Control of Methicillin-Resistant Staphylococcus aureus (MRSA) in Clinics & the Community
ACVIM 2008
J. Scott Weese, DVM, DVSc, DACVIM
Guelph, ON, Canada

Introduction

Staphylococcus aureus is a gram-positive opportunistic pathogen that is part of the commensal microflora in many species, including horses. As an opportunist, S. aureus can reside in or on a host without any apparent problems, however infections can occur in certain situations. One problematic aspect of S. aureus is its tendency to develop or acquire resistance to antimicrobials. Penicillin-resistant S. aureus was identified shortly after widespread use of penicillin in humans; first in hospitals, then in the general population. This resistance was mediated through beta-lactamase production, so antimicrobials that were resistant to the effects of beta-lactamase (i.e., methicillin) were developed. However, methicillin-resistant S. aureus (MRSA) emerged in humans shortly thereafter. The mechanism of resistance in MRSA is production of an altered penicillin binding protein, which renders S. aureus not only resistant to methicillin, but to all beta-lactam antimicrobials. MRSA strains are frequently resistant to various other antimicrobial classes and treatment options may be very limited. MRSA became a tremendous problem in human hospitals in the 1980's and 1990's, and is now a critically important cause of infections in both hospitals and the community. It has recently been estimated that over 94000 invasive MRSA infections occurred in the US in 2005,1 with unknown numbers of superficial infections. Similar to the pattern with penicillin resistance, MRSA eventually spread into people in the community, and community-associated MRSA is now a critically important problem in humans.2

Perhaps not co-incidentally, as MRSA rates in people in the community began to rise, MRSA infections were identified in domestic animals. Initial reports of MRSA infections in horses were case reports or case series,3,4 with the thought that equine MRSA was an aberrant and uncommon effect of direct infection of horses by colonized personnel. While there were anecdotal reports of further MRSA infections at equine hospitals, including outbreaks, a few years passed before there were reports of larger numbers of affected animals.5 Identification of larger numbers of affected animals, colonized horses (those carrying MRSA with no clinical signs) and transmission of MRSA between horses and humans led to a re-assessment of initial interpretations. These later studies reported MRSA infection and colonization in large numbers of horses, both in veterinary hospitals and in the community internationally6-10 and it is likely that MRSA is endemic in the horse population internationally. Colonization rates of 0-4.7% of horses have been reported in community-based prevalence studies5-8,11-13 but MRSA can cluster on farms, where the prevalence can approach or exceed 50%.6,14 People that have contact with horses, including equine veterinarians, also have rather high rates of MRSA colonization compared to the general population.15,16 The MRSA types that are found in these individuals tend to be strains commonly found in horses versus common human community or hospital strains, supporting horses as a possible source of infection. It is apparent MRSA can be transmitted between humans and horses, in both directions.

An interesting aspect of equine MRSA is the predominance of one clone. The clone, termed USA500 or Canadian epidemic MRSA-5 (CMRSA-5) is a recognized human epidemic clone that is uncommon in people but accounts for the vast majority of MRSA isolated from horses (and horse personnel) in North America. The disproportionate prevalence in horses and humans suggests that this strain is more adept at colonizing and/or infecting horses than other strains. The same strain, or closely related strains, has also been identified in Europe. This clone is of sequence type 8, possesses SCCmecIV, does not carry genes encoding for Panton-Valentine leukocidin (PVL) production and is multidrug resistant. The reason that this strain appears to be predominant in horses while relatively rare in humans, despite being a human-origin strain, is unclear.

Control: General

Control of MRSA infection and colonization are controversial topics in human medicine, and widely varied approaches are taken, ranging from minimal effort to aggressive 'search and destroy' programs. Little specific, objective information is available for MRSA control in horses. While information from human medicine is useful, extrapolation to the veterinary situation should be performed with care because of potential differences in the epidemiology of disease, particularly the prevalence of colonization, dynamics of colonization and shedding, types of contacts between horses and between horses and people, and duration of colonization.

One important factor for control is the observation that lifelong colonization may not be a concern in horses as it is in some humans. Persistent colonization has not yet been reported in horses, and most horses appear eliminate MRSA colonization within weeks if re-infection is prevented.14 This is an encouraging finding, and if it is confirmed with further studies, this may be an important factor for MRSA control.

In humans, antimicrobials such as topical mupirocin are often used for decolonization therapy, yet this approach is controversial because of variable efficacy and concerns about development of further antimicrobial resistance. When trying to control MRSA on a farm or in a clinic, active measures to eradicate MRSA are tempting but there is currently no information indicating that antimicrobials can eliminate MRSA colonization in horses. In general, it is difficult to eliminate commensal microorganisms from their ecological niche with systemic antimicrobials. Topical antimicrobials are not a practical solution because it is difficult if not impossible to adequately cover the nasal passages of a horse with antimicrobials. This, combined with the apparent ability of horses to eradicate MRSA naturally, suggests that there is no indication for active decolonization therapy in horses.

MRSA Control in Equine Hospitals

Identification of potentially infectious horses is a critical component of equine MRSA control. For horse with clinical infections, this requires submission of appropriate diagnostic culture specimens and proper laboratory techniques. There is variability in the quality of staphylococcal identification and testing amongst commercial diagnostic labs. Many provide excellent testing using rigorous quality control and follow standard (CLSI) guidelines. However, some labs (including large commercial labs) still inadequately identify staphylococci and may not perform proper testing for methicillin-resistance. Consistency in diagnostic testing is an area that requires improvement.

Even if all MRSA infections are identified, the number of colonized horses probably greatly exceeds the number of infected horses, and this large and 'silent' pool of MRSA could pose a significant risk. MRSA screening for colonized individuals is an important component of MRSA control in human hospitals and may be useful in equine hospitals depending on the 'infection pressure' in the population, the type of caseload, established infection control activities and risk adversity of administrators. Active screening of all horses at admission, weekly during hospitalization and at the time of discharge is performed at the Ontario Veterinary College Veterinary Teaching Hospital (OVC-VTH).7 This allows for earlier identification and isolation of colonized horses, facilitates identification of farms with high MRSA rates for increased scrutiny or assistance with farm-based eradication and helps differentiate hospital- versus community-origin of infections. While objective evidence is lacking, it is believed that this aggressive screening program is a major reason why MRSA rates have dramatically declined that this facility despite continued identification of MRSA in horses in the community. Currently, MRSA screening involves culture of nasal swabs. Objective comparison of screening sites has not been published however unpublished data indicate that the anterior nares are the most common and consistent site of colonization in horses. An inherent limitation of culture is the time required, and the delay from screening sample collection to receipt of results was implicated as a contributing factor in an outbreak of zoonotic MRSA infections in neonatal foal personnel.17 Molecular methods such as real time PCR are increasingly being used in humans for more rapid testing, however a recent study of a real time PCR assay used in humans reported significant problems when used in horses.8 This indicates that equine-specific validation of testing methods is required.

Once infected, or potentially infected, horses are identified, protocols must be in place to reduce the risk of transmission. All horses that are infected or colonized should be considered infectious and handled appropriately. This typically involves isolation and use of contact precautions. Because the nose is the prime site of MRSA colonization, any items that have come into contact with the nose (i.e., buckets, hay nets, twitches) should be considered infectious and handled appropriately. Environmental contamination with MRSA has been reported in an equine hospital,18 but the environment is an unlikely source of infection. Routine cleaning and disinfection practices, if used properly, should be adequate to eliminate MRSA in the environment. Good personal hygiene, especially hand hygiene, should further reduce the potential impact of environmental MRSA.

It is clear that equine veterinary personnel have high rates of MRSA colonization, which is of concern for patient health and occupational health. At this point, there is no evidence suggesting that equine hospital personnel should be routinely screened for MRSA colonization. Because 10-15% of personnel may be colonized at any given point, routine infection control protocols should be implemented to greatly reduce the risk of MRSA transmission even if many hospital personnel are colonized. Essentially, one should assume that multiple veterinary personnel are colonized at any given time and develop protocols to limit the risk of transmission. Individuals with persistent MRSA colonization have worked in equine hospitals with no evidence of any transmission to horses when good infection control practices were used (JS Weese, unpublished data). However, it is reasonable to develop contingencies to screen hospital personnel in certain situations. The OVC-VTH uses criteria similar to CDC recommendations for human healthcare centres whereby screening is only considered when there is epidemiological evidence of personnel-borne transmission and transmission persists despite proper application of enhanced infection control precautions. At the OVC-VTH, such screening is voluntary, individual results are not provided to anyone beyond the person's healthcare provider and there are no restrictions on job activities or status based on screening results.

Control of MRSA On Farms

The approach to MRSA control on individual farms depends on various factors including the risk of exposure and risk adversity of owners. Control programs can range from nothing more than good farm management and general infection control precautions to aggressive MRSA surveillance ('search and destroy'). As with most aspects of infection control, there is not a standard MRSA control program that should be applied in all situations, so farm personnel and veterinarians must work together to develop protocols approach for each facility.

General infection control practices including good hand hygiene, cohorting of different risk groups, isolation of new animals, prudent antimicrobial use and submitting culture specimens whenever bacterial infections are suspected are a critical aspect. MRSA-specific measures that could be used include active MRSA screening of all new animals and period screening of resident horses. Infected or colonized horses should be isolated and handled with barrier precautions until colonization has been eliminated. Periodic (every few weeks) re-culture of the nares should be performed and while objective data are lacking, the author currently considers two negative nasal screening swabs to indicate negative MRSA status, as long as proper laboratory practices are used. There is currently no indication that routine screening of farm personnel is warranted from an infection control standpoint, and personnel screening raises many complex issues involving occupational health, liability and medical privacy.

When an MRSA infection is identified on a farm, it often represents the 'tip of the iceberg' as many other horses may already be colonized. Identification of MRSA on a farm should trigger a discussion of whether there is a need and desire to try to eradicate MRSA on the farm. Infection control-based eradication has been successful,14 however specific components have not been evaluated, so it is impossible to say what, if any, of the described components are most useful. Briefly, infection control practices include screening of horses, cohorting of colonized and non-colonized horses, isolation of colonized horses, improvement in hygiene practices (particularly hand hygiene), cohorting of horse personnel whenever possible so that people working with colonized horses do not work with non-colonized horses, prevention of cross-contamination of items and repeated screening of horses with movement of previously colonized horses into an intermediate area while awaiting a repeated negative swab. Further objective study of eradication methods is needed.

Conclusions

While still uncommon, MRSA appears to be well on its way to becoming widely disseminated in the horse population. Because of the ability of MRSA to colonize horses without producing clinical signs, passive control of MRSA will be less rewarding than active programs designed to identify carriers and reduce the risk of transmission. Better means to control MRSA, both in clinical situations and at the population level, are required. However, given the rapid advances in the knowledge about MRSA in horses over the past few years, there is reason to be optimistic that the impact of MRSA on the horse population, and the accompanying public health risks, can be controlled. To achieve this, the field of veterinary MRSA research must continue to advance to further characterize the emergence of this concerning pathogen in horses and horse personnel, and to objectively evaluate treatment, prevention and infection control measures.

References

1.  Klevens et al. J Am Med Assoc 2007;298:1763,

2.  Tenover et al. J Clin Microbiol 2006;44:108,

3.  Hartmann et al. J Am Vet Med Assoc 1997;211:590,

4.  Seguin et al. J Clin Microbiol 1999;37:1459,

5.  Weese et al. Emerg Infect Dis 2005;11:430,

6.  Weese et al. J Am Vet Med Assoc 2005; 226:580,

7.  Weese et al. J Vet Int Med 2006;20:182,

8.  Anderson et al. Vet Microbiol 2007;122:185,

9.  Cuny et al. Euro Surveill 2006;11:44,

10. O'Mahony et al. Vet Microbiol 2005;109:285,

11. Vengust et al. Lett Appl Microbiol 2006;43:602,

12. Baptiste et al. Emerg Infect Dis 2005;11:1942,

13. Busscher et al. Vet Microbiol 2006;113:131,

14. Weese et al. Equine Vet J 2005;37:510,

15. Hanselman et al. Emerg Infect Dis 2006;12:1933,

16. Anderson et al. Vet Microbiol, ePub ahead of print,

17. Weese et al. Vet Microbiol 2006;114:160,

18. Weese et al. J Vet Int Med 2004;18:468.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

J. Scott Weese, DVSc, DACVIM
University of Guelph
Guelph, ON, Canada


SAID=27