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This thesis will focus on nosocomial transmission and resistance of S. aureus and CoNS. After the general introduction on S. aureus and coagulase-negative staphylococci, part II focuses on the nosocomial transmission capacity of different MRSA clones in the hospital setting. In chapter 2 the nosocomial transmission capacity of livestock-associated MRSA (LA-MRSA) in the Dutch hospital setting is discussed. Previous findings have suggested that the nosocomial transmission capacity of LA-MRSA is lower than that of other MRSA genotypes. We performed a 6-month nationwide study to quantify the single-admission reproduction number, RA, for LA-MRSA in 62 hospitals in the Netherlands and to compare this transmission capacity to previous estimates known from the literature. In chapter 3 we quantified the risk of MRSA-transmission, in the absence of barrier precautions, in outpatient clinics and during short-term exposure in hospital wards. The risk of transmission after short-term exposure of MRSA carriers to a health-care setting is still unknown. In Chapter 4 we quantified the transmission capacity by calculating RA of community-associated MRSA (CA-MRSA) compared to health-care MRSA (HA-MRSA) in four Danish hospitals. The emergence of these so-called CA-MRSA clones has changed the epidemiology of MRSA infections worldwide. Despite obvious epidemiological differences, it is unknown whether differences in nosocomial transmissibility exist between CA-MRSA and HA-MRSA. The rapid emergence and high attack rates of CA-MRSA in the United States suggests that CA-MRSA strains are highly transmissible. In Chapter 5 we investigate the molecular epidemiology of MRSA in thirteen European intensive care units. It is unknown to what extent the global changes in MRSA epidemiology affect ICU-populations in Europe. We determined the prevalence, acquisition rates and molecular epidemiology of MRSA in 13 intensive care units (ICUs) in eight European countries that participated in a prospective trial to control transmission of antibiotic resistance in ICUs (Mastering Hospital Antimicrobial Resistance in Europe (MOSAR) project). Part III focuses on the acquisition and dynamics of mupirocin resistance in S. aureus and CoNS. Mupirocin is a topical antibiotic and the cornerstone of decolonization strategies of methicillin susceptible and methicillin resistant S. aureus (MSSA and MRSA). Chapter 6 focuses on the clinical consequences of mupirocin resistance on decolonization success rates of S. aureus and MRSA, and on the associations between mupirocin use and the development of mupirocin resistance. In chapter 7 we evaluated longitudinal trends in high-level mupirocin resistance in S. aureus and CoNS and its association with increasing mupirocin use in our hospital. In chapter 8 we investigated the effects of a peri-operative universal decolonization strategy with topical mupirocin and chlorhexidine body washings, on developing mupirocin resistance in CoNS and S. aureus. Universal decolonization, as in treating everyone irrespective of S. aureus… Advisors/Committee Members: Bonten, M.J.M..