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Title: Impact of Pseudomonas aeruginosa Liverpool epidemic strain (LES) on cystic fibrosis patients
Author: Ashish, Abdul
ISNI:       0000 0004 5368 9673
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
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Cystic Fibrosis (CF) is the commonest life limiting inherited disease illness in the western world. Over the last few decades there have been many advances in the diagnosis and management of this condition. Patients born with the disease now are living into their fourth decade, which is a statement to the progress made over time. Along with the progress there have been new challenges in the world of CF. In the last two decades there have been several studies reporting the presence of transmissible Pseudomonas Aeruginosa (Psa) strains in CF clinics worldwide. The first one to be reported in UK Liverpool paediatric clinic was later identified as the Liverpool Epidemic Strain (LES). Previous studies have demonstrated chronic infection with LES can result in accelerated fall in lung function, increased hospitalisation and antibiotic requirements. This thesis looks at the effect of chronic infection of adults with CF and its implications on healthcare institutions caring for such patients. In particular on an individual level i investigated the health related quality of life associated with patients chronically infected with LES and compared it those with unique or no Psa strains. I have demonstrated that chronic infection with LES strain significantly worsens health related quality of life compared to those with unique or no Psa strains. Patients infected by transmissible Psa strains had worse physical functioning, respiratory symptoms, treatment burden, vitality, role, health perception and emotion than those with unique Psa strains (p < 0.01), and significantly poorer physical functioning, respiratory symptoms, treatment burden, body image, weight, role, and emotion than those without any Psa infection (p < 0.05). To understand the susceptibility of LES strains to common anti-pseudomonal antibiotics I studied the antibiograms of patients infected with LES strain over a 5-year period and compared the change in susceptibility to those infected with unique Psa strain. LES exhibited significantly more resistant isolates in 2004 (p < 0.0001). There was an increase in antibiotic resistance in both LES and other Psa strains over time (p < 0.001). Cox proportional hazards analysis of both unmatched (n=125) and matched (n=56) patients in 2004 revealed that LES infected patients were more likely to develop antibiotic resistant isolates over time (hazard ratio 8.1, p < 0.001). Fewer LES isolates were classed as fully sensitive in both matched and unmatched groups at the end of study period (p < 0.001). I then looked at the phenotypic characteristics exhibited by LES strain in comparison with unique Psa strain during an infective episode to elucidate whether it is a specific character of LES assisting to survive in harsh CF environment. We analyzed sets of 40 sputum samples isolates from 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 characterising nine phenotypic traits. All P. aeruginosa populations were highly diverse. The majority of phenotypic variation found was due to within-sample variation. I demonstrated that maintenance of diverse populations in the CF lung is a general feature of P. aeruginosa infections rather than a unique characteristic of LES. To assess the healthcare resource implication on institutions caring for such patients we carried out an economic analyses of healthcare utilisation of patients chronically infected with LES to those with unique Psa strain over a four-year period. Ascertainable costs were correlated in these two groups of patients. The mean cost per patient per year was higher for LES patients for inpatient care (£4393.37 v £1817, p=0.0006), outpatient attendance (£3764 v £2515.91, p=0.0035) and also hospital antibiotic therapy (£980 v £ 505, p=0.001). Regular prescription costs were similar in both groups. Overall, the healthcare cost of caring for an adult CF patient with LES chronic infection was significantly more (1.6 times) than that for a matched patient with unique Psa strain chronic infection. Finally, I looked the effects of segregation policies instituted at Liverpool adult Cf centre in limiting cross infection. Regular genotypic surveillance of sputum samples of all patients was instituted to monitor cross infection rates. This study elucidated the cross infection policies over a 7-year period and looked at the yearly number of patients with LES and other strains. There was a decline in the proportion of patients with LES (71% to 53%) and an increase in those with unique strains (23% to 31%) and without Psa infection (6% to 17%) over the study period. Areas of potential future research based on this thesis are also outlined.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
Keywords: QR Microbiology