Species-specific and Indication-based Use of Antimicrobials in Dogs, Cats, Cattle and Horses in Finland : Data collected using three different methods

Increasing antimicrobial resistance in bacteria has led to the need for better understanding of antimicrobial usage patterns. In 1999, the World Organisation for Animal Health (OIE) recommended that an international ad hoc group should be established to address human and animal health risks related to antimicrobial resistance and the contribution of antimicrobial usage in veterinary medicine. In European countries the need for continuous recording of the usage of veterinary antimicrobials as well as for animal species-specific and indication-based data on usage has been acknowledged. Finland has been among the first countries to develop prudent use guidelines in veterinary medicine, as the Ministry of Agriculture and Forestry issued the first animal species-specific indication-based recommendations for antimicrobial use in animals in 1996. These guidelines have been revised in 2003 and 2009. However, surveillance on the species-specific use of antimicrobials in animals has not been performed in Finland. This thesis provides animal species-specific information on indication-based antimicrobial usage. Different methods for data collection have been utilized. Information on antimicrobial usage in animals has been gathered in four studies (studies A-D). Material from studies A, B and C have been used in an overlapping manner in the original publications I-IV. Study A (original publications I & IV) presents a retrospective cross-sectional survey on prescriptions for small animals at the Veterinary Teaching Hospital of the University of Helsinki. Prescriptions for antimicrobial agents (n = 2281) were collected and usage patterns, such as the indication and length of treatment, were reviewed. Most of the prescriptions were for dogs (78%), and primarily for the treatment of skin and ear infections most of which were treated with cephalexin for a median period of 14 days. Prescriptions for cats (18%) were most often for the treatment of urinary tract infections with amoxicillin for a median length of 10 days. Study B (original publication II) was a retrospective cross-sectional survey where prescriptions for animals were collected from 17 University Pharmacies nationwide. Antimicrobial prescriptions (n = 1038) for mainly dogs (65%) and cats (19%) were investigated. In this study, cephalexin and amoxicillin were also the most frequently used drugs for dogs and cats, respectively. In study C (original publications III & IV), the indication-based usage of antimicrobials of practicing veterinarians was analyzed by using a prospective questionnaire. Randomly selected practicing veterinarians in Finland (n = 262) recorded all their antimicrobial usage during a 7-day study period. Cattle (46%) with mastitis were the most common patients receiving antimicrobial treatment, generally intramuscular penicillin G or intramammary treatment with ampicillin and cloxacillin. The median length of treatment was four days, regardless of the route of administration. Antimicrobial use in horses was evaluated in study D, the results of which are previously unpublished. Firstly, data collected with the prospective questionnaire from the practicing veterinarians showed that horses (n = 89) were frequently treated for skin or wound infections by using penicillin G or trimethoprim-sulfadiazine. The mean duration of treatment was five to seven days. Secondly, according to retrospective data collected from patient records, horses (n = 74) that underwent colic surgery at the Veterinary Teaching Hospital of the University of Helsinki were generally treated according to national and hospital recommendations; penicillin G and gentamicin was administered preoperatively and treatment was continued for a median of three days postoperatively. In conclusion, Finnish veterinarians followed well the national prudent use guidelines. Narrow-spectrum antimicrobials were preferred and, for instance, fluoroquinolones were used sparingly. Prescription studies seemed to give good information on antimicrobials usage, especially when combined with complementary information from patient records. A prospective questionnaire study provided a fair amount of valuable data on several animal species. Electronic surveys are worthwhile exploiting in the future.

Contrast-enhanced ultrasound of abdominal organs in cats

The primary aim of this thesis was the evaluation of the perfusion of normal organs in cats using contrast-enhanced ultrasound (CEUS), to serve as a reference for later clinical studies. Little is known of the use of CEUS in cats, especially regarding its safety and the effects of anesthesia on the procedure, thus, secondary aims here were to validate the quantitative analyzing method, to investigate the biological effects of CEUS on feline kidneys, and to assess the effect of anesthesia on splenic perfusion in cats undergoing CEUS. -- The studies were conducted on healthy, young, purpose-bred cats. CEUS of the liver, left kidney, spleen, pancreas, small intestine, and mesenteric lymph nodes was performed to characterize the normal perfusion of these organs on ten anesthetized, male cats. To validate the quantification method, the effects of placement and size of the region of interest (ROI) on perfusion parameters were investigated using CEUS: Three separate sets of ROIs were placed in the kidney cortex, varying in location, size, or depth. The biological effects of CEUS on feline kidneys were estimated by measuring urinary enzymatic activities, analyzing urinary specific gravity, pH, protein, creatinine, albumin, and sediment, and measuring plasma urea and creatinine concentrations before and after CEUS. Finally, the impact of anesthesia on contrast enhancement of the spleen was investigated by imaging cats with CEUS first awake and later under anesthesia on separate days. -- Typical perfusion patterns were found for each of the studied organs. The liver had a gradual and more heterogeneous perfusion pattern due to its dual blood flow and close proximity to the diaphragm. An obvious and statistically significant difference emerged in the perfusion between the kidney cortex and medulla. Enhancement in the spleen was very heterogeneous at the beginning of imaging, indicating focal dissimilarities in perfusion. No significant differences emerged in the perfusion parameters between the pancreas, small intestine, and mesenteric lymph nodes. -- The ROI placement and size were found to have an influence on the quantitative measurements of CEUS. Increasing the depth or the size of the ROI decreased the peak intensity value significantly, suggesting that where and how the ROI is placed does matter in quantitative analyses. --- A significant increase occurred in the urinary N-acetyl-β-D-glucosaminidase (NAG) to creatinine ratio after CEUS. No changes were noted in the serum biochemistry profile after CEUS, with the exception of a small decrease in blood urea concentration. The magnitude of the rise in the NAG/creatinine ratio was, however, less than the circadian variation reported earlier in healthy cats. Thus, the changes observed in the laboratory values after CEUS of the left kidney did not indicate any detrimental effects in kidneys. Heterogeneity of the spleen was observed to be less and time of first contrast appearance earlier in nonanesthetized cats than in anesthetized ones, suggesting that anesthesia increases heterogeneity of the feline spleen in CEUS. ---- In conclusion, the results suggest that CEUS can be used also in feline veterinary patients as an additional diagnostics aid. The perfusion patterns found in the imaged organs were typical and similar to those seen earlier in other species, with the exception of the heterogeneous perfusion pattern in the cat spleen. Differences in the perfusion between organs corresponded with physiology. Based on the results, estimation of focal perfusion defects of the spleen in cats should be performed with caution and after the disappearance of the initial heterogeneity, especially in anesthetized or sedated cats. Finally, these results indicate that CEUS can be used safely to analyze kidney perfusion also in cats. Future clinical studies are needed to evaluate the full potential of CEUS in feline medicine as a tool for diagnosing lesions in various organ systems.