What you need to know regarding methicillin-resistant Staphylococcus aureus (MRSA)

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).

In general, HA-MRSA strains are more multi-drug resistant than CA-MRSA strains. In addition to the β-lactams, HA-MRSA and CA-MRSA strains are frequently resistant to erythromycin; HA-MRSA strains are frequently and CA-MRSA are occasionally resistant to clindamycin, and there is recently an increased likelihood of resistance to fluoroquinolones in both types of MRSA. HA-MRSA strains are also frequently resistant to aminoglycosides and tetracyclines. In animals, a high-level resistance to mupirocin and variable resistance to erythromycin, fluoroquinolones, and inducible resistance to clindamycin have been reported.

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.

Diagnosis

Clinical diagnosis of MRSA infection involves isolation of S. aureus that is resistant to oxacillin from an infected body site. Microbiological analysis samples should be collected from pets with nonhealing wounds and nonantibiotic-responsive or nosocomial infections. In veterinary medicine, it is important for laboratories to differentiate S. aureus from S. intermedius since S. intermedius is more common in dogs and cats. Although methicillin-resistant S. intermedius has been reported in both animals and people, it rarely poses a public health threat. The Clinical and Laboratory Standards Institute (CLSI) recommends the use of the cefoxitin disk diffusion test, the PBP2a latex agglutination test, or a plate containing 6µg/ml of oxacillin in Mueller-Hinton agar supplemented with sodium chloride to screen for MRSA. Polymerase chain reaction (PCR) may also be used to detect the presence of mecA to confirm that S. aureus isolates are indeed MRSA.

Prevention

While there is a wealth of literature dealing with the control and prevention of MRSA transmission in people, there is very little corresponding information regarding animals. Hand hygiene is an integral part of preventing the spread of MRSA between people, and it's likely to be an integral part of controlling the spread between people and animals or between animals through people. After contact with any hospitalized person or any animal, hands should be washed thoroughly. Alcohol-based hand sanitizers are also effective as recommended. Strict attention to cleaning and disinfection of animal contact areas may discourage colonization or infection. Designated instruments such as thermometers, leashes, and collars may be used for those animals suspected of having MRSA infection or colonization. Since MRSA is carried in the rectum, disposable thermometer covers are recommended. Barrier nursing precautions, such as wearing gloves, disposable clothing or clothing that can be appropriately laundered, and using protective masks and eyewear are advocated when in contact with wounds or other body fluids that may be infected with MRSA. Within a colonized or infected pet's household, restricting high-risk contact (e.g., mucosal-to-mucosal contact) is indicated, in addition to preventing contact of colonized animals with high-risk people, such as those with a compromised immune system. Although there is no direct data to support it, avoiding close contact, such as sleeping on the same bed or sitting in the lap when either the pet or the person has a known MRSA infection, seems reasonable. Individual veterinary hospitals may choose to screen incoming cases for infection or colonization at the time of admission. A similar screening process is used in some, but not all, human hospitals. Where strictly enforced, such screening programs have dramatically cut the incidence of MRSA infection. If a colonized or infected animal is identified, quarantine may be performed either throughout hospitalization or at least until a negative culture status is achieved. Additionally, once admitted, all suspect cases of MRSA infection may be quarantined and nursed using barrier nursing precautions. At the Ontario Veterinary College, specific guidelines for suspected MRSA-infected patients are enforced. When arriving at the veterinary hospital, the animal with suspected or confirmed MRSA must wait in the car until the owner has checked in. Then, the animal is immediately taken to a consultation room. After discharge, all cage items, examination rooms, and medical equipment are disinfected. If appropriately used, disinfectants effective against other staphylococci are most likely also effective against MRSA.

Treatment

Treatment of infections in animals should be based on in vitro culture and sensitivity results in combination with patient and drug factors, such as concentration at the site of infection and drug penetration. Treatment success for skin infections also depends on the identification and treatment of any underlying dermatoses such as allergies, autoimmune disease, endocrinopathies, and keratinization defects.

Based on antibiotic therapy of MRSA in people, a reasonable choice for initial treatment of pets with suspected MRSA would be trimethoprim sulfonamide drugs. Resistance can emerge quickly to fluoroquinolones, making them a poor first option for therapy. While clindamycin susceptibility is commonly identified in vitro, inducible resistance may be present with certain MRSA isolates (especially those that are erythromycin-resistant). Therefore, in erythromycin-resistant strains, clindamycin should be avoided unless testing for inducible resistance has been performed. Ideally, antimicrobials such as vancomycin that are used in critically ill people should be avoided unless the animal has a life-threatening infection that is resistant to all other treatments. Some superficial infections may be treated topically with antimicrobials or antiseptics. Topical agents may be used for wounds or skin infections and may include silver sulfadiazine, fusidic acid, mupirocin, or a combination of 1 percent silver sulfadiazine and 0.2 percent chlorhexidine gluconate. Other topical treatments to consider include chlorhexidine alone, 1 percent acetic acid, allicin (garlic extract), and tea tree oil.

Superficial pyoderma in dogs should be treated for a minimum of three weeks (at least one week beyond clinical resolution) and deep pyoderma should be treated for a minimum of six weeks (at least two weeks beyond clinical resolution). Some infections of deep interdigital pyoderma or acral lick granulomas may require therapy for three months or longer. For best results, bacterial culture and sensitivity testing should be performed at the start of therapy and owners should be counseled to finish the entire course of antibiotic therapy.

Successful treatment of MRSA infection is possible, but depends upon early recognition, appropriate antibiotic usage (including correct dosage and duration), and identification and treatment of underlying dermatologic conditions. In general, knowledge of MRSA is extremely relevant for veterinarians who are called upon not only to attend to animal diseases, but also to aid in prevention of zoonoses.