Food-borne Zoonotic Transmission of Pathogens Expressing Carbapenemase-Mediated Antimicrobial Resistance as an Emerging Food Safety Issue

<p>NON-TECHNICAL SUMMARY:<br/> Carbapenemase-producing enterobacteriaceae have been described as heralding the end of the antibiotic era. These potential pathogens harbor highly-mobile genes that confer resistance to our most critically important, live-saving antimicrobial drugs. The presence of these organisms has not yet been reported in US food-animal populations, but the widespread use of powerful cephalosporin drugs in agriculture likely provides significant selection pressure favoring organisms with carbapenemase genes because carbapenemases confer resistance to all extended-spectrum cephalosporins. Because enteric pathogens and commensal flora from livestock commonly contaminate fresh retail meat products available in grocery stores, there exists potential for the emergence of zoonotic food-borne pathogens expressing this new mechanism of resistance that pose a serious
risk to food safety and public health. Our central hypothesis is that metallo-beta-lactamase antimicrobial resistance genes encoding bacterial carbapenemase production are currently present but undetected in US livestock populations. Our objectives are to: 1. Identify the animal and commensal flora reservoirs of metallo-beta-lactamase resistance genes in livestock populations in the US, 2. Detect the presence of Salmonella, a recognized zoonotic food-borne pathogen, harboring metallo beta-lactamase resistance genes in livestock populations in the US, and 3. Describe the characteristics of animals and populations from which metallo-beta-lactamase producing pathogens and resistance genes are recovered to provide a basis for developing potential intervention strategies to prevent food-borne zoonotic transmission. To accomplish these objectives, we will use targeted surveillance of
veterinary diagnostic submissions to state diagnostic laboratories, as well as Salmonella diagnostic isolates submitted for serotyping at the National Veterinary Service Laboratories. We will then conduct representative sampling of livestock populations with carbapenem resistance in order to fully describe their epidemiologic characteristics. These results will provide critical data for assessing the true food safety risk of emerging carbapenem resistance, and for identifying effective interventions and control measures.
<p>APPROACH:<br/> To accomplish objective 1, we will to screen livestock fecal submissions to multiple state veterinary diagnostic laboratories using selective media to identify existing gram negative commensal carbapenemase-producing reservoirs in livestock flora. This is an appropriate population for targeted surveillance because clinical submissions to diagnostic laboratories likely originate from animals that have recently received antimicrobial therapy and experienced the consequent in vivo selection pressure. Thus, enteric bacteria from these submissions are far more likely than typical samples from healthy animals to contain rare resistance genes. Salmonella isolates from clinical diagnostic submissions also have a higher probability of resistance because they are associated with selection pressure from therapeutic use of antimicrobial drugs. Many Salmonella isolates
from livestock diagnostic submissions in the US are ultimately submitted to the USDA National Veterinary Services Laboratories (NVSL) Diagnostic Bacteriology Laboratory for serotyping. As a result, if carbapenemase-producing Salmonella are present in US livestock, we hypothesize that there is a high probability that this resistance determinant will be present in the population of isolates submitted to the NVSL. We will therefore screen clinical Salmonella isolates that are submitted for serotyping to the NVSL over the initial 2 years of the study. The results of the targeted surveillance of veterinary diagnostic fecal submission and Salmonella isolates completed during the first two project years will identify the livestock populations where carbapenemresistant organisms are present. Based on those results we will identify a representative sample of commercial operations to estimate
prevalence and identify potential risk factors for the presence of CPE.