**6. MRSA in companion animals**

#### **6.1. Canine and feline MRSA**

The first MRSA from pet animals was isolated from dogs in Nigeria in 1972 [188]. *S. intermedius* is the strain most isolated from dogs [189]. However, the predominant canine species among staphylococci was *S. sciuri* in Japan [190]. Various coagulase-positive and -negative staphylococci have been reported in pet animals [191]. Among coagulase-negative staphylococci, *S. felis* was dominant in Brazil [116], and a coagulase-positive *S. intermedius* was dominant in canine species in the UK [192, 193]. The prevalence of canine MRSA was 0.7% in Portugal, 2.3–9% in UK, and ≤20% in Canada [194–197]. Conversely, in cats, it was 1.48% in the UK, ≤4% in Portugal [195, 198] and 21.4% from wounds and skin lesions of cats in the USA [199]. *S. aureus* was found in 8% of dogs with inflammatory skin disease in the USA and one isolate was MRSA [200]. In addition, one MRSA was detected among the *S. aureus* strains isolated from 29% of 48 cats suffering with inflammatory skin disease and two MRSA were found among the *S. aureus* strains from 20% of 50 healthy cats [201]. Previous surgery, hospitalization, antimicrobial agent treatment, contact with humans possessing MRSA, and use of implant devices are regarded as risk factors for MRSA infection in companion animals [195, 202]. Rich and Robert [203] reported that MRSA were isolated from 1.4% of the postoperative and wound infection samples of pet animals in the UK. Lilenbaum et al. found 3% MRSA in Brazilian cats [193]. Southwest Pacific clone-associated community-acquired MRSA (USA1100) and methicillin-resistant *S. pseudintermedius* (MRSP)-associated with the European clone (ST71) were first reported in South America in cats [204].

MRSA isolates from Austria, Belgium, Germany, Ireland, and Portugal were resistant to ciprofloxacin and enrofloxacin, perhaps because of the fluoroquinolone approval for use in companion animals in Europe in the middle of 1990 (**Table 2**). MRSA ST398 that was identified in dogs and cats in France carried a chloramphenicol acetyltransferase gene, *cat*, that mediates resistance to nonfluorinated phenicols [117]. On the other hand, MRSA isolated in Portugal and Thailand from dogs and Germany from cats possessed a florfenicol-chloramphenicol exporter gene, *fexA*, that mediates resistance to both fluorinated and nonfluorinated phenicols [205–207]. MRSA ST398 isolated from an Austrian dog suffering from vaginitis harbored the *vatC* gene that inactivates streptogramin A [208]. An ABC transporter gene, *lsaE* (responsible for combined resistance to lincosamides, pleuromutilins, and streptogramin A), and a lincosamide nucleotidyltransferase *lunB* gene (confers resistance only to lincosamides), were present in the MRSA ST45 isolated from dogs in Thailand [205]. In France, an MRSA strain (*agr* III-t008–IV) isolated from a synovial fluid of dog was positive for *pvl* [117]. It carried *sek* and *seq* genes and was suspected to be a USA300 variant that was imported from the USA. *tsst1* positive MRSA (*agr* II-t002-SCC*mec* I-truncated) was recovered from pet animals in France (**Table 3**). Leukotoxin genes, most prevalently *lukF* and/or *lukS* followed by *lukD* and/or *lukE*, are reported to be present in most of the MRSA isolated from companion animals, but those from dogs, cats and horses in Austria and the USA did not possess any leukotoxin genes. MRSA isolates CC5-t002–II, CC5-t062 and CC22-t032–IV, isolated in Portugal from a dog, a horse and human, respectively, harbored IEC genes suggesting adaptation to different hosts [206]. The presence of host-adaptive, virulence, and toxin genes makes the companion animal MRSA isolates prime candidates for zoonotic transfer. The first outbreak of human MRSA associated with cats was reported in a rehabilitation geriatric ward in the UK in 1988 [209] but others have since been reported in Australia, Canada, Germany, New Zealand, South America, and the Netherlands [193, 210–212]. Human-associated MRSA, such as EMRSA-15 and CMRSA-2, show a close relationship with pet-associated MRSA [211–214]. Since MRSA ST398 has been isolated from many farm animals, this MLST type found in dogs or cats may have originated from them or people who had contact with them [215]. MRSA SCC*mec* II strains, which are those most frequently affiliated with nosocomial human infections, have been isolated from cats [216].

#### **6.2. Equine MRSA**

were found in dust samples, nasal swabs, and a blood isolate from workers on the same pig farm [177], suggesting multiple acquisitions of SCC*mec* cassettes by MSSA precursors. Coagulase-negative staphylococci in the farming environment are suspected as sources of SCC*mec* [176], and the progeny of emerging MRSA strains are spreading locally rather than globally [178–180]. While SCC*mec* acquisition seems to be fairly common in MRSA ST398, the transfer of staphylococcal toxin genes, including the Panton-Valentine leukocidin gene (*pvl*) appears to be rarer [20, 43, 44, 57, 165, 181–184]. Only a handful of studies have found *pvl* positive ST398 [20, 165, 185–187]. Additionally, horizontal transfer of the protein A gene has been suggested, due to the finding of the *spa* type t899 in both ST398 strains and ST9

The first MRSA from pet animals was isolated from dogs in Nigeria in 1972 [188]. *S. intermedius* is the strain most isolated from dogs [189]. However, the predominant canine species among staphylococci was *S. sciuri* in Japan [190]. Various coagulase-positive and -negative staphylococci have been reported in pet animals [191]. Among coagulase-negative staphylococci, *S. felis* was dominant in Brazil [116], and a coagulase-positive *S. intermedius* was dominant in canine species in the UK [192, 193]. The prevalence of canine MRSA was 0.7% in Portugal, 2.3–9% in UK, and ≤20% in Canada [194–197]. Conversely, in cats, it was 1.48% in the UK, ≤4% in Portugal [195, 198] and 21.4% from wounds and skin lesions of cats in the USA [199]. *S. aureus* was found in 8% of dogs with inflammatory skin disease in the USA and one isolate was MRSA [200]. In addition, one MRSA was detected among the *S. aureus* strains isolated from 29% of 48 cats suffering with inflammatory skin disease and two MRSA were found among the *S. aureus* strains from 20% of 50 healthy cats [201]. Previous surgery, hospitalization, antimicrobial agent treatment, contact with humans possessing MRSA, and use of implant devices are regarded as risk factors for MRSA infection in companion animals [195, 202]. Rich and Robert [203] reported that MRSA were isolated from 1.4% of the postoperative and wound infection samples of pet animals in the UK. Lilenbaum et al. found 3% MRSA in Brazilian cats [193]. Southwest Pacific clone-associated community-acquired MRSA (USA1100) and methicillin-resistant *S. pseudintermedius* (MRSP)-associated with the European

MRSA isolates from Austria, Belgium, Germany, Ireland, and Portugal were resistant to ciprofloxacin and enrofloxacin, perhaps because of the fluoroquinolone approval for use in companion animals in Europe in the middle of 1990 (**Table 2**). MRSA ST398 that was identified in dogs and cats in France carried a chloramphenicol acetyltransferase gene, *cat*, that mediates resistance to nonfluorinated phenicols [117]. On the other hand, MRSA isolated in Portugal and Thailand from dogs and Germany from cats possessed a florfenicol-chloramphenicol exporter gene, *fexA*, that mediates resistance to both fluorinated and nonfluorinated phenicols [205–207]. MRSA ST398 isolated from an Austrian dog suffering from vaginitis harbored the *vatC* gene that inactivates streptogramin A [208]. An ABC transporter gene, *lsaE* (responsible

strains [29, 30, 80, 177].

58 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

**6. MRSA in companion animals**

clone (ST71) were first reported in South America in cats [204].

**6.1. Canine and feline MRSA**

Since the first report of MRSA from mares with metritis in Japan [217], many isolates have been found in Europe, North America, and Asia (**Table 2**) [142–144, 218–220]). Haenni et al. [221] identified four *mecC*-positive MRSA from horses in France exhibiting *spa* types, t208, t843, t6220, t11015 and ST types ST49, ST130, and ST1245. Among them, MRSA CC130 (ST130, ST1245) and CC49 (ST49) were documented in animals and humans, respectively. Multidrugresistant ST8 MRSA was detected in Belgium, Germany, Switzerland, and the USA. A single locus variant of ST8 classified as ST254 MRSA was isolated from horses in Austria, Germany, Ireland, and the UK [183, 208, 222, 223]. Twelve different MLST types have been reported and most of the MRSA strains were grouped into the CC8 or CC398 classes [224]. The CC8-SCC*mec* IV genotype in horses was likely from a contaminated veterinary hospital and later spread to various clinics [219]. This genotype was reported in veterinary hospitals in Canada and the USA [118, 225]. It was first found in infected horses in Ireland and thereafter reported in the Netherlands, Austria, and Germany [226–228]. Many MRSA isolates from Canada showed ST8-SCC*mec* IV-t064 genotype [93]. They were designated as a Canadian epidemic MRSA-5 (CMRSA-5) and were very close to a human clone, USA500. Although the CC8-SCC*mec* IV genotype has been the most frequently found, CC398-SCC*mec* IV has recently become a major genotype. CC398-SCC*mec* IV was first found from infected horses in the Veterinary University of Vienna in Austria [222]. CC398 isolated from nasal samples of horses in the Netherlands and Belgium exhibited high prevalence rates, 9.3 and 10.9%, respectively [227, 229]. More than 25 *spa*-types have been reported, and three types, such as t011, t064 and t451, were the most



Belgium

Belgium

Belgium

Belgium

Belgium

P†

ST9,

+ ++

 +

 ++

 +

 ++

 +++

 ++

*aacAaphD,* 

[121]

*aadD,* 

*aphA3-sat,* 

*blaI, blaR,* 

*blaZ, cfr,* 

*dfrS1,* 

*ermB,* 

*ermC,* 

*fexA, fosB,* 

*lnuA,* 

*tetK, tetM,* 

*vgaA*

Belgium Belgium Belgium

Brazil

Central

P

9

+++

Europe

 B

 398

+

 ++

P

398

+ +

+

++

+

 +

 +

+

++

 +

*ant4,* 

[257]

*aac(6′)-*

*aph(2″),* 

*blaZ,* 

*mecA,* 

*tetK, tetM*

+

+

[258]

 ++

P

398

+ +

+

 ++

 +

 +

P

398

+

+

++

 +

+

+

 ++

 ++

[256]

[66]

[133]

80, 239,

398

 C

 398

+

+

+

+

+

[133]

 C†

239,

++

 +

 +

 ++

 +

+

 +++

 +

398

 B

 398

+ +

+

++

 +

 B†

398

\*

+\*\*

+

++

 +

++

+

 ++

 + +

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

[87]

[133]

[34]

60 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

#### Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 61



Germany

Germany

P

398

+

 ++

 ++

 ++

 + +

+

 ++

+

*aacAaphD,* 

[44]

62 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*aadD,* 

*blaZ,* 

*dfrG, dfrK,* 

*ermA,* 

*ermB,* 

*ermC,* 

*fexA,* 

*mecA,* 

*qacC, tetK,* 

*tetL, tetM,* 

*vga vgaA*

Hong Kong

Hong Kong P

Hong Kong P

9

+

 +

+ +

+ +

++++

 +

*aacAaphD,* 

[134]

*aadD,* 

*aadE,* 

*blaZ/I/R,* 

*dfrK,* 

*ermC,* 

*lnuB, lsaE,* 

*mecA, tetL,* 

*spw*

9

+ ++

 +

+

+

 C

 9

+

 ++

 ++

 ++

 + +

 +

+++++

 ++

*aacAaphD,* 

[134]

*aadD,* 

*aadE,* 

*blaZ/I/R,* 

*dfrK,* 

*ermC,* 

*lnuB, lsaE,* 

*mecA, spw,* 

*tetL*

*ermB,* 

[81]

*ermC*

 B

 398

+

+

**+**

+

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

[102]



Italy

Italy

 P

 1

+

 ++

 +

+ +

+++

+

*aacAaphD,* 

[119]

*aadD, blaI,* 

*blaR, blaZ,* 

*cfr, dfrS1,* 

*ermA,* 

*ermC,* 

*ermR,* 

*fexA,* 

*mecA,* 

*qacC,* 

*sdrM,* 

*tetK, tetM,* 

*vgaA*

Italy &

P

 1+

++

 +

+ +

++

 +

*aacAaphD,* 

[265]

*aadD,* 

*blaZ, cat,* 

*dfrA,* 

*ermA,* 

*ermC,* 

*lnuA,* 

*mecA,* 

*tetK, tetL,* 

*tetM,* 

*vgaA,* 

*vgbA*

Spain

 P

CC97

+

 ++

 +

+ +

+

 +++

 +

*aacAaphD,* 

[110]

*aadD, blaI,* 

*blaR, blaZ,* 

64 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*cat, ermB,* 

*ermC,* 

*mecA,* 

*qacC,* 

*sdrM,* 

*tetK, tetM,* 

*vgaA*

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References** Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 65



Portugal

Spain

 P

398,

+

 +

+ +

++

 +

 +

*aacAaphD,* 

[255]

*aadA,* 

*aadD,* 

*aphA3,* 

*dfrA,* 

*dfrG, dfrK,* 

*ermC,* 

*ermT,* 

*msrA, str,* 

*tetK, tetM,* 

*tetL*

+

 +

> +

[234]

[267]

Spain

Spain

 P

1, 398,

++

 +

1965,

1966,

1967,

1968,

1969

Switzerland

 B

 1, 398 +

 +

+

 +

+

*aphA,blaI,* 

[42]

*blaR, blaZ,* 

*ermC,* 

*mecA,* 

*tetM*

 P

398

+

 + +

 ++

+

 +

 ++

+

1379

 P

 NA

++

 +

+ +

++

 ++

*aacAaphD,* 

[206]

*aadD,* 

*apmA,* 

66 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*dfrK,* 

*ermC,* 

*fexA, qacG,* 

*qacJ, tetK,* 

*tetM, vgaA*

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

> **Table 1.** Antimicrobial resistance pattern of bovine, poultry, and porcine MRSA isolates.

spectinomycin, STR: streptomycin, TET: tetracycline, TIA: tiamulin, TOB: tobramycin, TRI: trimethoprim, SXT: trimethoprim-sulfamethoxazole.


*tetK*


Austria

 D†

22,

\*

+\*\*

+

+

+

+

*aacA-aphD,* 

[208]

*dfrA, ermC,* 

*tetK, tetM,* 

*vatC*

68 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*aacA-aphD,* 

[208]

*ermC, tetK,* 

*tetM*

254,

398

Austria Austria

Austria

Belgium Belgium

Belgium Belgium

Brazil

Brazil

Canada Canada &

H

 NA

+

+ +

+

USA

China

 C, D

 59, 398

+

+

D

 NA

 +

+++

 +

 ++

+ + +

*aacA-aphD,* 

[273]

*ermB,* 

*mecA, linA,* 

*tetK*

+

+

[271]

[272]

 C

NA

 +

 C

 30

+

H

398

+

 +

+

+

+

+

[229]

[204]

[193]

H

8, 398,

+

 +

++

 +

+

+

2197

 C

 398

D

398

+ + + +

+

+

++

 + +

 +

+ +

+

+

 ++

[133]

[133]

[270]

 H

1, 254,

+

 +

+

+

398

 H†

1, 254,

++

 +

+

+

+

*aacA-aphD,* 

[208]

*dfrA, ermC,* 

*tetK, tetM,* 

*vatC*

*aph2″-*

[222]

*aac6′,* 

*ermC,* 

*mecA,* 

*tetM*

398

C†

1, 5,

++

 +

+

+

398

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

#### Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 69



Japan

Japan

Korea Korea Malaysia

Malaysia Netherlands

Nigeria

Portugal

 D

22,

+ ++

105,

398

Portugal Portugal

Portugal

 H

5, 398

+

 +

 ++

 +

+

+

*aacAaphD,* 

[287]

*blaZ, dfrK,* 

*ermC,* 

*fusC, tetM*

 D

22

++

 +

 ++

 +

+

+

 +

C

 5, 22

++

 +

 +

 D

 NA

 + + + +

 +

 ++

+

+

+ +

*fexA,* 

[206]

*ermA,* 

*ermC, tetM*

*ermC,* 

[206]

*fusC,* 

*mphC,* 

*msrA*,

*aac(6′)-*

[286]

*aph(2″),* 

*ant(4′)-Ia,* 

*aph(3′)-*

*III, ermB,* 

*ermC,* 

*msrA,* 

*tetM*

+

[285]

 D

 NA

 +

C

55

+

 D

59

+

D

 NA

 +

 + +

 + + + + +

+

+

+

+

+

+ + + +

 +

[282]

[283]

[283]

[284]

D

72

+

 D

 NA

 +

 D

5, 30

+

+ +

+

+ +

+ + +

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

[279]

[280]

[281]

70 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

#### Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 71


**Table 2.** Antimicrobial resistance pattern of feline, canine and equine MRSA isolates.


USA USA

USA USA USA & UK D

USA

 H

8, 830 +

 NA

C

NA

+

 ++ +++

 + +

+ C†: cats, D†: dogs, H†: horses, \*: not tested or sensitive, \*\*: resistant, AMP: ampicillin, CEF: cefoxitin, CHL: chloramphenicol, CIP: ciprofloxacin, CLI: clindamycin, ENR:

enrofloxacin, ERY: erythromycin, FLO: florfenicol, FUS: fusidate, GEN: gentamicin, KAN: kanamycin, LIN: lincomycin, LIZ: linezolid, QD: quinupristin/dalfopristin, SPE:

spectinomycin, STR: streptomycin, TET: tetracycline, TIA: tiamulin, TOB: tobramycin, TRI: trimethoprim, SXT: trimethoprim-sulfamethoxazole.

**Table 2.** Antimicrobial resistance pattern of feline, canine and equine MRSA isolates.

+

+

[118]

+

+

 +

+

C

NA

 D

 NA

C, D

NA

+

 ++

++

++

 +

 +

 +

+

+ + + +

+ +

[294]

[216]

+

[292]

[293]

[293]

72 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References** Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 73



Italy

Cattle

*lukD, lukE,* 

*hl, hlIII, hlb,* 

*seh*

*hysA1,* 

*aur, splA,* 

*ssl1, ssl2, ssl3,* 

*bbp, clfA,* 

*cap8,* 

*lmrP, mprF,* 

[119]

74 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*hsdS2, hsdS3,* 

*clfB, cna,* 

*capH8,* 

*ebh, ebpS,* 

*capI8,* 

*hsdSx*

*icaA, icaC,* 

*capJ8,* 

*icaD, eno,* 

*capK8*

*fib, fnbA,* 

*fnbB, sasG,* 

*sdrC, sdrD,* 

*vwb*

Pigs

*lukD, lukE,* 

*hl, hla, hlIII,* 

*seh*

*isaB, isdA,* 

*aur, splA,* 

*ssl1, ssl2, ssl3,* 

*bbp, clfA,* 

*cap8,* 

*lmrP, mprF,* 

*hsdS2, hsdS3,* 

*clfB, cna,* 

*capH8,* 

*ebh, ebpS,* 

*capI8,* 

*hsdSx*

*icaA, icaC,* 

*capJ8,* 

*icaD, eno,* 

*capK8*

*fib, fnbA,* 

*fnbB, sasG,* 

*sdrC, sdrD,* 

*vwb*

[265]

*tsst1*

[91]

Italy &

Pigs

*lukX*

 *hlb*

*entH, entU,* 

*entX, entY*

*sed, seg, sei,* 

*chp, sak,* 

*sej, sem, sen,* 

*scn*

*seo, sep, ser*

–

*seb, sed, seg,* 

*chp, sak,* 

*tsst1*

*sei, sej, sek,* 

*scn*

*sem, sen, seo,* 

*seq, ser*

–

Spain

Korea

Pigs Chicken

Cattle

*lukE/D, pvl*

*lukE/D*

*lukE/D*

*ssl4, ssl5, ssl6,* 

*ssl7, ssl8, ssl9,* 

*hysA1,* 

*splB, splE,* 

*hysA2*

*sspA,* 

*sspB, sspP*

*ssl10, ssl11*

*lukF, lukS,* 

*hlb, hlgA*

*lukX, lukY*

*ssl4, ssl5, ssl6,* 

*ssl7, ssl8, ssl9,* 

*hysA2,* 

*splB,* 

*isaB, isdA,* 

*sspA,* 

*sak, scn*

*sspB, sspP*

*ssl10, ssl11*

*lukF, lukS,* 

*hlgA*

*lukX, lukY*

 **Animals**

**Leukotoxins**

**Hemolysins**

**Enterotoxins**

 **Immuneinvasion** 

**Protease**

**Superantigenlike proteins**

**Biofilm- associated**

**Capsule**

**Miscellaneous genes**

**References**

**factors**

**Table 3.** Virulence profiles from food-producing and pet animals.

Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 75 widespread [230]. In addition, only three SCC*mec* types (IV, V, VI) have been discovered from horses [218]. Interestingly, no MRSA was isolated from 300 horses on 14 farms in Slovenia, 497 horses on 50 farms in Canada, 87 horses in Austria, and 200 horses in the Netherlands [231–233]. ST22 and ST1117 isolates from horses in Germany had IEC genes, such as *chp, sak*, and *scn* [183]. On the other hand, ST8, ST254, and ST398 strains did not carry those genes.

#### **6.3. Antibiotic resistance and enterotoxin genes in LA-MRSA CC398**

An analysis of MRSA and MSSA from animals and humans spanning 19 countries and four continents indicated that the CC398 lineage originated in humans as MSSA [167]. After its transmission to livestock, CC398 became resistant to tetracycline, probably because of the heavy tetracycline use in pig production [22]. However, many tetracycline-resistant MRSA strains are found in horses despite the fact that tetracycline is either not used much [229] or sparingly used [93, 229]. Among bovine MRSA isolates tested, most of them were resistant to β-lactam antibiotics [34] as well as tetracycline, erythromycin and gentamicin. CC398 has also been reported to be highly resistant to several other antibiotics, such as ciprofloxacin, tobramycin, clindamycin, and trimethoprim-sulfamethoxazole [234]. Antimicrobial resistance patterns of MRSA and MSSA isolates in Hong Kong were very similar [81]. The only MRSA CC398 isolate that has exhibited resistance against daptomycin and intermediate susceptibility to vancomycin has been described in a case-report from an Italian hospital [235]. Two other isolates, one from a ventilator-associated pneumonia of a farmer and one additional porcine isolate, were also described as resistant to linezolid and possessed the *cfr* gene which is located on transferable plasmids [235]. An outbreak with HA-MRSA ST125 containing *cfr*, reported from a Madrid hospital in 2010 [236], was followed by reports on the emergence of nosocomial coagulase negative staphylococci containing *cfr* [40]. This gene was previously found in staphylococci from animals in Europe [237, 238] but has also been reported in humans in Colombia and the USA [239, 240]. Distribution of the *cfr* gene in MRSA isolates is alarming because, besides linezolid, it confers resistance to oxazolidinones, phenicols, lincosamides, streptogramin A, and pleuromutilins, including the topical antibiotic retapamulin that is used for treatment of human skin infections [239, 241, 242].

About 50% of LA-MRSA CC398 isolates, besides being resistant to antimicrobial agents, also exhibit resistance to copper and zinc mediated by the *czrC* gene [130, 243]. The use of zinc as feed additives may have favored spread of the *czrC* gene in LA-MRSA [130]. So far, this gene has only been found in LA-MRSA [130, 243] but an extended use of copper coating of biomaterials in orthopedic surgery and traumatology, as well as copper surfaces in hospitals, might select for *czrC*-positive HA-MRSA as well. The trimethoprim-resistance gene *dfrK*, located close to *tetL* in LA-MRSA ST398, has also been found on a plasmid [244]. The *tetL* gene was identified in MRSA isolated from diverse livestock animals and meats from different regions of the world [97, 245, 246]. Kadlec and Schwarz demonstrated the presence of plasmid pKKS25-associated resistance genes, *ermT, dfrK*, and *tetL*, in MRSA obtained from a nasal swab of a young sow in Germany [247]. A porcine MRSA ST398 was shown to contain a transposon Tn*6133* carrying *ant(9)-Ia* and *ermA* genes and a plasmid pKKS825 [248, 249] harboring the resistance genes *vgaC* and *vgaE, aadD, tetL*, and *dfrK* [248–250]. In Germany, the *vgaE* gene was detected in MRSA ST398 isolated from cattle, turkeys, and chicken and turkey meats [251]. An apramycin resistance gene, *apmA*, was discovered in a bovine MRSA ST398 [252] and in porcine MRSA ST398 [206, 253]. In Denmark, the quaternary ammonium compoundresistant genes, *qacC* and *qacG* were detected in MRSA CC30 isolates [254]. Wendlandt et al. identified a plasmid pV7037-associated multidrug resistance gene cluster, including the novel resistance genes *lsaE* and *spw*, and other resistance genes, such as *mecA, blaZ/I/R, tetL, dfrK, ermC*, and *aadD*, from frozen or chilled chicken carcasses in Hong Kong. The antimicrobial resistance patterns and associated genes from bovine, porcine, and poultry isolates are summarized in **Table 1** and those from companion animals are shown in **Table 2**.

Most of the animal isolates are negative for the *pvl* gene, but Belgian MRSA ST80–IV isolates from healthy pigs were positive for the *pvl* gene and corresponded to the communityacquired CA-MRSA ST80–IV European clone [121]. One Belgian pig CC80 strain contained an exfoliatin (*etd*), an epidermal cell differentiation inhibitor (*edinB*), and staphylococcal exotoxin-like protein (*setC*) and IEC genes (*isaB, isdA, hysA1, hysA2*) [121]. A comparison of the *pvl*-positive MRSA isolates (ST8-t008–IVa) from American pig and pet animals indicated the presence of common virulence profiles (*lukSF-PV, clfA, clfB, fnbA*, and *sek*) except for the *fnbB* gene of a canine isolate [118]. Spanish ST1379/CC97 porcine isolates carried an exfoliatin (*eta*), a leukotoxin (*lukE/D*), and a gamma-hemolysin (*hlg-2*) but were negative for *etb, etc, tst, pvl*, and enterotoxins [255]. The occurrence and prevalence of enterotoxin genes in MRSA isolates from food-producing or companion animals is summarized in **Table 3**. The presence of multidrug-resistant MRSA in companion and food animals, combined with the enterotoxin genes, will require constant monitoring and evaluation of mitigation strategies.
