An ecological approach to assessing the epidemiology of antimicrobial resistance in animal and human populations

Abstract

We examined long-term surveillance data on antimicrobial resistance (AMR) in Salmonella Typhimurium DT104 (DT104) isolates from concurrently sampled and sympatric human and animal populations in Scotland. Using novel ecological and epidemiological approaches to examine diversity, and phenotypic and temporal relatedness of the resistance profiles, we assessed the more probable source of resistance of these two populations. The ecological diversity of AMR phenotypes was significantly greater in human isolates than in animal isolates, at the resolution of both sample and population. Of 5200 isolates, there were 65 resistance phenotypes, 13 unique to animals, 30 unique to humans and 22 were common to both. Of these 22, 11 were identified first in the human isolates, whereas only five were identified first in the animal isolates. We conclude that, while ecologically connected, animals and humans have distinguishable DT104 communities, differing in prevalence, linkage and diversity. Furthermore, we infer that the sympatric animal population is unlikely to be the major source of resistance diversity for humans. This suggests that current policy emphasis on restricting antimicrobial use in domestic animals may be overly simplistic. While these conclusions pertain to DT104 in Scotland, this approach could be applied to AMR in other bacteria-host ecosystems.

Distinguishable Epidemics of Multidrug-Resistant Salmonella Typhimurium DT104 in Different Hosts

“…In our study, the inter-related epidemiologies of Salmonella and AMR were examined at the level of the genome. Our results challenge the established view that the human and animal epidemics are synonymous (8-11), and show that the phylogenetic relationships both within and between the resistance determinants and the host bacteria are different.…”

“…A) The numbers of shared and unique AMR determinants (acquired resistance genes or single nucleotide polymorphisms known to confer resistance) in the 147 Scottish human and animal DT104 isolates investigated for AMR diversity; B) The numbers of shared and unique AMR profiles (unique combinations of AMR determinants) in the 147 isolates; C) The numbers of shared and unique AMR phenotypic profiles (unique combinations of AMR phenotypes) in the original 5,200 surveillance isolates of DT104, 1990-2004, Scotland (11); D) Rarefaction curves, with 95% confidence intervals (vertical lines), of the number of genotypic AMR profiles in the 147 isolates investigated for AMR diversity, demonstrating similar sampling intensity.…”

“…This is the largest study of its kind, utilizing tools with the finest resolution available to investigate the relationships of Salmonella Typhimurium DT104 and AMR between and within co-located human and animal populations, and enabled us to address two separate issues with this dataset, those of the origins and dissemination of AMR and also of Salmonella . First, the greater diversity of AMR genes and profiles in the human DT104 isolates suggests that there were other sources contributing to the diversity of the human resistance burden than the local animals; it is noteworthy that this analysis of molecular data leads to identical conclusions to those based on phenotype (11). Second, we show that a large proportion of transmission of the bacterium appears to have occurred within each host population, and/or that there were separate sources of DT104 for the humans and local animals, with a small degree of spill-over in both directions.…”

Antibiotic resistance in human Salmonella isolates are related to animal strains

“…In my opinion, the conclusions given in the recent paper published on antimicrobial-resistant Salmonella in your Journal [1] are erroneous and opposite to what emerges from any objective analysis of the data. In contrast to their conclusions, there seems an obvious and clear association between antibiotic-resistant Salmonella isolates in animal and human ones.…”

“…Nowhere in the paper do they give the numbers of isolates with these different phenotypes. This is found only in the supplementary material of Mather et al [1]. While there were large numbers of resistance profiles only seen in humans isolates (30), this mainly involved single isolates.…”