Staphylococcus aureus is part of the normal flora of the skin, mucous membranes, urogenital tract, and alimentary tract of people, while Staphylococcus intermedius is the more common mucosal Staphylococcus spp. recovered from pets (although recent evidence suggests that the staphylococci cultured from pets may be more correctly identified as S. pseudointermedius). Methicillin-resistant Staphylococcus aureus (MRSA) is S. aureus that has acquired the mecA gene, which encodes for an altered protein (referred to as PBP2a), and is involved in cell wall peptidoglycan synthesis. It is expressed in the bacterial cell wall and has a low affinity for β-lactam antimicrobials. MRSA is, therefore, resistant to β-lactam antimicrobials in addition to a variety of other antimicrobials.

The host animal is considered colonized when staphylococci are part of the normal flora. Infection occurs only when the bacteria are found outside of their normal niche and are associated with tissue inflammation and pathogenic changes. Infection with S. aureus and MRSA may cause significant morbidity and mortality, whereas colonization usually does not. However, people colonized by MRSA are at a much higher risk of developing MRSA infection in certain situations. A recent study that evaluated colonization with MRSA in people associated a four-fold increase in the risk of infection with MRSA. Colonized pets may serve as a reservoir source of infection for people or animals within the household.

Increasingly, S. aureus isolates have been found that are resistant to previously effective antimicrobial drugs. Methicillin-resistant bacterial strains were discovered in 1961 and throughout the 1970s, and MRSA emerged as a serious problem in the United States. By the 1990s, MRSA was identified as a major problem in nosocomial (i.e., hospital-acquired) infections in people along with other multidrug-resistant organisms such as vancomycin-resistant enterococci (VRE). Subsequently, vancomycin-resistant S. aureus strains have been identified. Most recently, MRSA infections have become common outside hospital and institutional healthcare settings. These infections are referred to as community-associated or community-acquired MRSA (CA-MRSA), as opposed to healthcare-associated strains (HA-MRSA).

Infections with HA-MRSA or CA-MRSA can cause skin and soft tissue lesions, life-threatening necrotizing fasciitis, necrotizing pneumonia, and sepsis. Fatal cases of both HA- and CA-MRSA have been reported, even in people without known risk factors. The mortality rate is higher for invasive MRSA infections such as bloodstream infections (50 percent) and pneumonia (33 percent) than for simple skin lesions. Risk factors associated with developing a clinical infection in people include prolonged antimicrobial therapy, surgery, prolonged hospitalization, trauma, concurrent infection, skin lesions, treatment in an intensive care unit, and close proximity to other patients infected or colonized with MRSA.

Clinical infections in animals are similar to those reported in people. The prevalent risk factors in animals are largely unknown although they are suspected to be similar. The most common types of MRSA infections in small animals are postoperative and wound infections. Intravenous catheter infections, urinary tract infections, pneumonia, and skin infections are less common. There is no way to clinically distinguish methicillin-resistant S. aureus from methicillin-susceptible S. aureus skin infections in dogs and cats. Superficial pyoderma may present as pustules, epidermal collarettes, papules, patchy alopecia, or superficial spreading pyoderma, whereas deep pyoderma typically manifests as furuncles, nodules, or draining tracts.