Bacterial infections in dogs with special reference to urinary tract infections, surgical site infections and methicillin-resistant Staphylococcus pseudintermedius

An increase in antimicrobial resistance in canine bacterial pathogens, including multidrug-resistance, has been reported worldwide. Increasing antimicrobial resistance is of concern, not only as it complicates therapy in dogs, but also as it is a public health problem when the pathogens are zoonotic, or the location of resistance genes enables transfer between bacteria of animal and human origin. The overall aims of this thesis were to gain knowledge of bacterial infections in dogs with special reference to urinary tract infections (UTI), surgical site infections (SSI) and their antimicrobial susceptibility patterns, and of carriage of methicillin-resistant Staphylococcus pseudintermedius (MRSP). The results were intended to aid in choice of antimicrobial treatment of canine UTI and SSI, and in designing recommendations on prevention and control of carriage of MRSP. First-line antimicrobials were found to be a rational empirical antimicrobial therapy for the studied dog population. In total three percent of detected Escherichia coli isolates were resistant to extended-spectrum cephalosporins. Less than 3% of S. pseudintermedius isolates were methicillin resistant. No methicillin-resistant Staphylococcus aureus (MRSA) isolates were found. Dogs carried MRSP for several months without clinical signs. Systemic treatment for three weeks or longer with antimicrobials to which the bacterium was resistant was associated with prolonged carriage compared to shorter treatment periods. Three of five dogs treated with an antimicrobial to which the MRSP-isolates were susceptible remained MRSP-carriers. These findings support restricted use of systemic antimicrobial treatment in dogs with possible or confirmed MRSP carriage or infection. The risk of MRSP-colonization in dogs living in a household with an MRSP-infected dog might be lowered if the clinically infected dog (index dog) becomes MRSP -negative. Furthermore, all contact dogs in the family might not carry MRSP continuously during the time the index dog is MRSP-positive. The results of the evaluation of five body sites for MRSP carriage screening suggests that simultaneous sampling of pharynx, perineum and the corner of the mouth, as well as wounds when present, should be recommended. Furthermore, the results suggest that sampling of nostrils is not a priority when screening dogs for MRSP

Leptospira seroprevalence and associated risk factors in healthy Swedish dogs

Background Leptospirosis is an emerging zoonotic infection worldwide and a cause of life-threatening disease in dogs. Seroprevalence in Swedish dogs is unknown. The aims of the present study were to estimate seroprevalence of pathogenic Leptospira in healthy dogs in Sweden using the microagglutination test (MAT) and a rapid point-of-care enzyme-linked immunosorbent assay (ELISA), and to evaluate risk factors of Leptospira exposure in Swedish dogs. Results Positive MAT titres (>= 1:50) were detected in 27/369 (7.3%) of included dogs. Five different serovars were represented of which the Saxkoebing serovar was the most common (64.3%), followed by Copenhagi (14.3%), Bratislava (10.7%), Icterohaemorrhagiae (7.1%), and Canicola (3.6%). The ELISA test (SNAP (R) Lepto) was positive in 3/316 (0.9%) dogs. Living in urban areas and contact with stagnant water were found to be risk factors for Leptospira seropositivity (p < 0.05) in a multivariable logistic regression model. Conclusion In this first seroprevalence study of Leptospira in Swedish dogs, it was shown that healthy dogs without recent (24 months) travel history and antileptospira vaccination had been exposed to pathogenic Leptospira interrogans serovars. Contact with stagnant water and living in urban areas were independent risk factors for seropositivity

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia

Development and Validation of a Quantitative UHPLC-MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats

Carriage of methicillin-resistant Staphylococcus pseudintermedius in dogs--a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Methicillin-resistant <it>S. pseudintermedius </it>strains (MRSP) are reported with increasing frequency in bacterial cultures from dogs. The objectives of this study were to determine whether MRSP could be found in dogs several months after a clinically apparent infection and whether the length of carriage varied depending on systemic antimicrobial treatment, diagnosis at time of the first positive MRSP culture and the presence of skin disease or wounds. Thirty-one dogs previously diagnosed with a clinical infection were sampled repeatedly for a minimum of eight months or, with the exception of two dogs, until two consecutive negative results were obtained. Five specified locations were sampled, and the results were evaluated to determine future recommendations concerning sample strategies when screening for MRSP carriage. Information was collected from medical records and questionnaires to evaluate factors that may influence length of carriage.</p> <p>Results</p> <p>The overall median length of MRSP carriage was 11 months (48 weeks). The presence of wounds and signs of dermatitis did not influence length of carriage. Systemic treatment for three weeks or longer with antimicrobial agents to which the bacterium was resistant was associated with prolonged carriage compared to dogs treated for a shorter period of time. Three of five dogs treated with an antimicrobial to which their MRSP-isolates were susceptible (tetracycline) were found to still be MRSP-positive when sampled after the end of treatment. Wound samples had the highest positive MRSP yield (81%) for the positive sample sites, compared to less than 70% for each of the other four sample sites. Cultures from the nostrils were less likely to detect MRSP carriage relative to the pharynx, perineum, wounds and the corner of the mouth.</p> <p>Conclusions</p> <p>Dogs can carry MRSP for more than a year after a clinically apparent infection. Systemic antimicrobial treatment of infections with antimicrobial agents to which the MRSP-bacteria are resistant should be avoided when possible in dogs with possible or confirmed MRSP carriage or infection, since it may prolong time of MRSP carriage. Simultaneous sampling of pharynx, perineum, and the corner of the mouth as well as wounds when present is recommended when screening for MRSP. Cultures from nostrils were shown to be less likely to detect MRSP carriage.</p

The role of activation functions 1 and 2 of estrogen receptor-α for the effects of estradiol and selective estrogen receptor modulators in male mice

Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-α. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a non-functional ERα had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ERα for the effects of E2 and SERMs on bone mass in males. Three mouse models lacking either ERαAF-1 (ERαAF-1(0)), ERαAF-2 (ERαAF-2(0)) or the total ERα (ERα(−/−)) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, while it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ERα(−/−) or ERαAF-2(0) mice. However, the effects of E2 in orx ERαAF-1(0) mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERαAF-1 for the effects of SERMs, we treated orx WT and ERαAF-1(0) mice with Raloxifene (Ral), Lasofoxifene (Las), Bazedoxifene (Bza) or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency towards increased cortical bone parameters. Importantly, all SERM-effects were absent in the orx ERαAF-1(0) mice. In conclusion, ERαAF-2 is required for the estrogenic effects on all evaluated parameters, while the role of ERαAF-1 is tissue specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERαAF-1. Our findings might contribute to the development of bone specific SERMs in males

Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis

<p>Abstract</p> <p>Background</p> <p>Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1^*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1^*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis.</p> <p>Methods</p> <p>Female B10.Q-ncf1^*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines.</p> <p>Results</p> <p>Raloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6.</p> <p>Conclusions</p> <p>This is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA.</p

Alpha-chloralose poisoning in cats : clinical findings in 25 confirmed and 78 suspected cases

Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time &lt;48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia

Development and Validation of a Quantitative UHPLC-MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats