Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand
Antibiotic drugs have been commercially available for 70 years. Throughout this time the numbers and varieties of drug-resistant bacterial pathogens have been increasing, and multidrug resistant (MDR) strains of pathogens have evolved. Infections with MDR bacteria present the clinician with fewer therapeutic options and an increased risk that the first-line treatment chosen will not be effective. The knock-on effects of this is that MDR infections are characterised by prolonged illness of greater severity leading to increased mortality rates and inflated healthcare costs.1,2
Historically, MDR pathogens were most frequently encountered in human hospital environments and were associated with nosocomial infections.3 Increasingly, however, infections with MDR bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and MDR Enterobacteriaceae are being acquired by people within the community.4 Furthermore, the emerging community-acquired strains of MRSA (CA-MRSA) carry additional virulence genes compared to the older nosocomial strains, resulting in an increased ability to cause infection in otherwise healthy people.5
New resistance genes continue to appear and spread within Gram-negative bacteria such as the members of the Enterobacteriaceae family. Of particular concern are the genes encoding for extended-spectrum beta-lactamases (ESBLs), such as the globally recognised family of CTX-M genes6 and plasmid-mediated AmpC beta-lactamase genes. Strains of bacteria producing these types of beta-lactamase enzymes not only show resistance to the majority of beta-lactam drugs, but they frequently carry genes encoding for resistance to other classes of antibiotics, which can render them resistant to many of the commonly used antibiotics.
In New Zealand, an annual survey of drug resistant bacteria in human populations has documented a substantial rise in ESBL-producing Enterobacteriaceae (ESBL-E), predominantly Escherichia coli and Klebsiella spp., from a handful of isolations in 2001 to over 7000 isolations in 2010.7 Moreover, the geographical distribution of human ESBL-E isolations is striking with the highest annualised incidence rates being seen in Auckland and the surrounding regions, whilst the rates in more southern regions of the country fall well below the national average rate.
Multidrug resistant bacteria can also colonise and infect animals, and the incidence of infections with MRSA and ESBL-E is also rising in animal populations around the world.8 For over 40 years, most research attention was focussed upon the agricultural use of antimicrobial drugs as a potential public health risk due to the possible evolution and maintenance of drug resistant bacteria within the food chain.9,10 However, more recently the potential transmission of MDR bacteria between people and their pets has been receiving increased attention due to close relationships people develop with their companion animals and the increase in the standard of veterinary care available.11,12 Studies have demonstrated that the same strains of MDR bacteria causing infections in humans can be isolated from companion animals13 and the likely transmission of clones of MDR bacteria between human patients and their pets, and vice versa, is becoming well documented.14-16 However, at this present time, few countries are conducting surveillance of MDR bacteria in companion animal populations.
In 2008, the Companion Animal branch of the New Zealand Veterinary Association funded a master's student at Massey University to conduct a 3-month study collating the culture and susceptibility data for bacteria isolated from companion animals from the seven veterinary diagnostic laboratories in the country.17 This study found that 13% of E. coli isolates (13 of 97) were resistant to four or more antibiotics, with 4 isolates showing resistance to between 7 and 11 drugs. The majority of E. coli had been isolated from urine samples, and the geographical distribution of the MDR strains was strikingly similar to the pattern seen within the human population with two thirds originating from cats and dogs living in and around Auckland. Subsequently, in the second half of 2012, three ESBL producing E. coli carrying plasmid-mediated AmpC genes were isolated from urinary tract infections in dogs and cats in the Auckland region.18 These three isolates showed a high degree of multidrug resistance leaving few treatment options - only the imipenems, aminoglycosides and phosphomycin were deemed to be effective.
In addition to causing clinical disease, multidrug resistant bacteria can be carried by some people and animals without accompanying pathological changes. These silent carriers may shed MDR bacteria into their environment for weeks to months, and they can act as a source of infection for other more vulnerable people and animals, such as neonates, pregnant females, the elderly, patients with concurrent disease and those taking immunosuppressive drugs. However, there are even fewer data available regarding the prevalence of background carriage of MDR bacteria in healthy humans and animals. To this end a multidisciplinary team has come together to investigate the impact that MDR bacteria are having on companion animal health in New Zealand, and to assess the risks posed to animal and human health by the potential presence of silent animal carriers of these strains within the community. The team comprises veterinary and medical microbiologists and clinicians, human and veterinary public health experts, epidemiologists and mathematical modelers. The aims of the research this group is conducting are to use molecular epidemiology to compare strains of MDR bacteria causing clinical disease in companion animals with those causing human disease in New Zealand; to estimate the background prevalence of carriage of MDR bacteria in healthy companion animals in the Auckland region; and to assess transmission of Gram-negative MDR bacteria in households containing pets and compare that with the transmission dynamics in households not containing pets. The results of these studies will contribute to the estimation of the risks currently posed to animal and human health due to the presence and transmission of MDR bacteria within our communities.
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