Methicillin-resistant Staphylococcus infections in veterinary medicine (Proceedings)

• Recognize that methicillin-resistant Staphylococcus (MRS) infections are being increasingly identified in veterinary medicine.

• Understand how MRS infections are transmitted, diagnosed, and treated.

• Be prepared to develop plans for managing animals infected with MRS.

• Be prepared to respond to concerns of staff about exposure to MRS-infected animals or about working while infected with MRS.

• Be prepared to respond to client questions and concerns about the role of animals in the epidemiology of MRS infections in human beings.

Methicillin-resistant Staphylococcus infections have been a concern in human medicine since the first healthcare-associated MR Staphylococcus aureus (HA-MRSA) infections were reported in human beings in 1961. The incidence of HA MRSA in human hospitals has increased markedly in the past 10 years. The CDC reports that the proportion of HA staphylococcal infections due to MRSA was 2% of S. aureus infections in U.S. intensive-care units in 1974, 22% in 1995, and 64% in 2004. HA-MRSA may be highly invasive, and may be resistant to multiple antibiotics.

Community-associated MRSA (CA-MRSA) were first recognized in 1981, and the incidence of CA-MRSA infections in people has recently increased. In 2004, approximately 76% of purulent skin and soft tissue infections (SSTIs) in adults seen in 11 emergency departments were caused by S. aureus. Of these infections, 78% were caused by MRSA and overall, MRSA caused 59% of all SSTIs. Until recently, most CA-MRSA have not been considered highly invasive, and not as likely as HA-MRSA to be resistant to multiple types of antibiotics.

The epidemiology of human MRSA infections is changing. The most current information indicates that the most serious (invasive) MRSA infections are no longer strictly limited to the HA-MRSA infections, but that a small proportion of CA-MRSA infections may also be invasive. A report in the October 2007 Journal of the American Medical Association stated that 14% of invasive MRSA infections were CA-MRSA. The proportion of MRSA with a CA genotype in hospitalized humans is increasing relative to the proportion of MRSA with a HA genotype in hospitalized humans.

MRS infections in animals include MRSA, MR Staphylococcus intermedius, and some other Staphylococcus species. While most MRS associated with infections reported in veterinary patients are coagulase-positive staphylococci, there are also reports of MRS infections with coagulase-negative staphylococci such as S. epidermidis.

The role of animals in the epidemiology of human MRS infections is not well understood. There are reported instances of transmission of MRSA from human beings to companion animals, and it appears that human beings may acquire MRSA from animals also. Whether animals are important primary reservoirs for MRS infections, become temporary reservoirs for MRS infections when exposed to human beings with MRS infections, or whether both of these scenarios occur remains to be determined.

Veterinarians must be knowledgeable about MRS infections, understand the changing epidemiology of human MRS infections, and follow the developing knowledge base about animal MRS infections. Veterinary staff should receive clear education about MRS infections, and veterinarians should take appropriate precautions to avoid transmission of MRS infections among animal patients and between animals and human beings.

How MRS infections are defined, diagnosed and characterized

Definitions

Methicillin resistant staphylococcus

Methicillin-resistant staphylococci have a cell wall penicillin binding protein (PBP2a) that has a low affinity for all beta-lactam antibiotics, therefore conferring resistance to these antibiotics. The PBP2a protein is encoded for by the mecA gene, which is carried on a mobile genetic element, the staphylococcal chromosomal cassette mec (SCCmec). There are 5 SCCmec types commonly associated with MRS (types I through V). In addition to S. aureus, other coagulase-positive staphylococci (S. intermedius, S. schleiferi coagulans, S. hyicus) and several coagulase-negative staphylococci (S. epidermidis, S. felis, S. haemolyticus, S. saprophyticus, S. xylosus, S. hominis, S. sciuri, S. simulans) have been reported to carry the mecA gene.

Methicillin is no longer used in clinical practice, and does not appear on microbiology susceptibility panels. Resistance to oxacillin or cefoxitin may be used as initial indicators of possible MRS isolates. In order to determine whether an isolate is truly MRS, PCR testing is done to test for the presence of the mecA gene, or a latex agglutination test is done to determine the presence of PBP2a. MRS isolates are further characterized by SCCmec typing, multi-locus sequence typing (MLST), and by protein A typing (protein A is encoded by the spa gene, therefore this is referred to as spa-typing), among other methods. In addition, isolates may be screened for the presence of virulence factors. One such virulence factor is the Panton Valentine leucocidin (PVL) which is a pore-forming toxin associated with leukocyte damage, tissue necrosis and severe inflammation. The gene for this toxin is reported more often in CA-MRSA isolates than in HA-MRSA isolates.

Community-associated and healthcare-associated infections

Human medicine

Definitions from the CDC are as follows

Health care-associated MRSA: MRSA infections that patients acquire during the course of receiving treatment for other conditions within a healthcare setting.

Community-associated MRSA: MRSA infections that occur in otherwise healthy people who have not been recently (within the past year) hospitalized or had a medical procedure (such as dialysis, surgery, catheters).

The isolates associated with MRSA infections are changing.

Veterinary medicine

A distinction between healthcare-associated and community-associated veterinary MRS infections is not currently as well defined as it has been in human medicine. MRS infections in companion animals may be acquired in the hospital setting (nosocomial infections) or in the community. Many isolates from companion animals have SCCmec types identical to those of human CA-MRSA; some have SCCmec types found in HA-MRSA. Isolates from some species (horses, swine) have been of different types than those typically reported in human medicine.

Colonization vs. infection

Individuals may be colonized by methicillin-resistant or methicillin-sensitive staphylococci without exhibiting clinical signs. Nasal carriage of staphylococci occurs in many species. In human beings, nasal colonization by MRSA is associated with an increased risk of developing MRSA infections, particularly following surgery. The most recent CDC prevalence estimate for national (United States) S. aureus colonization states that 32.4% (95% confidence interval 30.7 – 34.1%) of the population are carriers; for MRSA 0.8% (95% confidence interval 0.4 – 1.4%). These estimates differ according to age group and other demographic features. The S. aureus colonization was highest in people 6-11 years old. The MRSA colonization was highest in people ≥60 years old. Staphylococcus carriage may be persistent or transient, and these estimates did not discriminate between persistent and transient carriers.

The proportion of animals that are colonized with S. aureus or MRSA, and whether they are persistently or transiently colonized, is not known. Some limited studies have been performed, reporting prevalences of colonization by MR coagulase-positive staphylococci ranging from approximately 0.7% to 3.1%. A cross-sectional survey of dogs in Hong Kong and their owners found that approximately 9% of 815 dogs were nasally colonized with S. aureus, and 0.72% were colonized with MRSA. Dog owners in that study had similar rates of colonization to those given by the CDC as estimates for prevalence in the U.S. population, with 23.6% of 736 people nasally colonized with S. aureus and 0.54% colonized with MRSA. No dog-owner pair was co-colonized with the same MRSA. Whether being colonized increases the risk for dogs of developing MRS infections, particularly following surgery, is not definitively proven, but is considered likely.

Many MRSA isolates from dogs are of the same SCCmec type as the isolates from humans with CA-MRSA, but isolates from dogs that are of the same SCCmec types as isolates from humans with HA-MRSA are also reported.

MRSA in veterinary patients

Small animals with MRS infections are most often those with wound infections, post-operative infections, or skin infections. Other reported infections have included intravenous catheter sites, urinary tract infections, and pneumonia. Whether these infections are most often acquired from the human beings handling the animals, or whether animals were asymptomatically colonized with MRS prior to developing the infections, is not known.

In contrast to what is reported for dogs and cats, a majority of isolates from horses appear to be of a type uncommon in human beings. An MRSA type recently isolated from swine is unlike MRSA previously isolated from human beings. This MRSA type has been isolated from people working with colonized swine.

When should you suspect MRS?

As noted, most MRS infections in small animals have been associated with wound infections, post-operative infections, or skin infections. A Staphylococcus isolate that is resistant to oxacillin or cefoxitin should be considered a possible MRS isolate and should be further characterized by the laboratory.

How should animals with MRS be handled?

When preliminary culture results indicate an oxacillin-resistant Staphylococcus infection, precautions should be taken to help prevent transmission of the infection. Adherence to standard precautions should be emphasized (washing hands before and after handling any patient, appropriate cleaning and disinfection of hospital surfaces and equipment, use of gloves when handling animals with infected skin or wounds, appropriate bandaging of wounds and handling of contaminated bandage materials, proper technique used when installing and managing catheters). For hospitalized animals, barrier nursing techniques (limiting the personnel that handle an infected animal, wearing barrier gowns along with gloves when handling infected animals, avoiding contact between infected animals and other animals, housing infected animals so that they are not adjacent to unaffected animals) should be implemented. Animals should have their own rectal thermometers while hospitalized; these thermometers should not be used for any other animals and should be discarded when the animal is discharged. All potentially contaminated surfaces should be cleaned and disinfected, following approved protocols that take into account the need for removal of all organic debris and adequate contact time of disinfectants on cleaned surfaces. Most standard disinfectants are effective for staphylococci when used properly.

How should affected animals be treated?

For some wound infections, topical treatment and good wound management may be all that is needed. When systemic antimicrobial therapy is required, the choice of antimicrobial agent should be based on the results of susceptibility testing and the normal principles of antimicrobial use (tissue penetration, concentration and activity of the agent at the infected site, etc.). Many MRS isolates, while resistant to all beta lactam antibiotics, are susceptible to multiple other antimicrobial agents. If an isolate is found to be resistant to multiple antimicrobials, it may be necessary to ask the laboratory to test an extended panel of agents. Vancomycin, and other antimicrobial agents that are reserved for use in treating seriously ill human patients, should not be used unless all other treatment options have been exhausted. Some MRSA isolates develop inducible resistance to clindamycin. These isolates may initially be susceptible to clindamycin and resistant to erythromycin, and develop clindamycin resistance quickly during treatment with clindamycin. Inducible clindamycin resistance has been reported in canine MRSA isolates, and should be considered when planning antibiotic therapy. Isolates with inducible clindamycin resistance are most often resistant to erythromycin.

Client education

Clients should be informed of the potential for spread of infection from people to animals, and from animals to people, when their pet is diagnosed with a methicillin-resistant Staphylococcus infection. If there are concerns about possible zoonotic or anthroponotic transmission, clients should be encouraged to visit their physician for further guidance. The CDC website (www.cdc.gov) has information for clients.

MRS infections are an emerging problem in veterinary medicine. Knowledge of the epidemiology of MRS infections is growing, but still considered limited. There are multiple reports of transmission of MRSA infections between human beings and animals, but whether animals serve as an important reservoir of MRSA for human infections is not clear. Nosocomial transmission of MRSA occurs in veterinary medicine, and we should monitor carefully for the possibility of MRSA infections in veterinary patients. Appropriate antibiotic therapy must be based on culture and susceptibility testing. Standard precautions against the spread of infectious agents should be routinely practiced in veterinary medicine. When a MRSA-infected animal is hospitalized, appropriate barrier nursing or isolation protocols should be followed. Proper cleaning and disinfection protocols should be clearly displayed, and adhered to.

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