AUDIT ON THE EFFECT OF REGULAR 3/4 MONTHLY ANTIBIOTICS ON LUNG FUNCTION AND WEIGHT IN CYSTIC FIBROSIS PATIENTS COLONISED WITH PSEUDOMONAS AERUGINOSA IN A CYSTIC FIBROSIS CENTRE

CHEST Journal ◽  
2008 ◽  
Vol 134 (4) ◽  
pp. 57S
Author(s):  
Bassey J. Asuquo ◽  
Mustopha Arshad ◽  
Obadiah Elekima
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Cystic Fibrosis Centre

scholarly journals Prevalence and impact of oprD mutations in Pseudomonas aeruginosa strains in cystic fibrosis

2019 ◽  
Author(s):  
Laura J. Sherrard ◽  
Bryan A. Wee ◽  
Christine Duplancic ◽  
Kay A. Ramsay ◽  
Keyur A. Dave ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Hazard Rate ◽  
Carbapenem Resistance ◽  
Adverse Outcomes ◽  
Nonsense Mutations ◽  
Allelic Variants ◽  
Novel Variants

ABSTRACTDefective OprD porins contribute to carbapenem resistance and may be important in Pseudomonas aeruginosa adaptation to cystic fibrosis airways. It is unclear whether oprD mutations are fixed in populations of shared strains that are transmitted between patients or whether novel variants arise during infection. We investigated oprD sequences and antimicrobial resistance of two common Australian shared strains, constructed P. aeruginosa mutants with the most common oprD allelic variants and compared characteristics between patients with or without evidence of infection with strains harbouring these variants. Our data show that three independently acquired nonsense mutations arising from a 1-base pair substitution are fixed in strain sub-lineages. These nonsense mutations are likely to contribute to reduced carbapenem susceptibility in the sub-lineages without compromising in vitro fitness. Not only was lung function worse among patients infected with strains harbouring the nonsense mutations than those without, but they also had an increased hazard rate of lung transplantation/death. Our findings further highlight that understanding adaptive changes may help to distinguish patients with greater adverse outcomes despite infection with the same strain.

scholarly journals Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation

2020 ◽  
pp. AAC.02327-20 ◽  
Author(s):  
Claire L Keating ◽  
Jonathan B Zuckerman ◽  
Pradeep K Singh ◽  
Matthew McKevitt ◽  
Oksana Gurtovaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Clinical Outcomes ◽  
Primary Endpoint ◽  
The United States ◽  
Study Endpoint ◽  
Primary Study ◽  
Antibiotic Exposure ◽  
Pulmonary Exacerbations

Rationale: Approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect susceptibility profiles of Pseudomonas aeruginosa (PA) isolates from cystic fibrosis (CF) patients.Objective: This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic PA infection.Methods: Sputum cultures were collected annually (2011-2016). The primary study endpoint was the proportion of subjects whose least susceptible PA isolate had an aztreonam minimum inhibitory concentration (MIC) that was >8 μg/mL (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and FEV1% predicted were obtained from the CF Foundation Patient Registry and compared between subjects meeting/not meeting the primary endpoint.Results: 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13-22%) met the primary endpoint each year; and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual decline in lung function was comparable for subjects meeting/not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it.Conclusions: Aztreonam susceptibility of PA remained consistent during the 5-year study. The relationship between PA isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with accelerated decline in lung function, but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure.

scholarly journals 259 Nutrition and lung function in a tertiary cystic fibrosis centre

2012 ◽  
Vol 11 ◽  
pp. S122
Author(s):  
N. Lagan ◽  
A. Walsh ◽  
L. Kelly ◽  
M. Morgan ◽  
F. Healy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Cystic Fibrosis Centre

scholarly journals Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators

2016 ◽  
Vol 114 (1) ◽  
pp. 136-141 ◽  
Author(s):  
Becca A. Flitter ◽  
Kelli L. Hvorecny ◽  
Emiko Ono ◽  
Taylor Eddens ◽  
Jun Yang ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Epoxide Hydrolase ◽  
Pulmonary Inflammation ◽  
Critical Role ◽  
Lavage Fluid ◽  
Lipid Mediator ◽  
Epoxyeicosatrienoic Acid

Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate diol, eliminating a proresolving signal that potently suppresses IL-8–driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.

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