Abstract

Antimicrobial agents are essential elements in the prevention and treatment of bacterial infections in humans, animals, and, to a lesser extent, in plant agriculture and aquaculture. In food animals, these agents are also used to promote growth and enhance feed efficiency. The increasing emergence of bacterial resistance to antimicrobials is of global public health concern, most notably due to the increasing incidence of multiple-drug resistant bacterial infections and higher rates in morbidity and mortality due to treatment failure. However, the impact of antimicrobial resistance may not be limited to human health. Because the emergence and spread of resistance is the result of complex interactions between bacterial communities, antimicrobial agents, the host species, and the environment, animal health and environmental health effects are also likely. This paper explores the evidence for an impact on wildlife species and their potential role in the dissemination of antimicrobial resistance throughout ecosystems.

Potential routes of transmission of antimicrobial resistance within ecosystems include contacts between animals, animal products, humans, manure, soil, and surface water.^13,19 Bacteria may acquire resistance to an antimicrobial agent as the result of a mutation or incorporation of transferable genetic resistance determinants via conjugation, transformation or transduction.^2,15 Exposure of bacterial populations to antimicrobials may alter the bacterial populations through the elimination of susceptible bacteria and enables the survival and amplification of resistant bacteria, thus creating a selective pressure for resistance. Factors such as the method of administration, dosage, and frequency and duration of use are likely to impact the magnitude of this selective pressure.

Although they receive the most attention, it is important to note that pathogenic bacteria are not the only populations of concern with respect to antimicrobial resistance. Commensal bacteria comprise a large potential reservoir of resistance genes for bacterial pathogens. As the number of resistant commensal bacteria increases, the pool of genetic resistance determinants also increases, facilitating more frequent transfer of resistance to pathogenic bacteria. The indirect transmission of resistance via commensal bacteria and the environment may be as significant as direct transmission through the food chain or direct contact between humans and animals.⁹ The high prevalence of antimicrobial resistance in commensal bacteria of humans probably reflects both the selective pressure exerted by antimicrobial usage in an environment as well as the potential for resistance in future infections in both humans and animals.^7,8,12,20

Although the high global prevalence of antimicrobial-resistant bacteria is widely attributed to use of antimicrobials in humans and domesticated animals, it is important to bear in mind that some bacterial populations are intrinsically resistant to certain antimicrobials, and others probably evolve resistance to certain of these drugs due to exposure to naturally produced antimicrobials in the environment. The extent to which the prevalence of resistance in bacteria from wildlife reflects such “natural” sources of resistance has not been well-characterized. For example, in a retrospective study of Enterobacteriacae isolated from wild mammals in Australia, Sherley et al. found that the rates of resistance were equal to rates seen in the natural, “antibiotic-free,” environment.¹⁷ In contrast, in a Finnish study of wild moose, deer and vole, there was an almost complete absence of resistance in Enterobacteriacae, from which the authors concluded that resistance is not a universal characteristic of bacterial populations and most likely results from use of these drug classes in humans and animals.¹⁴

While studies exploring antimicrobial resistance in wildlife are limited in number, resistance has been demonstrated in multiple species of pathogenic and nonpathogenic bacteria within free-ranging and captive wild mammals^5,10,17, birds^4,18,21, reptiles^1,6, and aquatic species¹¹. In particular, the spread of antimicrobial resistant bacteria and their persistence in the environment may be enhanced by wild birds populations due to their mobility and distances traveled during migration. Wild birds have been implicated as a possible source of Salmonella infections in humans and farm animals.^3,16 Antimicrobial-resistant Salmonella spp. have been observed in double-crested cormorants and common loons in Florida²¹, and Salmonella typhimurium were identified in black-headed gulls in the Czech Republic¹⁸. In a study in the United Kingdom, the range and serotypes of Salmonella carried by gulls was similar to the bacterial flora of human the population, which led the authors to suggest sewage as a possible source of infection.⁴ Evidence for cycles of anthropozoonotic and zoonotic transfer of Salmonella infection demonstrates the potential for transfer of resistance determinants between animal, human and environmental sources.

Escherichia coli is a common component of the commensal fecal flora in humans and most animals. In one study of E. coli strains from captive mammals, birds, and reptiles in Trinidad, approximately 97% of the isolates tested demonstrated resistance to one or more of eight antimicrobials tested.⁶ In a related study of E. coli isolates from both wild and captive mammals in Trinidad and Tobago, close to 96% of the isolates were resistant to one or more antimicrobial agents. In the second study, prevalence of resistance among the isolates from captive mammals was significantly higher for three of the antimicrobial agents tested. However, for ampicillin and cephalothin, the prevalence of resistance among the free-ranging animals was significantly higher than those from captive animals. The authors concluded that the high prevalence of resistance to antimicrobials among E. coli isolates within free-ranging and captive populations of wild animals may adversely affect treatment options available to veterinarians. In addition, the presence of resistant enteropathogenic serotypes among the isolates could pose a health hazard to consumers of wildlife meat.¹

In an ongoing study in the United Kingdom of E. coli isolates in wood mice and bank voles, wood mice are significantly more likely to carry antimicrobial resistance than bank voles, even though they occupy the same habitat (N. Williams, personal communication). In an earlier related study in the U.K., vancomycin-resistant enterococci (VRE) were discovered to be part of the normal flora in wood mice, bank voles, and other species of wild mammals. However, while both wood mice and bank voles are reservoirs for VRE, the bank voles did not excrete VRE.¹⁰ Wood mice tend to be omnivores and travel long distances in search of food and territory, whereas bank voles are herbivores and have limited territories. It was unclear how the animals acquired VRE and whether they were long-term carriers. Exposure to avoparcin (an antimicrobial related to vancomycin) was an initial consideration, but avoparcin had not been used in food animals in proximity to the study site and samples were collected after avoparcin was banned as a growth promoter.¹⁰ In any case, it seems possible that host mammal species, ecological niche, and geographic location may influence the antimicrobial resistance profile of isolates and the potential for transfer and spread of resistance within the environment.

These and other studies suggest that free-ranging and captive wildlife are involved in the complex ecology of antimicrobial resistance. Both pathogenic and commensal bacteria in wildlife may serve as reservoirs of antimicrobial resistance that may be selected for, amplified, and spread through the environment via various pathways. While the presence of antimicrobial resistance in wild mammals, birds, reptiles, and aquatic species does not necessarily pose a risk to these populations (assuming they are not treated with antimicrobials), they may play an important role as reservoirs for the potential transfer of resistant bacteria and genetic determinants, potentially impacting the health of humans, companion animals, food animals, and captive wildlife. Enhanced surveillance of pathogenic and commensal bacteria in wildlife is therefore warranted. Both the extent and significance of the risk to humans and nonhumans from antimicrobial resistance in wildlife should be evaluated, and, if deemed prudent, steps should be taken to mitigate the impact of resistance in wildlife populations.

Literature Cited

1.  Adesiyun AA. 1999. Absence of Escherichia coli O157 in a survey of wildlife from Trinidad and Tobago. J. Wildl. Dis. 35(1): 115–20.

2.  Collier L, A Barlows, et al. 1998. Topley’s and Wilson’s Microbiology and Microbial Infections. Ninth ed. Sydney, Australia: Arnold Press.

3.  Coulson JC, J Butterfield, et al. 1983. The herring gull Larus argentatus as a likely transmitting agent of Salmonella montevideo to sheep and cattle. J. Hyg. (Lond). 91(3): 437–43.

4.  Fenlon DR. 1981. Seagulls (Larus spp.) as vectors of salmonellae: an investigation into the range of serotypes and numbers of salmonellae in gull faeces. J. Hyg. (Lond). 86(2): 195–202.

5.  Gilliver M, M Bennett, et al. 1999. Enterobacteriae: antibiotic resistance found in wild rodents. Nature. 401: 233–234.

6.  Gopee NV, AA Adesiyun, et al. 2000. A longitudinal study of Escherichia coli strains isolated from captive mammals, birds, and reptiles in Trinidad. J. Zoo Wildl. Med. 31(3): 353–60.

7.  Hummel R, H Tschape, et al. 1986. Ecologic studies of the nourseothricin resistance of coliform bacteria of intestinal flora in humans and animals. Arch Exp Veterinarmed. 40(5): 670–675.

8.  Lester SC, M del Pilar Pla, et al. 1990. The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China. N. Engl. J. Med. 323(5): 285–289.

9.  Levy SB. 1998. The challenge of antibiotic resistance. Sci. Am. 278(3): 46–53.

10.  Mallon DJ, JE Corkill, et al. 2002. Excretion of vancomycin-resistant enterococci by wild mammals. Emerg. Infect. Dis. 8(6): 636–638.

11.  Mitchell M. 2003. AVMA Convention Notes. In American Veterinary Medical Association. 2003. Nashville, Tennessee.

12.  Murray BE. 1992. Problems and dilemmas of antimicrobial resistance. Pharmacotherapy. 12(6 Pt 2): 86S–93S.

13.  O’Brien TF. 2002. Emergence, spread, and environmental effect of antimicrobial resistance: how use of an antimicrobial anywhere can increase resistance to any antimicrobial anywhere else. Clin. Infect. Dis. 34 Suppl 3: S78–84.

14.  Osterblad M, Norrdahl K, et al. 1999. Antibiotic resistance. How wild are wild mammals? Nature. 401(6750): 233–234.

15.  Quintiliani R, D Sahm, et al. Mechanisms of resistance to antimicrobial agents. In: P. Murray E. Baron, et al., editors. Manual of Clinical Microbiology. 1999, ASM Press: Washington, D.C. p. 1505–1525.

16.  Reche MP, PA Jimenez, et al. Incidence of salmonellae in captive and wild free-living raptorial birds in central Spain. J Vet Med B Infect Dis Vet Public Health. 2003. 50(1): p. 42–4.

17.  Sherley M, DM Gordon, et al. Variations in antibiotic resistance profile in Enterobacteriaceae isolated from wild Australian mammals. Environ Microbiol. 2000. 2(6): p. 620–31.

18.  Sixl W, R Karpiskova, et al. Campylobacter spp. and Salmonella spp. in black-headed gulls (Larus ridibundus). Cent Eur J Public Health. 1997. 5(1): p. 24–6.

19.  Summers AO. Generally overlooked fundamentals of bacterial genetics and ecology. Clin Infect Dis. 2002. 34 Suppl 3: p. S85–92.

20.  van der Waaij D, C Nord. Development and persistence of multi-resistance to antibiotics in bacteria; an analysis and a new approach to this urgent problem. International Journal of Antimicrobial Agents. 2000. 16: p. 191–197.

21.  White FH, DJ Forrester. Antimicrobial resistant Salmonella spp. isolated from double-crested cormorants (Phalacrocorax auritus) and common loons (Gavia immer) in Florida. J Wildl Dis. 1979. 15(2): p. 235–7.