Staphylococcus aureus is a bacterium that can be found in the nose or on the skin of about one third of humans, [Kluytmans et al., 1997]. It can usually be found in the nares but throat, perineum and axillae are also carriage sites. Studies have shown that in a healthy population, about 20% of individuals are per-sistent Staphylococcus aureus nasal carriers, approximately 30% are intermittent carriers, and about 50% non-carriers, [Wertheim et al., 2005]. Once Staphylococ-cus aureus enters the blood stream, it can be harmful and cause from mild infec-tions such as skin and soft-tissue infecinfec-tions to more serious ones like sepsis that can sometimes be fatal, [Weber, 2005]. Factors that can lead to the development of antimicrobial resistant pathogens such as Staphylococcus aureus in hospitals, include transmission via health care workers and the use of antimicrobial treat-ment for infections, [Tenover and McGowan Jr, 1996].
MRSA belongs to a Staphylococcus aureus group of strains which is resistant to methicillin and other antibiotics. It is one of the most widespread nosocomial
pathogens and it can cause serious infections. Since it is resistant to many an-timicrobials, it is difficult and expensive to be treated effectively. MRSA first appeared in the UK in 1961, [Enright et al., 2002], and since then it has been an endemic problem in hospitals, especially in ICU wards and nursing homes in many countries around the world. Without treatment, MRSA can stay in the body for large periods ranging from several months to more than three years, [Robicsek et al., 2009; Scanvic et al., 2001; Vriens et al., 2005].
To fight MRSA in ICU wards, several control measures and rational use of an-tibiotics need to be taken into account. There have been great efforts to design proper control strategies that can be used for the detection and eradication of MRSA, although it is still under debate which approaches could improve its control and reduce its clinical impact. These strategies include early detection of asymptomatic MRSA carriers which may lead to rapid isolation and minimise the possibility of transmission, improvement of the hand hygiene protocol for health-care workers, decolonisation strategies using antiseptic as well as thor-ough environmental cleaning and careful antimicrobial treatments, [Harbarth, 2006].
Several mathematical models have been used to predict the impact of differ-ent control measures in order to eradicate MRSA transmission. Most of them suggest that improving the health worker hand hygiene is the most effective control strategy, [Austin and Anderson, 1999; McBryde et al., 2007; Raboud et al., 2005] along with the reduction of colonised patients admitted in the ward, [Cooper et al., 1999]. There are also a number of models that relate antibiotic consumption with MRSA colonisation, [Tacconelli et al., 2008].
1.2.1 The role of antimicrobial treatment
As an attempt to limit the spread of MRSA, many hospitals use either topical or oral antimicrobial treatment in order to eradicate MRSA from individuals who are colonized. Antibiotics that are not effective against MRSA encourage acquisitions, [Dancer, 2008]. Thus, many studies have focused on the investi-gation of the relationship between antibiotic treatments and MRSA resistance.
Most of them have underlined that antimicrobial use can increase the risk of MRSA colonisation or infection, [Loeb et al., 2003; Muller et al., 2006; Tacconelli
et al., 2008]. Others on the other hand, have found little change to the spread of MRSA when antibiotic control strategies were used, [Carling et al., 2003].
In [Lodise et al., 2003] a prediction model showed that 80% of the nosocomial and 60% of the community-acquired Staphylococcus aureus bacteremia will be methicillin resistant. This model indicated that there are no differences between the use of antimicrobial treatment and MRSA prediction. Other studies how-ever, have shown that the use of control practices was related with a decrease of MRSA, while some antibiotics were found to help its spread. More specifically, the use of Fluoroquinolones, third-generation Cephalosporins, Macrolides and Amoxicillin were related to increased MRSA incidents, [Aldeyab et al., 2008;
Dancer, 2001; Mahamat et al., 2007; Monnet et al., 2004; Muller et al., 2006; We-ber et al., 2003]. Nevertheless, there is a lot of uncertainty about the kind and amount of antimicrobial treatment which can be a threat to MRSA transmis-sion. This is due to heterogeneity between the studies that differ in the length of time each antimicrobial treatment was prescribed as well as the lack of data on the duration of antimicrobial use and dosages, [Tacconelli et al., 2008].
Antimicrobial treatment using Linezolid and Vancomycin is considered to be MRSA targeting. There are many surveys in the literature that try to find which one eradicates MRSA more efficiently. Many of them have shown that Line-zolid is as effective as Vancomycin for the treatment of MRSA, [Dennis et al., 2002] and that Linezolid is related to shorter hospital stays, [Itani et al., 2010].
Others claim that Linezolid can be more effective than Vancomycin in surgical sited infections, [Stevens et al., 2002; Weigelt et al., 2004] but can be equivalent to Vancomycin in the treatment of complicated skin and soft tissue infections, [Weigelt et al., 2005].
1.2.2 Decolonisation strategies
Decolonisation is considered an important part of infection control strategies.
Decolonisation policies can help control MRSA in ICU wards. Previous studies have shown that the introduction of a Chlorhexidine based decolonisation pro-tocol in an ICU can dramatically reduce the transmission of susceptible MRSA strains, [Batra et al., 2010; Kypraios et al., 2010]. There are also studies outside the ICU ward i.e. in Macfarlane et al. [Macfarlane et al., 2007], which report
successful decolonisation using a protocol for MRSA. Other studies however, found that such policies were not that effective, [Kurup et al., 2010], or other practices such as hand hygiene were more efficient, [McBryde et al., 2007].
These differences might be due to variability in the use of protocols or other control strategies, [Edgeworth, 2011].
In the next section we present the data we are going to use, which form the basis for the development of the stochastic models described in the following chapters in this thesis.