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Background: 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., Methods: 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., Results: 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 2 =0.14, p=0.02), but not AZLI+IV (r 2 =0.03, p=0.64)., Conclusion: 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., Clinical Trial Registration: EudraCT 2016-002832-34 ClinicalTrials.org NCT02894684., Competing Interests: Declaration of Competing Interest GY, LW, NH, MJW and JF declare no conflicts of interest. FF has received honoraria from Gilead Sciences, Vertex and Chiesi. CW has received honoraria from Chiesi. DN has received research grants from Gilead Sciences and honoraria from Gilead Sciences and Vertex., (Copyright © 2020. Published by Elsevier B.V.)

Background: Populations of the Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa undergo extensive diversification in the cystic fibrosis (CF) lung during long-term chronic infections., Methods: We analyzed sets of 40 isolates from the sputa of five CF patients, each chronically infected with a different non-LES strain of P. aeruginosa. For each sample (two per patient), diversity was assessed by characterizing nine phenotypic traits., Results: All P. aeruginosa populations were highly diverse, with the majority of phenotypic variation being due to within-sample diversity., Conclusions: Maintenance of diverse populations in the CF lung is a common feature of P. aeruginosa infections., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Early eradication therapy is key to keeping the airways Pseudomonas aeruginosa infection-free and rapid identification is essential., Methods: We used rapid DNA extraction and qPCR assays to detect bacterial, P. aeruginosa and strain-specific targets in samples using two qPCR chemistries. Using 459 respiratory samples from adult and children CF patients, we compared two qPCR methods to culture-based methods in terms of sensitivity and time to result., Results: For adult samples, there was 100% concordance between methods. There was no clear pattern in fluctuations in P. aeruginosa number during exacerbation. In child samples, qPCR methods identified additional P. aeruginosa positive samples. The time-to-result was reduced by over 24h and copy number and colony forming unit could differ dramatically in some samples., Conclusion: If adopted, these methods could significantly improve early P. aeruginosa detection in diagnostic laboratories and therefore play a pivotal role in prolonging infection-free airways in CF patients., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Individual PCR amplification tests have been developed for three UK CF epidemic strains, the Liverpool epidemic strain (LES), Midlands 1 and the Manchester epidemic strain (MES). We report a simple diagnostic multiplex PCR test that can be used to screen for all three of these strains. To evaluate the test, we screened collections of LES, MES and Midlands 1 isolates, along with various CF and non-CF non-epidemic Pseudomonas aeruginosa strains. The test was 100% sensitive and 100% specific in the identification of these UK CF epidemic strains.