Source: MICHIGAN STATE UNIV submitted to
COMPARATIVE EPIDEMIOLOGY OF ANTIMICROBIAL RESISTANCE IN ANIMALS, HUMANS, AND THEIR ENVIRONMENTS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0198365
Grant No.
(N/A)
Project No.
MICL02082
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Apr 1, 2009
Project End Date
Mar 31, 2014
Grant Year
(N/A)
Project Director
Kaneene, J.
Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824
Performing Department
Large Animal Clinical Sciences
Non Technical Summary
Antimicrobial drug resistance, or the failure of a drug to treat an infectious disease for which the drug was previously effective, was recognized soon after the widespread use of antibiotics. The use of antimicrobial drugs has been associated with the emergence of antimicrobial resistance in bacteria in humans and animals, by creating selective pressure that allows resistant bacteria to survive while susceptible bacteria are killed. The development of resistance to many drugs currently used for disease treatment increases the risk for treatment failures in both animals and humans. The maintenance of antimicrobial-resistant bacteria in the gastrointestinal tracts of human and animals hosts makes fecal transmission of resistant bacteria a serious health threat: exposure to resistant bacteria can occur through consuming contaminated food or water, or through physical contact with humans or animals infected with drug-resistant bacteria. Manure contaminated with drug-resistant bacteria poses a threat to humans and animals that come into contact with it, and runoff contaminated with manure can introduce drug-resistant bacteria to surface waters that are used by wildlife, livestock, and humans. Unfortunately, several studies have shown that drug resistance will persist even after the selective pressure of antimicrobial drug use has been discontinued. Furthermore, if resistance develops in one species of bacteria, it can be transferred to other species, thereby allowing drug resistance to spread easily across a wide range of bacterial species. Because of the interdependence of drug resistance observed between veterinary medicine, human medicine, and the environment, potential sources of antimicrobial resistance must be eliminated to slow this trend. The main goal of our research is to identify factors associated with the development and spread of drug resistance in bacteria from humans, domestic animals, and wildlife, and to apply this information to develop measures to reduce and control the spread of drug resistance. To meet this goal, our research will: 1) Determine if reducing on-farm use of antimicrobial drugs will reduce drug resistance in bacteria isolated from cattle and cattle farms over time, and identify the most cost-effective drug usage and disinfection programs for eliminating drug-resistant bacteria on the farm and in homes. 2) Compare drug resistance patterns in wildlife, livestock, and humans to describe how antimicrobial resistance is transmitted between these groups. 3) Use drug resistance and genetic analysis to identify and track surface water contamination by different sources of fecal contamination (e.g., manure, sewage) 4) Describe the transmission of drug resistance between pets (dogs, cats) and their human caregivers in a veterinary hospital and at home.
Animal Health Component
75%
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3110899117010%
3113830117010%
3113910117010%
3114010110310%
3116010117010%
7220899117010%
7223830117010%
7223910110310%
7223910117010%
7226010117010%
Goals / Objectives
Our main objective is to promote an increased understanding of the mechanisms and dynamics of antimicrobial resistance transmission between humans, animals, and the environment. The overall goal of our research is to identify modifiable factors associated with the development and spread of antimicrobial resistance in bacteria from humans, domestic animals, and wildlife, and to apply this information to the development of strategies designed to reduce and control the spread of drug resistance in Michigan ecosystems. To complete this long-term goal, the following objectives will be pursued: 1) Determine if reducing on-farm use of subtherapeutic levels of antimicrobial agents results in increased susceptibility to select antimicrobial agents in enteric bacteria isolated from cattle and cattle environments. a) Conduct long-term studies of changes in antimicrobial resistance patterns of enteric bacteria on cattle farms under different management approaches to reducing the development of drug resistance; b) Identify the costs and benefits associated with reducing antimicrobial use in food animal production. 2) Compare antimicrobial resistance patterns found in wildlife, livestock, and humans. a) Determine if terrestrial wildlife can serve as a reservoir of antimicrobial resistance for human and livestock pathogens by demonstrating resistance in these hosts; b) Describe antimicrobial resistance patterns of fish in different watersheds throughout the state of Michigan, and determine the risk of humans acquiring resistant bacteria through sport fishing and the consumption of these fish. 3) Use molecular tools and spatio-temporal analytic approaches in a long-term study to identify and track surface water contamination in watersheds with different sources of fecal contamination (e.g., rural areas versus highly urbanized areas). 4) Describe the transmission of antimicrobial resistance between dogs and cats and their human caregiver: a) Describe this process in a veterinary teaching hospital; b) Expand this research to encompass humans and their pets in the home. 5) Develop decontamination methods that will eliminate drug-resistant bacteria and resistance factors (e.g. plasmids) from the environment, for use on farms and in homes.
Project Methods
A prospective study will track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms using different resistance reduction strategies. Herds feeding medicated milk replacer will be recruited and randomly assigned to 1 of 3 groups: no change; stop medicated milk replacers only; stop all medicated feeds. Herds will be visited monthly over a 3-year period to collect samples (calf & cow feces, housing, maternity pens, manure storage, water) and herd inventory and health, management, housing, and antimicrobial use data. Bacteria will be cultured and susceptibility testing on 3 isolates from each sample will be done using automated microbroth dilution. Differences in patterns of susceptibility between groups and multivariable analyses will be used to identify factors associated with long-term changes in susceptibility. Health and management data will be used in a cost-benefit analysis to determine if different resistance-reducing practices are economically feasible. Long-term changes in genetic and antimicrobial resistance patterns of enteric bacteria in wildlife and surface waters near study herds, and other sources of fecal contamination and sites along the main waterways within the watershed will be sampled and tested. Associations between changes in susceptibility and genetic patterns of wildlife, livestock, and human bacterial isolates will be measured. Discriminant function and spatial analyses will be applied to susceptibility and genetic profiles of contamination sources to determine sources of bacterial contamination and the effects of distance from sources of fecal contamination, geology, hydrology, and land cover. A cross-sectional study will describe patterns of antimicrobial resistance in bacteria from freshwater fish in these watersheds, by testing bacteria from mucous scrapings and gill plates from several fish species. A prospective study will determine if pets and their caregivers acquire antimicrobial resistance from each other. Pets admitted to a veterinary teaching hospital (VTH) and VTH staff will be asked to give fecal and nasal swabs to be tested for resistant bacteria, and environmental swabs will be taken in the VTH. Susceptibility testing will be conducted using microbroth dilution. Multivariable models will be used to describe the relationships between risk factors and susceptibility patterns, and the associations between resistance patterns from caregivers, pets, and environmental samples. Clients bringing pets to the VTH for routine visits will be asked to collect uncontaminated fecal samples and nasal swabs from themselves and their pets at recruitment and 6 weeks later. Experimental studies will determine the best decontamination methods for eliminating drug resistant bacteria and resistance factors. Substrates will be sterilized and inoculated with resistant E. coli, and different decontamination methods will be used. Samples will be collected before and after treatment, and molecular tools will be used to determine the presence of any E. coli or major resistance factors. The best methods will be taken to farms, VTH, and private homes, where sampling and testing will be repeated.

Progress 04/01/09 to 03/31/14

Outputs
Target Audience: Target audiences include pet owners, dairy farmers, veterinary practitioners, medical doctors, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the zoonotic spread of antimicrobial resistance from domestic animals to humans. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? This project supported training of two PhD graduate students, including study design,biostatistics and analytics; training in field and laboratory methodologies; interaction with stakeholders on farms and in the veterinary teaching hospital; teaching; manuscript preparation; and preparation and presentation of oral and poster reports of their research at scientific conferences. 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 study of antimicrobial resistance in companion animals and their healthcare providers has demonstrated that several sites within a veterinary hospital can harbor Staphylococcus spp. and Enterococcus spp. that are resistant to more than five antibiotics. Additionally, antimicrobial resistant Staphylococcus spp. and Enterococcus spp. have been detected in companion animals and the healthcare providers in the same veterinary hospital. Results from this study have been used to change infection control procedures in the veterinary hospital, and prudent methods for selection and administering of antibiotics to the companion animals have been enhanced. Results of this study are being prepared in special modules for teaching of veterinary and vet-technology students. The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has demonstrated that discontinuing the practice of feeding medicated milk replacers to calves increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease, but declines in effectiveness after 3 months suggests other factors contribute to decreasing susceptibility on the farm. This information adds to the current body of knowledge regarding the associations between farm management practices and antimicrobial resistance, and can be used by researchers, extension agents, and producers to formulate changes to calf management programs to reduce the development and spread of resistance on farms, and decrease the levels of resistant bacteria potentially entering the human food chain.

Publications


    Progress 01/01/13 to 09/30/13

    Outputs
    Target Audience: Target audiences include pet owners, dairy farmers, veterinary practitioners, medical doctors, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the zoonotic spread of antimicrobial resistance from domestic animals to humans. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Graduate students have been trained in the study of antimicrobial resistance in companion animals (E. Hamilton, PhD), the study of long-term changes inantimicrobial resistance in cattle (G. Habing, PhD), and the study of the effect of probiotics on antimicrobial resistance in calves (E. Corbett, currently in PhD program). How have the results been disseminated to communities of interest? Results from the study of antimicrobial resistance in companion animals and their healthcare providershave been used to change infection control procedures in the veterinary hospital, and prudent methods for selection and administering of antibiotics to the companion animals have been enhanced. Results of this study are being prepared in special modules for teaching of veterinary and vet-technology students. Information from the studies of antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replaceradds to the current body of knowledge regarding the associations between farm management practices and antimicrobial resistance, and can be used by researchers, extension agents, and producers to formulate changes to calf management programs to reduce the development and spread of resistance on farms, and decrease the levels of resistant bacteria potentially entering the human food chain. What do you plan to do during the next reporting period to accomplish the goals? Work will continue on the study to determine the effects of feeding probiotics to dairy calves on antimicrobial resistance profiles of fecal coliforms.

    Impacts
    What was accomplished under these goals? The study of antimicrobial resistance in companion animals and their healthcare providers has demonstrated that several sites within a veterinary hospital can harbor Staphylococcus spp. and Enterococcus spp. that are resistant to more than five antibiotics. Additionally, antimicrobial resistant Staphylococcus spp. and Enterococcus spp. have been detected in companion animals and the healthcare providers in the same veterinary hospital.Two manuscripts have been published, and two submitted for publication. The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has demonstrated that discontinuing the practice of feeding medicated milk replacers to calves increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease, but declines in effectiveness after 3 months suggests other factors contribute to decreasing susceptibility on the farm. A study to determine the effects of feeding probiotics to dairy calves on antimicrobial resistance profiles of fecal coliforms has been initiated by Drs. B. Norby and J.B. Kaneene, and is ongoing.

    Publications

    • Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Corbett, E.M., Norby, B., Halbert, L.W., and Kaneene, J.B. The Effect of Feeding a Direct Fed Microbial on Antimicrobial Resistance in Fecal Coliforms from Dairy Calves. 23rd Annual Phi Zeta Research Day. Michigan State University College of Veterinary Medicine, East Lansing, MI. October 4, 2013.
    • Type: Journal Articles Status: Published Year Published: 2013 Citation: Hamilton, E., Kruger, J.M., Schall, W., Beal, M., Manning, S.D., & Kaneene, J.B. 2013. Acquisition and persistence of antimicrobial-resistant bacteria isolated from dogs and cats admitted to a veterinary teaching hospital. Journal of the American Veterinary Medical Association, 243(7), 990-1000.
    • Type: Journal Articles Status: Submitted Year Published: 2013 Citation: Hamilton, E., May, K., Kruger, J.M., Schall, W., Beal, M., Hauptman, J., DeCamp, C., and Kaneene, J.B. Temporal Clusters of Antimicrobial Resistant E. coli, E. faecium, and S. aureus Isolated from Dogs, Healthcare Providers, and Environmental Surfaces of a Veterinary Teaching Hospital. Journal of Clinical Microbiology
    • Type: Journal Articles Status: Other Year Published: 2013 Citation: Hamilton, E., Gardiner, J.C., and Kaneene, J.B. Longitudinal Study of Resistant Bacteria Isolated from Students, Faculty, and Staff of a Veterinary Teaching Hospital. Journal of Zoonoses and Public Health


    Progress 01/01/12 to 12/31/12

    Outputs
    OUTPUTS: The comparative study of antimicrobial resistance in companion animals and their healthcare providers has been completed. One manuscript has been published, and one submitted for publication. The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has been completed, and two manuscripts have been published. PARTICIPANTS: Co-Investigators: J.B. Kaneene, J. Wirth, S. Manning, J.M. Kruger, W. Schall, M. Beal, J. Hauptman, C. DeCamp, Michigan State University. Research and Tech Assistants: K. May, Laboratory Technician; R. Miller, Research Assistant; J. Hattey, Laboratory Technician, Michigan State University. TARGET AUDIENCES: Target audiences include pet owners, dairy farmers, veterinary practitioners, medical doctors, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the zoonotic spread of antimicrobial resistance from domestic animals to humans. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

    Impacts
    The study of antimicrobial resistance in companion animals and their healthcare providers has demonstrated that several sites within a veterinary hospital can harbor Staphylococcus spp. and Enterococcus spp. that are resistant to more than five antibiotics. Additionally, antimicrobial resistant Staphylococcus spp. and Enterococcus spp. have been detected in companion animals and the healthcare providers in the same veterinary hospital. Results from this study have been used to change infection control procedures in the veterinary hospital, and prudent methods for selection and administering of antibiotics to the companion animals have been enhanced. Results of this study are being prepared in special modules for teaching of veterinary and vet-technology students. The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has demonstrated that discontinuing the practice of feeding medicated milk replacers to calves increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease, but declines in effectiveness after 3 months suggests other factors contribute to decreasing susceptibility on the farm. This information adds to the current body of knowledge regarding the associations between farm management practices and antimicrobial resistance, and can be used by researchers, extension agents, and producers to formulate changes to calf management programs to reduce the development and spread of resistance on farms, and decrease the levels of resistant bacteria potentially entering the human food chain.

    Publications

    • Hamilton, E., May, K., Kruger, J.M., Schall, W., Beal, M., Hauptman, J., DeCamp, C., and Kaneene, J.B. 2012. Temporal Clusters of Antimicrobial Resistant E. coli, E. faecium, and S. aureus Isolated from Dogs, Healthcare Providers, and Environmental Surfaces of a Veterinary Teaching Hospital. Journal of Clinical Microbiology, (pending).
    • Hamilton, E., Gardiner, J.C., and Kaneene, J.B. 2012. Longitudinal Study of Resistant Bacteria Isolated from Students, Faculty, and Staff of a Veterinary Teaching Hospital. Journal of Zoonoses and Public Health (pending).
    • Habing, G.G., Lo, Y., and Kaneene, J.B. 2012. Changes in the antimicrobial resistance profiles of Salmonella isolated from the same Michigan dairy farms in 2000 and 2009. Food Research International, 56(2):919-924, doi:10.1016/jfoodres.2011.02.054.
    • Habing, G., Lomgard, J.E., Kopral, C.A., Dargatz, D.A. and Kaneene, J.B. 2012. Farm-level Associations with the Shedding of Salmonella and Antimicrobial Resistant Salmonella in U.S. Dairy Cattle. Foodborne Pathogens and Diseases, 9:815-821.
    • Hamilton, E., Kaneene, J.B., May, K., Kruger, J.M., Schall, W., Beal, M., Hauptman, J., and DeCamp, C. 2012. Prevalence and Antimicrobial Resistance of Enterococcus spp and Staphylococcus spp isolated from surfaces in a Veterinary Teaching Hospital. Journal of the American Veterinary Medical Association, 240(2):1463-1473.


    Progress 01/01/11 to 12/31/11

    Outputs
    OUTPUTS: A comparative study of antimicrobial resistance in companion animals and their healthcare providers is being conducted. Most of the data collection, laboratory work, and data analysis have been completed. A manuscript has been accepted for publication and three presentations have been made at scientific meetings. PARTICIPANTS: Co-Investigators: J.B. Kaneene, J. Wirth, S. Manning, J.M. Kruger, W. Schall, M. Beal, J. Hauptman, C. DeCamp, Michigan State University. Research and Tech Assistants: K. May, Laboratory Technician, R. Miller, Research Assistant, J. Hattey, Laboratory Technician, Michigan State University. TARGET AUDIENCES: Target audiences include dairy farmers, veterinary practitioners, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the spread of antimicrobial resistance from the farm to the human food supply. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

    Impacts
    The study of antimicrobial resistance in companion animals and their healthcare providers has demonstrated that several sites within a veterinary hospital can harbor Staphylococcus spp. and Enterococcus spp. that are resistant to more than five antibiotics. Additionally, antimicrobial resistant Staphylococcus spp. and Enterococcus spp. have been detected in companion animals and the healthcare providers in the same veterinary hospital. The results from this study have been used to change infection control procedures in the veterinary hospital. Additionally, prudent methods for selection and administering of antibiotics to the companion animals have been enhanced. Results of this study are being prepared in special modules for teaching of veterinary and vet-technology students.

    Publications

    • Hamilton, E., Kaneene, J.B., May, K., Kruger, J.M., Schall, W., Beal, M., Hauptman, J., and DeCamp, C. Prevalence and Antimicrobial Resistance of Enterococcus spp and Staphylococcus spp isolated from repeated sampling of surfaces within a Veterinary Teaching Hospital 2007 to 2009. J. Am. Vet. Med. Assoc. (accepted, 2011).


    Progress 01/01/10 to 12/31/10

    Outputs
    OUTPUTS: The prospective study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has been completed, and the third paper from the study have been published. PARTICIPANTS: Co-Investigators: J.B. Kaneene, Michigan State University; L.D. Warnick, Cornell University; C.A. Bolin, Michigan State University; R.J. Erskine, Michigan State University. Researchers: K. May, Laboratory Technician, Michigan State University; R. Miller, Research Assistant, Michigan State University; J. Hattey, Laboratory Technician, Michigan State University. TARGET AUDIENCES: Target audiences include dairy farmers, veterinary practitioners, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the spread of antimicrobial resistance from the farm to the human food supply. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

    Impacts
    The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has demonstrated that discontinuing the practice of feeding medicated milk replacers to calves increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease, but declines in effectiveness after 3 months suggests other factors contribute to decreasing susceptibility on the farm. The study also documented an unusual outbreak of highly drug-resistant S. enterica serotype Oranienburg in dairy calves, which is of interest to researchers in food safety and antimicrobial drug resistance. This information adds to the current body of knowledge regarding the associations between farm management practices and antimicrobial resistance, and can be used by researchers, extension agents, and producers to formulate changes to calf management programs to reduce the development and spread of resistance on the farms. This can decrease the levels of resistant bacteria potentially entering the human food chain, which will result in broad-scale improvements to food safety and public health.

    Publications

    • Kaneene JB, Miller R, May K, Hattey JA. 2010. An outbreak of multi-drug resistant Salmonella enterica serotype Oranienburg in Michigan dairy calves. Foodborne Path. Dis. 7(10):1193-1201.


    Progress 01/01/09 to 12/31/09

    Outputs
    OUTPUTS: The prospective study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has been completed. The first and second papers from the study have been published, and a new paper, "Multi-drug resistant Salmonella enterica serotype Oranienburg in Michigan dairy calves", has been submitted for publication. PARTICIPANTS: Co-Investigators: J.B. Kaneene, Michigan State University; L.D. Warnick, Cornell University; C.A. Bolin, Michigan State University; R.J. Erskine, Michigan State University. Researchers: K. May, Laboratory Technician, Michigan State University; R. Miller, Research Assistant, Michigan State University. TARGET AUDIENCES: Target audiences include dairy farmers, veterinary practitioners, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the spread of antimicrobial resistance from the farm to the human food supply. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

    Impacts
    The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has demonstrated that discontinuing the practice of feeding medicated milk replacers to calves increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease, but declines in effectiveness after 3 months suggests other factors contribute to decreasing susceptibility on the farm. The study also documented an unusual outbreak of highly drug-resistant S. enterica serotype Oranienburg in dairy calves, which is of interest to researchers in food safety and antimicrobial drug resistance. This information adds to the current body of knowledge regarding the associations between farm management practices and antimicrobial resistance, and can be used by researchers, extension agents, and producers to formulate changes to calf management programs to reduce the development and spread of resistance on the farms. This can decrease the levels of resistant bacteria potentially entering the human food chain, which will result in broad-scale improvements to food safety and public health.

    Publications

    • Kaneene JB, Warnick LD, Bolin CA, Erskine RJ, May K, Miller R. 2008. Changes in Tetracycline Susceptibility of Enteric Bacteria following Switching to Nonmedicated Milk Replacer for Dairy Calves. J. Clin. Microbiol. 46(6):1968-1977.
    • Kaneene JB, Warnick LD, Bolin CA, Erskine RJ, May K, Miller R. 2009. Changes in multidrug resistance of enteric bacteria following an intervention to reduce antimicrobial resistance in dairy calves. J. Clin. Microbiol. 47(12):4109-4112.


    Progress 01/01/08 to 12/31/08

    Outputs
    OUTPUTS: The prospective study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has been completed. The first paper from the study has been published, and the next paper, "Changes in Multi-drug Resistance of Enteric Bacteria Following an Intervention to Reduce Antimicrobial Resistance in Dairy Calves", is being prepared for publication. PARTICIPANTS: Co-Investigators: J.B. Kaneene, Michigan State University; L.D. Warnick, Cornell University; C.A. Bolin, Michigan State University; R.J. Erskine, Michigan State University. Researchers: K. May, Laboratory Technician, Michigan State University; R. Miller, Research Assistant, Michigan State University. TARGET AUDIENCES: Target audiences include dairy farmers, veterinary practitioners, state and federal agencies and programs involved in the development and improvement of the dairy industry in Michigan and the United States, and other researchers and agencies concerned with the spread of antimicrobial resistance from the farm to the human food supply. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

    Impacts
    The study to track long-term changes in antimicrobial resistance patterns in enteric bacteria on cattle farms that stop feeding medicated calf milk replacer has demonstrated that discontinuing the practice of feeding medicated milk replacers to calves increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease, but declines in effectiveness after 3 months suggests other factors contribute to decreasing susceptibility on the farm. This information adds to the current body of knowledge regarding the associations between farm management practices and antimicrobial resistance, and can be used by researchers, extension agents, and producers to formulate changes to calf management programs to reduce the development and spread of resistance on the farms. This can decrease the levels of resistant bacteria potentially entering the human food chain, which will result in broad-scale improvements to food safety and public health.

    Publications

    • Kaneene JB, Warnick LD, Bolin CA, Erskine RJ, May K, Miller R. 2008. Changes in tetracycline susceptibility of enteric bacteria following switching to nonmedicated milk replacer for dairy calves. J. Clin. Microbiol. 46(6):1968-1977.


    Progress 01/01/07 to 12/31/07

    Outputs
    OUTPUTS: The data analysis phase of the study is complete, and two manuscripts are in preparation for submission for publication. A total of 804 intervention and 1,026 control calf fecal samples, and 122 intervention and 136 control environmental samples were used for both manuscripts. There were a total of 1785 E. coli, 168 Salmonella, and 78 Campylobacter isolates collected from calf fecal samples, and 174 E. coli, 26 Salmonella, and 12 Campylobacter isolates collected from environmental samples. Low numbers of isolates did not permit extensive analysis of antimicrobial susceptibility in Campylobacter. No differences were seen in owner-reported calf morbidity and mortality between treatment groups. The first manuscript, "Changes in Tetracycline Susceptibility of Enteric Bacteria Following Switching to Non-Medicated Milk Replacer in Dairy Calves", focused on tetracycline susceptibility in E. coli and Salmonella. There were significantly higher increases in susceptibility to tetracycline in E. coli and Salmonella from intervention versus control herds. Tetracycline susceptibility increased in intervention herds for the first 3 months after switching to non-medicated milk replacer, but eventually returned to pre-intervention levels. The paper concludes that discontinuing the practice of feeding medicated milk replacers to calves appears to have increased tetracycline susceptibility in E. coli and Salmonella on dairy farms, without increasing cattle disease. The second manuscript, "Changes in Multi-drug Resistance of Enteric Bacteria Following an Intervention to Reduce Antimicrobial Resistance in Dairy Calves", focused on multi-drug resistance (resistance to more than one antimicrobial agent) in E. coli, Salmonella, and Campylobacter. Multi-drug resistance was significantly higher in E. coli and Salmonella from control calf fecal samples, and remained higher over the 12 months after intervention started. There were significantly higher declines in resistance to several antimicrobial agents in E. coli and Salmonella from intervention versus control herds. Discontinuing the practice of feeding medicated milk replacers to calves appears to have reduced the frequency of antimicrobial resistance in E. coli and Salmonella, and multi-drug resistant E. coli and Salmonella on dairy farms, without increasing cattle disease. PARTICIPANTS: Participants on this project include: Dr. John B. Kaneene (Principal Investigator), overall project management and producing manuscripts; Dr. Linda S. Mansfield (Co-Investigator), providing technical expertise for bacterial isolation and identification; Dr. Ronald Erskine (Co-Investigator), overseeing contact with dairy producers involved in the study; Dr. Carole Bolin (Co-Investigator), providing technical expertise for bacterial isolation and identification; Dr. Lorin Warnick (Co-Investigator, Cornell University), managing the project in New York, and assisting the PI in producing manuscripts; Katherine May (Laboratory Technician), conducting bacterial isolation, identification, and antimicrobial susceptibility testing; and RoseAnn Miller (Research Assistant), conducting statistical analysis and assisting the PI in producing manuscripts. TARGET AUDIENCES: Target audiences for this study include: Cattle producers - Educational materials can be provided by their veterinary practitioners or in articles published in trade journals, regarding the effects of feeding milk replacer with or without antimicrobial agents on calf health and on-farm development of antimicrobial resistance; Veterinarians - Publication of this study can reach veterinarians with clients that will benefit from the research; and Public and private agencies concerned with food safety and the emergence of antimicrobial resistance - Information from this study can be used to aid in the development of policies or protocols to assist in the reduction of antimicrobial resistance in the human food chain.

    Impacts
    Discontinuing the feeding medicated milk replacers to calves appears to have reduced multi-drug antimicrobial resistance in E. coli and Salmonella on dairy farms without increasing cattle disease, but did not have long-term effects on tetracycline susceptibility of bacteria. This approach can be used to reduce levels of multi-resistant bacteria on dairy farms without compromising animal health, which will reduce the risk of resistant bacteria in dairy cattle and milk from the farm, and in turn reduce the risk of resistant bacteria entering the human food chain.

    Publications

    • No publications reported this period


    Progress 01/01/06 to 12/31/06

    Outputs
    The data collection phase of the study is complete. A total of 8 dairy herds (four each from Michigan and New York), using medicated milk replacer, completed at least 12 months of sample collection, and 7 of the 8 completed 12 months. E. coli was collected from all farms and samples throughout the study, while lower levels of Salmonella and Campylobacter were intermittently collected. There were no significant differences seen in disease rates between control and intervention herds, and before and after the intervention in the intervention herds. The 8 herds yielded 1,830 calf fecal samples and 258 environmental samples (calf pens and maternity pens), from which 533 E. coli, 281 Salmonella and 44 Campylobacter isolates were available for antimicrobial susceptibility testing after banking. Recovery rates for E. coli, Salmonella and Campylobacter from fecal samples were 97%, 9% and 4%, respectively, while recovery rates from environmental samples were 67%, 10% and 5%, respectively. Calf fecal samples had the highest levels of resistance (95.5% and 95.6% of E. coli and Salmonella, respectively), followed by calf pens (81.0% and 40% of E. coli and Salmonella, respectively) and maternity pens (22.2% and 9.1% of E. coli and Salmonella, respectively), and only 10% of all E. coli isolates and 25 (15.5%) of all Salmonella isolates were not resistant to any antimicrobials. The highest levels of resistance seen in E. coli were to tetracycline, kanamycin, streptomycin and sulfamethoxazole, with significant differences between intervention and control herds, while there were significantly higher levels of resistance in control herds for amoxicillin-clavulanic acid, ceftiofur, cephalothin, chloramphenicol, cefoxitin, sulfamethoxazole, and trimethoprim-sulfamethoxazole in Salmonella from fecal and environmental samples. Multi-drug resistance was seen in 88.5% of all E. coli isolates and 84.5% of all Salmonella isolates. The average number of agents to which isolates were resistant was highest in control herds, and control herd isolates having higher levels of isolates that were at least penta-resistant over time. A paper, using the results of this study, is being prepared for submission to a refereed scientific journal for publication. Preliminary results were presented at the 87th Annual Meeting of the Conference of Research Workers in Animal Diseases, Chicago, IL, December 3-5, 2006.

    Impacts
    Since discontinuing the feeding medicated milk replacers to calves appears to have reduced antimicrobial resistance in E. coli and Salmonella on dairy farms without increasing cattle disease, this approach can be used to reduce levels of resistant bacteria on dairy farms without compromising animal health. Reducing the risk of resistant bacteria in dairy cattle and milk from the farm will in turn reduce the risk of resistant bacteria entering the human food chain.

    Publications

    • Kaneene, J.B., Warnick, L.D., Mansfield, L.S. Bolin, C.A., Erskine, R.J. Interventions for Controlling Antimicrobial Resistance in Dairy Cattle. 87th Annual Meeting of Conference of Research Workers in Animal Diseases, Chicago, IL, December 3-5, 2006.


    Progress 01/01/05 to 12/31/05

    Outputs
    Ten dairy herds (four from Michigan and six from New York) using medicated milk replacer were enrolled for the study. Three fecal samples (one each month) were collected from all calves on each of the six farms prior to the implementation of the intervention study. These samples were collected to establish whether there was evidence of resistance to tetracycline in E. coli isolates. Five herds were selected to continue using medicated milk replacer, while the remaining five began to feed milk replacer without medication. Following the demonstration of resistance to tetracycline on these farms, fecal samples from calves are being collected on a monthly basis to test for resistance to tetracycline in the three organisms isolated. Standard microbiological methods are being used for isolation and identification of Campylobacter, Salmonella, and E. coli. The agar dilution method is being used for the in vitro susceptibility testing of Campylobacter isolates, while the SensiTitre system is being used for Salmonella and E. coli. These tests are being conducted following the recommendations of the National Committee on Clinical Laboratory Standards. In addition to the collection of biological samples, data relating to various management practices on these farms have been (and will continue to be) collected. The study is in the 12th month of the expected 15-month study period. A total of 1,600 fecal samples have been collected from 943 animals (55% have been sampled more than once) and 226 environmental samples from calf housing and maternity pens. The isolation rate of E. coli from fecal samples and environmental samples was 98 and 72 percent, respectively. Our preliminary results show more resistance to tetracycline in E. coli isolates in calves on medicated milk replacer than those receiving a non-medicated milk replacer. Work is ongoing to determine resistance to this antimicrobial agent in Campylobacter and Salmonella isolates.

    Impacts
    If we find that discontinuing the practice of feeding medicated milk replacers to calves reduces the frequency or likelihood of pathogen resistance to tetracycline or similar antimicrobial agents, this will be a major strategy for the dairy industry to reduce the risk of the development of resistant bacteria on the farm, and subsequently in the human food chain.

    Publications

    • No publications reported this period


    Progress 01/01/04 to 12/31/04

    Outputs
    Ten dairy herds (four from Michigan and six from New York) using medicated milk replacer were enrolled for the study. Three fecal samples (one each month) were collected from all calves on each of the six farms prior to the implementation of the intervention study. These samples were collected to establish whether there was evidence of resistance to tetracycline in E. coli isolates. Five herds were selected to continue using medicated milk replacer, while the remaining five began to feed milk replacer without medication. Following the demonstration of resistance to tetracycline on these farms, fecal samples from calves are being collected on a monthly basis to test for resistance to tetracycline in the three organisms isolated. Standard microbiological methods are being used for isolation and identification of Campylobacter, Salmonella, and E. coli. The agar dilution method is being used for the in vitro susceptibility testing of Campylobacter isolates, while the SensiTitre system is being used for Salmonella and E. coli. These tests are being conducted following the recommendations of the National Committee on Clinical Laboratory Standards. In addition to the collection of biological samples, data relating to various management practices on these farms have been (and will continue to be) collected. The study is in the 12th month of the expected 15-month study period. A total of 1,600 fecal samples have been collected from 943 animals (55% have been sampled more than once) and 226 environmental samples from calf housing and maternity pens. The isolation rate of E. coli from fecal samples and environmental samples was 98 and 72 percent, respectively. Our preliminary results show more resistance to tetracycline in E. coli isolates in calves on medicated milk replacer than those receiving a non-medicated milk replacer. Work is ongoing to determine resistance to this antimicrobial agent in Campylobacter and Salmonella isolates.

    Impacts
    If we find that discontinuing the practice of feeding medicated milk replacers to calves reduces the frequency or likelihood of pathogen resistance to tetracycline or similar antimicrobial agents, this will be a major strategy for the dairy industry to reduce the risk of the development of resistant bacteria on the farm, and subsequently in the human food chain.

    Publications

    • No publications reported this period