The clinical and microbiological utility of inhaled aztreonam lysine for the treatment of acute pulmonary exacerbations of cystic fibrosis: An open-label randomised crossover study (AZTEC-CF)

Frost, Freddy ORCID: 0000-0002-3902-6502, Young, Gregory R, Wright, Laura, Miah, Nahida, Smith, Darren L, Winstanley, Craig ORCID: 0000-0002-2662-8053, Walshaw, Martin J, Fothergill, Joanne L ORCID: 0000-0002-7012-1508 and Nazareth, Dilip ORCID: 0000-0002-6114-0467 (2021) The clinical and microbiological utility of inhaled aztreonam lysine for the treatment of acute pulmonary exacerbations of cystic fibrosis: An open-label randomised crossover study (AZTEC-CF). JOURNAL OF CYSTIC FIBROSIS, 20 (6). pp. 994-1002.

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Official URL: http://dx.doi.org/10.1016/j.jcf.2020.12.012

Abstract

<h4>Background</h4>The objective of this study was to explore the clinical and microbiological outcomes associated with substituting inhaled aztreonam lysine for an intravenous antibiotic in the treatment of acute pulmonary exacerbations of CF.<h4>Methods</h4>An open-label randomised crossover pilot trial was conducted at a UK CF centre among 16 adults with CF and P. aeruginosa infection. Median [IQR] age was 29.5 [24.5-32.5], mean ± SD forced expiratory volume in 1 second (FEV1) was 52.4 ± 14.7 % predicted. Over the course of two exacerbations, participants were randomised to sequentially receive 14 days of inhaled aztreonam lysine plus IV colistimethate (AZLI+IV), or dual IV antibiotics (IV+IV). Primary outcome was absolute change in % predicted FEV1. Other outcomes evaluated changes in quality of life, bacterial load and the lung microbiota.<h4>Results</h4>The difference between mean change in lung function at day 14 between AZLI+IV and IV+IV was +4.6% (95% CI 2.1-7.2, p=0.002). The minimum clinically important difference of the Cystic Fibrosis Revised Questionnaire (CFQ-R) was achieved more frequently with AZLI+IV (10/12, 83.3%) than IV+IV (7/16, 43.8%), p=0.05. No differences were observed for modulation of serum white cell count, C-reactive protein or sputum bacterial load. Microbiome compositional changes were observed with IV+IV (Bray-Curtis r<sup>2</sup>=0.14, p=0.02), but not AZLI+IV (r<sup>2</sup>=0.03, p=0.64).<h4>Conclusion</h4>In adults with CF and P. aeruginosa infection experiencing an acute pulmonary exacerbation, AZLI+IV improved lung function and quality of life compared to the current standard treatment. These findings support the need for larger definitive trials of inhaled antibiotics in the acute setting.<h4>Clinical trial registration</h4>EudraCT 2016-002832-34 ClinicalTrials.org NCT02894684.

Item Type:	Article
Uncontrolled Keywords:	Humans, Pseudomonas Infections, Cystic Fibrosis, Aztreonam, Anti-Bacterial Agents, Administration, Inhalation, Pilot Projects, Cross-Over Studies, Adult, Female, Male, Symptom Flare Up, United Kingdom
Depositing User:	Symplectic Admin
Date Deposited:	13 Jan 2021 12:04
Last Modified:	18 Jan 2023 23:05
DOI:	10.1016/j.jcf.2020.12.012
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3111809