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Note to Users NOTE TO USERS This reproduction is the best copy available. UMI' ANTIMICROBIAL RESISTANCE, ANTIMICROBIAL USE AND INFECTION CONTROL IN COMMUNITY SMALL ANIMAL VETERINARY HOSPITALS IN SOUTHERN ONTARIO A Thesis Presented to The Faculty of Graduate Studies of The University of Guelph by COLLEEN P. MURPHY In partial fulfilment of requirements for the degree of Doctor of Philosophy March, 2010 © Colleen P. Murphy, 2010 Library and Archives Bibliotheque et 1*1 Canada Archives Canada Published Heritage Direction du Branch Patrimoine de I'edition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre reference ISBN: 978-0-494-64536-9 Our file Notre reference ISBN: 978-0-494-64536-9 NOTICE: AVIS: The author has granted a non­ L'auteur a accorde une licence non exclusive exclusive license allowing Library and permettant a la Bibliotheque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par I'Internet, preter, telecommunication or on the Internet, distribuer et vendre des theses partout dans le loan, distribute and sell theses monde, a des fins commerciales ou autres, sur worldwide, for commercial or non­ support microforme, papier, electronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriete du droit d'auteur ownership and moral rights in this et des droits moraux qui protege cette these. Ni thesis. Neither the thesis nor la these ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent etre imprimes ou autrement printed or otherwise reproduced reproduits sans son autorisation. without the author's permission. In compliance with the Canadian Conformement a la loi canadienne sur la Privacy Act some supporting forms protection de la vie privee, quelques may have been removed from this formulaires secondaires ont ete enleves de thesis. cette these. While these forms may be included Bien que ces formulaires aient inclus dans in the document page count, their la pagination, il n'y aura aucun contenu removal does not represent any loss manquant. of content from the thesis. 1+1 Canada ABSTRACT ANTIMICROBIAL RESISTANCE, ANTIMICROBIAL USE AND INFECTION CONTROL IN COMMUNITY SMALL ANIMAL VETERINARY HOSPITALS IN SOUTHERN ONTARIO Colleen P. Murphy Advisors: University of Guelph, 2009 Dr. Scott McEwen Dr. Richard Reid-Smith This thesis is a study of components of the epidemiology of antimicrobial resistance in companion animals. The effect of antimicrobial treatment on the occurrence of antimicrobial resistance in fecal Escherichia coli isolates, antimicrobial use by companion animal veterinarians and the recovery of environmental bacteria from companion animal veterinary practices were investigated. The effect of antimicrobial treatment on the occurrence of antimicrobial resistance was examined using a cohort design studying in dogs requiring treatment with amoxicillin- clavulanic acid, cephalexin, fluoroquinolones or penicillin. Resistance to amoxicillin-clavulanic acid, cefoxitin, ceftiofur and ceftriaxone in fecal E. coli from dogs was significantly associated with treatment with cephalexin. Also, isolation of fecal Clostridium difficile was significantly associated with treatment with amoxicillin-clavulanic acid. Antimicrobial use by companion animal veterinarians was investigated using journals recording diagnosed new disease events and associated treatments. Antimicrobials were the most frequently prescribed treatment. Non-topical (oral, parenteral) antimicrobials were the most common type of antimicrobial prescribed, and P- lactams were the most frequently prescribed antimicrobial class. In dogs, 67% of new disease events associated with canine infectious tracheobronchitis were treated with antimicrobials. In cats, 70% and 74% of disease events associated with feline upper respiratory tract disease and feline lower urinary tract disease, respectively, were treated with antimicrobials. The recovery of environmental bacteria from community veterinary hospitals was investigated in a cross-sectional study. The proportion of hospitals with positive environmental samples were: E. coli-92%, C. difficile-58%, methicillin-resistant Staphylococcus aureus -9%, CMY-2 producing E. coli-9%, methicillin-resistant Staphylococcus pseudintermedius-7%, Salmonella-2%. Antimicrobial resistance in E. coli was infrequent, but several important potential pathogens were recovered: Canadian epidemic strains MRSA-2 and MRSA-5, and C. difficile ribotype 027. An evaluation of infection control practices demonstrated deficiencies that could be improved: development of formal infection control policies, use of isolation for infectious patients, and disinfectant selection for environmental disinfection. The overall study results suggest that use of common antimicrobials in companion animal practice and associated antimicrobial resistance may pose a risk to animal and human health, and that companion animal veterinary hospitals are a reservoir for environmental and antimicrobial resistant pathogens. Acknowledgements Firstly, I would like to thank my advisors: Drs Richard Reid-Smith and Scott McEwen. You gently guided me through the various research projects and have provided invaluable assistance in the preparation of this thesis and other manuscripts. Thank you as well to the members of my advisory committee: Scott Weese, Patrick Boerlin and John Prescott. Your additional support and insight are truly appreciated. I extend a huge thanks and owe a debt of gratitude to the numerous individuals who worked in the field, the laboratory and the office: Nicol Janecko, Virginia Young, Joyce Rousseau, Gabriel Jantzi, Meredith Craig, Rebeccah Travis, Gerry Lazarek, Alyssa Calder, Karlee Thomas, Adriana Sage, Nicole Rolfe, staff of the Canadian Research Institute for Food Safety, the Laboratory for Foodborne Zoonoses, and Prairie Diagnostics Services. I need to thank Nicol Janecko especially for managing the projects and working so patiently with me. I am also gratefully for the statistical support that I received from members of the department of Population Medicine: William Sears, Olaf Berke, David Pearl and Zvonimir Poljak. Thank you to all the veterinarians, veterinary practices, pet owners and dogs that participated in my research projects. I also need to acknowledge the Ontario Veterinary College Pet Trust, the Public Health Agency of Canada, Federal Student Work Employment Program and the Ontario Veterinary College Fellowship for funding the projects and the graduate student stipend. I also thank Denise Coleman of the Laboratory for Foodborne Zoonoses for managing my affairs at PHAC. Lastly, thanks to David, Hannah, Brian and my other family members for their patience and much needed help that gave me the time I needed to complete this degree. i Table of Contents Chapter 1 Introduction and Literature Review 1 1.0. Introduction 2 2.0. Antimicrobial resistance in Escherichia coli 2 2.1. Escherichia coli as an opportunistic pathogen in companion animals 3 2.2. Escherichia coli as commensal organisms in companion animals 5 3.0 Salmonella enterica 5 4.0. Beta-lactamase cephamycinase-2 (blacMY-2) 5 5.0. Methicillin-resistant Staphylococcus aureus 6 6.0. Methicillin-resistant Staphylococcus pseudintermedius 8 7.0. Hospital-acquired infections and veterinary hospital-based infection control 9 8.0. Antimicrobial drug use in companion animals 14 P.O. Research objectives 20 Table 47 Chapter 2 Escherichia coli, and selected veterinary and zoonotic pathogens isolated from environmental sites within companion animal veterinary hospitals in southern Ontario: Prevalence and factors associated with recovery 49 Abstract 49 1.0. Introduction 50 2.0. Materials and methods 51 2.1. Sample size calculations 51 2.2. Veterinary hospital selection 51 2.3. Sampling 52 2.4. Microbiology 53 2.5. Antimicrobial susceptibility testing 58 2.6. Generalized linear mixed models of factors potentially associated with environmental recovery of bacteria 58 3.0. Results 60 3.1. Generalized linear mixed models of potential factors associated with environmental recovery of bacteria 62 4.0. Discussion 63 Acknowledgements 70 Figure 80 Tables 81 ii Chapter 3 A prospective cohort study of the effects of antimicrobial treatment on the incidence of antimicrobial resistance in generic fecal Escherichia coli isolates and isolation of Clostridium difficile, Salmonella enterica, blaCMY- 2 positive E. coli, methicillin-resistant Staphylococcus aureus, Staphylococcus pseudintermedius, and vancomycin-resistant Enterococcus spp. from dogs treated in community companion animal practices in southern Ontario 88 Abstract 88 1.0. Introduction 89 2.0. Materials and methods 91 2.1. Veterinary hospital and dog recruitment 91 2.2. Sample size 93 2.3. Laboratory methods 93 2.4. Statistical Analysis 95 3.0. Results 98 3.1. Kaplan Meier survival functions 100 3.2. Cox proportional hazard models 103 4.0. Discussion 104 Acknowledgements Ill References 112 Figure 118 Tables 120 Chapter 4 Out-patient antimicrobial drug use in dogs and cats for new disease events from community companion animal practices in Ontario 124 Abstract 124 1.0. Introduction 125 2.0. Materials and methods 126 2.1. Veterinarian recruitment 126 2.2. Data-entry journal pre-test 127 2.3. Eligibility criteria
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