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Heidi Ammerlaan

Thursday 11 November 2010

The clinical impact of methicillin-resistant Staphylococcus aureus on morbidity, mortality, and burden of disease

Promotor: Prof.dr M.J.M. Bonten
Defence: 11 November 2010
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The aim of this thesis was to get a detailed insight into the clinical epidemiology of MRSA and how this affects patient outcome.

Part I: Effectiveness of treatment of MRSA carriage
In Chapter 2 we systematically review several treatment strategies of MRSA carriage to determine the most effective approach for eradicating MRSA. In Chapter 3 we summarize the contents of a Dutch guideline on treatment of MRSA carriage, taking into account results of the review as described in Chapter 2. In Chapter 4 we present results of a study in which we aimed to evaluate the effectiveness of decolonisation treatment based on the guideline, after its implementation in medical practice, together with a suggestion on adaptation of the guideline based on the results of this study.

Part II: The effect of MRSA on temporal trends of nosocomial bacteraemias
In Chapter 5 we determine temporal trends of NB in a Dutch tertiary care centre using different incidence definitions in order to quantify the temporal changes of episodes caused by antibiotic-susceptible and antibiotic-resistant pathogens. The quantified trends in NB provide a convenient tool for comparison between different settings, regions and countries. In Chapter 6 we present the results of a study in which we determine temporal trends in all cause bacteraemia and the influence of ARB, and MRSA in particular, on total burden of NBs in seven MRSA endemic versus seven MRSA non-endemic hospitals in nine countries.

Part III: The effect of methicillin-resistance on adequacy of treatment and SAB associated mortality
In Chapter 7 we concisely present the results of a pilot study of MRSA treatment patterns in Europe and variables of influence on choice of treatment in six European countries. In Chapter 8 we present the results of a study that aimed to quantify inadequate treatment in hospitalized patients with SAB (MRSA versus MSSA) in Western Europe, and to identify how inadequate treatment is associated with 30-day mortality (SEPIA study). In the appendix of this chapter we debate the importance of timely adequate antimicrobial therapy in response to a comment on the SEPIA study results. In Chapter 9 we systematically reviewed all observational studies that report on MRSA versus MSSA associated mortality in patients with SAB, in order to quantify the risk of mortality associated with MRSA versus MSSA, and to determine the effect of confounding variables hereon.

Part IV: Summary and discussion
Finally, in Chapter 10 study results will be summarized, and remaining challenges regarding research on nosocomial bacteraemias, S. aureus and MRSA will be discussed.