In vitro evaluation of bactericidal effects of fluorescent light energy on Staphylococcus pseudintermedius and S. aureus.

BACKGROUND: Staphylococcus pseudintermedius and S. aureus are bacterial species of importance in veterinary medicine. The increasing incidence of antibiotic resistance necessitates the implementation of novel treatment modalities. Fluorescent light energy (FLE) is used as an adjunctive and primary treatment for canine pyoderma. However, no in vitro studies exist investigating its bactericidal effects against S. pseudintermedius or S. aureus. OBJECTIVES: To determine the bactericidal effects of FLE on S. pseudintermedius and S. aureus isolates. MATERIALS AND METHODS: Two meticillin-susceptible S. pseudintermedius (MSSP) isolates, three meticillin-resistant S. pseudintermedius (MRSP) isolates and one meticillin-resistant S. aureus (MRSA) isolate were studied. A commercially available blue light-emitting diode (bLED) lamp and photoconverting hydrogel FLE system was used. All bacteria were exposed to five conditions following inoculation: (i) no treatment (control); (ii) blue light (bLED) once; (iii) bLED twice consecutively; (iv) FLE (bLED and photoconverting hydrogel) once; and (v) FLE (bLED and photoconverting hydrogel) twice consecutively. Each individual exposure was 2 min long. RESULTS: No statistically significant differences (p < 0.05) were found for any treatment group when each bacterial isolate was evaluated individually, MSSP isolates were grouped, MRSP isolates were grouped, when all S. pseudintermedius isolates were combined, or when all isolates of both Staphylococcus species were combined. CONCLUSIONS AND CLINICAL RELEVANCE: While clinical success is reported when using FLE to treat Staphylococcus infections in animals, no in vitro antibacterial efficacy was identified for S. pseudintermedius or S. aureus under experimental conditions. The clinical success observed with FLE may be the result of a more complex in vivo response.

Influence of a single oral dose of trazodone on intradermal histamine reactivity in clinically healthy dogs.

BACKGROUND: Drug interactions are significant considerations for intradermal testing (IDT). Trazodone (TRZ) is an anxiolytic and selective histaminergic (H1 ) antagonist with no interaction in human prick tests; however, interaction in canine IDT is unknown. HYPOTHESIS/OBJECTIVES: Trazodone will not adversely affect intradermal histamine reactions in dogs. ANIMALS: Fourteen nonanxious, nonatopic, healthy client-owned dogs were enrolled in this randomised, blinded, cross-over study. MATERIALS AND METHODS: Dogs were randomised to receive low-dose TRZ (4 mg/kg) (Teva Pharmaceuticals), high-dose TRZ (8 mg/kg) or no TRZ per os two hours before intravenous sedation with dexmedetomidine (5 mcg/kg) (Dexdomitor; Zoetis). Intradermal testing was performed with five quadrupling dilutions of histamine (1:100,000 to 1:25,600,000 w/v; Greer) and 0.9% saline (Hospira), observing a minimum two weeks washout period between treatments. Two observers, who were blinded to treatment and the identity of the injections, evaluated each test using previously established subjective and objective methods. RESULTS: The mean wheal diameter of histamine 1:1,600,000 w/v was significantly smaller with low-dose TRZ (4 mg/kg) compared to the control group (p = 0.048; repeated measures ANOVA with post hoc Tukey's test). For all other histamine dilutions and saline, mean wheal diameter was not significantly different among groups. There were no significant differences in the subjective scores of all histamine dilutions and saline (p > 0.05; Friedman test). CONCLUSION AND CLINICAL RELEVANCE: A single oral dose of TRZ does not adversely affect intradermal histamine reactions in dogs.

Oclacitinib 10 years later: lessons learned and directions for the future.

Oclacitinib was approved in the United States 10 years ago for the management of atopic dermatitis (AD) and allergic skin disease in dogs. Many studies and case reports have been published in the past 10 years on the efficacy and safety of this medication, both at labeled doses to treat allergic dogs and off label to treat other diseases and given to other species. Concerns and confusion have occurred for both clinicians and owners regarding the long-term safety of this drug. The purpose of this review is to present the current knowledge on the efficacy, speed of action, effects on the immune system, and clinical safety of oclacitinib, based on evidence and published literature. We also aim to summarize the lessons learned in the past 10 years and to propose directions for the future.

Rifampicin treatment of canine multidrug-resistant meticillin-resistant staphylococcal pyoderma: A retrospective study of 51 cases.

BACKGROUND: Rifampicin (RFP) is a potential treatment for canine multidrug-resistant (MDR) meticillin-resistant staphylococci (MRS), yet the use of lower doses based on recent MIC data has not been evaluated in vivo. HYPOTHESIS/OBJECTIVES: To provide information on the efficacy and safety of low-dose range RFP (≤6 mg/kg/day) for the treatment of canine MDR MRS pyoderma. ANIMALS: Fifty-one client-owned dogs. MATERIALS AND METHODS: Retrospective review of dogs medical records. Dogs were from 11 US dermatology referral practices and had oral RFP at ≤6 mg/kg/day. Data evaluated included response to treatment, adverse events, and serum changes in alanine aminotransferase (ALT) and alkaline phosphatase (ALP). RESULTS: Complete resolution of pyoderma occurred in 39 of 51 dogs (76.5%). Topical antimicrobials were used concurrently in most cases (47 of 51; 92.2%). ALP elevation >1.5-fold of baseline or the high end of the reference range occurred in nine of 37 (24.3%) dogs, while ALT elevation above baseline and the high end of the reference range occurred in two of 36 (5.6%). Only six of 51 (11.8%) had clinical adverse events during treatment; five of six (83.3%) were mild reactions consisting of lethargy and gastrointestinal signs, while one dog had a possible cutaneous adverse drug reaction. Of those that experienced clinical adverse events, four of six (66.7%) did not have concurrent increased liver enzyme activity, while two of six (33.3%) had elevations in ALP alone. CONCLUSIONS AND CLINICAL RELEVANCE: Low-dose RFP (≤6 mg/kg/day) appears to be a relatively safe and effective single-agent systemic antibiotic in combination with topical antimicrobials for canine MDR MRS pyoderma.

CONTEXTE: La rifampicine (RFP) est un traitement potentiel des staphylocoques canins multirésistants (MDR) résistants à la méticilline (MRS), mais l'utilisation de doses plus faibles sur la base de données récentes sur la CMI n'a pas été évaluée in vivo. Hypothèse/Objectifs : Fournir des informations sur l'efficacité et l'innocuité des RFP à faible dose (≤ 6 mg/kg/jour) pour le traitement de la pyodermite MDR-MR canine. Animaux : Cinquante et un chiens de propriétaires. Matériels et méthodes : Revue rétrospective de chiens ayant reçu RFP par voie orale à des doses ≤ 6 mg/kg/jour provenant des dossiers médicaux de 11 centres de référés en dermatologie aux États-Unis. Les données évaluées comprenaient la réponse au traitement, les événements indésirables et les modifications sériques de l'alanine aminotransférase (ALT) et de la phosphatase alcaline (ALP). Résultats : Une résolution complète de la pyodermite s'est produite chez 39 des 51 chiens (76,5 %). Des antimicrobiens topiques ont été utilisés simultanément dans la plupart des cas (47 sur 51 ; 92,2 %). Une élévation de l'ALP> 1,5 fois la ligne de base ou l'extrémité supérieure de la plage de référence s'est produite chez neuf des 37 (24,3%) chiens, tandis qu'une élévation de l'ALT au-dessus de la ligne de base et de l'extrémité supérieure de la plage de référence s'est produite chez deux des 36 (5,6%). Seuls six sur 51 (11,8 %) ont eu des événements indésirables cliniques pendant le traitement ; cinq des six (83,3 %) étaient des réactions bénignes consistant en une léthargie et des signes gastro-intestinaux, tandis qu'un chien a eu un possible effet indésirable cutané au médicament. Parmi ceux qui ont subi des événements indésirables cliniques, quatre sur six (66,7 %) n'ont pas eu d'augmentation simultanée de l'activité des enzymes hépatiques, tandis que deux sur six (33,3 %) ont présenté des élévations de l'ALP seule. Conclusions et pertinence clinique : La RFP à faible dose (≤ 6 mg/kg/jour) semble être un antibiotique systémique à agent unique relativement sûr et efficace en association avec des antimicrobiens topiques pour la pyodermite MDR MRS canine.

Introducción- la rifampicina (RFP) es un tratamiento potencial para los estafilococos resistentes a múltiples fármacos (MDR) y meticilina (MRS), sin embargo, el uso de dosis más bajas basado en datos recientes de MIC no se ha evaluado in vivo. Hipótesis/Objetivos- Proporcionar información sobre la eficacia y seguridad de RFP en el rango de dosis bajas (≤6 mg/kg/día) para el tratamiento de la pioderma canina MDR MRS. Animales- Cincuenta y un perros propietarios particulares. Materiales y métodos- revisión retrospectiva de perros que recibieron RFP oral a dosis ≤6 mg/kg/día obtenida de historiales clínicos de 11 prácticas de referencia de dermatología de los Estados Unidos. Los datos evaluados incluyeron la respuesta al tratamiento, los eventos adversos y los cambios séricos en la alanina aminotransferasa (ALT) y la fosfatasa alcalina (ALP). Resultados- una resolución completa de la pioderma ocurrió en 39 de 51 perros (76,5 %). Antimicrobianos tópicos se usaron al mismo tiempo en la mayoría de los casos (47 de 51; 92,2%). En nueve de 37 (24,3 %) perros se produjo una elevación de ALP >1,5 veces respecto al valor inicial o el extremo superior del rango de referencia, mientras que en dos de 36 (5,6 %) se produjo una elevación de ALT por encima del valor inicial y en el límite superior del rango de referencia. Solo seis de 51 (11,8%) tuvieron eventos adversos clínicos durante el tratamiento; cinco de seis (83,3 %) fueron reacciones leves que consistieron en letargo y signos gastrointestinales, mientras que un perro tuvo una posible reacción cutánea adversa al medicamento. De los que experimentaron eventos adversos clínicos, cuatro de seis (66,7 %) no tuvieron un aumento simultáneo de la actividad de las enzimas hepáticas, mientras que dos de seis (33,3 %) tuvieron elevaciones en la ALP por sí sola. Conclusiones y relevancia clínica- la dosis baja de RFP (≤6 mg/kg/día) parece ser un antibiótico sistémico de uso único relativamente seguro y efectivo en combinación con antimicrobianos tópicos para la pioderma canina MDR MRS.

Contexto - A rifampicina (RFP) é um tratamento potencial para estafilococos resistentes à meticilina (MRS) multirresistentes (MDR) e a utilização de doses mais baixas baseado em dados recentes de MIC não foi avaliada in vivo. Hipótese/Objetivos: Fornecer informações sobre a eficácia e segurança de RFP em menor dosagem (≤6 mg/kg/dia) para o tratamento de piodermite canina por MRS MDR. Animais: Cinquenta e um cães de clientes. Materiais e métodos: Uma revisão retrospectiva dos prontuários de cães que receberam RFP oral na dose de ≤6 mg/kg/dia em 11 clínicas dermatológicas nos Estados Unidos. Os dados avaliados incluíram resposta ao tratamento, eventos adversos, alterações séricas de alanina aminotransferase (ALT) e fosfatase alcalina (FA). Resultados: Resolução completa da piodermite ocorreu em 39 de 51 dos cães (76,5%). Antimicrobianos tópicos foram utilizados concomitantemente na maioria dos casos (47 de 51; 92,2%). Elevação de mais de 1,5 vezes na FA ou para o limite superior do intervalo de referência ocorreu em nove de 37 cães (24,3%), enquanto a elevação de ALT acima do valor inicial e o limite superior do valor de referência ocorreu em dois de 36 (5,6%). Apenas cinco de 51 (11,8%) apresentaram efeitos adversos durante o tratamento; cinco de seis (83,3%) tiveram reações leves caracterizadas por letargia e sinais gastrointestinais, enquanto um cão apresentou uma possível farmacodermia. Dos que apresentaram eventos adversos, quatro de seis (66,7%) não apresentaram aumento concomitante de enzimas hepáticas, enquanto dois de seis (33,3%) tiveram aumento de FA isoladamente. Conclusões e relevância clínica - RFP em baixa dosagem (≤6 mg/kg/dia) aparenta ser relativamente segura e eficaz em monoterapia no tratamento da piodermite canina por MRS MDR por via sistêmica, associada a antimicrobianos tópicos.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Systematic review of the venous thromboembolism risk assessment models used in aesthetic plastic surgery.

BACKGROUND: A reliable venous thromboembolism (VTE) risk assessment model (RAM) can assist surgeons in identifying patients who would benefit from VTE prophylaxis. This systematic review was aimed at summarising the current available evidence on VTE RAMs used in aesthetic plastic surgery. METHODS: A comprehensive search was performed in the PubMed, EMBASE and Cochrane databases to include primary studies describing VTE RAMs in aesthetic plastic surgery from 1946 to February 2019. The objective was to compare the different VTE RAMs described for aesthetic plastic surgery to recommend a reliable model to stratify patients. RESULTS: Of the 557 articles identified in the PubMed, EMBASE and Cochrane databases, six articles were included in the final review. Five different RAMs were used in the included studies: Caprini 2005 RAM, Caprini 2010 RAM, Davison-Caprini 2004 RAM, the American Society of Anaesthesiologist's (ASA) physical status grading system and a tool developed by Wes et al. The difference in risk weightage amongst the tools along with the VTE incidences for different categories was compared. The Caprini 2005 RAM was the most widely reported tool and validated in plastic surgery patients. CONCLUSION: Amongst the five different tools currently used, the Caprini 2005 RAM was the most widely reported. This tool was validated in plastic surgery patients and reported to be a sensitive and reliable tool for VTE risk stratification; therefore, current data support its use until further higher quality evidence becomes available. Because of the heterogeneity of the data and low quality of the current evidence, a definitive recommendation cannot be made on the best VTE RAM for patients undergoing aesthetic plastic surgery. This paper highlights the need for randomised controlled trials evaluating the various RAMs which are essential to support future recommendations and guidelines.

Genomic and in vitro pharmacodynamic analysis of rifampicin resistance in multidrug-resistant canine Staphylococcus pseudintermedius isolates.

BACKGROUND: Antimicrobial resistance is a growing concern in canine Staphylococcus pseudintermedius dermatitis. Treatment with rifampicin (RFP) is considered only in meticillin-resistant and multidrug-resistant S. pseudintermedius (MDR-MRSP). HYPOTHESIS/OBJECTIVES: To determine an optimal RFP dosing for MDR-MRSP treatment without induction of RFP resistance and identify causal mutations for antimicrobial resistance. METHODS AND MATERIALS: Time-kill assays were performed in a control isolate and three MDR-MRSP isolates at six clinically relevant concentrations [32 to 1,024 × MIC (the minimum inhibitory concentration)]. Whole-genome resequencing and bioinformatic analysis were performed in the resistant strains developed in this assay. RESULTS: The genomic analysis identified nine antimicrobial resistance genes (ARGs) in MDR-MRSP isolates, which are responsible for resistance to seven classes of antibiotics. RFP activity against all four isolates was consistent with a time-dependent and bacteriostatic response. RFP resistance was observed in six of the 28 time-kill assays, including concentrations 64 × MIC in MDR-MRSP1 isolates at 24 h, 32 × MIC in MDR-MRSP2 at 48 h, 32 × MIC in MDR-MRSP3 at 48 h and 256 × MIC in MDR-MRSP3 at 24 h. Genome-wide mutation analyses in these RFP-resistant strains discovered the causal mutations in the coding region of the rpoB gene. CONCLUSIONS AND CLINICAL RELEVANCE: A study has shown that 6 mg/kg per os results in plasma concentrations of 600-1,000 × MIC of S. pseudintermedius. Based on our data, this dose should achieve the minimum MIC (×512) to prevent RFP resistance development; therefore, we recommend a minimum daily dose of 6 mg/kg for MDR-MRSP pyoderma treatment when limited antibiotic options are available.

Clinical features, treatment, and outcome of aural hematomas in horses: 7 cases (2008-2019).

OBJECTIVE: To characterize the clinical features, treatment, and outcome of aural hematomas in horses. ANIMALS: 7 horses with 1 or 2 aural hematomas (8 ears in total) treated at a veterinary teaching hospital in 2008 through 2019. PROCEDURES: Data retrieved from medical records included signalment, pertinent historical information, clinical signs, diagnostic procedures (including dermatologic assessment), and treatments. Case outcome was determined from documentation in the medical record or via telephone communication with owners or referring veterinarians. RESULTS: 3 horses were presented after recurrence of aural hematoma following treatment by the referring veterinarian. Four horses had a history of allergic skin disease prior to aural hematoma development. Most (6/7) horses were unilaterally affected. Diagnostic assessments included otoscopic evaluation (3 horses), ultrasonography (3 horses), cytologic examination of ear canal swab samples (3 horses), and histologic examination of a pinnal biopsy specimen (1 horse). Of the 8 pinnae, 2 were treated by nonsurgical needle drainage (1 with concurrent corticosteroid injection) and the remaining 6 underwent surgical incision and placement of compressive sutures. Follow-up information was available for 6 horses, and all affected pinnae were fibrotic with 4 horses having permanent drooping of the pinna. One horse developed a hematoma in the contralateral pinna 1 year after hospital discharge. CONCLUSIONS AND CLINICAL RELEVANCE: Equine aural hematoma is a rare condition. The main principle of treatment is drainage, and treatment options commonly used in small animal practice can be successfully applied in horses. Permanent changes in the cosmetic appearance of the pinna are likely to develop owing to secondary fibrosis.

Successful management of cutaneous paralagenidiosis in a dog treated with mefenoxam, minocycline, prednisone, and hyperbaric oxygen therapy.

Cutaneous oomycotic infections are a rare dermatological disease primarily affecting horses and dogs. Response to medical management with antifungal therapies is poor because these organisms are not true fungi. Complete cure is unlikely if the infected tissue is unable to be completely surgically excised. This is a case report of successfully-managed cutaneous paralagenidiosis infection of the perianal tissue in an 11-month-old male intact Labrador retriever utilizing hyperbaric oxygen therapy, corticosteroids, minocycline, mefenoxam, and surgery.

Draft Genome Assemblies of Two Staphylococcus pseudintermedius Strains Isolated from Canine Skin Biopsy Specimens.

Staphylococcus pseudintermedius is a Gram-positive bacterial species highly relevant to animal and human health. In this study, we report the draft genome sequences of two clinical isolates of S. pseudintermedius from canine skin biopsy specimens at the Dermatology Service of the Auburn University Small Animal Teaching Hospital.

Intergenerational effects of CO2-induced stream acidification in the Trinidadian guppy (Poecilia reticulata).

Rising atmospheric carbon dioxide levels are driving decreases in aquatic pH. As a result, there has been a surge in the number of studies examining the impact of acidification on aquatic fauna over the past decade. Thus far, both positive and negative impacts on the growth of fish have been reported, creating a disparity in results. Food availability and single-generation exposure have been proposed as some of the reasons for these variable results, where unrealistically high food treatments lead to fish overcoming the energetic costs associated with acclimating to decreased pH. Likewise, exposure of fish to lower pH for only one generation may not capture the likely ecological response to acidification that wild populations might experience over two or more generations. Here we compare somatic growth rates of laboratory populations of the Trinidadian guppy (Poecilia reticulata) exposed to pH levels that represent the average and lowest levels observed in streams in its native range. Specifically, we test the role of maternal acclimation and resource availability on the response of freshwater fishes to acidification. Acidification had a negative impact on growth at more natural, low food treatments. With high food availability, fish whose mothers were acclimated to the acidified treatment showed no reduction in growth, compared to controls. Compensatory growth was observed in both control-acidified (maternal-natal environment) and acidified-control groups, where fish that did not experience intergenerational effects achieved the same size in response to acidification as those that did, after an initial period of stunted growth. These results suggest that future studies on the effects of shifting mean of aquatic pH on fishes should take account of intergenerational effects and compensatory growth, as otherwise effects of acidification may be overestimated.

Presumptive iatrogenic hypoadrenocorticism induced by high-dose ketoconazole administration in a dog.

A 11-year-old male neutered Shih Tzu was referred to a tertiary facility with a history of weight loss, decreased appetite, polydipsia, and lethargy. The dog had a 10-year history of nonspecific allergic dermatitis and was being treated with 16 mg/kg of ketoconazole q12h for Malassezia dermatitis. Vague gastrointestinal signs, hypocholesterolemia, and lack of a stress leukogram increased suspicion for hypoadrenocorticism (HA). An adrenocorticotropic hormone (ACTH) stimulation test identified hypocortisolemia on pre- and post-ACTH samples and ketoconazole was discontinued. After a short course of corticosteroid treatment, an ACTH stimulation test was repeated and pre-ACTH cortisol concentration was within the reference range, and the post-ACTH cortisol concentration was mildly increased. The temporal association between return of adequate adrenocortical cortisol production and discontinuation of ketoconazole led to the conclusion that the dog had developed iatrogenic HA secondary to ketoconazole treatment.

Effects of Ovariohysterectomy and Hyperbaric Oxygen Therapy on Systemic Inflammation and Oxidation in Dogs.

Introduction: Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen in a specialized compression chamber leading to hyperoxia. This treatment modality is associated with anti-inflammatory, antioxidant, and healing properties in people and laboratory animals. However, there are relatively few reports that evaluate the effects of HBOT in companion animals. The goal of this study was to investigate the physiological effects of HBOT on surgically induced systemic inflammation and oxidation in dogs. Material and Methods: Twelve healthy female beagle dogs were spayed and randomized into control and HBOT groups (n = 6). Both groups received conventional post-ovariohysterectomy therapy, and the HBOT group received two hyperbaric treatments at 2.0 atmosphere of absolute pressure and 100% oxygen for 35 min, 6 and 18 h after surgery. Blood samples were collected 3 h prior to ovariohysterectomy, 6, 18, and 30 h after surgery, prior to HBOT when applicable. Inflammatory biomarkers, including C-reactive protein, circulating cytokines, and changes in iron homeostasis were evaluated at each time point to determine the effects of surgery and HBOT on inflammation. Similarly, serum total oxidant status and total antioxidant status were measured to assess the oxidative stress. Pain and incision scores were recorded and compared between groups. Results: Following ovariohysterectomy, all dogs had significantly increased serum concentrations of C-reactive protein, KC-like, IL-6, and increased unsaturated iron-binding capacity compared to their pre-surgical values (p < 0.02), while serum iron, total iron-binding capacity and transferrin saturation were significantly decreased after surgery (p < 0.02). There was no significant difference between the control group and the HBOT group for any of the variables. There were no overt adverse effects in the HBOT group. Conclusion: This is the first prospective randomized controlled study to investigate the effects of HBOT on surgically induced systemic inflammation in dogs. While elective ovariohysterectomy resulted in mild inflammation, the described HBOT protocol portrayed no outward adverse effect and did not induce any detectable pro-inflammatory, anti-inflammatory, or antioxidant effects. Additional investigation is required to identify objective markers to quantify the response to HBOT and determine its role as an adjunctive therapy in dogs with more severe, complicated or chronic diseases.

The Academic Surgical Collaborative: A three-year review of a trainee research collaborative.

INTRODUCTION: The Academic Surgical Collaborative (ASC) is a trainee research collaborative (TRC) formed in the UK in October 2014. Three years on, the achievements are presented along with advice for emerging and established TRCs. Methods: A retrospective review of internal, member-maintained ASC records was conducted. Membership numbers, PubMed indexed publications, presentations and prizes awarded were all calculated over time. Google Scholar was used to calculate citations per ASC publication. An online survey was distributed to members to ascertain member satisfaction. RESULTS: With 62 active members (predominantly medical students) the ASC has published 33 PubMed indexed papers over three years, with a mean of 21 citations per paper (SD 89, range 0-491). 54 presentations have been delivered and eight prizes have been awarded for ASC research projects. 60% of ASC members believe the ASC delivers research that improves patient care. Key learning points for the ASC have been the use of a set of resources distributed to new members, the value of regular meetings, close mentoring throughout research projects to develop the skills of junior researchers, encouragement for junior members to present at conferences, and an ongoing focus on research conduct and improving evidence based medicine. CONCLUSIONS: The ASC has fulfilled many of its goals set out at its inception. The ASCs subsequent aims are to enhance existing research training for junior members, advances in the field of core outcome development and also multi-collaborative research.

Minimum inhibitory concentration and killing properties of rifampicin against canine Staphylococcus pseudintermedius isolates from dogs in the southeast USA.

BACKGROUND: Meticillin-resistant (MR) staphylococcal pyoderma in dogs has led to increased use of alternate antibiotics such as rifampicin (RFP). However, little information exists regarding its pharmacodynamics in MR Staphylococcus pseudintermedius. HYPOTHESIS/OBJECTIVES: To determine the minimum inhibitory concentration (MIC) and killing properties of RFP for canine Staphylococcus pseudintermedius isolates. METHODS: The MIC of RFP was determined using the ETEST® for 50 meticillin-susceptible (MS) and 50 MR S. pseudintermedius isolates collected from dogs. From these isolates, two MS isolates (RFP MIC of 0.003 and 0.008 µg/mL, respectively) and two MR isolates (RFP MIC of 0.003 and 0.012 µg/mL, respectively) were subjected to time-kill studies. Mueller-Hinton broth was supplemented with RFP at 0, 0.5, 1, 2, 4, 8, 16 and 32 times the MIC for 0, 2, 4, 10, 16 and 24 h. The number of viable colony forming units in each sample was determined using a commercial luciferase assay kit. RESULTS: The MIC50 and MIC90 were the same for MS and MR isolates, at 0.004 µg/mL and 0.008 µg/mL, respectively. Rifampicin kill curves were not indicative of concentration-dependency, suggesting time-dependent activity. Two isolates (MS 0.003 and 0.008 µg/mL) exhibited bacteriostatic activity, whereas two others (MR 0.003 and 0.012 µg/mL) exhibited bactericidal activity. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrated that MS and MR S. pseudintermedius isolates were equally susceptible to rifampicin and that dosing intervals should be designed for time-dependent efficacy. These data can support pharmacokinetic studies of RFP in dogs with susceptible infections caused by S. pseudintermedius.

Single blinded, randomized, placebo-controlled study on the effects of ciclosporin on cutaneous barrier function and immunological response in atopic beagles.

Ciclosporin (CsA) is a common treatment for canine atopic dermatitis (cAD). cAD is a very common skin disease with a multifactorial pathogenesis due to complex interactions between the host and the environment. The purpose of this study was to describe the physical and immunological effects of CsA in cAD using a canine model of AD. Fourteen beagles were enrolled; seven received CsA orally every 24 h for 28 days, and seven received placebo. All dogs were exposed to relevant allergens, house dust mite solution, one day prior to treatment and once weekly thereafter for 28 consecutive days. Canine atopic dermatitis extent and severity index-03 (CADESI-03) and skin biopsies were performed on day 0, 14, and 28. Quantitative RT-PCR was used to determine levels of cutaneous cytokines and barrier function markers. Indirect immunofluorescence was used to determine protein expression and distribution of nuclear messengers, barrier function and inflammatory [thymic stromal lymphopoietin (TSLP)] markers. The data were tested for normality and then the upaired two samples Student's t-test and the repeated measurements ANOVA, followed by the Dunnett's Multiple Comparison Test as post-hoc analysis, were performed. A P value of <0.05 was considered statistically significant. A significant decrease in CADESI-03 occurred for the treatment group compared to placebo (p = 0.023) on day 28. On day 14, a significant increase in TSLP protein expression [p = 0.019 (placebo); p = 0.02 (CsA)] and a significant decrease in Transforming Growth Factor (TGF)-ß mRNA [p = 0.01 (placebo); p = 0.015 (CsA)] were noted in both groups compared to baseline. On day 28, a significant increase in canine beta defensin (cBD)103 [p = 0.012 (placebo)] and cBD3-like mRNAs [p = 0.044 (placebo)], and filaggrin [p = 0.035 (CsA)] and TSLP protein expressions [p = 0.0092 (CsA)] were seen compared to baseline. In contrast, a significant decrease in mRNA of Tumor Necrosis factor (TNF)-α [p = 0.013 (CsA)], Interleukin (IL)-10 [p = 0.038 (CsA)], TGF-ß [p = 0.017 (CsA)], and caspase 14 [p = 0.014 (CsA)] was seen on day 28 compared to baseline. Comparison of the groups revealed no significant effect on skin immunologic milieu or barrier markers despite evident improvement of physical signs in the treatment group. Although this study confirmed the usefulness of CsA for the treatment of cAD, a clear involvement of CsA on some of the currently known immunological alterations present in cAD was not determined. However, it is important to note that there was no measurable exacerbation of skin barrier dysfunction secondary to CsA administration in this model.

Determining canine skin concentrations of terbinafine to guide the treatment of Malassezia dermatitis.

BACKGROUND: Terbinafine (TBF) is known to concentrate and persist in human skin. Its use is increasing in veterinary medicine, but there are limited data concerning its tissue concentration and efficacy in dogs. HYPOTHESIS/OBJECTIVES: (i) Describe TBF accumulation in canine skin; (ii) Integrate pharmacokinetic data with historical minimum inhibitory concentration (MIC) results for Malassezia pachydermatis to verify the currently used dosage of TBF for the treatment of Malassezia dermatitis. ANIMALS: Ten healthy, client-owned dogs. METHODS: Dogs were given TBF (generic preparation, 250 mg tablets) 30 mg/kg per os (p.o.) once daily for 21 days. Serum, sebum and stratum corneum (SC) samples were collected on days 1, 5, 7, 11, 14, 21, 28 and 35. High-pressure liquid chromatography was used to determine drug concentrations in samples. RESULTS: Relevant (mean ± standard deviation) parameters for TBF in serum, paw SC, thorax SC and sebum, respectively, were: maximum concentration (Cmax , µg/mL) 23.59 ± 10.41, 0.31 ± 0.26, 0.30 ± 0.32 and 0.48 ± 0.25; half-life (t1/2 , d) 4.49 ± 2.24, 6.34 ± 5.33, 4.64 ± 3.27 and 5.12 ± 3.33; time to maximum concentration (Tmax , d) 10.40 ± 6.98, 13.20 ± 5.16, 11.90 ± 8.62 and 10.60 ± 3.69. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that TBF does not achieve high concentrations in canine SC or sebum compared to serum. The mean Cmax of all skin tissues (paw SC, thorax SC and sebum) barely exceeded the reported Malassezia MIC90, of 0.25 µg/mL, which indicates that doses higher than 30 mg/kg p.o. once daily may be necessary.