Melbourne Veterinary School - Theses
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ItemPhylogeny and virulence factor genes of canine urinary Escherichia coli in relation to clinical disease and antimicrobial resistance( 2018)Traditionally, urinary tract infections (UTIs) have been categorised as either uncomplicated or complicated in veterinary medicine, with treatment differing for the two categories. In human medicine, there is an additional category: asymptomatic bacteriuria, which is the presence of bacteriuria without symptoms of infection. Escherichia coli is the most common bacterial species involved in UTIs in dogs. Clinical signs can be absent in dogs with complicated UTIs, and this has been likened to asymptomatic bacteriuria in people and has been termed subclinical bacteriuria (SBU). Treatment recommendations for SBU in dogs have been adapted from human recommendations. Many E. coli strains are resistant to multiple antibiotics and uropathogenic E. coli possess virulence factor genes that facilitate overcoming host defence mechanisms. These E. coli commonly belong to phylogenetic groups B2 and D. Some studies suggest that human E. coli isolated from asymptomatic bacteriuria differ from those causing clinical UTI. While the virulence factor genes and phylogeny of canine urinary E. coli isolated from UTIs are well characterised, little is known about virulence factor genes and phylogeny in E. coli isolated from SBU. Furthermore, these genomic characteristics have not been studied in detail in multi-drug resistant (MDR) canine urinary E. coli. Thus, the pathogenic potential of canine urinary E. coli is not well described and the benefit of antibiotic therapy in SBU and MDR infections is unknown. This study used whole genome sequencing to characterise 47 E. coli isolated from dogs with SBU and 67 E.coli from dogs with clinical UTI in terms of their phylogeny and virulence factor gene profile. From those strains, the 15 MDR strains were characterised. When the phylogeny and virulence factor gene profile of E. coli isolated from dogs with SBU were compared with clinical UTIs, results showed that most clinical UTI and SBU E. coli belonged to phylogenetic group B2. The virulence factor gene profile was similar between the two groups, and no association was found between them and the 83 virulence factor genes analysed. Many of the MDR E. coli belonged to phylogenetic group B1 and these isolates possessed fewer virulence factor genes than non-MDR E. coli. Based on the results of this study, it was concluded that phylogeny and the presence of virulence factor genes do not influence the manifestation of clinical disease. Host immunity and rather than presence and the expression of or mutations of virulence factor genes may have a role in the development of clinical disease. ii MDR E. coli have fewer virulence factor genes than non-MDR isolates, with MDR isolates commonly belonging to commensal phylogenetic groups. This suggests that treatment of MDR isolates is not always indicated because they tend to have commensal bacterial phylogeny, which can have implications for reducing the development of antimicrobial resistance. While whole genome sequencing is an accurate method for determining phylogeny and the presence of virulence factors, it is unable to easily differentiate the pathogenicity potential of urinary E. coli and therefore treatment recommendations cannot be made based on this technique.
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ItemInflammation and endothelial perturbation in canine abdominal surgery: the potential modulatory effect of lidocaine( 2019)Complication rates following emergency laparotomy surgery are high, with organ dysfunction being a commonly encountered post-operative complication. Given the endothelium acts as the interface between the systemic circulation and the organs, its function is vital to maintaining organ health. The endothelium is in a constant state of flux, impacted largely by the local environment of which it is a part. In the presence of wide-spread systemic inflammation, inflammatory mediators precipitate change to the structure of the endothelial glycocalyx. These changes result in shedding of the endothelial glycocalyx and alteration of the endothelial phenotype. The endothelium may, as a result, lose the capacity to regulate vasomotor tone, and shift toward a pro-inflammatory and pro-coagulant state. This predisposes to reduced tissue oxygen delivery, and organ dysfunction may ensue. This thesis aimed to answer two key questions: does surgical trauma induced in canine patients undergoing emergent abdominal surgery invoke a systemic inflammatory response and subsequent endothelial activation? And if so, does lidocaine, a proposed immunomodulatory drug, mitigate this effect when given in the post-operative period? Chapter two provides a detailed review of endothelial structure and function, and current literature pertaining to systemic inflammation and endothelial activation in the context of abdominal surgery. Chapter two also examines the literature regarding the proposed mechanisms through which lidocaine acts as an immunomodulatory drug, and reviews publications that investigate the use of lidocaine as an anti-inflammatory drug in human patients after abdominal surgery. Chapter three is a randomized, blinded clinical trial quantifying the effect of emergency abdominal surgery on the concentration of markers of systemic inflammation and endothelial perturbation in canine patients in the post-operative period. The trial also assessed the potential use of lidocaine as a post-operative immunomodulatory therapy in dogs having undergone laparotomy. Fifty canine patients undergoing abdominal surgery were enrolled in the study. Patients were randomized into two separate groups: a study group receiving lidocaine intravenously, and a control group receiving 0.9% NaCl intravenously for a twelve-hour period following abdominal surgery. Blood samples were gathered prior to surgery, followed by six and twelve hours post-operatively. Concentrations of markers of systemic inflammation (IL-6) and markers of endothelial perturbation (VEGF and HA) were quantified via means of ELISA at each time point. Results revealed a significant increase in the concentration of markers of systemic inflammation and endothelial perturbation in post-operative blood samples. No immunomodulatory or endothelial preserving effect of lidocaine was appreciated.
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ItemEvaluating effectiveness of a Continuous Glucose Monitoring System (CGMS) in diabetic dogs and cats( 2018)Real-time continuous glucose monitoring systems (CGMS) measure interstitial glucose concentrations, and have been used in the management of diabetes mellitus in people, dogs and cats. The devices are used for up to 72 hours, and provide glucose measurements every 5 minutes, with 288 data points provided in a 24-hour period. This provision of a detailed insight into glycaemic control over a longer period of time than traditional methods of monitoring holds the potential for improved management of diabetes mellitus. The primary aim of this study was to determine if CGMS (using the Guardian™ system) resulted in different clinical decision making compared with monitoring serial blood glucose curves and serum fructosamine concentration in diabetic dogs and cats. Secondary aims were to determine the incidence of nocturnal hypoglycaemia and rebound hyperglycaemia in diabetic dogs and cats. Continuous glucose monitoring and fructosamine measurement were performed in client-owned dogs and cats, both newly and previously diagnosed with diabetes mellitus. A retrospective serial glucose curve was plotted with glucose measurements every 2 hours obtained from the CGMs data. Results of the three monitoring modalities along with historical data (i.e. appetite, thirst, insulin dosage) were collated and a blinded review performed by two board certified small animal internal medicine clinicians. Statistical analysis showed a difference in clinical treatment recommendations for the management of diabetic dogs and cats when using CGMs versus both serial glucose curves and serum fructosamine. Nocturnal hypoglycaemia was seen in 14.6% of diabetic dogs and cats and the 9.8% had episodes of the Somogyi effect.