**3. MRSA colonization and decolonization**

Studies on colonization intend to elucidate the mechanism by which certain individuals are persistently or intermittently colonized while others are non-carriers. MRSA colonization is an important predisposing factor, since colonized individuals are at increased risk of acquiring infections (van Belkun et al., 2009). Colonization is well studied in inpatients due to the risk of dissemination and the fact that it can facilitate severe infections.

Nasal colonization is the main form, and colonization can occur in other extra-nasal sites as in the skin, pharynx and perineum, but some sites are considered unusual such as the vagina, axilla and gastrointestinal tract. Studies may help to define carriers as in most crosssectional studies only a culture classifies individuals as carriers or not, while longitudinal studies usually classify three categories of carriers: intermittent, persistent or non-carriers. Often cultures are harvested in three different time periods to define the carriers (Werthein et al., 2005). A study concluded that a "culture rule" which combines qualitative and quantitative results of two nasal cultures with an interval of one week could accurately classify nasal carriage (Nouwen et al., 2004).

The treatment of MRSA infections is variable. Within a hospital environment, there are several options such as linezolid, daptomycin, quinupristin/dalfopristin, but vancomycin is one of the most commonly used to treat several types of infections, but the emergence of strains resistant to this antimicrobial agent limits its use. Historically the emergence of vancomycin resistance occurred primarily in isolates of *Enterococcus* spp. in 1986 and reported only in 1988 in a European hospital. In 1989, in the United States, Vancomycin-Resistant Enterococci (VRE) were detected in clinical isolates and in 1993 accounted for 7.9% of the enterococci samples in nosocomial environments reported by the CDC. The most important reservoir is the gastrointestinal tract and transmission occurs mainly through contact with healthcare workers, and indirectly by contaminated hands in contact with the

Vancomycin resistance in VRE is due to the presence of *van* genes (A to G) that encode for the synthesis of peptidoglycan by an alternative pathway that produces precursors ending in D-Ala-D-Lac or D-Ala-D-Ser instead of D-Ala-D-Ala. In *S. aureus,* however the main mechanism involved in vancomycin resistance relies on a thickened cell wall, production of abundant extracellular material that remains not well characterized and it ends up compromising the ability of division. These characteristics result in the synthesis of an altered peptidoglycan with an increased number of terminal D-Ala-Ala-D capable of binding free vancomycin in the outer cell wall, thus leading to a lower availability of the antimicrobial target molecule in the intracellular region. Strains of *S. aureus* with intermediate resistance to vancomycin (VISA) may contain 2 to 4 times more layers of D-Ala-D-Ala than susceptible strains, being capable of binding to three to six times more vancomycin molecules. Some chromosomal changes are necessary to maintain this resistance , and in addition require a larger amount of precursors than normal strains, thus compromising their fitness in an environment free of this antimicrobial. This may explain the reason for the loss of the vancomycin resistance of VISA strains when they are in environments without antibiotics, giving rise to heteroresistant strains called hetero-VISA

Studies on colonization intend to elucidate the mechanism by which certain individuals are persistently or intermittently colonized while others are non-carriers. MRSA colonization is an important predisposing factor, since colonized individuals are at increased risk of acquiring infections (van Belkun et al., 2009). Colonization is well studied in inpatients due

Nasal colonization is the main form, and colonization can occur in other extra-nasal sites as in the skin, pharynx and perineum, but some sites are considered unusual such as the vagina, axilla and gastrointestinal tract. Studies may help to define carriers as in most crosssectional studies only a culture classifies individuals as carriers or not, while longitudinal studies usually classify three categories of carriers: intermittent, persistent or non-carriers. Often cultures are harvested in three different time periods to define the carriers (Werthein et al., 2005). A study concluded that a "culture rule" which combines qualitative and quantitative results of two nasal cultures with an interval of one week could accurately

to the risk of dissemination and the fact that it can facilitate severe infections.

hospital objects where at least one of the patients had diarrhea (Mayall, 2002).

(Van Bambeke et al., 2004).

**3. MRSA colonization and decolonization** 

classify nasal carriage (Nouwen et al., 2004).

Persistent carriers are usually colonized by a single strain of *S. aureus* over a long period of time, whereas intermittent carriers may carry different strains over time (Werthein et al., 2005). MRSA colonization in individuals in the community remains a low burden as demonstrated in a study of high school boys where no individuals were found colonized with MRSA. The fact that there were no carriers among this population may be a reflection of improvement in hygiene practices among these individuals due to previous reports of outbreaks in team sports (Lear et al., 2011). Although they did not found MRSA in the population, other studies have found colonization rates in individuals in the community ranging from 0.8 to 3% (Keuhnert et al., 2006; Salgado et al., 2003; Ellis et al., 2004).

MRSA colonization in a hospital environment is a matter of utmost importance since it is characterized as a predisposing factor to infection. Nasal decolonization is usually performed with the application of mupirocin and is useful for reducing symptoms and its spread in hospital environments. However, the practice of decolonization with antimicrobials remains controversial because of the risk of acquiring drug resistance, which limits its use. Despite this risk, it is advised to perform decolonization in healthcare settings because of the risk of developing infections especially in individuals who are under invasive treatments and are immunocompromised (Coates et al., 2009).

But how should we manage individuals living in the community who are characterized as persistent carriers of CA-MRSA, but show no clinical manifestations and are healthy? This is a controversial subject because a previous study showed that individuals might be cocolonized with MSSA and MRSA, where the strains of MSSA have better fitness than MRSA, most likely due to the additional mechanism of resistance, which requires a cost in the feasibility and competitiveness of these strains. Thus, when decolonization is performed with mupirocin, both are eliminated and there will be competition, thus increasing the chances of colonization by resistant strains if both were competing for the same ecological niche (Dall'Antonia et al., 2005). Studies are needed to evaluate the cost-effectiveness of nasal colonization among residents in the community as a predisposition to infections, but there are chances of acquisition of resistant strains.

The nasal vestibule is composed of highly keratinized cells including apocrine and sebaceous glands and hair follicles. These factors are poorly studied compared to the mucosa and its linkage to mucins. Some of the pathogen virulence factors contribute to successful colonization; for example, the clumping factor B is highly associated with nasal colonization (Wertheim et al., 2007). Studies have reported the binding of *S. aureus* surface protein G (SasG) to a ligand in nasal epithelial cells. Other factors such as: Teichoic acid and cell wall components recognizing microbial surface adhesive matrix molecules (MSCRAMMS) responsible for the adherence protein in fibronectin, fibrinogen and collagen, may play an important role in colonization (Wertheim et al., 2005).
