**11. Vancomycin resistance**

Another concern is the emergence of resistance to the antibiotic of choice for treating MRSA, vancomycin. Few drugs are available to control MRSA, and vancomycin is one of them. Reports of resistance and low sensitivity to this antibiotic are present in nosocomial environments worldwide (Martins & Cunha et al., 2007).

The first case of reduced susceptibility to vancomycin was reported by Hiramatsu (1997) in a pediatric patient with positive culture for MRSA who was treated with glycopeptide. Phenotypic analysis showed that the MIC for this strain was 8 µg/mL in the microdilution test, and molecular analysis did not detect the presence of *vanA* or *vanB* genes. Strain Mu50, recovered from this patient, represents the first strain of *S. aureus* to demonstrate this level of resistance to vancomycin (Hiramatsu, 1997).

The first report of vancomycin resistance in the U.S. was described by Sievert et al. (2002). The patient was treated with several courses of antibiotics including vancomycin and subsequently developed MRSA bacteremia due to a hemodialysis catheter. He received vancomycin, rifampin and required removal of this catheter. The cultures of the catheter revealed the presence of *S. aureus* resistant to oxacillin and vancomycin. After one week, VRSA and vancomycin-resistant Enterococcus (VRE) were isolated. Cultures did not recovered VRSA from the patient being treated with trimethoprim/sulfamethoxazole, successfully. Molecular analysis revealed the presence of the *vanA* gene from enterococci, which explains the resistance to glycopeptides, and *mecA* (Sievert et al., 2002).

Cases of *S. aureus* with intermediate resistance to vancomycin (VISA) in addition to presenting heteroresistance are increasingly common in health centers where MRSA infections are treated with vancomycin (Trakulsomboon et al., 2001; Van Duijkeren et al., 2005; Kim et al., 2000).

Kim et al. (2000) observed that the vancomycin-resistant strains showed changes in the cell wall due to selective pressure caused by prolonged use of vancomycin in the treatment of

Choosing the best option for treating infections caused by CA-MRSA has risks and benefits of each antimicrobial agent that must be considered before prescribing. The ideal antimicrobial agent would be one of low toxicity to the individual, the rapid bactericidal activity, excellent tissue penetration, consistent pharmacokinetics and pharmacodynamics that would allow a predetermined dose, low potential for development of resistance during therapy and a proven clinical efficacy and microbiological (Nguyen & Graber, 2010). Finding a single antimicrobial agent with these characteristics may be complex, whereas a

It is not enough to choose antimicrobials with these characteristics; it is also essential to observe antimicrobial participation in the various mechanisms of virulence of the microorganism. In several reports of infections caused by CA-MRSA, PVL appears simultaneously as a virulence factor. The use of antimicrobials may act in the synthesis of Leukocidin improving the patient's condition in cases of pneumonia caused by CA-MRSA PVL positive strains treated with linezolid and clindamycin which suggests that this is a good choice, acting on the protein production mechanism, these antibiotics prevent PVL

Another concern is the emergence of resistance to the antibiotic of choice for treating MRSA, vancomycin. Few drugs are available to control MRSA, and vancomycin is one of them. Reports of resistance and low sensitivity to this antibiotic are present in nosocomial

The first case of reduced susceptibility to vancomycin was reported by Hiramatsu (1997) in a pediatric patient with positive culture for MRSA who was treated with glycopeptide. Phenotypic analysis showed that the MIC for this strain was 8 µg/mL in the microdilution test, and molecular analysis did not detect the presence of *vanA* or *vanB* genes. Strain Mu50, recovered from this patient, represents the first strain of *S. aureus* to demonstrate this level

The first report of vancomycin resistance in the U.S. was described by Sievert et al. (2002). The patient was treated with several courses of antibiotics including vancomycin and subsequently developed MRSA bacteremia due to a hemodialysis catheter. He received vancomycin, rifampin and required removal of this catheter. The cultures of the catheter revealed the presence of *S. aureus* resistant to oxacillin and vancomycin. After one week, VRSA and vancomycin-resistant Enterococcus (VRE) were isolated. Cultures did not recovered VRSA from the patient being treated with trimethoprim/sulfamethoxazole, successfully. Molecular analysis revealed the presence of the *vanA* gene from enterococci,

Cases of *S. aureus* with intermediate resistance to vancomycin (VISA) in addition to presenting heteroresistance are increasingly common in health centers where MRSA infections are treated with vancomycin (Trakulsomboon et al., 2001; Van Duijkeren et al.,

Kim et al. (2000) observed that the vancomycin-resistant strains showed changes in the cell wall due to selective pressure caused by prolonged use of vancomycin in the treatment of

which explains the resistance to glycopeptides, and *mecA* (Sievert et al., 2002).

production compared with vancomycin and nafcillin (Stevens et al., 2007).

combination of agents can be a successful alternative.

environments worldwide (Martins & Cunha et al., 2007).

of resistance to vancomycin (Hiramatsu, 1997).

**11. Vancomycin resistance** 

2005; Kim et al., 2000).

infections caused by MRSA. On the other hand, *in vitro* gene transfer of *vanA* resistance was observed from vancomycin-resistant *Enterococcus* strains to *S. aureus* (Sievert et al., 2002).

The detection of resistance is a matter of controversy. Some authors Defend the idea that the disk diffusion method may not be effective in detecting resistance to glycopeptides, particularly vancomycin (Kim et al., 2000; Walsh et al., 2001).

In San Francisco, USA, a patient with subsequent complications was initially diagnosed with MRSA susceptible to trimethoprim-sulfamethoxazole. A more accurate survey was conducted showing that the strain belonged to the PFGE USA 300-0114 of community origin and had intermediate resistance to vancomycin. This strain is closely related to infections of skin and soft tissues as well as lung disease. Surveillance in the United States in San Francisco shows an explosive increase of infections by USA300 CA-MRSA, can also replace other strains (Graber et al., 2007).
