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Title: Investigating the role of antibiotic exposure and demographic/socioeconomic factors on the development of bloodstream infections in primary care
Author: Lishman, Hannah
ISNI:       0000 0004 8504 6891
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Background In recent years the UK has seen a rise in the incidence of Gram-negative bloodstream infections (BSIs), particularly those acquired in the community, half of which have been recorded as being preceded by a urinary tract infection (UTI) - one of the most common infections treated with antibiotics. Antibiotic resistance has been postulated as exacerbating or even partially causing the progression from a UTI to a BSI. For these reasons the UK Government has introduced a number of measures through the NHS Quality Premiums related to BSI incidence and the reduction of inappropriate antibiotic prescribing for UTIs in the community in the hope of reducing the incidence of BSIs by improving antibiotic stewardship for preceding infections. Aim To investigate whether the risk of developing a BSI following antibiotic treatment for a community-acquired UTI is affected by differing patterns of antibiotic prescribing for community-acquired UTIs. Methods For all studies a number of routinely-collected healthcare data sources linked at the national level are used. An ecological design is used to investigate the volume of GP practice antibiotic prescribing for UTI and UTI-related E. coli bacteraemia (ECB) risk, taking antibiotic susceptibility into account. An algorithm is built to determine the level of antibiotic prescribing for UTI in England was does not adhere to prescribing guidelines as well as the reasons for non-adherence at the patient-level. This algorithm is then used in a patient-level retrospective cohort study to determine whether developing a BSI is associated with guideline adherence of antibiotic treatment for a preceding UTI. Lastly, a retrospective cohort study is used to examine whether longer durations of antibiotic treatment for UTI confer a greater risk of subsequent BSI compared with shorter durations. Results The ecological study demonstrates that GP practices with higher levels of trimethoprim prescribing, after adjusting for case-mix and practice characteristics, have a higher incidence of UTI-related trimethoprim-resistant ECB than practices with lower levels. The algorithm demonstrates that the majority of antibiotic prescriptions for UTI in England do not adhere to national prescribing guidelines, mainly due to antibiotic choice or duration of treatment. The first retrospective cohort study does not find evidence of greater or lesser risk of BSI following UTI antibiotic treatment which was not in line with national prescribing guidelines. The second retrospective cohort study found weak evidence of higher risk of BSI following a longer course of trimethoprim treatment for a UTI compared with a shorter course in women with uncomplicated UTI. Conclusions Improving antibiotic prescribing for UTI in the community (through using nitrofurantoin as the first-choice antibiotic and prescribing shorter durations of treatment where appropriate) may have an effect on subsequent BSI risk, although improvements in data acquisition and linkage to overcome the limitations outlined in this work will provide further clarity to this infection pathway.
Supervisor: Aylin, Paul ; Johnson, Alan ; Costelloe, Ceire Sponsor: National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral