiotics
  • Inhaled liposomal ciprofloxacin
  • Non-cystic fibrosis bronchiectasis
  • Pseudomonas aeruginosa

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