1 Department of Veterinary Pathobiology, The Royal Veterinary and Agricultural University, Stigbøjlen 4, 1870 Frederiksberg C, Denmark; 2 Institut für Tierzucht, Bundesforschungsanstalt für Landwirtschaft (FAL), Höltystr. 10, 31535 Neustadt-Mariensee, Germany; 3 Department of Veterinary Clinical Sciences, The Royal Veterinary College, Hawkshead Campus, North Mymms, Herts AL9 7TA, UK
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Abstract |
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Keywords: dogs , cats , antimicrobial resistance
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Introduction |
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Cats and dogs represent potential sources of spread of antimicrobial resistance due to the extensive use of antimicrobial agents in these animals and their close contact with humans. The number of cats and dogs has substantially increased in modern society, with an estimated population of above 70 million in the EU countries.5 The relationship between companion animals and humans has radically changed through the years, with cats and dogs being more and more in close contact with humans. While in the past dogs usually were maintained outside households, today they are often kept inside houses. Close physical contact by touching, petting and licking occurs at high frequency on the basis of the current perception of household pets as actual family members.
This article reviews the current knowledge on antimicrobial use and prevalence of antimicrobial resistance in dogs and cats. The role of these animals as reservoirs of antimicrobial resistance is discussed on the basis of available data on transmission of resistant bacteria between pets and humans as well as on exchange of resistance genes. Light is shed on the sharp contrast existing between the current policies on antimicrobial usage in food-producing animals and pet animals, with focus on the possible implications for human health.
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Antimicrobial use in pet animal veterinary practice |
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Today, increased attention is devoted to small animal welfare, resulting in increased expenditure on veterinary care, and prevention and therapy of infectious diseases. As a consequence of these changes, antimicrobial agents are now frequently used in pet animals, particularly in canine medicine, including antimicrobial preparations licensed for human use and compounds of primary importance in the treatment of human infections. In 2002, the use of pharmaceutical products in companion animals and other non-food animals accounted for 36.5% of animal health sales in the European Union, with anti-infective products representing 17% of pharmaceutical sales in animals, excluding parasiticides and medicinal feed additives.6 Compared with large animal veterinarians, colleagues working in small animal practice can count on a stronger economic basis to support laboratory analysis and antimicrobial therapy. However, this situation may result in some laxity in antimicrobial prescription, especially in difficult cases when diagnostic uncertainty, concern about risks of secondary infection, empirical selection of antibiotics and pressure by the owner can lead to inappropriate use of antimicrobial agents. Furthermore, bacterial identification and antimicrobial susceptibility testing are often not carried out for guiding antimicrobial therapy in pet animals, thus leading to inappropriate empirical treatment (e.g. cases of viral feline upper respiratory infection).
Antimicrobial classes frequently used in small animal veterinary medicine include penicillins, cephalosporins, macrolides, lincosamides, fusidic acid, tetracyclines, chloramphenicol, potentiated sulphonamides, aminoglycosides and fluoroquinolones.7 The most frequent causes of antimicrobial treatment in dogs and cats are skin and wound infections, otitis externa, respiratory infections, and urinary tract infections (UTI). Gastrointestinal infections are also common but antimicrobial therapy is not warranted in most of these syndromes. Some canine infections (e.g. pyoderma and some forms of otitis externa) often require repeated and prolonged treatment. Recurrent pyoderma caused by S. intermedius is often treated with cefalexin and sometimes with continuous low-dose or regular pulse therapy.8 Difficult cases are often treated with fluoroquinolones and can involve continuous therapy for periods as long as 7 months.9 Fusidic acid is commonly used topically in canine eye and skin infections, and mupirocin is used as an alternative to fusidic acid in skin infections. Aminoglycosides, such as gentamicin and neomycin, are routinely used for topical therapy in canine otitis. Chronic otitis externa, which commonly involves multiresistant Pseudomonas aeruginosa, is often treated topically and/or systemically with fluoroquinolones or ticarcillin.10,11 First-line drugs and alternatives for treatment of common UTI and respiratory infections in dogs and cats are described in Table 1.
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Data on overall antimicrobial use
Data on overall use of veterinary antimicrobial formulations are available in various European countries but generally do not include specific figures on antimicrobial use in different species or groups of animals. An exception is the national surveillance programme on use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark (DANMAP 2002),13 where antimicrobial use in different animal groups is inferred from pharmacy sales and use in veterinary practice. In Denmark in 2002, a total of 422 kg of antimicrobials were sold from pharmacies to pet owners with veterinary prescriptions (Table 2). Reporting of antimicrobial usage in pet animals is not required by veterinarians and this causes difficulties in the estimation of the total amount of antimicrobials used in these animals. Certain antimicrobial preparations for veterinary use (e.g. tablets and topical products) are mainly administered by veterinarians to pet animals. Based on data concerning consumption of such antimicrobial preparations, it is estimated that an additional 15002000 kg of antimicrobials were administered to pet animals in veterinary practice in 2002 (Vibeke Frøkjer Jensen, Danish Institute of Food and Veterinary Research, personal communication).
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The use of animal daily dosages (ADDs) has been recently adopted by the Danish national surveillance programme in order to enable standardization of drug dosage.13 ADDs are defined for each therapeutic formulation as the daily dosage required for treating an animal of a certain weight and are calculated for each age group. The general principles for standardization of dosage are the same as those used to calculate defined daily doses (DDDs) in humans. Table 2 reports the overall antimicrobial use expressed in ADDs for each group of animals in Denmark in 2002. Comparison amongst different groups indicates that the antimicrobial selective pressure exerted on pet animals (11 780 000 ADDs) is markedly lower than in pigs (207 988 000 ADDs), lower than in poultry (21 025 000 ADDs) and higher than in cattle (2 235 000 ADDs). These figures are based on sales from pharmacies and feed mills, and exclude a large amount of antimicrobials administered to pet animals in veterinary practice. Furthermore, it should be noted that the selective pressure exerted on a population, animal as well as human, depends on the amount of antimicrobials used but also on the size of the population under study. This aspect is particularly important when comparing data on antimicrobial usage between food animals and pet animals in Denmark, since the populations of poultry and pigs substantially exceed the size of the pet animal population (Table 2).
Data on use of different antimicrobial classes
Qualitative differences in the use of antimicrobials occur between different countries, even within the same geographical area. Odensvik et al.14 reported the amounts (kg of active compound) of oral antibacterial drugs approved for use in dogs and cats sold by wholesalers to pharmacies in Sweden and Norway between 1990 and 1998. The most heavily sold antibacterial preparations in Sweden were ß-lactams, although the relative use of these antimicrobials fell from 84% in 1990 to 63% in 1998. The use of sulphonamides, macrolides, lincosamides and fluoroquinolones increased by over 100% between 1992 and 1998. In Norway, sulphonamides/trimethoprim represented the vast majority of veterinary preparations prescribed for dogs and cats, with oscillations between 77% and 90% during the study period.14
According to DANMAP 2002,13 the usage of cephalosporins in animals in Denmark increased by 27% from 302 kg in 2001 to 385 kg in 2002, mainly due to increased usage in pet animals. A large proportion of the preparations containing aminopenicillins with clavulanic acid, cephalosporins and fluoroquinolones used in veterinary practice are administered to pet animals. If pharmacy sales to pet owners are included (Table 3), the total amounts of aminopenicillins with clavulanic acid, cephalosporins and fluoroquinolones used in pet animals in 2002 were estimated to be 133, 247 and 20 kg, respectively, which correspond to 88%, 64% and 21% of total veterinary use of these antimicrobials (Vibeke Frøkjer Jensen, Danish Institute of Food and Veterinary Research, personal communication). An increasing trend in the prescription of cephalosporins was noted in Sweden since 1997, when this class of antimicrobials was introduced for use in pets.16 This trend was probably due to increased prescription of commercial preparations authorized for veterinary use instead of off-label prescription of products authorized for humans, but could also reflect an actual increase in the use of cephalosporins in small animal practice. A similar increase was also observed in the sales of aminopenicillins, broad-spectrum penicillins that are often commercialized in the form of tablets and therefore sold mainly for use in pet animals.16
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Antimicrobial resistance in bacteria from dogs and cats |
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The consequences of antimicrobial use in small animal veterinary practice do not differ from those observed in human medicine and animal production. The amounts and patterns of use determine the rate at which resistance develops and spreads in the exposed bacterial population. Various longitudinal retrospective studies in Europe and the United States have reported an increase in the prevalence of antimicrobial resistance in different bacterial species isolated from pet animals. In the UK, Lloyd et al.18 examined antimicrobial susceptibility in 2296 isolates of coagulase-positive staphylococci from canine infections (predominantly S. intermedius) of the skin, ears and mucosae in referral practice over the period 19801996. Resistance to penicillin increased from 69% to 89%, whereas oxytetracycline resistance remained constant at about 40%. A peak in the prevalence of resistance to erythromycin and lincomycin (20%), and to sulphonamides/trimethoprim (15%) was observed amongst staphylococcal isolates from 1987 to 1989, followed by a slight decrease in the following years. Normand et al.,19 also reporting from the UK, found significant rising trends for amoxicillin, co-amoxiclav and streptomycin resistance in Escherichia coli, and for erythromycin resistance in Staphylococcus species obtained from clinical cases in a small animal hospital between 1989 and 1997. There was an equivocal rising trend for resistance of Staphylococcus species to cefalexin. In France, a study conducted at the National Veterinary School in Nantes showed that the proportion of multiresistant (3 drugs) strains of S. intermedius increased from 11% in the period 19861987 to 28% in the period 19951996.20 Similarly, a significant temporal increase in resistance to penicillin, neomycin, sulphonamides, co-trimoxazole and erythromycin was reported amongst S. intermedius isolated from dogs in Switzerland.21
National monitoring programmes on antimicrobial resistance in animals generally do not provide data on companion animals. The only exceptions are the surveillance programmes in Sweden (SVARM)16 and Norway (NORM-VET).22 SVARM has reported data on antimicrobial resistance in canine isolates of S. intermedius from skin infections and E. coli from UTI since 1992. Such data indicate a common occurrence of S. intermedius isolates resistant to macrolides, lincosamides and tetracyclines (1830%) and E. coli isolates resistant to ampicillin, streptomycin, tetracycline and sulphonamides/trimethoprim (1124%).16 In Norway,22 canine isolates of S. intermedius from skin infections and otitis externa were analysed in 2002, revealing a high prevalence of resistance to fusidic acid (59%) and tetracycline (53%), which concomitantly often were associated with penicillin resistance (33%). There was a sharp increase in the levels of resistance to fusidic acid and tetracycline compared to NORM-VET 2000 (46% and 36%) and even more compared to data for the periods 19861987 (1% and 20%) and 19931994 (45% and 28%) from previous studies in Norway.23 In both countries, high prevalences of penicillin resistance (7286%) have been reported in the last 10 years for canine isolates of S. intermedius, indicating that penicillinase-sensitive penicillins are not efficient for treatment of canine pyoderma.
A study carried out in Canada on large numbers of clinical canine isolates of S. aureus (n=867) and S. intermedius (n=1339) indicated different trends of antimicrobial resistance depending on species, site of isolation, sex and age of the animal.24 For example, S. aureus isolates were significantly more resistant to cloxacillin and erythromycin compared with S. intermedius isolates. Independent of their species, ear isolates were markedly more resistant to cefalothin compared with isolates from other body sites. The authors concluded that the observed variation of resistance patterns complicates the empirical selection of antimicrobial agents, emphasizing the need for bacterial culture with species identification and susceptibility testing of site-specific isolates in order to choose appropriate antimicrobial therapy.24
Although the authorization of fluoroquinolones for use in small animal veterinary practice is quite recent in Europe (mid 1990s), resistance to this antimicrobial class is emerging in pet animal bacteria. The licensing of fluoroquinolones for use in small animals has been associated with increasing resistance to these antimicrobials amongst Pseudomonas isolates from otitis externa in dogs,11 S. intermedius isolates from pyoderma in dogs,25 and E. coli and -haemolytic Streptococcus spp. from canine UTI.26 Lloyd et al.25 reported a prevalence level of 0.9% fluoroquinolone resistance amongst 858 S. intermedius isolates from dogs examined between 1996 and 1998. A higher prevalence of fluoroquinolone resistance is observed amongst S. intermedius from dogs in Sweden, where constant resistance prevalences (812%) have been reported between 1992 and 2002.16 Although enrofloxacin is still efficient in the treatment of canine infections caused by S. intermedius, cases of treatment failure have been reported for dogs with recurrent deep pyoderma.9,27 A further increase in the prevalence of fluoroquinolone resistance is expected to occur in coming years as a consequence of the rising use of enrofloxacin and other fluoroquinolones in small animal veterinary practice. In vitro studies indicate that prolonged or inappropriate use (e.g. low dose or pulse-dose) might favour development of resistant strains in vivo, particularly when long-term treatment is required.28
Association between antimicrobial use and antimicrobial resistance in pet animal pathogens
Some studies indicate a possible association between antimicrobial use and emergence of antimicrobial resistance in pets. For example, the increased use of lincosamides observed in Sweden during the period 19901998 corresponded with a parallel increase in lincosamide resistance among staphylococcal isolates from canine pyoderma.29 The study also showed that resistance to macrolides, lincosamides, fusidic acid, tetracycline and streptomycin was significantly more common in isolates from recurrent cases than from first-time cases. These differences were probably due to the selective pressure exerted by previous antimicrobial treatment in recurrent cases of pyoderma. Another study conducted at a veterinary teaching hospital in the USA showed an increase in enrofloxacin resistance amongst E. coli isolates from dogs with UTI.30 The increase in enrofloxacin resistance observed in 1997 followed a marked increase in enrofloxacin usage at the veterinary hospital from 1334 g in 1995 to 2358 g in 1996. The increased prevalence of enrofloxacin-resistant E. coli in urine of dogs with UTI was not attributable to a single enrofloxacin-resistant clone but rather to acquisition of resistance in genetically unrelated strains.
Prescott et al.17 demonstrated fluctuations in levels of resistance amongst coagulase-positive staphylococci isolated in a veterinary teaching hospital in Canada during 19841998 and concluded that these reflected changing uses of different classes of antimicrobials in the hospital. They also demonstrated an increase in the prevalence of multiresistant Enterococcus spp. associated with urinary tract infections. Nosocomial infections with multiresistant Gram-negative bacteria such as Acinetobacter baumannii,31 E. coli32 and Salmonella enterica serovars33 have been recently recognized in hospitalized dogs, especially in intensive care units. The emergence of multiresistant nosocomial pathogens in dogs is likely to reflect the abundant use of broad-spectrum antimicrobials in intensive care units at veterinary hospitals.
Occurrence of antimicrobial-resistant human pathogenic bacteria in pets
Household pets can be reservoirs of bacterial species and resistance genes of clinical importance in humans, like methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE) and multidrug-resistant Salmonella Typhimurium DT104. The occurrence of MRSA in a dog was first described in 1994,10 but more widespread occurrence was not reported until 1999, including cases in the United States,34 in the UK,35 and in South Korea.36 Canine infection has been subsequently reported in Canada37 and in the Netherlands.38 MRSA was first described in healthy cats by Lilenbaum et al.39 in a study of the staphylococcal flora of 148 cats in Brazil. In the UK, recent reports of MRSA isolation from small animals40,41 suggest that MRSA is much more prevalent in small animal veterinary practice than has been hitherto recognized. MRSA carriage can be a hazard to owners, especially if they have increased susceptibility to infection. However, it should be noted that pet animals appear to become reservoirs of MRSA through exposure to infected humans and thus probably do not constitute the primary reservoir for MRSA but act as a small secondary reservoir.
Methicillin resistance is also recognized in S. intermedius, coagulase-negative staphylococci and coagulase-variable species such as Staphylococcus schleiferi. Lilenbaum et al.39 described the occurrence of methicillin-resistant S. intermedius and coagulase-negative staphylococci in clinically healthy Brazilian cats. In the USA, Frank et al.42 reported the isolation of methicillin-resistant S. schleiferi from 11 dogs with recurrent pyoderma. Although infection in man is uncommon, S. schleiferi is increasingly recognized as the cause of hospital-acquired infections.43 Thus, canine infections or carriage of such organisms represent a potential hazard for people in contact with dogs.
VRE are another important cause of concern in human medicine due to the importance of vancomycin for treatment of nosocomial infections caused by multiresistant Gram-positive bacteria. In order to preserve the effectiveness of vancomycin in human medicine, the use of avoparcin as a growth promoter in animal production was banned in the EU in 1997 because it was liable to induce resistance to vancomycin (Commission Directive 97/6/EC of 30 January 1997). Recent studies in Europe have documented a relatively high occurrence (723%) of VRE (mainly Enterococcus faecium) in dogs living in contact with farm animals,44 as well as in dogs living in urban areas.45 A study conducted on healthy animals in Spain revealed a higher prevalence of VRE in pets (23%) compared with pigs (4%).46 The occurrence of VRE has also been reported in New Zealand47 and in the USA,48 where the occurrence of VRE has not been documented in food animals. Canine VRE isolates generally contain the vanA resistance gene cluster and exhibit multiple resistance to other antimicrobials such as macrolides [erm(B) gene], tetracycline [tet(M) gene] and aminoglycosides [aac(6')-aph(2'') genes].45,46,48 Thus, although vancomycin is normally not used in small animal veterinary practice, VRE are likely to be co-selected by the use of such antimicrobials.
The occurrence of multiresistant S. Typhimurium phage type DT104 in cats has been reported in the UK,49,50 in Germany,51 and in the USA.52 These strains are usually resistant to at least five antimicrobials, including ampicillin, chloramphenicol, streptomycin, sulphonamides and tetracycline. A study on a large number (n=6589) of diarrhoeic dogs in the Netherlands revealed the presence of Salmonella in 69 (1%) animals tested.53 Amongst the 80 canine isolates analysed in this study, 53% were resistant to cefalexin, 37% to tetracycline, 14% to amoxicillin with clavulanic acid, 6% to sulphonamides with trimethoprim and 4% to enrofloxacin. Recently, the occurrence of Salmonella serovars has been demonstrated in animal-derived dog treats.54 The study indicated that animal-derived dog treats could be a potential source of animal and human infections with Salmonella, including multidrug-resistant S. Typhimurium DT104 with the characteristic penta-resistance phenotype.
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Transmission of antimicrobial-resistant bacteria between pet animals and humans |
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Transmission of resistant human pathogens between pet animals and humans
Most information available in the scientific literature on bacterial transmission between pets and humans relates to human pathogenic bacteria. Dogs and cats are potential sources of various zoonotic bacteria that can be transmitted via faecaloral transmission, physical injuries (i.e. dog bites and cat scratches) or vectors (i.e. ticks).55 Pet-associated zoonoses are usually sporadic and their frequencies are not easily determined because of the difficulty in recognizing and validating disease transmission from pets. Transmission of antimicrobial-resistant bacteria from pet animals to humans represents a particular risk when the strains harbour resistance genes of clinical relevance in human medicine. Bite wounds in humans present opportunities for the transfer of resistant organisms from cats and dogs to man and can have serious consequences unless the susceptibility of infecting organisms is determined and appropriate therapy given.12,56
At least 1% of annually-reported salmonellosis cases in the USA are likely to be associated with companion animals.57 Transmission of S. Virchow from two household dogs to an infant was substantiated by pulsed-field gel electrophoresis (PFGE),58 a highly discriminatory method for bacterial typing. In 1999, outbreaks of multiple-resistant S. Typhimurium associated with small animal veterinary facilities were reported in Idaho, Minnesota and Washington.52 The strains causing these outbreaks exhibited the aforementioned penta-resistance phenotype typical of S. Typhimurium DT104. In all outbreaks, illness in animal health care workers and pet owners followed illness in cats attending the veterinary facilities. Feline and human isolates from the outbreaks in Minnesota and Washington were indistinguishable by PFGE. Direct evidence of zoonotic transmission could not be demonstrated in the Idaho outbreak because the cats died before the onset of clinical symptoms in humans and stool specimens were not cultured from these animals. However, the 10 humans involved in this outbreak were infected with the same PFGE type and had no common exposure outside the veterinary facility where they worked.52
It has been estimated that approximately 6% of enteric campylobacteriosis is transmitted from pet animals.59 Various studies, including casecontrol studies, indicate that pet ownership is a significant risk factor for Campylobacter jejuni infections in humans, particularly young children.5963 The same PFGE profiles have been identified in C. jejuni isolates from dogs, cats and humans living in different geographical regions,64 suggesting the possible existence of clones able to adapt to different hosts. Direct evidence of transmission of C. jejuni between human patients and pets living in the same households has been shown based on amplified-fragment length polymorphism (AFLP)65 and PFGE.64 In the latter study,64 a 2-year-old girl and her dog were found to share the same fluoroquinolone-resistant strain. Neither of them had ever been treated with fluoroquinolones, indicating that the strain was not selected by previous exposure of any of the two individuals to quinolones but that it was acquired from an external source. Even though the dog was fed a commercial diet, acquisition from a common food source was possible, since the dog was occasionally given human food scraps.
Various studies have documented transmission of MRSA or methicillin-susceptible S. aureus between human patients, their family members and dogs living in the same household.6669 However, the typing methods used in two of these studies66,67 were not sufficiently discriminatory to draw inference on the genetic relationship of human and pet isolates. MRSA are more likely to be transmitted from humans to pets, as indicated by the frequent recovery of MRSA from pets living with human patients or medical staff. However, these animals can play an important role as reservoirs of MRSA within family households. Recurrent MRSA infection has been reported in a patient with diabetes, who had an infected wound, and his wife.69 PFGE analysis indicated that the MRSA infecting the two owners was the same as that which could be cultured from the family dog. The human infections were eliminated and ceased to recur after successful removal of the MRSA from the dog's nares.
E. coli strains causing UTI in dogs are phylogenetically related to human extraintestinal pathogenic E. coli (ExPEC) and exhibit virulence genes that are characteristic of human clinical isolates.70,71 Over 15% of environmental canine faecal deposits have been found to contain E. coli strains closely related to human virulent ExPEC clones.72 Although direct evidence of transmission has not been documented yet, these data indicate that canine faeces could represent an important reservoir for the acquisition of ExPEC by humans. Dogs and cats have also been addressed as a potential source of VRE for hospitalized patients based on the strong similarity of AFLP patterns amongst human clinical isolates and pet isolates.73 In New Zealand, a vancomycin-resistant Enterococcus faecalis isolate from mastitis in a dog was shown to have the same PFGE profile found in poultry and human isolates, therefore supporting the hypothesis of a clonal lineage in this country.47 A recent study in the USA48 showed that a vancomycin-resistant E. faecium isolate from a dog with UTI infection contained a specific type of Tn1546-like elementthe transposable element associated with vanAthat has only been described in human clinical VRE isolates unique to the USA, suggesting a possible exchange of this transposable element between human and canine strains.
Transmission of resistant commensal bacteria between pet animals and humans
Little is known about the possible exchange of commensal bacteria between pets and humans living in contact. The current knowledge on this subject is mainly limited to the transmission of S. intermedius, a commensal, but also pathogen of dogs and cats.74 S. intermedius appears to be common in veterinary staff in constant contact with dogs and owners of dogs with atopic dermatitis.75 The fact that S. intermedius is normally rare in humans76,77 suggests dog-to-human transmission. Strains carried by humans generally correlate with strains recovered from their dogs.78,79 Owners of dogs affected by deep pyoderma frequently carry the same strains occurring in their dogs and such strains can be resistant to a variety of antimicrobial agents, including penicillins, fusidic acid, macrolides, lincosamides, tetracyclines and chloramphenicol.80 Since antimicrobial resistance in canine S. intermedius strains is common,81 there is a risk that resistance genes are transferred from S. intermedius to human pathogenic staphylococci.
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Gene transfer between bacteria from pet animals and humans |
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For example, the sulphonamide resistance genes sul1 and sul2, the streptomycin resistance genes strA, strB and aadA2, and the tetracycline resistance genes tet(A) and tet(B) have been shown to occur in E. coli strains from UTI in dogs and cats.82 However, all these genes are associated with mobile genetic elements such as transposons, integrons or plasmids. Therefore, it is not surprising that the same resistance genes can also be found in E. coli strains from humans and other animals,82,83 as well as in other enteric bacteria such as Salmonella Typhimurium.51 The genes sul2, strA, strB and tet(B) have even been identified in distantly related bacteria such as Pasteurella multocida and other members of the family Pasteurellaceae,84 indicating that such genes are not only present in bacteria of the urinary and intestinal tract, but also in those of the respiratory tract.
The genetic basis of antimicrobial resistance in S. intermedius is the most extensively studied amongst bacteria from pet animals. Small plasmids mediating resistance to tetracyclines via tet(K), macrolides and lincosamides via erm(C) and chloramphenicol via catpC221 have been detected in a few canine S. intermedius isolates.85 These plasmids closely resemble the tet(K)-, erm(C)- or catpC221-carrying plasmids previously described in other staphylococci of human or animal origin.81,86 However, the vast majority of the S. intermedius strains appear to prefer transposon-borne resistance genes such as the tetracycline resistance gene tet(M) which is located on the conjugative transposon Tn91687,88 and the macrolide/lincosamide resistance genes erm(A) or erm(B) which are located on transposons Tn554 or Tn917, respectively.89 Only for chloramphenicol resistance, plasmid-borne cat geneswhich occasionally can also be located in the chromosomal DNAare commonly found.85,90
Surprisingly, canine S. intermedius resistant to tetracyclines and macrolides contain the resistance genes prevalent in resistant enterococci and streptococci [i.e. tet(M) and erm(B)] more frequently than those prevalent in resistant S. aureus [i.e. tet(K) and erm(C)],8789,91 suggesting that S. intermedius might preferentially acquire such resistance genes from enterococci. It has been recently suggested that Tn5405-like elements associated with erm(B) in S. intermedius of canine origin might originate from enterococci since similar elements have been detected on enterococcal plasmids.91 Interspecies transfer of the plasmid-borne aminoglycoside resistance gene aac(6')-aph(2'') has been shown to occur from E. faecalis to S. intermedius under laboratory conditions.92 These studies indicate that canine S. intermedius strains are able to acquire resistance genes from enterococci but little is known to date whether they are able to pass them to other bacterial species.
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Conclusions |
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Prudent use guidelines have been established by various national and international organizations. These guidelines usually refer to the use of antimicrobials in the veterinary field in general, thereby also including the use of antimicrobials in pet animals. However, there are few or no mechanisms to control the prudent use of antimicrobials in small animal practice. Thus, it remains the responsibility of every veterinarian to observe these guidelines so as to minimize the development of antimicrobial resistance and thus retain the efficacy of the currently available antimicrobial agents. This latter aspect is of particular importance, since there are unlikely to be any new antimicrobials for the veterinary field in the near future.
In order to ensure success of antimicrobial therapy, veterinarians frequently tend to use newer and/or broad-spectrum drugs, such as fluoroquinolones or cephalosporins, as first-line antimicrobials in the treatment of certain infections in pet animals. As a consequence, resistance to these drugs has emerged in pathogenic bacteria (e.g. S. intermedius, E. coli and P. aeruginosa) as well as in commensal bacteria (Enterococcus spp.) of pet animals. Although resistances to fluoroquinolones and cephalosporins appear to still be infrequent, such antimicrobials should receive a last choice status and their use should be limited to those situations in which other antimicrobial agents cannot be used. This precautionary measure would preserve the efficacy of these important drugs in human medicine as well as in veterinary medicine, when their use is required for the eradication of infections caused by multiresistant strains.
Virtually all data on the prevalence of resistance genes in bacteria from pet animals come from selected studies that often refer to small- to medium-sized test populations for which the selection criteria are often unknown. Thus, it is questionable how representative such studies are. The same situation is true for representative data on in vitro susceptibility of bacteria from pet animals. In this regard, it must be considered that differences in the prevalence of resistance as observed in various studies can also result from the use of different methods for susceptibility testing and different breakpoints for evaluation of the results. Most national monitoring programmes focus on food animals and do not include data on antimicrobial resistance in companion animals. Some long-term studies in Europe have described trends in antimicrobial resistance among isolates of selected bacterial species from cats and dogs,1821 but such studies are rather the exception than the rule. Accordingly, more efforts should be undertaken to obtain reliable data of the antimicrobial susceptibility of bacteria from pet animals, following the examples of the national surveillance programmes in Sweden16 and Norway.22 In Germany, the first monitoring programme (BfT-GermVet), which includes canine, feline and equine bacteria from selected indications, has been started in January 2004.
In conclusion, the role of pet animals as reservoirs of antimicrobial resistance needs further investigation. There is a risk of transfer of resistant bacteria and/or resistance genes from pet animals to humans, including bacterial species and resistance genotypes of clinical interest. Studies from different countries indicate that bacteria from pet animals show trends of increasing resistance to a wide range of antimicrobial agents. The location of many resistance genes on mobile elements favours their spread amongst bacterial and host populations (Figure 1). Transmission of antimicrobial resistance is likely to be enhanced by the close physical contact between household pets and humans as well as by the fact that virtually the same classes of antimicrobial agents are used in human medicine and in small animal practice. However, quantification of this risk is highly problematic since key data on consumption of antimicrobials in small animal practice and on antimicrobial susceptibility, prevalence and mobility of resistance genes amongst bacterial pathogens in pet animals are currently not available.
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Acknowledgements |
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Footnotes |
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References |
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