Part 1 of this two-part article will give you the information you need to understand methicillin resistance in veterinary practice. Next month in part 2, you'll learn how to diagnose and treat methicillin-resistant skin infections as well as implement measures to reduce the spread of infection.
WHAT IS METHICILLIN RESISTANCE?
Methicillin is a beta-lactam antimicrobial introduced in the 1950s. It is relatively resistant to beta-lactamase, so it was used to treat penicillin-resistant staphylococci. However, bacterial resistance to methicillin emerged soon after its introduction.
Methicillin resistance is mediated by bacterial production of an altered penicillin-binding protein (PBP2a), which does not allow microbial binding of beta-lactam antibiotics. Therefore, methicillin-resistant isolates are resistant to all beta-lactam antibiotics (penicillins, cephalosporins, and carbapenems) and are also frequently resistant to other classes of antibiotics.1,2 The protein PBP2a is encoded by the mecA gene that resides on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec).
A laboratory diagnosis of MRSP is actually done by testing for bacterial resistance against oxacillin, a similar antibiotic that is more stable for testing purposes.1,2 For S. aureus, cefoxitin has supplanted oxacillin as the marker for methicillin resistance.
MRSA: THE ORIGINAL MRS
MRSA in people
Staphylococcus aureus is often commensal in humans and is carried in (colonizes) the nasal passages of 29% to 38% of people.2,3 The prevalence of MRSA colonization in people in the United States is estimated to be 0.8% to 3.5%, but 30% to 40% of clinical S. aureus organisms isolated from human infections are methicillin resistant, and MRSA is now one of the most common nosocomial pathogens in the world.2,3
MRSA first emerged in the form of hospital-acquired infections within a year of the introduction of methicillin, but it was not until the mid-1980s that this problematic pathogen became a steadily increasing clinical problem. In 2003, a national hospital infection surveillance report revealed that 64.4% of healthcare-associated S. aureus infections in intensive care units were caused by MRSA, compared with 35.9% in 1992.4
Hospital-acquired MRSA is typically associated with resistance to multiple antibiotic classes in addition to beta-lactams, and it is reported to cause increased morbidity and mortality in people compared with methicillin-susceptible staphylococcal infections, usually associated with bacteremia, pneumonia, cellulitis, osteomyelitis, endocarditis, and septic shock.5 Identified risk factors for increased transmission of hospital-acquired MRSA include:
In the mid- to late 1990s, methicillin-resistant staphylococcal infections that were genetically different from the hospital-acquired MRSA strains (and often susceptible to non-beta-lactam antimicrobials) were identified in healthy people without prior hospital exposure; since then community-associated MRSA has become an increasing problem.8 Although most community-associated MRSA infections have involved skin and soft tissue infections, serious invasive infections have also occurred, and the strains responsible for these infections have now entered the healthcare setting, obscuring the line between community and hospital strains.9 Identified risk factors that increase transmission of community-acquired MRSA include:
MRSA in pets
Methicillin-resistant staphylococci have been documented since the 1970s in large animals but was not reported in dogs until the 1990s.10 The prevalence of S. aureus colonization in dogs and cats is low and, when present, is usually assumed to have originated from an in-contact human.11-17 Epidemiological studies generally show that MRSA in pets belongs to the same strains as the dominant regional hospital-acquired and community-associated MRSA (in contrast to MRSA from livestock animals, which usually belongs to unique animal-associated lineages).18
Most small animals exposed to MRSA do not develop clinical disease; some become temporarily colonized, and most eliminate the organism. Colonization involves survival of MRSA on the body without any adverse effect. As in people, colonized animals usually show no adverse effects unless risk factors allow for development of clinical infection, including surgery, trauma, skin wounds, and immunosuppression. Optimal sites for MRSA screening in small animals have not been identified, but most references cite the use of nasal, rectal, and perineal swabs for bacterial culture.11,12,15,16,19
MRSA in dogs and cats is most frequently cultured from wounds, abscesses, otitis, and pyodermas.20 In one review of 40 dogs infected with MRSA compared with 80 dogs with methicillin-susceptible S. aureus (MSSA), risk factors identified were receipt of antimicrobial drugs (especially fluoroquinolones and beta-lactams, which increased risk of MRSA by five and three times, respectively) and intravenous catheterization.21 In a study comparing carriage of S. aureus in 50 dogs with normal vs. 59 dogs with inflamed skin, 16% of healthy dogs carried MSSA, and none carried MRSA. Staphylococcus aureus was cultured in 12% of dogs with inflamed skin, and 17% of these cases were methicillin resistant.20
Unlike MRSA in people, which is often associated with increased morbidity and mortality, there does not appear to be a significant difference in patient outcome between dogs infected with MSSA vs. MRSA, possibly because most infections are superficial (pyodermas and otitis) and not invasive. This is an important point to consider when counseling owners of pets with MRSA.21
Do pets contract MRSA from their owners?
MRSP: A MORE COMMON CULPRIT IN PETS
While S. aureus is not considered to be a normal flora on dogs, companion animals do normally carry other species of Staphylococcus bacteria that can become pathogenic—S. pseudintermedius (previously known as Staphylococcus intermedius) most commonly and, less commonly, S. schleiferi (see below).16,19,20,25,26 In recent years, MRSP has emerged as a clinically important pathogen causing infections in dogs and cats.
Like MRSA, methicillin-resistance in S. pseudintermedius is mediated by PBP2a, which is encoded by the mecA gene. In addition to beta-lactam antibiotic resistance, most MRSP strains are also resistant to other classes of antibiotics.12,27
MRSP in people
MRSP in pets
Most clinical reports of methicillin-resistant infections have included superficial and deep pyoderma, otitis, and wound infections. Unlike MRSA in people, there is no indication that MRSP is more virulent than methicillin-susceptible S. pseudintermedius (MSSP), and most reported infections have been treated successfully, though possibly with a longer time to resolution.41
For example, treatment outcomes in dogs with methicillin-resistant pyoderma compared with outcomes in methicillin-susceptible cases were evaluated in a study of 123 MSSP and 93 MRSP clinical cases.42 The study found that most cases resolved (with topical treatment, systemic antimicrobial therapy, or both), regardless of methicillin sensitivity, although some MRSP cases took longer to resolve compared with the MSSP dogs. Corticosteroid administration was significantly associated with lack of resolution of all pyodermas at the first three- to four-week recheck examination.42
In a study comparing 56 dogs with MRSP infection with 112 control dogs with MSSP infections (most patients had pyoderma), mortality rate was not significantly different between study groups, and systemic administration of antimicrobials within 30 days before diagnosis of infection was significantly associated with risk of MRSP.40
Clinical cure of MRSP does not necessarily equate to microbiologic cure. In a sampling of dogs that initially had an MRSP pyoderma, 26 of 42 (61.9%) were still colonized with MRSP at follow-up, even though the pyoderma had clinically resolved. Additionally, in the same study of 60 dogs with pyoderma that did not have MRSP initially, MRSP was isolated from the skin after treatment in 17 dogs (28.3%).43
MRSS: A NEW PLAYER ON THE FIELD
Staphylococcus schleiferi subspecies coagulans is a relatively newly described coagulase-positive staphylococcal pathogen in dogs.13,20 Staphylococcus schleiferi subspecies schleiferi is a coagulase-negative variant that has been reported to be a normal component of human preaxillary flora and also has been implicated in human nosocomial infections, postsurgical infection, osteomyelitis, and endocarditis.44 This variant can also be pathogenic in animals and is increasingly found in methicillin-resistant infections.44
Although S. schleiferi is isolated less commonly in veterinary patients, one study found that S. schleiferi has a higher incidence of methicillin resistance then either S. aureus or S. pseudintermedius.45 In a study of 225 dogs with S. schleiferi infections (usually of the skin and ears), the most common underlying cause was atopy, and prior treatment with beta-lactam antibiotics was a risk factor for methicillin resistance. Of the 225 isolates (117 coagulase-negative and 95 coagulase-positive; 13 had no coagulase status reported), 129 (57%) were methicillin resistant, and coagulase-negative isolates were more likely to be methicillin resistant than coagulase-positive isolates.44
Now that you know more about how common methicillin-resistant staphylococci are in pets and the risks of infection to both people and pets in your veterinary practice, see next month's issue for a guide to diagnosing and treating these stubborn infections in your patients and steps you can take to curtail their occurrence.
Kimberly S. Coyner, DVM, DACVD
Dermatology Clinic for Animals of Las Vegas
5231 W. Charleston Blvd.
Las Vegas, NV 89146
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