**10. Current antimicrobial drug choice**

Given the great potential of CA-MRSA infections to develop into serious and/or systemic infections, there is an interest in reintroducing drugs such as trimethoprim/ sulfamethoxazole, tetracycline and clindamycin for treatment of CA-MRSA. In severe cases where there is need for hospitalization and intravenous therapy, antibiotics such as vancomycin, linezolid and daptomycin are reliable options (LaPlante et al., 2008).

The combination of trimethoprim/sulfamethoxazole (cotrimoxazole) has been considered a good therapeutic option for the treatment of patients affected by CA-MRSA. *In vitro* tests show that it has excellent bactericidal activity, but its activity can be reduced in the presence of rifampicin. Several antimicrobial combinations were tested, such as linezolid and cotrimoxazole, rifampicin,. Cotrimoxazole, minocycline, linezolid, clindamycin or moxifloxacin, cotrimoxazole alone proved to be more effective in *in vitro* tests (Kaka et al., 2006).

However, in another study with patients affected by CA-MRSA treated with trimethoprim/sulfamethoxazole, clindamycin and cephalexin resulted in a treatment failure rate of 26%, 25% and 33%, respectively. In addition, patients who received the drainage of abscesses in addition to antibiotic therapy had lower rates of treatment failure (25%) than patients who received only incision and drainage (60%) (Frei et al., 2010).

One of the main strains in the community, the USA300 had plasmid-mediated resistance to tetracycline, clindamycin, and mupirocin (Han et al., 2007). In addition, there is the possibility of clindamycin inducible resistant strains resulting in treatment failure. In places where there is high frequency of isolation of strains with this characteristic, it is necessary to choose alternative treatments. It is estimated that this phenomenon occurs in approximately 13% of CA-MRSA strains (LaPlante et al., 2007) and from 36% to 56% of HA-MRSA (Siberry et al., 2003). The treatment of clindamycin-sensitive strains was assessed showing that the best options were daptomycin, clindamycin, doxycycline, vancomycin, linezolid and trimethoprim/sulfamethoxazole, respectively, with the latter three being equally effective. Treatment with daptomycin was better than vancomycin and linezolid, the latter two having equal effect, but all three overcame the effects of clindamycin since these strains can show induced resistance and the treatment with clindamycin also induces the emergence of constitutive resistance (LaPlante et al., 2008).

CA-MRSA: Epidemiology of a Pathogen of a Great Concern 69

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,

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

Coagulase-negative staphylococci (CoNS) are part of the microbiota of the skin, most often presenting a benign relationship with the host. However, they are the major opportunistic pathogens of immunocompromised patients in hospitals (Bisno & Stevens, 1996; Cunha et al., 2004). Important infectious processes related to CoNS have been reported in recent decades. They are commonly isolated from blood cultures of patients undergoing invasive procedures such as prostheses, catheters, organ transplants, as well as from premature

The main species of CoNS that are involved in infections in humans are *S. epidermidis* (may cause bacteremia, osteomyelitis, peritonitis, surgical site infections, infections due to the installation of catheters and prostheses, endophthalmitis, etc.), *S. haemolyticus* (urinary tract infection, peritonitis, injuries, etc.) and *S. saprophyticus* (urinary tract infection and septicemia) (Cunha et al., 2004). Specifically regarded to the occurrence of bacteremia in hospitals, the species *S. epidermidis* was found to be the etiologic agent in 80% of cases

Resistance to methicillin in species of CoNS (MRSCoN) colonizing healthy individuals can overcome MRSA in the same population as demonstrated by a Japanese study (Hisato et al., 2005). Analysis of 818 children revealed that 35 (4.3%) carried MRSA, while 231 (28.2%) MRSCoN. The fact that MRSCoN strains are prevalent in the community suggests that they are important reservoirs of SCC*mec* that can be carried to strains of *S. aureus*

Strains of vancomycin-resistant CoNS are common in hospitals due to this antibiotics' selective pressure in this environment, but few studies have been published on this community. A surveillance study assessed the cultures of saliva collected from employees of a private school and 37 hospital staff. The identification of specimens recovered from samples revealed that 98.5% were carriers of *Staphylococcus spp.* and 76.5% were carriers of more than one *Staphylococcus* spp. species. Four strains were resistant to vancomycin according to phenotypic tests isolated from two school officials and two hospital employees, and two identified as *S. capitis* and the other two as *S. haemolyticus* and *S. epidermidis.* All samples carried the *mecA* gene of resistance to oxacillin and were negative for the genes

particularly vancomycin (Kim et al., 2000; Walsh et al., 2001).

other strains (Graber et al., 2007).

infants (Cunha et al., 2004).

(Gongora-Rubio et al., 1997).

(Hisato et al., 2005).

**12. Resistance in** *Staphylococcus* **spp.**

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 combination of agents can be a successful alternative.

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