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Title: The infective pulmonary exacerbation in cystic fibrosis : an ecological perspective
Author: Jones, Andrew
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Introduction: In CF, infective pulmonary exacerbations are common. Despite this, significant aspects of pathogenesis and patient responses to treatment remain poorly understood. This study examined a cohort of subjects receiving antibiotic therapy for exacerbations, correlated clinical findings with microbiological data and examined the factors leading to non-response to treatment. Methods: Subjects were recruited when they commenced IV antibiotics. Measures of lung function, inflammatory markers and quality of life scores were collected with sputum samples during treatment. Samples were analysed for (i) routine microbiology, (ii) Pseudomonas aeruginosa (PA) hypermutator frequency (ii) 16S rRNA gene sequences to identify bacteria present, (iv) PA quorum-sensing (QS) molecule concentrations using LC-MS/MS. Results: Patients who failed to return lung function to baseline at the end of treatment were shown to have a larger decline in FEV1 at exacerbation and a longer time since stable measures. In treatment success, no significant improvement in lung function was seen after 7 days treatment. No association was seen between severity of exacerbation or treatment response and PA mucoidy or presence of Staphylococcus aureus. Hypermutator PA was seen more in older patients and associated with milder exacerbations. Bacterial diversity was shown not to change significantly during antibiotic treatment but there was a significant relationship between the change in diversity and change in PA bacterial density. Meropenem was shown to have greater effect on diversity than ceftazidime. A significant association between QS molecule concentration and lung function decline at exacerbation was shown. QS concentrations were seen to decrease significantly during antibiotic treatment which was not associated with a decline in bacterial numbers. Discussion: Current durations of antibiotic treatment may not be appropriate as most improvement is seen within 7 days. The effect of repeated course of meropenem on bacterial diversity requires investigation. QS inhibition may provide alternative therapeutic options to exacerbation treatments.
Supervisor: Bilton, Diana ; Davies, Jane ; Hodson, Margaret Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available