Methicillin-resistant staphyloccocus aureaus (MRSA) (Proceedings)

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a major human health concern has heightened awareness of the occurrence of this agent in companion animals, including horses. The purpose of this presentation is to review what basic knowledge equine practitioners should have regarding MRSA and other methicillin-resistant staphylococcal species in horses.

There are numerous species of Staphylococcus. All are Gram-positive and catalase-positive. Most of the pathogenic species are coagulase-positive, including S. aureus. S. aureus is a commensal organism that colonizes the skin, mucous membranes, gastrointestinal tract, and urogenital tract of approximately ⅓ of humans. In domestic animals, other species of coagulase-positive staphylococci are the predominant commensal organisms. Infection with staphylococcus outside of their normal commensal niche can result in pathology. From a historical perspective, it is worth remembering that S. aureus infections were associated with high rates of disease and death.

Bacteria can either be intrinsically resistant to 1 or more antimicrobials, or can acquire resistance via genetic changes.6 Genetic changes can occur through spontaneous mutation or by acquisition of resistance genes from other organisms. Genes can be acquired by conjugation, transduction by bacteriophages, or transformation (i.e., acquiring and incorporating DNA from other lysed bacteria). Resistance to penicillin and other β-lactam antibiotics can occur from intrinsic and acquired mechanisms. Some staphylococci can produce β-lactamases that destroy the β-lactam ring and consequently the ability of penicillin to bind to a transpeptidase thereby interfering with bacterial cell-wall synthesis. Resistance to methicillin occurs by a different mechanism. MRSA have acquired a mobile genetic element known as the staphylococcal cassette chromosome mec (SCCmec), which includes a gene known as mecA. The mecA gene encodes for an altered penicillin-binding protein that has lower affinity for β-lactam antibiotics, thereby rendering mecA-carrying isolates resistant to methicillin and other β-lactam antibiotics. The SCCmec can be transferred horizontally among staphylococci. Moreover, it also can accept other antimicrobial resistance genes, such that many methicillin-resistant Staphylococcus species (including MRSA) also are resistant to other organisms.3 Coagulase-positive staphyloccoci (CPS) other than MRSA are rare in horses, unlike dogs where methicillin-resistant Staph. intermedius/pseudintermedius are an important pathogen. Horses are commonly colonized by coagulase-negative staphylococci (CNS). These isolates can be mecA-positive. The significance of mecA-positive CNS in horses is unknown, but they might cause infection and can serve as a reservoir of the gene for CPS. Isolates of MRSA are not necessarily more pathogenic than methicillin-susceptible Staph. aureus. The principal concerns with MRSA are the potential for human infection from horses and nosocomial infection.

DIAGNOSIS:

Staphylococci are not routinely tested for methicillin. Rather, they are tested for susceptibility with either oxacillin or cefoxitin. The Clinical and Laboratory Standards Institute recommends that staphylococci be tested with the cefoxitin disk test, the latex agglutination test for the penicillin binding protein 2a (PBP2a, encoded by the mecA gene), or a plate containing 6 µg/ml of oxacillin in modified Mueller-Hinton agar. Some laboratories use a combination of these screening tests. In addition, a polymerase chain reaction (PCR) test for the mecA gene can be performed. The PCR test is considered most accurate because there are some subpopulations of MRSA that carry but don't express the mecA gene. It is important, however, that culture as well as PCR be performed because there can be other CPS and CNS that carry the mecA gene.

MRSA IN HORSES:

The first report of isolation of MRSA in horses described 13 mares with metritis from Japan that had identical genotype using pulsed-field gel electrophoresis. Since then, MRSA also has been isolated from horses in Europe and North America.11-18 In one study, 9 of 65 Staph. aureus infections at veterinary teaching hospitals in North America were MRSA, and 4 of these 9 were from horses.

The reported prevalence of colonization of MRSA in horses has varied. One study in Atlantic Canada failed to detect MRSA among 497 horses. In contrast, Weese et al. found colonization in approximately 5% of horses at a veterinary teaching hospital and horse farms in Ontario, Canada.

In western Canada, prevalence of colonization of 458 horses was a little more than 1%.Recently, MRSA was isolates from nearly 11% of horses admitted to a Belgian equine hospital, 5% of horses in Ireland (including 2% of healthy horses), 2% of horses admitted to a teaching hospital in Switzerland.23 Thus, it appears that nasal carriage in horses varies from between ~1% and 10%. Molecular typing of isolates has been performed. In North America, most isolates have been of genotypes isolated rarely from humans. In Europe, isolates have been primarily of types associated with livestock origin.

Risk factors for colonization with MRSA from a Canadian study include previous colonization of the horse, presence of colonized horses at the farm, admission to the neonatal ICU, administration to a servive other than surgery, and antimicrobial administration within 30 days prior to admission.16 Although colonized or infected animals are likely the most important reservoir of the organism, evidence exists that the environment and fomites at clinics can serves as reservoirs for MRSA.24 Among 115 horses from 6 veterinary teaching hospitals in North America, surgical site infections represented 38% of all MRSA infections.17 Failure of MRSA-infected horses to survive was significantly associated with IV catheterization, community-acquired MRSA, and disseminated infection.17

Clinical management, including control, varies by whether one is concerned with colonized horses or infected horses. For colonized horses, uncontrolled observations from a Canadian study suggest that infection control measures (principally contact-isolation and hand hygiene) were successful in eliminating nearly all colonized horses without use of antimicrobials.25 Colonization of horses in North America is usually of the Canadian MRSA-5 (CMRSA-5) type. It is unclear whether colonization with other strains would respond similarly. Treatment of colonized horses with antimicrobials should be restricted to horses with persistent colonization and for which infection control measures either cannot be implemented or have failed.4 Although many antimicrobials commonly used in horses may be effective in vitro against MRSA, the clinical efficacy of antimicrobials for eliminating persistent colonization in horses remains unknown. The efficacy of topical antimicrobials for eliminating nasal carriage also has not been examined in horses.

Because MRSA infections can pose a clinical challenge and because they are frequently associated with surgical wounds,17 it is important to perform microbiologic culture of post-operative wound infections. Culture also is recommended for non-healing wounds and infections that do not respond to antimicrobials.4 Delayed recognition of MRSA can compromise case management of individuals and delay identification of outbreaks.26 Non-antimicrobial options for MRSA include antiseptics such as glycerol, chlorhexidine, or povidone iodine.4 Antimicrobial treatment of MRSA infections should be guided by antimicrobial susceptibility testing. As previously stated, many MRSA isolates from horses are susceptible in vitro to many antimicrobials commonly used in equine practice; however, clinical data are lacking. Treatment with antimicrobials that are vital for therapy of human MRSA cases such as vancomycin or linezolid should be avoided because of ethical considerations.

Consistent with recommendations for small animals,27 It is recommended that MRSA-infected horses be isolated to their stalls to minimize nosocomial and zoonotic transmission. At our clinic, we recommend barrier precautions for handling horses (wearing gowns, gloves, and boot covers that are not worn elsewhere and are disinfected or properly disposed after use). Persons handling infected horses must use caution to avoid contaminating themselves by contact. All items that contact an infected horse should be considered to be potentially contaminated.4 Hand hygiene is considered of principal concern because evidence exists that this is an important mode of transmission of MRSA. Alcohol-based hand sanitizers (ABHS) are effective against MRSA. Either an ABHS or hand-washing with soap should be carried out between contact with patients irrespective of whether gloves have been worn. Owners of MRSA-colonized or –infected horses must be informed and advised about precautions to be taken. This should include advising that they consult their physician and follow recommendations for preventing spread by using barrier precautions and hand hygiene.

RISKS OF HUMAN-HORSE CONTACT:

Occupational and recreational use of horses has been associated with human colonization.28 Veterinarians, in particular equine practitioners, are at increased risk for being colonized.3,4,11,18,28,29 Risk of colonization is significantly increased among persons having treated a horse with MRSA.29 MRSA isolates from people working with horses are similar to each other and differ from MRSA isolates from the general human population.3,4,11-18,20 During an outbreak of MRSA at a veterinary hospital, those in close contact with horses were more likely to be infected than those without.29 Thus, people can infect horses by contact and vice versa.

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