Hyaluronidase

ABSTRACT

Staphylococci form part of the normal flora of man and a wide variety of animals. Some staphylococcal species also cause a wide variety of pyogenic infections. The main pathogenic staphylococcus in man is Staphylococcus aureus. Increasingly, methicillin-resistant S. aureus (MRSA) has been a problem in the healthcare setting. Reports of MRSA in animals have been infrequent; however, evidence suggests that MRSA is being isolated increasingly from animals, in particular household pets and other companion animals. This article reviews the prevalence of pathogenic Staphylococci in animals, with an emphasis on the emergence of MRSA as a possible animal pathogen.

KEY WORDS: Animals. Pets. Staphylococci.

Staphylococcus aureus,

methicillin-resistant.

Introduction

Staphylococci are facultative anaerobic, Gram-positive, catalase-positive cocci in the family Micrococcaceae. Staphylococci form part of the normal bacterial flora of the skin, mucous membranes and alimentary and urogenital tracts of a wide variety of mammals and birds. As well as making up part of the normal flora, some species of Staphylococci may also cause a wide variety of usually pyogenic processes in various parts of the body (e.g., skin, wounds, ears and joints) in animals and humans.

In veterinary medicine, three staphylococcal species are of particular importance in specific diseases: Staphylococcus aureus, a cause of mastitis in animal species such as cattle, sheep, goats and horses and of dermatitis in sheep and goats; botryomycosis in pigs and horses; and suppurative conditions similar to those caused by S. intermedius in cats and dogs.

S. intermedius is a primary cause of pyoderma in dogs, and causes a range of other suppurative infections such as endometritis, cystitis and otitis externa in this species of animal. S. intermedius causes various pyogenic conditions in cats. S. hyicus causes exudative epidermitis (greasy pig disease) and arthritis in pigs. S. aureus subsp. anaerobius has been implicated in lymphadenitis in sheep, S. schleiferi subsp. coagulans in otitis externa in dogs and S. delphini as been reported as causing suppurative skin lesions in dolphins.1

The Staphylococci mentioned above are loosely termed coagulase-positive staphylococci; however, care must be taken in the identification of these organisms as there is wide variation between the coagulase and thermonuclease reactions in some of these species. A variety of coagulase-negative Staphylococci are also isolated from animals (Table 1). Most coagulase-negative staphylococci associated with animals, as with humans, are opportunistic pathogens that lack many of the virulence factors associated with coagulase-positive staphylococci.

This review of the literature will consider the prevalence of coagulase-positive staphylococci in animals, and will concentrate on the data supporting evidence of the emergence of methicillin-resistant S. aureus (MRSA) as a pathogen in cats and dogs, the implications for human owners of MRSA-infected animals and the possibility of transfer between humans and animals.

Staphylococci in cats and dogs

The most prevalent Staphylococcus species in cats and dogs is S. intermedius. Raus et al.2 used a range of biochemical procedures to identify 160 staphylococcal isolates from a variety of clinical diseases. A total of 123 strains were isolated from dogs, 10 from horses, 10 from cats and 17 from various other animals. After initial screening for coagulase production, all strains were tested for acid production from maltose, acid formation anaerobically from mannitol, production of acetoin, tellurite reduction, pigmentation of colonies, hyaluronidase activity and a modification of the coagulase test that inhibits the coagulase of S. intermedius.3

Of the strains studied, 27 were S. aureus, 115 were S. intermedius and 18 were either coagulase-negative by the original method or were unidentified to species level using this battery of tests and were not identified further. The study found that the most useful discrimatory tests were acid production from maltose and production of acetoin; however, it did not indicate which Staphylococcus species were isolated from which animals. This is significant deficiency as different staphylococci are more prevalent in certain species of animals.

Biberstein et al.4 assessed the species distribution of 268 isolates of coagulase-positive staphylococci among various animals, of which 91.8% of 195 isolates from dogs and 46.6% of 15 isolates from cats were S. intermedius. The remaining isolates in both cases were S. aureus. In this study, all staphylococcal isolates were screened for coagulase production using a tube coagulase test with rabbit plasma. Further biochemical characterisation was carried out using the API Staph-Ident system (Analytab Products, Plain view, NY, USA).

Incidentally, the study also assessed the site of infection of the original isolate and the susceptibility pattern of the isolates tested. It concluded that there were no meaningful differences in the site of infection or the susceptibility pattern between S. aureus and S. intermedius and questioned the clinical value of routine distinction between the two species.

Cox et al.5 investigated 100 clinical isolates of staphylococci from animals, identifying them using a commercial biochemical micromethod. Of these isolates, 79 were from a canine source and 70 (88.6%) were confirmed as S.intermedius. In a further study in 1988 by Cox et al.,6 11 healthy dogs were followed up over a one-year period by monthly sampling of 12 sites (five skin, seven mucous membranes), and a total of 804 isolates of Staphylococcus species were recovered. S. intermedius accounted for 40.2% of the isolates (12 other species of staphylococci were identified). Nine dogs completed the yearlong study and S. intermedius was a persistent isolate from eight of the dogs. In a similar study in cats, Cox et al.7 also found that S. intermedius was the most commonly isolated coagulase-positive Staphylococcus.

Lilenbaum et al.8 assessed 98 strains of staphylococci from cats in Brazil. Coagulase-positive staphylococci were isolated from 40 cats, 26 (65%) of which were S. intermedius. In Japan, Igimi et al.9 isolated nine (42.9%) S. intermedius from a total of 21 coagulase-positive staphylococci (the remainder being S. aureus) out of a total of 93 staphylococci recovered from cats.

A small study carried out by Krogh and Kristensen10 in Norway investigated the microflora on normal skin in 10 dogs and 10 cats. Interestingly, they isolated S. aureus from nine (90%) of the dogs and four (40%) of the cats, with no isolates of S. intermedius. However, Hajek published 'Staphylococcus intermedius, a new species isolated from animals'11 in the same year. With this in mind, it is possible that a proportion of the S. aureus isolates in Krogh and Kristensen's study may have been S. intermedius, which, at that time, would not have been recognised as a separate species.

Susceptibility of coagulase-positive stapylococci in animals

Increasing antimicrobial resistance in clinical bacterial isolates is of growing concern in both human and veterinary medicine. Although antimicrobial resistance is fairly stringently monitored in human medicine, both on a national and international level, there is little information in the literature on trends in antimicrobial resistance in bacteria isolated from companion animals, nor is there currently a single-source database from which this information can be obtained. A summary of a selection of studies carried out on antimicrobial susceptibility of coagulase-positive staphylococci isolated from companion animals is shown in Table 2.

In 1984, Biberstein assessed the susceptibility of 268 coagulase-positive staphylococci from various clinical sources from dogs (n=195), horses (n=25), cats (n=15), monkeys, (n=11), goats (n=6), cattle (n=7) and four other species.4 Of these isolates, 63 were identified as S. aureus and 200 as S. intermedius. Biberstien concluded that there was no demonstrable significant difference between the susceptibility patterns between these strains.

Kruse et al., in Norway, retrospectively analysed the susceptibility of S. intermedius over two periods, 1986-1987 and 1993-1994.12 A significant increase in resistance to penicillin was seen between the two periods, from 46% to 58.6%. This was accompanied by in a significant rise in resistance to lincomycin (3% to 24.8%), clindamycin (2.1% to 19.5%) and erythromycin (3.3% to 24.8%).

Werckenthin et al.13 reviewed three studies carried out in 1986 in the USA,14 in 1992 in the UK15 and in 1992 in both the USA and Germany.16 The study carried out in the USA reported the highest rates of penicillin and tetracycline resistance (83% and 52%, respectively).

Pellerin17 compared 131 S. intermedius strains from apparently healthy animals and 187 S. intermedius strains from dogs with pyoderma. These strains were collected during three one-year periods (1986, 1992 and 1995). Minimum inhibitory concentration susceptibility testing was performed and results categorised as susceptible or resistant according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines.

Comparison of susceptibility data between the 1986 and 1995 groups in the healthy dogs showed little difference in resistance rates, except for chloramphenicol susceptibility, which dropped from 78% in 1986 to 53% in 1995. This was reflected in the isolates from the dogs with pyoderma, in which chloramphenicol susceptibility rates dropped from 76% in 1986 to 60% in 1995. Further reduction was also seen in the susceptibility of S. intermedius for tetracycline (81% in 1986, 60% in 1995) and trimethoprim/sulphonamide (94% in 1986, 64% in 1995) in the pyoderma group. Pellerin suggested that there are similarities and differences between the resistance in these strains and in human strains.

It was stated that an increase in the prevalence of resistance follows increased use of antimicrobial agents, and also that resistance to the penicillins, tetracycline and erythromycin is the most frequent. It was suggested that a key difference is the location of the resistance genes, with chromosomal genes more prevalent in S. intermedius and plasmid resistance genes more common in S. aureus.

A study carried out in Switzerland by Boerlin et al.18 investigated 77 S. intermedius strains isolated from routine diagnostic submissions from four cats and 73 dogs. Disc diffusion susceptibility testing was performed using NCCLS guidelines. The main focus of the study was to assess the genetic linkage of macrolide and aminoglycoside resistance in S. intermedius. The susceptibility profile of the main battery of antimicrobial agents tested did not reveal anything remarkably different from previous studies. Also, all 23 isolates shown to be erythromycin-resistant were also resistant to the aminoglycosides streptomycin and neomycin and the macrolide spiramycin.

All the erythromycin-resistant isolates showed reduced susceptibility to clindamycin. Susceptibility testing using adjacent erythromycin and clindamycin discs showed the typical D-shaped inhibition around the clindamycin disc, indicative of inducible resistance.

According to Boerlin, erythromycin resistance to S. intermedius is due to the presence of the erm (B) gene. This study found that the erm (B) gene is linked physically to adjacent aminoglycoside resistance genes in all the isolates tested.

Tejedor et al.19 found no significant difference between the susceptibility of coagulase-positive staphylococci (mainly S. intermedius) from 22 healthy dogs and 45 dogs suffering from otitis media. Overall, 35.8% of the 67 strains were susceptible to all of the antibiotics tested, with penicillin and ampicillin showing the lowest activity.

This study also demonstrated that polymixin B had low activity against the isolates tested. Although polymixin B is primarily an agent that acts against Gram-negative organisms, it does have in vitro activity against S. intermedius (although not against S. aureus). The paper claimed to have used NCCLS guidelines for the interpretation of the susceptibility tests performed, but NCCLS does not provide guidelines for topical agents such as polymixin B. However, with the concentration present in a topical application, it is likely that this agent would be effective against S. intermedius in vivo. Unpublished data from a commercial veterinary diagnostic laboratory (IDEXX Laboratories) demonstrate a similar pattern of resistance to the above studies among 6575 S. intermedius strains tested.

Erythromycin and clindamycin resistance in staphylococci are mediated by a group of similar methylases that are the products of a class of genes termed erm (erythromycin ribosome methylation).20 Approximately 30 erm genes have been identified. Previous reports show that erm (C) is the major methylase gene in staphylococci of human origin, followed by a minority of erm (A)-positive isolates and a very few erm (B)-positive isolates. Boerlin18 showed that the erythromycin resistance methylase encoded by the erm (B) gene is the major macrolide determinant in S. intermedius.

Tetracycline resistance is encoded by tetracycline resistance (tet) genes, of which there are 18 different types. These genes are located on mobile elements, which favours their exchange with other organisms.20 To date, four different tet genes, assigned to classes K, L, M and O, have been detected in staphylococci of animal origin.14

Schwartz et al.21 analysed 228 tetracycline-resistant staphylococci from a total of 838 staphylococci isolated from a wide range of animals. This study demonstrated that all strains carried either the tet K, L, M or O gene. Only fourteen isolates carried more than one tet gene.

Aminoglycoside resistance is usually conferred by three different mechanisms. First, ribosome alteration leads to high-level resistance resulting from single-step mutations in chromosomal genes (rpsL, rpsD or rpsE) encoding ribosomal proteins. Second, decreased permeability as a result of an absence or alteration in the aminoglycoside transport system. Third, modification in the lipopolysaccharides phenotype can result in cross resistance to all aminoglycosides.

Aminoglycosides may also be inactivated by three main enzymes: acetyltransferases, nucleotidyltransferases and phosphotransferases. Clinically, deactivation of aminoglycosides is of most importance because the genes encoding aminoglycoside-modifying enzymes can be disseminated by plasmids or transposons.22

Resistance to sulphonamides is caused primarily by plasmids and, less frequently, by chromosomal mutations. Plasmids code for proteins that interfere with drug penetration, for change in enzyme affinity or for a high production of para-aminobenzoic acid (PABA). In Grampositive bacteria, the primary target for fluoroquinolones is DNA topoisomerase IV, and the secondary target is DNA gyrase. These are encoded by the genes gyrA, gyrB, parC and parD. Resistance is usually chromosomally mediated so the spread of resistant bacteria contributes to the numbers of resistant strains rather than the transfer of resistance plasmids.23

Although a common form of penicillin-resistance, β-lactamase production is not the only mechanism of penicillin/β-lactam resistance. Susceptibility of staphylococci to β-lactam antibiotics is due to these antibiotics binding proteins known as penicillin-binding proteins (PBPs), which are membrane-bound enzymes responsible for cell-wall synthesis.

β-lactamase catalyses the opening and hydrolysis of the β-lactam ring of β-lactam antibiotics, with intrinsic resistance due to the modification of the PBPs. This takes place following the production of PBP2a, which is encoded by the mecA gene, β-lactam antibiotics are not capable of binding to this form of PBP, thus strains carrying the mecA gene are resistant to the β-lactamase-stable penicillins (e.g., the methicillin, oxacillin, cloxacillin group).24 S. aureus isolates with this form of resistance are popularly known as methicillin-resistant S. aureus (MRSA).

Currently, MRSA is one of the most important infection-control issues in the UK and in many countries worldwide. The isolation of MRSA from companion animals is a relatively new phenomenon. Thus, the remainder of this review will focus on the emergence of MRSA as an issue in animals.

Methicillin-resistant staphylococci in animals

Methicillin-resistant S. aureus in animals has been reported in the literature since 1975.25 Devriese reported 68 MRSA isolates from mastitis milk samples originating in 20 Belgian dairy herds, and suggested that these strains might have come from a single human source. Transmission of 'human' strains of S. aureus to farm animals was also reported by Moeller et al.26 in 1963. In this study, phage types of staphylococci found in hospitals were compared to the phage types of staphylococci found in the milk of dairy herds owned by recently discharged patients. Moeller found that recently discharged hospital patients who could have been responsible for transfer of staphylococci to their animals were present on 7% of 122 farms studied.

In 1997, Hartmann et al.27 reported a post-operative wound from a horse that had become infected with MRSA. In light of the increasing incidence of MRSA in both hospitals and the community, it was thought likely that infections in animals would become more frequent.

The possibility of humans being primarily involved in the transfer of MRSA to animals was supported by Seguin et al.28 in 1999. Eleven horses admitted to a veterinary teaching hospital for various medical and surgical procedures over a 13-month period were assessed. All the animals were re-admitted to the hospital with wound infections in the site of the original procedure two to three weeks after initially being discharged.

Follow-up screening was carried out on five members of the medical and surgical staff involved with the surgery. Three of the human screening swabs were culture-positive for MRSA. All isolates were subjected to pulsed-field gel electrophoresis (PFGE) typing. This revealed that all 11 equine stains and the strains isolated from the three members of the medical team were considered to have originated from the same strain. Seguin concludes that the initial source of the outbreak was probably of human origin, as the horses arrived at the hospital over a 13-month period from a variety of locations and with no apparent staphylococcal infection at the time of arrival.

Lee29 collected 1913 specimens over a two-year period from cattle, pigs and chickens. Of these specimens, 421 contained S. aureus and of the 28 that showed increased minimum inhibitory concentration (MIC, >2 g/mL) to oxacillin, 15 strains (12 from dairy cattle and three from chickens) were confirmed to possess the mecA gene, confirming them as MRSA. Random amplified polymorphic DNA (RAPD) patterns were generated for these 15 isolates.

Four human MRSA isolates that were representative of 38 strains collected from hospitals during the time of the study were also analysed by RAPD. Typing revealed eight visually distinct RAPD patterns from the animal isolates. Comparison of these patterns with those of the human strains did give concordant results in some cases; however, the study snowed little in the way of conclusive proof that animals were the source of infection in humans. This study was carried out in Korea, where it was reported that the rate of methicillin-resistance among S. aureus was around 50%. It was suggested that once interspecies transfer of this organism has occurred, these isolates can become widespread in the veterinary environment.

In Belgium. Cheirs et al. isolated 75 strains of S. aureus from 512 samples obtained from horses with skin disorders.30 Of these, two (2.6%) were found to carry the mecA gene and were therefore confirmed as MRSA. No attempt was made to follow-up the source of MRSA, but the possibility of human origin was suggested.

However, the relationship between animal and human MRSA isolates has been disputed by Shimizu et al. in a study in Japan.31 Fifteen equine isolates of MRSA were compared with nine human isolates of MRSA using PFGE. Although this showed that all 15 equine MRSA strains were closely related, none of the nine human isolates showed any similarity to the equine strains. A weakness in this study was that the human strains were taken from a source unrelated to the 15 equine strains.

All the human strains were similar to the most prevalent genotype at the time of the study, which accounted for over 70% of all MRSA isolates across Japan in the 1990s. The equine strains were similar to a genotype that was prevalent in Japan in the early 1980s but which declined in incidence dramatically in the 1990s. Clearly, screening and typing of strains isolated from humans associated with the horses involved would have proved of greater value, especially if a rare genotype were to be detected by the human screens.

Weese et al.2 collected nasal swabs from 2283 horses at admission to a veterinary teaching hospital in Canada. One hundred and twenty MRSA isolates (5.3%) were detected. A similar detection rate was found in a study carried out in the north-west of England by Williams et al.33 Eight horses out of a total of 106 were found to carry strains of MRSA. These were distinct from the most prevalent MRSA strains in the UK at the time (EMRSA-15 and EMRSA-16). Williams proposed that the acquisition of the mccA gene in these cases was either by transfer of the original strain from the human sources or by acquisition of the mecA gene from coagulase-negative strains that harboured it.

Another possible source of MRSA for animals is the environment. Weese et al.34 collected 260 samples from stalls, examination and treatment rooms, public areas, personal items, medical equipment and handling equipment at a veterinary teaching hospital.34 Overall, MRSA was isolated from 25 (9.6%) of the 260 sites. The most commonly contaminated sites were in stalls housing MRSA-positive horses, where 18 (62%) out of 29 surfaces were contaminated. Incidentally, a clinician's mobile phone was also MRSA-positive and subsequently the owner was identified as an asymptomatic nasal carrier of MRSA. Due to the manner in which horses explore their surroundings, it is possible that this could be a source of either contamination by MRSA carriers or of spread via the environment.

A recent national newspaper article35 focused attention on the potential for companion animals, mainly cats and dogs, to act as a reservoir for the carriage of MRSA. Links with MRSA infection in a companion animal were reported from a ward cat that was heavily colonised with MRSA on a geriatric ward in which intensive screening of the patients and staff revealed an unusually high MRSA carriage rate (38%).36 Appropriate infection control measures and the removal of the cat led to a rapid reduction in human carriage.

Cefai et al.37 reported a case of MRSA conjunctivitis in a pet dog that was associated with human carriage of MRSA. Lillenbaum et al. in Brazil examined samples taken from 148 adult cats for the presence of staphylococci.8 S. aureus was isolated in 14 (9.5%) samples, with three (2%) isolates proving to be MRSA.

Tomlin et al.38 described the diagnosis and management of MRSA infection in 11 dogs. Three originated in the United Kingdom and eight were from two different locations in the United States. The dogs comprised a variety of breeds and ages. According to the clinical history, six infections developed after surgical treatment, two as a complication of wounds and three in dogs with recurrent pyoderma. Typing by PFGE was only performed on the three isolates from the UK, and revealed that these had similar PFGE band patterns. As discussed later, larger studies have since found that this is not unusual.

Antibiotic treatment based on the susceptibility patterns of the organisms involved improved or resolved the MRSA infection in nine out of the 11 dogs. Detailed evaluation of the environment and human contacts involved was not carried out and hence the origin of the MRSA in these dogs was uncertain.

In a study in Korea in 1999,39 12 strains of MRSA recovered from dogs hospitalised with underlying disease were characterised by PFGE and the organisms were investigated for their toxin production profiles. Ten out of the 12 isolates produced one or more toxins. Six strains produced staphylococcal enterotoxin B (SEB), one produced toxic-shock syndrome toxin-1 (TSST-1) and three produced both TSST-1 and staphylococcal enterotoxin C (SEC). Typing by PFGE revealed six different PFGE patterns, one of which accounted for six of the isolates. This study concluded that there were several different strains involved at the veterinary hospital. Again no environmental or human carriage screening was undertaken to investigate the source of these isolates.

As demonstrated by Simoons-Smit et al.,40 typing of stains isolated from human contacts may be beneficial in determining the source of possible infection. In this study, six strains of S. aurcus (methicillin-sensitive) isolated from a 20-year-old woman suffering from pyoderma, her boyfriend, her mother, two isolates from her cat and one from her dog were collected. All isolates were analysed using an amplified fragment length polymorphism (AFLP) technique. This is based on the selective polymerase chain reaction (PCR) amplification of restriction fragments from a total digest of genomic DNA.

Analysis of the strains revealed indistinguishable patterns at a high correlation level. All the strains were clearly distinguishable from unrelated strains run as controls. Although the isolates in this study were MSSA and not MRSA, the transmission of S. aureus between humans and animals in a single household was demonstrated and there is no reason why this might not occur with MRSA.

Further evidence of possible human-to-animal transmission of MRSA is provided by Oughton et al.41 This study describes 14 cases of MRSA in animals where transmission was most likely derived from community sources. Six equine and two feline cases were followed up. The feline strains were isolated from cats within the same household and were shown to be indistinguishable. Of the six canine isolates included in the study, one dog and its owner were each infected by indistinguishable (by PFGE) strains of MRSA. The owner had been hospitalised for surgery the previous year and had positive screening swabs for MRSA. This isolate was also indistinguishable from the strains obtained from subsequent screening swabs from the owner and the isolate from the pet dog.

Of the remaining five canine cases, four dogs had been exposed to healthcare environments, either through their owners or by attendance at various therapeutic centres. As is the case with human outbreaks, Oughton suggests that contact tracing and attempts at MRSA eradication would be highly advisable.

A study in Canada, undertaken by Willey et al.,42 investigated a cluster of MRSA isolates from horses, and included a follow-up human and equine surveillance programme. Nasal MRSA isolates from horses (n=82) and from human contacts (n=29) were characterised by a variety of methods, including PFGE. Typing showed that 95% of equine and 93% of human MRSA strains were indistinguishable. No single route of transmission was demonstrated and it was concluded that a combination of human-to-horse, horse-to-human and horse-to-horse transmission was likely.

Manian43 described the case of a 48-year-old diabetic with a leg-stump infection that subsequently proved to be MRSA. Four months later the patient's wife developed a skin infection and the MRSA isolated proved indistinguishable from that which was grown from her husband's stump. The only other household member was a healthy 18-month-old Dalmatian dog that frequently slept in the couple's bed. Nares cultures were performed on the dog and these revealed an MRSA indistinguishable from those obtained from the owners.

Treatment and decolonisation of the owners and the dog failed to clear the MRSA infection from all, with the original patient, the patient's wife and the dog being re-infected or recolonised in the nares over a six-month period until full decolonisation was achieved. All remained free of MRSA infection four months after the completion of decolonisation therapy. Manian suggested that the evaluation of patients with recurrent MRSA colonisation or infection that does not have an obvious source should prompt enquiries about regular contact with household pets and further investigation of such hidden carriers.

Rich et al.44 reported 95 isolates of MRSA from companion animals over a 12-month period from January 2003. These isolates originated mostly from post-operative and wound infections in 69 dogs, 24 cats, one horse and one rabbit. Twelve isolates were investigated by phage and PFGE typing and were found to belong to the two most prevalent strain types currently carried by humans in the UK (epidemic-MRSA-15 and epidemic-MRSA-16). The authors suggested that MRSA carriage in companion animals was most likely a result of acquisition from a human source.

In The Netherlands, Duijkeren et al.45 reported MRSA isolated from two dogs that underwent surgery in a foreign country. One of the isolates was said to be similar to a human MRSA cluster, which the authors described as unusual. In response to this article, Rich et al.46 state that, far from being unusual, this is a common occurrence. Thirty-one randomly selected MRSA isolates from a total of 210 MRSA strains isolated from companion animals were characterised by a range of phenotypic and genotypic tests. In contrast to the findings of Duijkeren et al., 29 (93.5%) of the animal isolates in the study were indistinguishable from human healthcare-associated epidemic MRSA strains currently prevalent in the United Kingdom. Rich et al. suggested that detailed characterisation of such strains may be prudent, not only from a public health perspective but also to provide insight into the transmission dynamics of MRSA in human and animal populations.

It is clear that there is a need for continued vigilance and systematic study to further our understanding of the origins and epidemiology of MRSA in companion animals. It is hoped that further planned study will determine whether or not an association exists between MRSA infection in dogs and cats, and MRSA colonisation or infection in humans closely associated with the affected animals. Specific objectives are to determine risk factors for MRSA infection in dogs and cats, the relationship between animal carriage and human carriage, and the genetic relationship of animal and human strains.

References

1 Quinn PJ, Markey BK, Carter ME, Donnelly WJC, Leonard FC, Magure D. Veterinary microbiology and microbial disease. London: Blackwell Science, 2002.

2 Raus J, Love DN. Characteristics of coagulase-positive Staphylococcus intermedius and Staphylococcus aureus isolated from veterinary clinical specimens. J Clin Microbiol 1983; 18: 789-92.

3 Engels M, Kamps MA, van Boven CE Rapid and direct staphylocoagulase assay that uses a chromogenic substrate for identification of Staphylococcus aureus. J Clin Microbiol. 1981; 14: 496-500.

4 Biberstein EL, Jang SS, Hirsh DC. Species distribution of coagulase-positive staphylococci in animals. J Clin Microbiol 1984; 19: 610-5.

5 Cox HU, Newman SS, Roy AF, Hoskins JD. Species of Staphylococcus isolated from animal infections. Cornell Vet 1984; 74: 124-35.

6 Cox HU, Hoskins JD, Newman SS, Foil CS, Turnwald GH, Roy AF. Temporal study of staphylococcal species on healthy dogs. Am J Vet Res 1988; 49: 747-51.

7 Cox HU, Hoskins JD, Newman SS et al. Distribution of staphylococcal species on clinically healthy cats. Am J Vet Res 1985; 46: 1824-8.

8 Lilenbaum W, Nunes EL, Azeredo MA. Prevalence and antimicrobial susceptibility of staphylococci isolated from the skin surface of clinically normal cats. Lett Appl Microbiol 1998; 27: 224-8.

9 Igimi S, Atobe H, Tohya Y, Inoue A, Takahashi E, Konishi S. Characterisation of the most frequently encountered Staphylococcus species in cats. Vet Microbiol 1994; 39: 255-60.

10 Krogh HV, Kristensen S. A study of skin diseases in dogs and cats. II. Microflora of the normal skin of dogs and cats. Nord Vet Med 1976; 28: 459-63.

11 Hajek V. Staphylococcus intermedius, a new species isolated from animals. Int J Syst Bacteriol 1976; 26: 401-8.

12 Kruse H, Hofshagen M, Thoresen SI, Bredal WP, Vollset I, Soli NE. The antimicrobial susceptibility of Staphylococcus species isolated from canine dermatitis. Vet Res Commun 1996; 20: 205-14.

13 Werckenthin C, Cardoso M, Martel JL, Schwarz S. Antimicrobial resistance in staphylococci from animals with particular reference to bovine Staphylococcus aureus, porcine Staphylococcus hyicus and canine Staphylococcus intermedius. Vet Res 2001; 32: 341-62.

14 Medleau L, Blue JL. Frequency and antimicrobial susceptibility of Staphylococcus species isolated from feline skin lesions. J Am Vet Med Assoc 1988; 193: 1080-1.

15 Noble WC, Kent L. Antibiotic resistance in Staphylococcus intermedius isolated from cases of pyoderma in the dog. Vet Dermatol 1992; 3: 71-4.

16 Greene RT, Schwarz S. Small antibiotic resistance plasmids in Staphylococcus intermedius. Zentralbl Bakteriol 1992; 276: 380-9.

17 Pellerin JL, Bourdeau P, Sebbag H, Person JM. Epidemiosurveillance of antimicrobial compound resistance of Staphylococcus intermedius clinical isolates from canine pyodermas. Comp Immun Microbiol Infect Dis 1998; 21: 115-33.

18 Boerlin P, Burnens AP, Frey J, Kuhnert P, Nicolet J. Molecular epidemiology and genetic linkage of macrolide and aminoglycoside resistance in Staphylococcus intermedius of canine origin. Vet Microbiol 2001; 79: 155-69.

19 Tejedor MT, Barrasa JL. Identification and antimicrobial susceptibility of coagulase-positive staphylococci isolated from healthy dogs and dogs suffering from otitis externa. J Vet Med 2002; 49: 419-23.

20 Lorian V Antibiotics in laboratory medicine (4th edn). St. Louis: Williams and Wilkins, 1996.

21 Schwartz S, Roberts MC, Weckenthin C, Pang Y, Lange C. Tetracycline resistance in Staphylococcus species from domestic animals. Vet Microbiol 1998. 63: 217-27.

22 Shaw KJ, Rather PN, Hare RS, Miller GH. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev 1993; 57: 138-63.

23 Piddock LJV. Fluoroquinolone resistance. BMJ 1998; 317: 1029-30.

24 Anon. Methicillin resistance in staphylococci. Topics in Infectious Diseases Newsletter. January 2001.

25 Devriese LA, Hommez J. Epidemiology of methicillin-resistant Staphylococcus aureus in dairy herds. Res Vet Sci. 1975; 1: 23-7.

26 Moeller RW, Smith IM, Shemaker AC, Tjalma RA. Transfer of hospital staphylococci from man to farm animals. J Am Vet Med Assoc 1963; 142: 613-7.

27 Hartman FA, Trostle SS, Klohnen AA. Isolation of methicillin-resistant Staphylococcus aureus from a postoperative wound Infection in a horse. J Am Vet Med Assoc 1997; 211: 590-2.

28 Seguin JC, Walker RD, Caron JP et al. Methicillin-resistant Staphylococcus aureus outbreak in a veterinary teaching hospital: potential human-to-animal transmission. J Clin Microbial 1999; 37: 1459-63.

29 Lee JH. Methicillin (oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans. Appl Environ Microbiol 2003; 69: 6489-94.

30 Chiers K, Decostere A, Devriese LA, Haesebrouck F. Bacteriological and mycological findings, and in vitro antibiotic sensitivity of pathogenic staphylococci in equine skin infections. Vet Rec 2003; 138-40.

31 Shimizu A, Kawano J, Yamamoto C, Kakutani O, Anzai T, Kamada M. Genetic analysis of equine methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis. J Vet Med Sci 1997; 59: 935-7.

32 Weese JS, Archambault M, Low DE. Methicillin-resistant Staphylococcus aureus (MRSA) surveillance in horses at a veterinary teaching hospital (Abstract). 11th Annual International Symposium on Staphylococci and Staphylococcal infections. 2004. Charleston, SC, USA.

33 Williams K, Baptiste K, Williams N, Clegg P, Hart CA. Preliminary survey of horses as carriers of methicillin-resistant Staphylococcus in the north-west of England (Abstract). European College of Veterinary Surgeons' 14th Annual Scientific Meeting, Marcy l'Etoile, France. 7-9 July 2005.

34 Weese JS, DaCosta T, Button L, Goth K, Ethier M, Boehnke K. Isolation of methicillin-resistant Staphylococcus aureus from the environment in a veterinary teaching hospital. J Vet Intern Med 2004; 18: 468-70.

35 Revill J. Hospital superbug MRSA spreads to animals. Observer 14 December 2003.

36 Scott GM, Thompson R, Malone-Lee J, Ridgway GL. Cross-infection between animals and man: possible feline transmission of Staphylococcus aureus infection in humans? J Hosp Infect 1988; 12: 29-34.

37 Cefai C, Ashurst S, Owens C. Human carriage of methicillin-resistant Staphylococcus aureus linked with a pet dog. Lancet 1994; 344: 539-40.

38 Tomlin J, Pead MJ, Lloyd DH et al. Methicillin-resistant Staphylococcus aureus infections in 11 dogs. Vet Rec 1999; 144(3): 60-4.

39 Pak S, Han HR, Shimizu A. Characterization of methicillin-resistant Staphylococcus aureus isolated from dogs in Korea. J Vet Med Sci 1999; 61: 1013-8.

40 Simoons-Smit AM, Savel Koul PHM, Stoof J, Starink TM, Vandenbroucke-Grauls CMJ. Transmission of Staphylococcus aureus between humans and domestic animals in a household. Eur J Clin Microbiol Infect Dis 2000; 19: 150-2.

41 Oughton MT, Dick HLN, Willey BM et al. Methicillin-resistant Staphylococcus aureus as a cause of infections in domestic animals: evidence for a new humanotic disease? 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, USA, 16-19 December 2001.

42 Willey BM, Low DE, Archambault M et al. Methicillin-resistant Staphylococcus aureus (MRSA) infection in horses and horse personnel, 2000-2002 (Abstract). Canadian Association for Clinical Microbiology and Infectious Diseases. Montreal, Quebec. 2-5 Nov 2003.

43 Manian FA. Asymptomatic nasal carriage of mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in household contacts. CID 2003; 36: 26-8.

44 Rich M, Roberts L. Methicillin-resistant Staphylococcus aureus isolates from companion animals. Vet Rec 2004; 154 (10): 310.

45 van Duijkeren E, Box ATA, Heck MEOC, Wannet WJB, Fluit AC. Methicillin-resistant staphylococci isolated from animals. Vet Microbiol 2004; 103: 91-7.

46 Rich M, Roberts L, Kearns A. Methicillin-resistant staphylococci isolated from animals. Vet Microbiol 2005; 105(3-4): 313-4.

M. RICH

Microbiology Deportment, IDEXX Laboratories, Grange House, Sandbeck Way, Wetherby, West Yorkshire LS22 7DN, UK

Accepted: 31 March 2005

Correspondence to: Michael Rich

Email: mick-rich(@idexx.com

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