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Title: Pulmonary exacerbations of cystic fibrosis : development and validation of the oral antibiotics indicator score
Author: Orchard, Christopher
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Introduction: Cystic fibrosis pulmonary disease is characterised by recurrent exacerbations. These are more than temporary declines in lung function and have longer term effects on quality of life and survival. Traditional treatment has involved prolonged courses of IV antibiotics. Oral antibiotics are effective for treating pulmonary exacerbations in some patients, however, thus far it has been difficult to identify this group. This thesis aimed to develop and validate a score to identify patients in any care setting in whom pulmonary exacerbations could be treated effectively with oral antibiotics. Methods - Derivation: A retrospective database of oral and IV antibiotic use in a cohort of 254 CF patients for treatment of pulmonary exacerbations over 1 year of follow up was used. Effectiveness of oral and IV antibiotic treatment and time to next exacerbation (TTNE) were analysed to develop a scoring system (Oral AntibioticS Indicator Score, OASIS) for use in stratifying patients into different treatment groups. Validation: The OASIS score was tested prospectively in a new cohort of 59 patients, who were recruited at the start of a new pulmonary exacerbation and outcome of treatment with oral and IV antibiotics was examined at day 14. Results: - Derivation cohort - there was no significant difference in outcomes between oral and IV antibiotics. From this the OASIS, a simple 3-point scoring system was developed including previous recent use of intravenous antibiotics, new respiratory symptoms and CXR Northern score. Validation cohort - There was no significant difference in successful treatment outcome between oral (57% success) and IV (77%) antibiotics (p=0.198). The OASIS score could not identify patients in whom oral antibiotics would be successful (p=0.348), but elevated day 14 CRP was associated with treatment failure (p=0.001) and increased exacerbation rate in the 4 subsequent 6 months. Factors associated with treatment failure in the oral antibiotic group when reanalysed included baseline and day 1 of exacerbation FEV1 %predicted and number of pulmonary exacerbations in the preceding 12 months. Conclusion: The OASIS score could not accurately predict outcome for patients treated with oral antibiotics, but upon reanalysis factors associated with treatment failure of oral antibiotics were identified. A new approach, with more sophisticated biomarkers validated in larger studies is required to enable better targeting of oral antibiotic therapy to treat CF pulmonary exacerbations.
Supervisor: Bilton, Diana ; Bush, Andrew ; Simmonds, Nicholas Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral