The risks of patients acquiring an infection as a result of healthcare are considerable, with between 6.4% and 9.1% of patients in hospital found to have an healthcare associated infection (HCAI). These infections account for a considerable burden of disease; they are associated with significant morbidity and mortality, and incur costs to the patient, healthcare organisations and society. There is considerable evidence for measures that are effective in preventing HCAI, however there are challenges in ensuring that healthcare workers are aware of the risks and adhere to recommended practice. Surveillance systems that systematically capture, analyse and feedback data on rates of HCAI have been found to be a key component of effective infection control strategies, especially when they incorporate benchmarking. The large datasets captured by national surveillance systems also provide a unique opportunity to explore the epidemiology of HCAI, factors that contribute to their occurrence and their impact on public health. This thesis concerns the design and application of surveillance systems for infections associated with healthcare. It reflects the programme of research originating from my involvement with the development and delivery of national HCAI surveillance systems in England from the mid-1990s. This research has addressed my underpinning hypothesis that: 'there are real differences in rates of HCAI which reflect variation in clinical practice and indicate where improvement may prevent these infections'. The thesis includes eight primary publications focused on two key types of HCAI, surgical site infections (SSI) and bloodstream infections (BSI). The publications related to SSI describe my work on: the risks of SSI in terms of mortality and increased length of hospital stay; significant independent risk factors for SSI following hip prosthesis; the relationship between duration of operations and risk of SSI; inter-country comparisons of rates; an innovative approach to performance monitoring based on funnel plots; and the impact of psot-discharge surveillance on benchmarking. They are based on the analysis of data contributed to the national SSI surveillance system. A further two publications related to BSI explored trends in causative pathogens and source of methicillin resistant Staphylococcus aureus. The thesis describes the main methods and findings of these studies, their contribution to contemporary knowledge and subsequent contributions to the field, ilustrating my contribution to each of the works and my professional development as a researcher. The body of work has identified important trends in pathogens causing BSI, in particular the emergence of Escherichia coli as a major cause of these infections, and provided evidence of possible contributory factors. It has also identified factors contributing to the reduction of methicillin resistant Staphylococcus aureus as a cause of BSI. It has added to the body of knowledge on outcomes of SSI, demonstrating that SSI doubles the length of hospital stay and the more severe infections significantly increases the risk of mortality in some types of surgery. It has informed the design and delivery of SSI surveillance systems in England and Europe through identifying the impact of key risk factors, such as the duration of operation and type of hip replacement procedure, and exploring the impact of variation in application of surveillance methods, in particualr post-discharge surveillance, on rates of SSI. It has enhanced the value of surveillance as a performance monitoring through the application of innovative approaches to adjusting and comparing rates, such as the use of funnel plots for the detection of outliers. In conclusion, these analyses of data on HCAI have informed the development of national surveillance systems, improved understanding of variation in rates, and identified factors that may influence them. Further work is required to enhance and develop surveillance systems in order that they can continue to support the evaluation of effective infection prevention strategies in a rapidly changing healthcare environment.

Background: The introduction of highly active antiretroviral therapies (HAART) in 1996 to treat patients living with the human immunodeficiency virus type 1 (HIV-1), led to dramatic improvements in their mortality and morbidity. However, high levels of adherence to HAART regimens are required and due to the very nature of HIV-1: its high replicative capacity and lack of a proof reading mechanism, drug resistance mutations emerge, which impact on the ability of the drugs to suppress the patient’s circulating viruses. Genotypic resistance testing can determine whether mutations have developed which confer resistance to specific antiretrovirals (ARV) and thus enhance clinical care. Methods: A clinical cohort database was developed to host the demographic, treatment and resistance mutation data for patients living with HIV-1 across the United Kingdom (UK) who had a genotypic resistance test (tests) conducted as part of their clinical care. These data were pooled and interrogated to determine the evolution and dynamics of resistance in targeted sub-groups of patients including treatment-naïve patients; treatment-experienced patients and their potential susceptibility to new ARV drugs; and the evolution of new subtype profiles within the clinical cohort and the impact of this on clinical outcomes. The over-riding aim of each of the studies was to improve the clinical care of patients with HIV-1 infection in the UK. Results: In the treatment-naïve patient cohort (n=380), a resistance prevalence rate of 16.5% was determined. In the treatment-experienced cohort (n=1,786), the resistance prevalence rate was 68.1%. Of those treatment-experienced, 91.3% would be susceptible to the new ARV Etravirine (ETV) and 89.7% to Darunavir (DRV). In the subtype patient cohort (n=1,642), an increase in the prevalence of pure and recombinant non-B subtypes over time was demonstrated and characterised, as well as the identification of polymorphisms specific to non-B subtypes compared to subtype B. Conclusions: The resistance prevalence rate of >10.0% in the treatment-naïve patient cohort supported the need to conduct genotypic resistance tests for all treatment-naïve patients with HIV-1 infection before commencement of HAART in order to ensure the patient was starting on the optimal first-line treatment regimen to control their virus. National and European guidelines were subsequently amended to reflect this requirement. The treatment-experienced patient cohort analyses confirmed the resistance mutations circulating within the treated HIV-1 community which are the source of transmitted resistance to the treatment-naïve patients. Further analyses of the treatment-experienced cohort suggested two new ARVs which were due to be licenced for use with HIV-1 patients would be “theoretically susceptible”, providing further treatment options for these patients with resistance mutations. The subtype patient cohort work determined that subtype characterisation should be introduced as part of clinical care due to the impact of non-B subtypes on the success of genotypic resistance testing, and the different mutational pathways which might occur, leading to resistance in different subtypes. All these studies provided data and evidence of current issues which impacted on the clinical care of patients living with HIV-1 in the UK and influenced changes in guidelines on how best to manage and improve patient care.

digitalisering@umu.se

digitalisering@umu.se

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.