Prevention of Healthcare Associated Staphylococcus aureus Infections

Abstract

S. aureus colonizes the skin and mucosae of a proportion of the human population. Carriers of S. aureus are at increased risk of developing infections with this pathogen. The aim of this thesis was to add to the prevention of healthcare associated S. aureus infections. We conducted a RCT which aimed to identify S. aureus carriers upon admission to hospital, and treated carriers with either mupirocin ointment and chlorhexidin soap, or with placebo ointment and placebo soap. The mup/chx treated group developed significantly less S. aureus infections than the placebo treated group. In this study, many types of patients, both surgical and nonsurgical, were included. Chapter 3 describes, based on mortality rates, which groups of patients benefit most from this strategy. In chapter 4, we compared hospital costs of cardiothoracic and orthopedic patients who were allocated to mup/chx and to placebo. Total costs of care for patients who had received placebo were on average €1911 higher than the costs for patients who had received mup/chx. In chapter 5, we argue that mupirocin should be used in carriers only, since high-level mupirocin resistance in CoNS is significantly more frequent on wards where the highest amounts of mupirocin are dispensed. Exogenous infections with S. aureus also make up an important part of the total burden of S. aureus infection. The size of that burden is estimated in Chapter 6. This underlines the importance of preventive measures that do not only target endogenous S. aureus infections, but all patients admitted to hospital. In Chapter 7 we aimed to unravel the underlying immunological basis for the phenomenon that colonization with S. aureus seems to have a protective effect on mortality due to S. aureus bacteremia. By investigating the humoral immune response to S. aureus bacteremia using immune proteomics, we were able to show that the immune response patterns for endogenous and exogenous infections differed. We showed that exogenous S. aureus infections are unexpected events for the human immune system, which does not have the potential to build up an effective immune response rapidly enough. In Chapter 8 the MRSA carriage prevalence upon admission to hospital is reported for the period 2005-2007 (0.11%). The prevalence did not significantly differ for the reported prevalence in 1999-2000, when it was 0.03%.