Methicillin-Resistant Staphylococcus aureus: An Emerging Pathogen in Small Animals

Nosocomial Infections

Nosocomial infections are a tremendous problem in humans, and MRSA is one of the most important pathogens. Infection with MRSA is associated with increased morbidity and mortality.^21,22 Mortality rates of 50% for bloodstream infections and 33% for MRSA pneumonia have been reported.²³ People with MRSA infections tend to spend longer times in the hospital than other patients. It has been estimated that antimicrobial resistance results in an annual cost of $100 million to $30 billion (USD), as a consequence of poorer response to treatment, longer hospitalization, and the use of more expensive treatments.¹⁹ Even when controlled for underlying illness, MRSA infections result in higher treatment costs than equivalent methicillin-susceptible S. aureus infections.²³ One study reported an average additional cost of $14,000 (Canadian) per patient with MRSA infection and $1360 (Canadian) per colonized patient.²⁴

Community-Associated Infections

A concerning shift in the epidemiology of MRSA infection in humans has recently developed. Similar to the situation encountered with movement of penicillin resistance from hospitals to the community, MRSA appears to be emerging as an important community-associated pathogen.^25–27 Community-associated infections usually involve soft tissue, and bacteremia occurs less commonly, although fatal infections have been reported.^21,27

Initially, most community-associated MRSA infections involved humans with known risk factors, such as contact with health care facilities and previous antimicrobial therapy.^28,29 Strains associated with these infections were often referred to as “feral” strains, based on the assumption that they were hospital strains that had been carried into the community. More recent reports of community-associated MRSA have involved humans with no known risk factors, and the origin of infection was unclear.^26,30,31 The isolates in these latter cases tend to differ from typical nosocomial isolates. They often contain SCCmecIV, an uncommon type in nosocomial isolates, and they frequently produce Panton-Valentine leukocidin (PVL), an important virulence factor.^20,26,32,33 Because the SCCmecIV element is much smaller than other SCCmec types, it has been suggested that SCCmecIV may be more mobile and easily transferred to diverse community methicillin-susceptible S. aureus isolates.³⁴ This theory raises concern, because easy mobility could allow for further dissemination of MRSA in the community, with the creation of new MRSA strains from methicillin-susceptible strains. Community-associated MRSA isolates are sometimes more susceptible to antimicrobials, and in some cases they may be resistant only to the β-lactam antibiotics.³²

Identification and Sources of Isolates

A variety of typing methods can be used to compare MRSA isolates. Pulsed field gel electrophoresis is most commonly used, while sequencing of the X region of the protein a gene (spa typing) and typing of the SCCmec can provide additional information.^46,47 In both North America and Europe, most studies comparing small animal and human MRSA isolates have reported that small animal isolates correspond to recognized, common human isolates.^3,40,42 These results have led to the suspicion that most MRSA infections of household pets are of human origin, and that pets become infected from direct contact with colonized or affected humans. This finding is potentially important, because it suggests that animals might only be aberrantly affected with MRSA and may not be primary reservoirs of MRSA in the community.⁴⁸ If this supposition is true, the prevalence of carriage of MRSA by pets may remain low and directly reflect the prevalence (and type distribution) of MRSA in the human population. Additionally, if household pets are not primary hosts, then long-term colonization might be uncommon and animals would be a less important source of infection in households.

It may be premature to rely on the above conclusion, and changes in the epidemiology of MRSA may be encountered as increased exposure of animals from affected humans in the household occurs. Recent epidemiological analysis of MRSA colonization in horses revealed that one clone, which is uncommon in people, accounts for virtually all infected and colonized horses.⁴⁵ While most horses only carry MRSA for a relatively short period of time (i.e., weeks to months), some persistently colonized horses have been identified, and widespread transmission of MRSA from horses to humans and other horses has been documented.^a,b Therefore, it appears that a specific clone is adapted for horses, an event that has not been identified in other animal species, but requires further evaluation.

Prevalence

Overall, the prevalence of MRSA colonization in the general small animal population appears to be low. Murphy et al. reported no MRSA isolates from rectal swabs collected in a survey of 139 dogs and 39 cats from primary care veterinary clinics in Ontario.⁴⁹ Similarly, Hanselman et al. only isolated MRSA from one of 195 (0.5%) dogs upon admission to a veterinary teaching hospital,^c and Lefebvre et al. did not isolate MRSA from any of 102 dogs enrolled in human hospital visitation programs.^d These results further support the hypothesis that animals are most often directly infected by humans, as opposed to MRSA existing in a reservoir in the pet population. However, it must be remembered that MRSA may be an emerging pathogen in small animals and that the epidemiology may be changing.

Care of the Animal

The first factor that must be considered is whether infection or colonization is present. Clinical infection with MRSA almost always requires some form of treatment, although systemic antimicrobial therapy is not necessarily needed. Superficial infections such as uncomplicated wound or incisional infections may be treated topically with a variety of compounds, such as silver sulfadiazine, a combination of 1% silver sulfadiazine and 0.2% chlorhexidine digluconate, fusidic acid, mupirocin, or vancomycin.^51–54 Additionally, other compounds such as allicin (garlic extract) and tea tree oil have been investigated because of their anti-MRSA activity in vitro. Their in vivo effects are still undefined.^55–57 Topical chlorhexidine or 1% acetic acid has been used in combination with systemic antimicrobials in horses with MRSA incision infections; however, their efficacy is unclear. If topical therapy alone is chosen, animals should be monitored closely for progression of local disease or development of bacteremia and systemic disease.

In most situations, systemic antimicrobial therapy is required to treat MRSA infections. Because of the variability of MRSA isolates, standard recommendations for antimicrobial use are not practical. Rather, drug choices should be based on in vitro antimicrobial susceptibility testing in combination with other animal and drug factors (i.e., drug penetration, concentration at the site of infection, activity at the site of infection, drug interactions, etc.).

Not all MRSA isolates are highly drug resistant. In particular, some community-associated MRSA strains in humans may only be resistant to the β-lactam antimicrobials.³² It is critical to remember that commonly used antimicrobials can be highly effective if the isolate is sensitive in vitro and if the chosen drug is able to achieve therapeutic levels at the site of infection. Therefore, identification of an MRSA infection does not mean that the latest generation or most potent antimicrobials are required, particularly for infections that are not life threatening. High-level resistance to multiple classes of antimicrobial agents is not uncommon for MRSA isolates, however.^3,38 Frequently, MRSA isolates are resistant to all antimicrobials typically tested for in veterinary medicine. Any good diagnostic laboratory should offer expanded antimicrobial sensitivity testing when multiple drug-resistant pathogens are isolated, either routinely or upon request. An expanded panel should be requested for all MRSA isolates. Ideally, drugs that are important for treatment of critically ill humans should be avoided.

In veterinary medicine, the use of drugs such as vancomycin is controversial. The emergence of multiple drug-resistant pathogens like MRSA increases the pressure to use these drugs, which may result in further development of resistance. Increased scrutiny of antimicrobial use in veterinary practices is warranted. In situations where multiple drug-resistant pathogens are likely to be encountered (i.e., tertiary care referral centers), development of antimicrobial use guidelines is recommended. At the Ontario Veterinary College Veterinary Teaching Hospital (OVC-VTH), vancomycin use is restricted. Vancomycin may only be used in animals with life-threatening disease caused by a bacterium that is resistant to all other reasonable drug options and is susceptible to vancomycin in vitro. Its usage also must be approved by two designated members of the Infection Control Committee.

Despite the potential severity of MRSA infections, successful treatment is possible. Tomlin et al. reported improvement or resolution of MRSA infection with oral antimicrobial therapy in nine of 11 dogs.³⁸ If MRSA infections become more common, it will become increasingly important to emphasize submission of diagnostic samples prior to initiation of empirical antimicrobial therapy. Often, empirical therapy for wound and incisional infections involves use of β-lactam antimicrobials, which would be ineffective against MRSA.

The best approach to management of colonized pets is unclear. In humans, MRSA colonization is associated with an increased risk of MRSA infection in hospitalized patients.⁵⁸ This has also been demonstrated in hospitalized horses, but the risk to household pets is unclear, and further study is required.⁴⁵ In the absence of documented risk to the pet, eradication therapy is probably not warranted on a disease-prevention basis for healthy animals in the community because of the concerns about excessive antimicrobial use. However, risk to the colonized animal is not the only factor to consider. Colonized animals may be a source of infection to other animals, household members, veterinary personnel, or other human contacts. Colonized horses have been implicated in MRSA transmission to other horses and humans,^a,b but antimicrobial-based eradication therapy is not routinely used by the author; rather, infection control measures are used to reduce the risk of transmission.

Infection Control Precautions

Infection control protocols need to address three main areas: prevention of nosocomial MRSA infection and/or colonization of animals, management of individuals infected or colonized animals, and management of outbreaks. The greatest success in MRSA control in humans has been achieved through use of rigorous infection control protocols, including active surveillance to identify colonized patients and strict application of barrier protocols.⁵⁹ At the OVC-VTH, all horses are screened for nasal MRSA colonization at admission and are screened weekly during hospitalization and again at discharge. However, based on the current epidemiology of MRSA in household pets, it does not appear that active screening of all pets presented to veterinary clinics is practical or useful. Attention must be paid to trends in MRSA in animals to determine if, when, and how screening should be implemented. If risk factors for MRSA colonization or infection are identified, then selected screening may be useful.

All animals that are (or are suspected to be) infected or colonized with MRSA must be treated as infectious. They should be housed in an appropriate isolation area and restricted to that isolation unit unless emergency medical procedures are required. Barrier contact precautions (e.g., wearing gloves, gowns, or dedicated lab coats) should be used when handling animals or any in-contact items (i.e., bowls, bandages, etc.). It is important to remember that MRSA can be found in the veterinary hospital environment when infected animals are present.⁶⁰ The entire cage environment can be contaminated and should be considered infectious.

Following discharge, any cage items or medical equipment used on MRSA-infected animals must be disinfected or discarded. Most disinfectants are effective against MRSA as long as they are used properly. Disinfection must include appropriate dilution, adequate contact time, and precleaning so that organic debris does not inhibit disinfection. Certain items such as digital thermometers are very difficult to disinfect. Because MRSA can be carried in the rectum, disposable thermometer covers are recommended, or thermometers should be discarded after the animal is discharged.

Veterinary clinic personnel have been implicated in the transmission of MRSA to animals.^3,61 Human testing is an important component of an infection control program; however, liability, confidentiality, and occupational safety and health considerations must be addressed proactively. If, when, and how human testing is performed and what to do with colonized personnel should be considered prior to identification of MRSA-infected people. This preparation allows for a controlled, organized approach and provides the option of consulting relevant external parties (e.g., infection control specialists, physicians, Occupational Safety and Health Association agents, etc.).

The Centers for Disease Control and Prevention Guideline for Infection Control in Healthcare Personnel state that screening and treatment of personnel in human hospitals are indicated if there is epidemiological evidence linking personnel with infections.⁶² At the OVC-VTH, periodic or targeted surveillance of hospital personnel is performed as determined by the Infection Control Committee. To date, this screening has only involved large animal clinic personnel. Screening has been instituted based on identification of a cluster of equine infections with an indistinguishable subtype that suggests a common nosocomial source, for potential unprotected high-risk exposure of personnel to infected or colonized horses, or when human colonization is likely based on the number of infected or colonized horses in the hospital. The Occupational Health and Safety Department monitors treatment of colonized individuals and performs follow-up cultures. In addition, protocols are in place to restrict animal access to personnel that refuse to undergo eradication therapy or where eradication therapy has not been successful and the person is a suspected source of animal infection.

Client Communication

Because MRSA may be transmitted between animals and people in the household, owners of infected or colonized animals should be informed of this potential and counseled about measures to reduce the risk of transmission. For the average healthy person, there is probably minimal risk of disease from routine contact with an infected or colonized animal. However, reports of community-associated MRSA infection in immunocompetent people are on the rise, and clinical infection in people working with infected horses has occurred.^{25,31,32,63,c}

Contact with an infected or colonized animal may be of particular concern, particularly when high-risk (i.e., immunocompromised) individuals are in the household, or when household members are in contact with high-risk people (i.e., healthcare workers). In these situations, additional measures may be required and may include hospitalization of animals until MRSA has been eliminated, use of enhanced infection control protocols in the house, or restriction of animal contact with certain individuals. Involvement of physicians, particularly infection control or infectious disease specialists, is prudent, because veterinarians should not make specific recommendations for prevention or diagnosis of disease in humans. Testing of household members may be appropriate in certain circumstances, as directed by physicians or public health personnel. Unfortunately, awareness of animals as reservoirs of MRSA infection is not widespread in the medical community, and the emergence of MRSA infection in animals highlights the need for better communication and cooperation between the veterinary and human medical fields.