**1. Introduction**

78 Epidemiology Insights

Van Bambeke, F.; Laethem, Y.V.; Courvalin, P. & Tulkens, P.M. (2004) Glycopeptide

Van Belkum, A.; Verkaik, N.J.; Vogel, C.P.; Boelens, H.A.; Verveer, J.; Nouwen, J.L.;

Van Duijkeren, E.; Wolfhagen, M.J.H.M.; Heck, M.E.O.C. & Wannet, W.J.B. (2005).

Walsh, T.R.; Howe, R.A.; Wootton, M.; Bennett, P.M. & MacGowan, A.P. (2001). Detection of

Wang, R.; Braughton, K.R.; Kretschmer, D.; Bach, T.H.L.; Queck, S.Y.; Li, M.; Kennedy, A.D.;

Wertheim, H.F.L.; Walsh, E.; Choudhurry, R.; Melles, D.C.; Boelens, H.A.M.; Miajlovic, H.;

Wey, S.B.; Cardo, D.M.; Halker, E.; Carratu, F.P. & Saes, A.C. (1990). Distribution and

Zhang, K.; McClure, J.A.; Elsayed, S.; Louie, T. & Conly, J.M. (2005). Novel Multiplex PCR

Zhang, K.; McClure, J.A.; Elsayed, S.; Conly, J.M. (2009). Novel Staphylococcal Cassette

*of Clinical Microbiology*, Vol. 43, No. 10, pp. 5026–5033, ISSN 1098-660X. Zhang, K.; McClure, J.A.; Elsayed, S.; Louie, T. & Conly, J.M. (2008). Novel Multiplex PCR

*Microbiology*, Vol. 43, No. 12, pp. 6209–6211, ISSN 1098-660X.

*Chemotherapy*, Vol. 47, pp. 357-358, ISSN 1460-2091.

1, (January), pp. e17, ISSN 1549-1676.

46, No. 3, pp. 1118–1122, ISSN 1098-660X.

531–540, ISSN 1460-2091.

pp. 913–936, ISSN 1179-1950.

1537-6613.

1546-170X.

1806-9460.

antibiotics: from conventional molecules to new derivatives. *Drugs,* Vol. 64, No. 9,

Verbrugh, H.A. & Wertheim, H.F.L. (2009). Reclassification of *Staphylococcus aureus* Nasal Carriage Types. *Journal of Infectious Diseases*, Vol. 199, pp. 1820 – 1826, ISSN

Transmission of a Panton-Valentine Leucocidin-Positive, Methicillin-Resistant *Staphylococcus aureus* Strain between Humans and a Dog. *Journal of Clinical* 

glycopeptide resistence in *Staphylococcus aureus*. *Journal Antimicrobial and* 

Dorward, D.W.; Klebanoff, S.J.; Peschel, A.; DeLeo, F.R. & Otto, M. (2007). Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. *Nature Medicine,* Vol. 13, No. 12, pp. 1510-1514, ISSN

Verbrugh, H.A.; Foster, T. & van Belkum, A. (2008). Key Role for Clumping Factor B in *Staphylococcus aureus* Nasal Colonization of Humans. *PLoS Medicine*, Vol. 5, No.

analysis of 8,268 nosocomial infections at the Hospital São Paulo: 1985 to 1989. *Revista do Hospital São Paulo Escola Paulista de Medicina*, Vol. 1, pp. 169-174, ISSN

Assay for Characterization and Concomitant Subtyping of Staphylococcal Cassette Chromosome *mec* Types I to V in Methicillin-Resistant *Staphylococcus aureus*. *Journal* 

Assay for Simultaneous Identification of Community-Associated Methicillin-Resistant *Staphylococcus aureus* Strains USA300 and USA400 and Detection of *mecA* and Panton-Valentine Leukocidin Genes, with Discrimination of *Staphylococcus aureus* from Coagulase-Negative Staphylococci. *Journal of Clinical Microbiology*, Vol.

Chromosome *mec* Type, Tentatively Designated Type VIII, Harboring Class A *mec* and Type 4 *ccr* Gene Complexes in a Canadian Epidemic Strain of Methicillin-Resistant *Staphylococcus aureus*. *Journal Antimicrobial and Chemotherapy*, Vol. 53, pp. Until the 1990s, methicillin-resistant *Staphylococcus aureus* (MRSA) was traditionally considered a pathogen causing nosocomial infections, being the so-called HA-MRSA (healthcare-associated methicillin-resistant *Staphylococcus aureus*). However, over time, cases of MRSA-positive individuals were observed who never had contact with hospital services, and strains from these individuals were identified and named CA-MRSA (communityassociated methicillin-resistant *Staphylococcus aureus*). In 2003 in the Netherlands, a new MRSA strain arose in patients that could not be typed through PFGE (pulsed field gel electrophoresis) with *Sma*I, with resistance to digestion by this enzyme (Bens et al., 2006), being called since then NT-MRSA (non typeable methicillin-resistant *Staphylococcus aureus*). Investigations of this NT-MRSA intensified, and it was observed that these patients carrying this strain had previous contact with pigs and the geographic distribution of cases showed clusters near pig farms (van Loo et al., 2007). With more advanced studies, it was possible to determine strains strictly related to animals, such as those found in pigs, which were named LA-MRSA (livestock-associated methicillin-resistant *Staphylococcus aureus*) in 2010 (Vanderhaeghen et al., 2010).

The resistance to methicillin in staphylococci is mediated by the *mecA* gene that encodes a modified penicillin-binding protein (PBP), the PBP2a or 2', which shows reduced affinity to the resistant penicillins to penicillinase, such as methicillin and oxacillin and for all other beta-lactam antibiotics (van Duijkeren et al., 2004). Due to the need for better characterizing these isolates, they have been classified in a more detailed manner, beginning with the SCC*mec* types and patterns identified by PFGE, and are currently based on sequence type and *spa* typing. With the use of techniques such as MLST (multi locus sequence typing) and *spa* typing, characteristic clones from animals have been observed, and it is suspected that some have tropism by determined host species. An example of this is ST398, which in addition to being strictly linked to pigs, has carried novel types of SCC*mec*. Li et al. (2011) analyzed the *SCCmec* element structure carried by 31 CC398 MRSA strains isolated from participants of a conference. The strains were classified into novel types, IX and X, type V (5C2&5) subtype c and type IVa, all carriers of genes conferring resistance to metals. The SCC*mec* structures from CC398 strains were distinct from those usually found in humans, complementing evidence that humans are not the original host for CC398. With the absence of a complete evaluation of risk factors

MRSA Epidemiology in Animals 81

Pets have been shown to act as reservoirs of bacteria resistant to antimicrobials, and MRSA transmission between humans and animals has been described. For strains of MRSA with a low specificity to the host, the transference is likely to occur in both directions between humans and pets living at the same household (Nienhoff et al., 2009). The infections by MRSA in companion animals are predominantly of skin and soft tissues, especially during

Nienhoff et al. (2009) reported two cases of transmission of MRSA strains between humans and dogs. Three positive dogs to MRSA were identified in a survey carried out in 803 dogs and 117 cats admitted to the Small Animal Clinic of the University of Veterinary Medicine Hannover, Germany. The first case was a 6-month-old female admitted to the clinic for teeth extraction. The owner, MRSA-positive, was a specialist veterinarian in swine diseases, working in pig barns 4-5 days per week and having access to MRSA ST398-positive farms. The dog and owner strains were identical through molecular typing, belonging to ST398 and *spa* type t034. The second case was an 11-year-old male admitted to the clinic because of a cardiac problem. The likely origin of the strain was the mother-in-law of the dog's owner, who is diabetic, having received nursing care at home and presenting an infected wound on the foot and an ulcer in the right eye. The MRSA isolates found in these lesions and in the

Cows with mastitis have been the most likely to harbor MRSA, and they may be related to horizontal transfer via wet hands of colonized or infected dairy farm workers, and selection by the use of antibiotics to treat mastitis (Morgan, 2008). The first known case of MRSA transmission between cows and a person was reported by Juhász-Kaszanyitzky et al. (2007). MRSA strains isolated from cows with subclinical mastitis were phenotypically and genotypically indistinguishable from the strain from the person who worked with these animals. These strains were determined as ST1, *spa* type t127, SCC*mec*IVa. The authors considered these strains epidemiologically related, indicating transmission from cow to

Feβler et al. (2010) studied 25 MRSA ST398 isolates from cases of bovine clinical mastitis and two isolates from farm workers originating from 17 dairy farms in Germany, evaluating the genetic relatedness, antimicrobial resistance and virulence properties. Nine major ApaI PFGE patterns were found, three *spa types* (t011, t034 and t2576) and two types of SCC*mec* (IV and V) were identified. As described previously for ST398 from pigs, isolates from this sequence type originating in cases of bovine mastitis have also shown a high degree of variability when the ApaI PFGE profile and other genotypic and phenotypic characteristics were compared. A uniform pattern of virulence genes appeared to be conserved between

Türkyιlmaz et al. (2010) detected 14 of 16 strains from bovine milk of the lineage MRSA ST-239-III in which one was related to hospital-associated clones, and two strains were ST8/IV, which correspond to USA300, which causes severe community-acquired infections. The presence of MRSA ST239-III lineage can indicate a transmission from humans to animals, and the presence of ST8-IV can show emergence of strains from the community in the Aydin

dog belonged to ST225, which is frequently found in humans.

**3.1 Companion animals** 

post-surgical (Morgan, 2008).

human or from human to cow.

ST398 isolated from both animal species.

**3.2 Cattle** 

for carrying this strain as much in animals as in humans, Graveland et al. (2010) carried out the first study that showed direct association between animal and human carriage of ST398. This association, in addition to the association between MRSA and the antimicrobial use in calves, highlights the need for prudent use of antibiotics in farm animals.

One clone of special interest in ruminants is the CC133. The great majority of isolates from small ruminants is represented by this clonal complex of *S. aureus*, but its evolutionary origin and molecular basis for its host tropism remain unknown. Guinane et al. (2010), attempting to determine whether the CC133 developed as result of a transmission from human host to ruminant followed by an adaptative diversification of the genome, carried out a comparative sequencing of the complete genome. Several novel mobile genetic elements were observed in the CC133 isolates encoding virulence proteins with attenuated or enhanced activity and they were widely distributed, suggesting a key role in their hostspecific interaction. These data provide broad and new insights into the origin and basis molecular of *S. aureus* ruminant host specificity. The MRSA evolution and epidemiology in animals are discussed in this chapter.
