Methicillin Resistant: Staphylococcus Aureus
Methicillin Resistant: Staphylococcus Aureus
Resistant
Staphylococcus
aureus
MRSA
Last Updated: February 2011
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this factsheet, with citations
is available at
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Importance
Staphylococcus aureus is an opportunistic pathogen often carried
asymptomatically on the human body. Methicillin-resistant S. aureus (MRSA) strains
have acquired a gene that makes them resistant to all beta-lactam antibiotics.
Hospital-associated strains of this organism are serious nosocomial pathogens that
have become resistant to most common antibiotics, and treatment can be
challenging. Community-associated MRSA strains occur in people who have not
been hospitalized or recently had invasive procedures. They first appeared in highrisk populations (e.g., intravenous drug users, people with chronic illnesses), but are
now found even in healthy children. Until recently, community-associated strains
were susceptible to many antibiotics other than beta-lactams; however, resistance
seems to be increasing, and multiple antibiotic resistant strains have started to
emerge. Human-adapted MRSA can be transmitted to animals in close contact,
which can sometimes act as carriers and re-infect people.
Animal-adapted MRSA strains also exist. The pig-associated lineage MRSA
CC398 is a particular concern. This lineage, which apparently emerged between 2003
and 2005, has spread widely among swine in some locations. Colonization with
CC398 has also been reported in other species, including veal calves and poultry.
Asymptomatic carriage is common among people who work with colonized swine or
other livestock, and these organisms can cause opportunistic infections. Other MRSA
strains can also affect animals. Outbreaks in horses suggest that MRSA might be an
emerging problem in this species. Dogs and cats seem to be infected infrequently, and
mainly by human-adapted strains; however, carriage rates can be higher during
outbreaks in veterinary hospitals and other facilities. While colonization of pets is
often transient, it might contribute to maintaining MRSA within a household or
facility.
Etiology
Staphylococcus aureus is a Gram positive, coagulase positive coccus in the family
Staphylococcaceae. Methicillin-resistant S. aureus strains have acquired the mecA
gene, which is carried on a large mobile genetic element called the staphylococcal
chromosomal cassette mec (SCCmec). This gene codes for a penicillin binding
protein, PBP2a, which interferes with the effects of beta lactam antibiotics (e.g.
penicillins and cephalosporins) on cell walls. It confers virtually complete resistance
to all beta-lactam antibiotics including the semi-synthetic penicillins.
Acquisition of mecA seems to have occurred independently in a number of S.
aureus strains. Some clonal lineages of S. aureus have a tendency to colonize specific
species, and may be adapted to either humans or animals. Other lineages (extended
host spectrum genotypes) are less host-specific, and can infect a wide variety of
species. Some MRSA strains, called epidemic strains, are more prevalent and tend to
spread within or between hospitals and countries. Other sporadic strains are isolated
less frequently and do not usually spread widely. There are also MRSA strains that
produce various exotoxins (e.g., toxic shock syndrome toxin 1, exfoliative toxins A or
B, and enterotoxins) associated with specific syndromes, such as toxic shock
syndrome. Community-associated MRSA strains that express a toxin called PantonValentine leucocidin (PVL) have been linked to skin and soft tissue infections and
severe necrotizing pneumonia. It is possible that PVL are associated with increased
virulence in general, although this remains to be proven.
Phenotypic methicillin resistance and/or the mecA gene has been reported
occasionally in various animal-adapted Staphylococcus species. Some of these
organisms can cause zoonotic infections or colonize people asymptomatically. There
are also concerns that they may transfer mecA to human-adapted staphylococci.
Naming conventions for S. aureus strains
There are at least three different genetic techniques currently used for the
classification of S. aureus strains, including pulsed-field gel electrophoresis (PFGE),
multilocus sequence typing (MLST), and DNA sequencing of the X region of the
protein A gene (spa typing). Additional methods were used in the past. Consequently,
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Species Affected
Colonization or infection with MRSA has been
reported in many species including domesticated ruminants,
pigs, horses, dogs, cats, rabbits, rodents, captive marine
mammals, a captive elephant, a bat, birds (including
poultry, pigeons and psittacine birds) and turtles.
Pigs seem to be true reservoir hosts for MRSA CC398,
which is also called non-typeable MRSA (NT-MRSA)
because most isolates cannot be typed by PFGE (although
they can be typed by other methods), or livestock-associated
MRSA (LA-MRSA). CC398 does not seem to be particularly
host specific, and it has been detected in other species
including horses, cattle, poultry and dogs, as well as rats
living on pig farms. Other strains may be common among
pigs in some areas (e.g., CMRSA2 [EMRSA3] in Canada,
or ST9 in parts of Asia). In cattle, many MRSA strains that
cause mastitis seem to be of human origin, although bovineassociated strains have been suggested and CC398 has been
identified. Poultry infected with either CC398 or ST9 have
been found in Europe. MRSA strains in horses are varied
and their origin is largely unknown. Many of the common
strains in this species (e.g., CMRSA5 [USA500; MRSA
ST8 SCCmecIV]) belong to older human lineages that were
common in the past, but have been superceded by other
strains, or to less common groups. Equine-adapted strains
may exist, and may be spreading in horse populations. Cats
and dogs seem to be colonized only sporadically, mainly by
human hospital-associated or community-associated
strains. Most infections in these species are thought to be
acquired from people, and carriage is often transient.
There is little information about MRSA in exotic animals. In
case reports, humans seemed to be the source of the organism
for an elephant calf with skin disease, and for captive
dolphins and walruses at a marine park.
Zoonotic potential
A number of MRSA strains predominantly colonize
people and circulate in human populations. They include a
the common hospital-associated clones CC5, CC8, CC22,
CC30 and CC45, and additional community-associated
strains. There is evidence that these organisms can be
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Geographic Distribution
MRSA can be found worldwide, although the
prevalence varies between regions. CC398 is the
predominant MRSA among pigs in Europe, but it has also
been recognized in North America and Singapore. ST9
appears to be the prevalent MRSA strain among pigs in
China, Hong Kong and Malaysia, and CC398 may be
uncommon or absent in these regions. The most common
strains in dogs and cats are those found in humans, which
differ between geographic regions. Equine MRSA isolates
also appear to vary with the location.
Transmission
Humans
In humans, S. aureus is an opportunistic pathogen. Both
methicillin-sensitive and methicillin-resistant strains can be
found as normal commensals on the skin (especially the
axillae and perineum), the nasopharynx and anterior nares of
some of the population. Most people who develop
symptomatic infections with hospital-associated MRSA
carry the organism in the nares, but community-associated
MRSA may colonize sites other than the nares, and clinical
cases often occur in patients who are not colonized.
Colonization with S. aureus can occur any time after birth,
and carriage may be transient or persistent.
MRSA are usually transmitted by direct contact, often
via the hands, with colonized or infected people. Humans
remain infectious as long as the carrier state persists or the
clinical lesions remain active. MRSA can also be
disseminated on fomites (including food that has been
contaminated by human carriers) and in aerosols. S. aureus
(and presumably MRSA) can be transmitted from the
mother to her infant during delivery.
Person-to-person spread of the pig-adapted MRSA
strain CC398 seems to be infrequent and limited, and to
occur mainly within families or in hospitals and institutions.
However, a recent outbreak in a hospital in the Netherlands
suggests that more extensive person-to-person transmission
can be seen under some conditions. People can also
transmit CC398 to animals such as dogs.
Animals
Asymptomatic colonization with MRSA, including both
nasal and rectal carriage, has been reported in animals. The
organisms can colonize more than one site. Carrier animals
may serve as reservoirs for disease in themselves, and they
may transmit MRSA to other animals or people. Infection or
colonization has been observed in people after as little as 4
hours of close contact with a sick, MRSA colonized foal.
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Disinfection
S. aureus is susceptible to various disinfectants
including sodium hypochlorite, alcohols, quaternary
ammonium
compounds,
iodophors,
phenolics,
glutaraldehyde, formaldehyde, and a combination of iodine
and alcohol. This organism can also be destroyed by moist
heat (121C for a minimum of 15 minutes) or dry heat
(160-170C for at least 1 hour).
Infections in Animals
Incubation Period
The incubation period varies with the syndrome.
Animals can be colonized for prolonged periods without
developing clinical signs.
Clinical Signs
Infection with MRSA results in the same syndromes as
S. aureus, which can cause a wide variety of suppurative
infections. MRSA has been specifically isolated from
various skin and wound infections including abscesses,
dermatitis including severe pyoderma, exudative dermatitis
in pigs, postoperative wound infections, fistulas, and
intravenous catheter or surgical implant infections. The
presence of suture material or orthopedic implants seems to
be linked to persistent infections in dogs and cats. MRSA
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Diagnostic Tests
Infection with MRSA, including colonization, can be
diagnosed by culture and identification of the organism.
MRSA can colonize more than one site, and in many
species including dogs and cats, the best sampling site to
detect carriers is uncertain. Nasal and rectal sampling
should both be done whenever possible. One study reported
that nasal swabs detected most colonized pigs, but some
animals carried MRSA in both locations, and a few carrier
pigs (all weanlings) could only be found using rectal swabs.
S. aureus grows on a number of media. On blood agar,
colonies are usually beta-hemolytic. Enrichment media, as
well as selective plates for MRSA, are available. On
microscopic examination, S. aurues is a Gram positive,
non-spore forming coccus, which may be found singly, in
pairs, in short chains or in irregular clusters. Biochemical
tests such as the coagulase test are used to differentiate it
from other staphylococci. S. aureus can also be identified
with the API Staph Ident system.
If S. aureus is isolated from an infection, genetic testing
or antibiotic susceptibility testing can identify methicillin
resistant strains. The presence of the mecA gene defines
MRSA, and tests to detect this gene, such as PCR, are the
gold standard for identification. A latex agglutination test can
detect PBP2a, the product of mecA. Phenotypic antibiotic
susceptibility tests (e.g., disk diffusion or MIC
determination) can also be used to identify MRSA, but have
some drawbacks compared to detecting mecA or PBP2a.
Methicillin-susceptible and resistant subpopulations can coexist in vitro; although the entire colony carries the resistance
genes, only a small number of bacteria may express
resistance in culture. The expression of resistance in
phenotypic tests can also vary with growth conditions such as
temperature. In addition, some susceptibility tests can
overestimate methicillin resistance; isolates that do not carry
mecA (and thus, are not MRSA) can appear to be
phenotypically resistant to methicillin.
MRSA clones or strains can be identified with
molecular tests such as PFGE, MLST, SCCmec typing, spa
typing and other assays. This is usually done mainly for
epidemiological purposes, such as tracing outbreaks. A
combination of methods may be needed to identify a strain.
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Prevention
Veterinary hospitals should establish guidelines to
minimize cross-contamination by MRSA and other
methicillin-resistant staphylococci. In addition to hand
hygiene, infection control measures (with particular
attention to invasive devices such as intravenous catheters
and urinary catheters), and environmental disinfection,
barrier precautions should be used when there is a risk of
contact with body fluids or when an animal has a
recognized MRSA infection. These animals should be
isolated. MRSA-infected wounds should be covered
whenever possible. Although colonized people can transmit
MRSA to animals, one study suggests that there may be
only a small risk of transmission from colonized surgical
personnel if infection control protocols are followed.
Researchers have recommended that veterinary
hospitals initiate surveillance programs for MRSA,
particularly in horses. Screening at admission allows
isolation of carriers, the establishment of barrier precautions
to prevent transmission to other animals, and prompt
recognition of opportunistic infections caused by these
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Infections in Humans
Incubation Period
The incubation period for S. aureus infections in
humans is highly variable. In susceptible patients, clinical
cases may become apparent 4 to 10 days after exposure;
however, opportunistic infections can also occur after an
indefinite period of asymptomatic carriage.
Clinical Signs
MRSA is an opportunist, like other S. aureus, and can
cause the same types of infections. It may be involved in
various skin and soft tissue infections, as well as invasive
conditions such as pneumonia, endocarditis, septic arthritis,
osteomyelitis, meningitis and septicemia. Hospital-acquired
MRSA strains are major causes of nosocomial infections
associated with indwelling medical devices and surgical sites.
Human community-acquired-MRSA strains are mainly
associated with superficial skin or soft tissue disease,
although they have also caused sepsis, necrotizing fasciitis,
necrotizing pneumonia and other conditions. MRSA strains
that carry the exotoxin TSST-1 have been found in cases of
toxic shock syndrome, especially in Japan. Other toxinexpressing MRSA strains (exfoliative toxins A or B) can
cause staphylococcal scalded skin syndrome, a disease
characterized by widespread blistering and loss of the outer
layers of the epidermis.
MRSA strains that produce enterotoxins while growing
in food can cause acute staphylococcal gastroenteritis (food
poisoning). However, antibiotic resistance is generally
irrelevant in this condition, because the preformed toxin is
eaten in food and the organism is not present in the body.
Invasive disease after ingesting S. aureus is very unusual,
although it was reported in a severely immunocompromised
patient who had received antacids, as well as antibiotics to
which the (methicillin-sensitive) strain was resistant.
Zoonotic MRSA can presumably cause the same types
of infections as human-associated MRSA strains. CC398
has mainly been found in superficial skin and soft tissue
infections, but some case reports have described aggressive
wound infection, destructive otomastoiditis, sinusitis,
endocarditis, nosocomial bacteremia, pneumonia, and
severe invasive infection with multiorgan failure.
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Treatment
Factors such as the location, severity and progression
of the infection, as well as the age and health of the patient,
can affect the type of treatment chosen. Skin infections are
sometimes treated by management techniques that do not
require systemic antibiotics (e.g., incision and drainage for
abscesses). Treatment may also require adjunct measures
such as the removal of catheters.
Antibiotics must be selected based on susceptibility
testing. It can be difficult to find an effective choice for
hospital-acquired MRSA, which are often resistant to most
common antibiotics. Agents used to treat serious infections
caused by multiple drug resistant MRSA strains include
vancomycin linezolid, tigecycline, quinupristin/dalfopristin
and daptomycin. Resistance has been reported to some of
these antibiotics. In particular, vancomycin resistance
seems to be increasing. Community-acquired MRSA strains
have often been resistant only to -lactam agents,
macrolides and azalides. However, resistance to other
antibiotics may be increasing, multiple antibiotic resistant
strains have started to emerge, and vancomycin-resistant
strains have been reported.
Prevention
Hand washing, avoidance of direct contact with nasal
secretions and wounds, barrier precautions when handling
animals with illnesses caused by MRSA, environmental
cleaning and other infection control measures are expected
to reduce the risk of acquiring MRSA from infected or
colonized animals. The best procedure to follow when a
resident animal becomes colonized in a healthcare facility is
still uncertain. In one recent outbreak, options presented to
the facility included removing the animal until it cleared the
bacterium, or allowing it to remain, with or without
antibiotic treatment, and with continued monitoring
(culture) and the encouragement of good hand hygiene
among human contacts.
Infection control measures, particularly hand washing,
are also important in preventing MRSA transmission from
humans. Outpatients with MRSA skin lesions should keep
them covered with clean, dry bandages. In some
circumstances, such as the inability to adequately cover a
MRSA-infected wound, close contact with other people (or
susceptible animals) should be avoided. The Netherlands and
Scandinavian counties have greatly reduced the incidence of
hospital-associated human MRSA by screening and
decolonization of hospital staff, and screening of patients on
admission. High risk patients, including people who work
with pigs or veal calves, are isolated until the screening test
demonstrates that they are MRSA-free. MRSA outbreaks are
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References
Aarestrup FM, Cavaco L, Hasman H. Decreased susceptibility to
zinc chloride is associated with methicillin resistant
Staphylococcus aureus CC398 in Danish swine. Vet
Microbiol. 2010;142(3-4):455-7.
Abbott Y, Leggett B, Rossney AS, Leonard FC, Markey BK.
Isolation rates of meticillin-resistant Staphylococcus aureus in
dogs, cats and horses in Ireland. Vet Rec. 2010;166(15):451-5.
Anderson ME, Lefebvre SL, Rankin SC, Aceto H, Morley PS,
Caron JP, Welsh RD, Holbrook TC, Moore B, Taylor DR,
Weese JS. Retrospective multicentre study of methicillinresistant Staphylococcus aureus infections in 115 horses.
Equine Vet J. 2009;41(4):401-5.
Last Updated: February 2011
2014
page 7 of 14
Coughlan K, Olsen KE, Boxrud D, Bender JB.Methicillinresistant Staphylococcus aureus in resident animals of a longterm care facility. Zoonoses Public Health. 2010;57(3):220-6.
Cui S, Li J, Hu C, Jin S, Li F, Guo Y, Ran L, Ma Y. Isolation and
characterization of methicillin-resistant Staphylococcus aureus
from swine and workers in China. J Antimicrob Chemother.
2009;64(4):680-3.
Cuny C, Friedrich A, Kozytska S, Layer F, Nbel U, Ohlsen K,
Strommenger B, Walther B, Wieler L, Witte W. Emergence of
methicillin-resistant Staphylococcus aureus (MRSA) in
different animal species. Int J Med Microbiol. 2010;300(23):109-17.
Cuny C, Kuemmerle J, Stanek C, Willey B, Strommenger B,
Witte W. Emergence of MRSA infections in horses in a
veterinary hospital: strain characterisation and comparison
with MRSA from humans. Euro Surveill. 2006;11(1).
Cuny C, Nathaus R, Layer F, Strommenger B, Altmann D, Witte
W. Nasal colonization of humans with methicillin-resistant
Staphylococcus aureus (MRSA) CC398 with and without
exposure to pigs. PLoS One. 2009 Aug 27;4(8):e6800.
Cuny C, Strommenger B, Witte W, Stanek C. Clusters of
infections in horses with MRSA ST1, ST254, and ST398 in a
veterinary hospital. Microb Drug Resist. 2008;14(4):307-10.
Declercq P, Petr D, Gordts B, Voss A. Complicated communityacquired soft tissue infection by MRSA from porcine origin.
Infection. 2008;36(6):590-2.
Denis O, Suetens C, Hallin M, Catry B, Ramboer I, Dispas M,
Willems G, Gordts B, Butaye P, Struelens MJ. Methicillinresistant Staphylococcus aureus ST398 in swine farm
personnel, Belgium. Emerg Infect Dis. 2009;15(7):1098-101.
Devriese LA, Hommez J. Epidemiology of methicillin-resistant
Staphylococcus aureus in dairy herds. Res Vet Sci.
1975;19:23-27.
Devriese LA, Van Damme LR, Fameree L. Methicillin (cloxacillin)resistant Staphylococcus aureus strains isolated from bovine
mastitis cases. Zentbl Vetmed. Reihe B. 1972;19:598-605.
Diller R, Sonntag AK, Mellmann A, Grevener K, Senninger N,
Kipp F, Friedrich AW. Evidence for cost reduction based on
pre-admission MRSA screening in general surgery. Int J Hyg
Environ Health. 2008;211(1-2):205-12.
Duquette RA, Nuttall TJ. Methicillin-resistant Staphylococcus
aureus in dogs and cats: an emerging problem? J Small Anim
Pract. 2004;45(12):591-7.
Durand G, Bes M, Meugnier H, Enright MC, Forey F, Liassine N,
Wenger A, Kikuchi K, Lina G, Vandenesch F, Etienne J.
Detection of new methicillin-resistant Staphylococcus aureus
clones containing the toxic shock syndrome toxin 1 gene
responsible for hospital- and community-acquired infections
in France. J Clin Microbiol. 2006;44(3):847-53.
Enoch DA, Karas JA, Slater JD, Emery MM, Kearns AM,
Farrington M. MRSA carriage in a pet therapy dog. J Hosp
Infect. 2005;60:186e8.
Fessler A, Scott C, Kadlec K, Ehricht R, Monecke S, Schwarz S.
Characterization of methicillin-resistant Staphylococcus
aureus ST398 from cases of bovine mastitis. J Antimicrob
Chemother. 2010;65(4):619-25.
Faires MC, Gard S, Aucoin D, Weese JS. Inducible clindamycinresistance in methicillin-resistant Staphylococcus aureus and
methicillin-resistant Staphylococcus pseudintermedius isolates
from dogs and cats. Vet Microbiol. 2009;139(3-4):419-20.
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