In this study, we analyzed the phylogenetic distribution and virulence genotypes of drug-susceptible and drug-resistant E. coli isolates from human volunteers and poultry products in Minnesota and Wisconsin. We found that drug-resistant human isolates, although overlapping somewhat with drug-susceptible human isolates, were more similar overall to poultry isolates than to drug-susceptible human isolates. In contrast, drug-susceptible human isolates differed from poultry isolates. This relationship was observed consistently with diverse analytical approaches and various stratifications of the population. It suggests that many of the drug-resistant human isolates were more likely to have originated in poultry (or a similar nonhuman reservoir) and to have been acquired by humans when these isolates were already drug resistant, than to have emerged de novo in humans by conversion of drug-susceptible human isolates to drug-resistant isolates.
We also found that, regardless of analytical approach and population analyzed, resistant and susceptible poultry isolates were highly similar. This suggests that the resistant poultry isolates likely derived from antimicrobial drug–susceptible, poultry-source E. coli by conversion to resistance. This most plausibly would occur within the avian fecal flora under selection pressure from on-farm use of antimicrobial drugs.
Our findings closely resemble those of a recent study of ciprofloxacin-resistant E
from humans and chickens in the late 1990s in Barcelona, Spain (12
). These data indicate that these relationships remain valid and are applicable in the United States, to additional resistance phenotypes (specifically quinolones, TMP-SMZ, and extended-spectrum cephalosporins), and to retail poultry products (12
). Moreover, similar results were obtained with retail poultry products and poultry carcasses from processing plants. This implies that drug-resistant poultry-source E
isolates originate in the birds, rather than being introduced from some exogenous reservoir later during the packaging and distribution process. This in turn suggests that on-farm practices, including use of antimicrobial agents for growth promotion, metaphylaxis, and therapy (21
), may influence characteristics of E
that contaminate retail poultry products and, seemingly, are then transmitted to humans (7
The greater overall similarity of drug-resistant human isolates to poultry isolates than to drug-susceptible human isolates applied not only to the hospital patient isolates compared with isolates from conventionally raised poultry, but also to the isolates from vegetarians compared with isolates from poultry raised with no antibiotics. This was surprising because the vegetarians ostensibly did not consume poultry and, therefore, should not have been directly exposed to poultry-source E
. However, this seeming paradox is consistent with the difficulty in confirming poultry consumption (along with most other individual-level exposures) as an epidemiologic risk factor for colonization with drug-resistant E
isolates among community-dwelling persons ([23
]; J.R. Johnson, unpub. data). Assuming that the drug-resistant human isolates were derived from poultry, occurrence of poultry-source E
in both vegetarians and persons with conventional diets suggests that poultry-source drug-resistant E
may spread extensively through the human population without requiring individual exposure to poultry products. This suggestion would be consistent with evidence that household-level risk factors may be more predictive of colonization with drug-resistant E
than individual-level risk factors, and that household members often share E
clones with each another (23
). The mechanisms for such diffusion, and methods to block the entry of such strains into the human population and their subsequent spread, need to be defined.
The virulence potential for humans of the present drug-resistant human and poultry E
isolates, which is related to their direct threat to human health, is unknown. Predictions regarding virulence potential await molecular comparisons with human clinical isolates (9
) and experimental virulence assessment in vivo (26
). Nonetheless, the abundance of ExPEC-associated virulence genes in some of these strains is of concern because it suggests a high likelihood of virulence. This would augment any health threat these strains may pose as passive vehicles for drug-resistance genes (6
Potential limitations of this study warrant comment. Because we did not examine alternative sources for drug-resistant human isolates, we cannot exclude the possibility that other foods (28
) or nonfood reservoirs (29
) might yield even closer similarities to drug-resistant human isolates. Whether persons in the study consumed poultry products from the same lots or suppliers as those sampled is not known. Because the study was conducted in Minnesota and Wisconsin in mostly rural communities and with newly hospitalized patients and nonhospitalized vegetarians, generalizability of the results is unknown. We combined several resistance phenotypes because of low frequencies, which may have obscured differences. We also did not assess other molecular characteristics of strains, e.g., pulsed-field gel electrophoresis profiles (12
), sequence types (30
), and resistance elements (28
). Use of multiple comparisons increased the likelihood of spurious associations (which we addressed by specifying a strict criterion for statistical significance), whereas the small sample size in certain subgroups reduced power for finding true associations.
Strengths of the study include substantial overall sample size, standardized concurrent processing of fecal and poultry samples, close matching of human and poultry samples, extensive molecular typing using virulence-relevant markers, and use of multiple analytical modalities. Additionally, we examined clinically relevant resistance phenotypes.
In summary, our findings suggest that in a contemporary US-based population, many human-source drug-resistant fecal E. coli isolates more likely originated in poultry than in humans, whereas drug-resistant poultry isolates likely derive from drug-susceptible poultry isolates. Our data extend this paradigm to clinically relevant agents other than fluoroquinolones, heighten concerns regarding the potential human health risk for antimicrobial drug use in poultry production, and suggest that avoidance of poultry consumption may not reliably provide personal protection.