Source: OHIO STATE UNIVERSITY - VET MED submitted to NRP
FOOD-BORNE ZOONOTIC TRANSMISSION OF PATHOGENS EXPRESSING CARBAPENEMASE-MEDIATED ANTIMICROBIAL RESISTANCE AS AN EMERGING FOOD SAFETY ISSUE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1000839
Grant No.
2014-67005-21709
Cumulative Award Amt.
$299,955.00
Proposal No.
2012-04387
Multistate No.
(N/A)
Project Start Date
Dec 15, 2013
Project End Date
Dec 14, 2017
Grant Year
2014
Program Code
[A4141]- Food Safety: Addressing Critical and Emerging Food Safety Issues
Recipient Organization
OHIO STATE UNIVERSITY - VET MED
1900 COFFEY ROAD, 127L VMAB
COLUMBUS,OH 43210
Performing Department
Veterinary Preventive Medicine
Non Technical Summary
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.
Animal Health Component
100%
Research Effort Categories
Basic
0%
Applied
100%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
72239991170100%
Knowledge Area
722 - Zoonotic Diseases and Parasites Affecting Humans;

Subject Of Investigation
3999 - Animal research, general;

Field Of Science
1170 - Epidemiology;
Goals / Objectives
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 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
Project Methods
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.

Progress 12/15/13 to 12/14/17

Outputs
Target Audience:Our target constituients were livestock producers, food processors and distributors, and food retailers. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?The results have been disseminated appropriately in the scientific literature What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The impact of this research is that important surveillance is being conducted to detect new foodborne antimicrobial resistance threats to food safety. We have accomplished this by describing new reservoirs of antibiotic resistance in livestock populations, in the environment, in veterinary hospitals, and and in teh flora of human patients. These results have all been dessiminated to appropriate audiences in the scientific literature.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: DF Mollenkopf, RL Faubel, P Pancholi, TF Landers, MM Erdman, JB Daniels, TE Wittum. Surveillance and characterization of carbapenemase-producing Klebsiella pneumoniae recovered from patient stool samples at a tertiary care medical center. Antimicrob Agents Chemotherapy 2015;59:5857-5859.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Landers, T. F., Mollenkopf, D. F., Faubel, R. L., Dent, A. , Pancholi, P. , Daniels, J. B. and Wittum, T. E. (2017), Extended?Spectrum ??lactam Resistance in the Enteric Flora of Patients at a Tertiary Care Medical Centre. Zoonoses Public Health, 64: 161-164. doi:10.1111/zph.12293
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Mollenkopf DF, Stull JW, Mathys DA, Bowman AS, Feicht SM, Grooters SV, Daniels JB, Wittum TE. 2017. Carbapenemase-producing Enterobacteriaceae recovered from the environment of a swine farrow-to-finish operation in the United States. Antimicrob Agents Chemother 61:e01298-16. https://doi.org/10.1128/AAC.01298-16.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Adams Rachael J., Mathys Dimitria A., Mollenkopf Dixie F., Whittle Andrea, Daniels Joshua B., and Wittum Thomas E..Vector-Borne and Zoonotic Diseases.Jun 2017.ahead of printhttp://doi.org/10.1089/vbz.2016.2083
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Mollenkopf Dixie F., Mathys Dimitria A., Feicht Sydnee M., Stull Jason W., Bowman Andrew S., Daniels Joshua B., and Wittum Thomas E..Foodborne Pathogens and Disease.http://doi.org/10.1089/fpd.2017.2355


Progress 12/15/15 to 12/14/16

Outputs
Target Audience:Scientists and researchers working in related areas of antimicrobial resistance. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?A scientific manuscript has been published, and additional manuscripts are in preparation. What do you plan to do during the next reporting period to accomplish the goals?Complete the project and publish multiple manuscripts.

Impacts
What was accomplished under these goals? The impact of this research is that important surveillance is being conducted to detect new foodborne antimicrobial resistance threats to food safety. Objective 1. Identify the animal and commensal flora reservoirs of metallo-beta-lactamase resistance genes in livestock populations in the US. For this objective we are continuing our veterinary diagnostic laboratory surveillance program for carbapenem resistant bacteria targeting high-risk samples. No carbapenemase-producing isolates have been identified and so we are nearing completion of this portion of the surveillance. Objective 2. Detect the presence of Salmonella, a recognized zoonotic food-borne pathogen, harboring metallo-beta-lactamase resistance genes in livestock populations in the US. We are performing this research in collaboration with the National Veterinary Services Laboratory, as described in the original proposal. Initial screening of isolates on selective media has been completed and we are finalizing isolate characterization and data analysis. We anticipate a scientific manuscript from this objective. Objective 3. Describe the characteristics of animals and populations from which metallo-beta-lactamase producing pathogens. We have identified a farm with a transmissible metallo-beta-lactamase gene. We have one manuscript accepted and are finalizing data collection for the second manuscript.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Mollenkopf DF, Faubel RL, Pancholi P, Landers TF, Erdman MM, Daniels JB, Wittum TE. 2015. Surveillance and characterization of carbapenemase-producing Klebsiella pneumoniae recovered from patient stool samples at a tertiary care medical center. Antimicrob Agents Chemother 59:58575859. doi:10.1128/AAC.01085-15.


Progress 12/15/14 to 12/14/15

Outputs
Target Audience:Scientists and researchers working in related areas of antimicrobial resistance related to healthcare and agricultural environments. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The impact of this research is that important surveillance is being conducted to detect new foodborne antimicrobial resistance threats to food safety. Objective 1. Identify the animal and commensal flora reservoirs of metallo-beta-lactamase resistance genes in livestock populations in the US. For this objective we are continuing our veterinary diagnostic laboratory surveillance program for carbapenem resistant bacteria targeting high-risk samples. We are working with laboratories in Ohio, North Carolina, Nebraska, Washington, and Texas. Standardized sampling, testing, and screening protocols have been implemented in each participating laboratory. 2. Detect the presence of Salmonella, a recognized zoonotic food-borne pathogen, harboring metallo-beta-lactamase resistance genes in livestock populations in the US. We are performing this research in collaboration with the National Veterinary Services Laboratory, as described in the original proposal. Initial screening of isolates on selective media has been performed and isolate characterization is underway. We are only waiting for the NVSL to indicate that they are prepared for us to initiate the project. 3. Describe the characteristics of animals and populations from which metallo-beta-lactamase producing pathogens. We are collecting and screening livestock fecal samples from farms in the US as described in the original proposal.

Publications


    Progress 12/15/13 to 12/14/14

    Outputs
    Target Audience:Scientists and researchers working in related areas of antimicrobial resistance related to healthcare and agricultural environments. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?We will continue to perform the field research projects and generate the appropriate data as described in our original proposal.

    Impacts
    What was accomplished under these goals? The impact of this research is that important surveillance is being initiated to detect new foodborne antimicrobial resistance threats to food safety. Objective 1. Identify the animal and commensal flora reservoirs of metallo-beta-lactamase resistance genes in livestock populations in the US. For this objective we have initiated our veterinary diagnostic laboratory surveillane program for carbapenem resistant bacteria targeting high-risk samples. We are working with laboratories in Ohio, North Carolina, Nebraska, Washington, and Texas. Standardized sampling, testing, and screening protocols have been disseminated to each participating laboratory. We anticipate recruiting additional diagnostic laboratories for surveillance in upcoming years. 2. Detect the presence of Salmonella, a recognized zoonotic food-borne pathogen, harboring metallo-beta-lactamase resistance genes in livestock populations in the US. We are preparing to initiate this work in conjunction with the National Veterinary Services Laboratory, as described in the proposal, in the near future. We are only waiting for the NVSL to indicate taht they are prepared for us to initiate the project. 3. Describe the characteristics of animals and populations from which metallo-beta-lactamase producing pathogens. This project will begin once objectives 1 and 2 are completed.

    Publications