Evaluation of topically applied enilconazole for the treatment of dermatophytosis in a Persian cattery

Many Persian catteries have long-standing dermatophyte infections and are particularly difficult to treat. Enilconazole is a topical antifungal agent that has demonstrated good efficacy in recent studies. Twenty-two Persian cats naturally infected with Microsporum canis in a breeding cattery were treated with topical 0.2% enilconazole and monitored for 180 days. The treatments were repeated every 3 days for a total of eight applications. All the cats improved clinically and became culture negative by day 28. By day 180, four cats had developed clinical dermatophytosis and all cats had positive fungal cultures. In this study, topical 0.2% enilconazole was generally well tolerated but may have caused hypersalivation, idiopathic muscle weakness and slightly elevated serum alanine aminotransferase (ALT) concentrations. This study suggests that enilconazole may be used safely with little risk to the young, aged and gravid animals.     

Surgical treatment of canine nasal aspergillosis by rhinotomy combined with enilconazole infusion and oral itraconazole

OBJECTIVES: To evaluate the effectiveness of rhinotomy and surgical debridement associated with topical administration of 2 per cent enilconazole and oral itraconazole in dogs with severe or recurrent sinonasal aspergillosis. METHODS: A standard rhinotomy was performed on seven dogs. In the initial study, the bone flap was left attached cranially and replaced at the end of the procedure. In the main study group, the bone flap was discarded. Nasal passages were debrided and irrigated with enilconazole solution for one hour. Oral itraconazole was administered to four dogs for one month postoperatively. Follow-up rhinoscopy was performed in all dogs. RESULTS: All three dogs in the initial study had recurrence of the disease and two dogs had a second surgery to remove the flap. The main study group included four dogs in which the flap was initially removed, and the two dogs from the initial study that required a second surgery. At follow-up rhinoscopy, five dogs were free of aspergillus but had bacterial or inflammatory rhinitis and one dog had a small aspergilloma but was subsequently asymptomatic. Telephone follow-up revealed that four dogs were asymptomatic, one dog had intermittent sneezing and serous nasal discharge, and one dog had intermittent epistaxis. CLINICAL SIGNIFICANCE: Rhinotomy with removal of the flap combined with one-hour infusion of 2 per cent enilconazole and oral itraconazole resulted in satisfactory outcome in dogs with severe or recurrent aspergillosis.     

Efficacy of pre-treatment with lufenuron for the prevention of Microsporum canis infection in a feline direct topical challenge model

Oral lufenuron is reportedly an effective treatment for some cats with dermatophytosis. The purpose of this study was to determine if lufenuron, when used as a pre-treatment prior to challenge exposure, would be protective against the development of infection after the direct topical application of fungal macrocondia (Microsporum canis spores). Three groups (n = 6/group) of juvenile cats were treated with either monthly oral lufenuron (30 or 133 mg/kg) or placebo. After 2 months of treatment, kittens were challenged using 10(5)Microsporum canis spores applied to the skin under occlusion. Cats were examined weekly and the following data collected: Wood's lamp examination; scoring for scale/crust, erythema and induration; lesion size; and the development of satellite lesions. Fungal cultures were performed bi-weekly. All cats became infected; the infections progressed, and then regressed, in a similar fashion in all groups. There were no consistent statistically significant differences in weekly infection scores between treated and untreated cats throughout the study. Treated cats did not recover faster than untreated cats. We conclude that oral lufenuron at the dosing schedule and conditions used in this study did not prevent dermatophytosis or alter the course of infection by direct topical challenge.     

Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs

OBJECTIVE: To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. DESIGN: Prospective nonrandomized clinical trial. ANIMALS: 25 dogs. PROCEDURE: Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h).The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. RESULTS: 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. CONCLUSIONS AND CLINICAL RELEVANCE: Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.     

Therapeutic use of enilconazole in broiler chicks with aspergillosis

The course of a spontaneous outbreak of aspergillosis in a broiler flock was studied. Up to the 10th day of life the total mortality was 8%. Surviving broiler had an average body weight of 141 g on the 7th day of life, in contrast to the normal body weight of 150 g per bird. Aspergillosis was diagnosed in another three broiler flocks as well in an early stage of infection. Treatment with Enilconazole (Clinafarm Spray, Janssen, Neuss) in these flocks at a single time via spray in a dosage of 1.5 g enilconazole per 10 m2 housing ground obviously reduced mortality from the second day on after treatment. The average body weight of 7-day-old broiler was in a normal range. The success of the treatment depends on an early diagnosis and immediate start of the therapy. The source of infection (hatchery, transport, litter etc.) should be discovered and eliminated to prevent flocks from further infections.     

Efficacy of oral terbinafine in feline dermatophytosis due to Microsporum canis

Microsporum canis is the dermatophyte most commonly responsible for ringworm in cats. The purpose of this paper was to evaluate the in vivo efficacy of oral terbinafine (Lamisil; Sandoz) in the treatment of feline ringworm caused by M canis, and to consider this drug as an alternative to griseofulvin or imidazoles. Fifteen cats infected with M canis were treated orally once daily with 30 mg/kg of terbinafine over a 2-week period. All treated animals were checked for dermatophytes on the last day of treatment, a month later and 3 months after the last administration of the drug. Only 12 cats could be used in the whole trial and 11 of these (92%) showed a complete cure. Terbinafine could be an effective alternative to griseofulvin when fungal resistance or idiosyncrasic intolerance are shown and, compared with griseofulvin, could give a faster rate of cure and less relapses.     

Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.     

盐酸特比萘芬对犬猫皮肤真菌病的疗效观察

笔者2001年7月至2002年1月对盐酸特比萘芬溶液及片剂(癣净溶液、抗癣特片)进行了临床验证,观察其对犬、猫皮肤真菌病的疗效,同时与克霉唑溶液进行平行比较,报告如下。     

Evaluation of topical nalbuphine or oral tramadol as analgesics for corneal pain in dogs: a pilot study

Objective To evaluate the effectiveness of topical nalbuphine or oral tramadol in the treatment of corneal pain in dogs. Animals studied Fourteen male Beagle dogs. Procedures Dogs were divided into three treatment groups and sedated with dexmedetomidine (5 μ/kg IV). A 4 mm corneal epithelial wound was created in the right eye (OD) of all dogs. Sedation was reversed with atipamazole IM. All dogs received pre/post ophthalmic examinations. Post operatively, Group NB (n = 5) received topical 1% preservative‐free nalbuphine OD q8 h and an oral placebo PO q8 h. Group TR (n = 5) received tramadol (4 mg/kg) PO q8 h and topical sterile saline OD q8 h. Group CNTRL (n = 4) received topical sterile saline OD q8 h and an oral placebo q8 h. All dogs received topical 0.3% gentamicin OD TID until healed. Dogs were pain scored using a pain scoring system modified from the University of Melbourne pain scale at 0, 1, 2, 4, and 6 h, then every 6 h by observers masked to treatment, until corneal wounds were healed. Treatment failure was recorded if cumulative pain scores were above a minimum threshold of acceptable pain and rescue analgesia of morphine (1.0 mg/kg IM) was administered subsequently. Result Four dogs in Group NB, one dog in Group TR, and two dogs in Group CNTRL required rescue analgesia. There was no significant difference in the incidence of treatment failure between groups (P = 0.184). Mean time to rescue was 9.16 h. All corneal wounds were healed by 84 h. Conclusions The results of this study suggest tramadol rather than nalbuphine should be further investigated for the treatment of corneal pain.     

In vitro efficacy of lufenuron against filamentous fungi and blood concentrations after PO administration in horses

Lufenuron is a benzoylphenyl urea-derived insecticide that has been recently introduced as a novel treatment for fungal infections in horses. The purposes of this study were to determine (1) the in vitro efficacy of lufenuron against Aspergillus and Fusarium spp. and (2) the ability of lufenuron to reach efficacious blood concentrations after PO administration in horses. Fungal colonies isolated from diseased equine corneas were tested against lufenuron solutions up to 700 microg/mL. Twenty-one adult horses received 1 of 3 PO lufenuron treatment regimens: 5 mg/kg body weight (BW) q24h for 3 days, 20 mg/kg BW q24h for 3 days, or 60 mg/ kg BW q24h for 1 day. Blood samples were collected up to 96 hours after drug administration and analyzed by high-performance liquid chromatography. Statistical analyses of lufenuron blood concentrations were performed by analysis of variance and Fischer's Least Significant Difference test, with statistical significance set at P < .05. Lufenuron showed no effect on the in vitro growth of Aspergillus or Fusarium spp. Lufenuron was detected in the blood of all but 1 horse and showed no adverse effects. The maximum blood lufenuron concentration (83.5 +/- 58.7 microg/L) was lower than the concentrations proven to be ineffective in vitro in this study. Further therapeutic use of lufenuron as an antifungal agent in horses should be based on proven efficacy against specific strains of clinically relevant fungi with pharmacokinetic data demonstrating sufficient lufenuron concentrations in target tissues.     

Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs

OBJECTIVE: To determine effectiveness of infusion of 1 and 2% enilconazole for treatment of nasal and sinusal aspergillosis, respectively, in dogs. DESIGN: Case series. ANIMALS: 26 client-owned dogs with aspergillosis. PROCEDURE: All dogs had typical clinical signs of aspergillosis and rhinoscopically visible intrasinusal or intranasal fungal plaques associated with turbinate destruction. During rhinoscopy, affected nasal cavities and frontal sinuses were debrided meticulously. Nineteen dogs (group A) were treated with 1% enilconazole by use of a modified noninvasive infusion procedure. Seven dogs (group B) were treated with 2% enilconazole via catheters that were placed via endoscopic guidance into the frontal sinuses. All dogs underwent follow-up rhinoscopy for determination of further treatment until cure was established. RESULTS: Age, disease duration, clinical score, and rhinoscopic score were similar for both groups before treatment. In group A, 17 of 19 dogs were cured; 9, 6, and 2 dogs were cured after 1, 2, or 3 treatments, respectively. The remaining 2 dogs were euthanatized before the end of the treatment protocol. In group B, all dogs were cured; 6 dogs and 1 dog were cured after 1 or 2 treatments, respectively. Only minor adverse effects such as nasal discharge, epistaxis, and sneezing developed. CONCLUSIONS AND CLINICAL RELEVANCE: After extensive rhinoscopic debridement, 1 and 2% enilconazole infused into the nasal cavities and the frontal sinuses, respectively, were effective for treatment of aspergillosis in dogs. Intrasinusal administration via endoscopically placed catheters appeared to require fewer infusions for success. Follow-up rhinoscopy is strongly advised.     

Use of lufenuron for treatment of generalized demodicosis in dogs

Abstract The efficacy of lufenuron for treatment of generalized demodicosis in dogs was investigated. Eleven dogs with generalized demodicosis received either low-dose lufenuron (mean 13.3 mg kg^-1 once a day on the first 5 days of the month) or high-dose lufenuron (mean 15.8 mg kg^-1 three times a week) orally for 2 or 3 months. None of the dogs showed a decrease in mite numbers on monthly examination of deep skin scrapings. To determine levels of orally administered lufenuron in the skin (epidermis and dermis), three adult dogs were each given lufenuron orally at a mean dose of 19.3 mg kg^-1 once a day for 5 days. Lufenuron was measured in samples of blood and skin collected on days 0, 1, 6, 16, 30, 44 and 60 after administering the drug. Mean skin levels of lufenuron were 10 times the corresponding blood levels. Lufenuron was ineffective as a treatment for generalized demodicosis in these dogs despite the fact that high drug levels were achieved in the skin. Résumé— L'efficacitée du Lufénuron dans le traitement de la démodécie généralisée du chien a étéévaluée 11 chiens présentant une démodécie généralisée ont reçu soit du lufeAnuron à dose faible (en moyenne 13, 3 mg kg^-1, 1 fois par jour les 5 premiers jours de chaque mois) ou à dose élevée (en moyenne 15, 8 mg kg^-1 fois par semaine) par voie orale pendant 2 à 3 mois. Aucun des chiens traités ne montre une diminution du nombre de parasites determine à partir de raclages cutanés profonds mensuels. Afin de déterminer les taux de lufénuron dans la peau (épiderme et derme), trois chiens adultes ont reçu chacun du lufénuron par voie orale à une dose moyenne de 19, 3 mg kg^-1, une fois par jour pendant 5 jours. Le lufénuron a été mesuré dans des échantillons sanguins et cutanés à JO, J1, J6, J16, J30, J44 et J60 après administration. Les taux moyens dans la peau sont 10 fois supérieurs aux taux sanguins correspondants. Le lufénuron est inefficace dans le traitement de la démodécie généralisée en dépit des concentrations élévées dans la peau. [Schwassmann, M., Kunkle, G. A., Hepler, D. I., Lewis, D. T. Use of lufénuron for treatment of generalized demodicosis in dogs. (Utilisation du Lufénuron pour le traitement de la démodécie généralisée du chien.) Veterinary Dermatology 1997; 8 : 11–18.] Resumen Se investigó la eficacia de lufénuron para el tratamiento de la demodicosis generalizada en perros. Once perros con demodicosis generalizada recibieron o bien una dosis baja de lufénuron (medía 13.3 mg kg^-1 una vez al día en los primeros 5 meses del mes) o una dosis alta de lufénuron (medía 15.8 mg kg^-1 3 veces a la semana) oralmente durante 2 o 3 meses. Ninguno de los perros mostró dismunición en el número de ácaros en los exámenes mensuales de raspados cutáneos profundos. Para detectar en la piel (epidermis y dermis) los niveles de lufénuron administrado oralmente, a tres perros adultos se les administró a cada uno lufénuron oral a una dosis medía de 19.3 mg kg^-1 una vez al día durante 5 días. Se cuantificó el lufénuron en muestras de sangre y piel tomadas a días 0, 1, 6, 16, 30, 44 y 60 después de la administración del fármaco. Los valores cutáneos medios de lufénuron fueron 10 veces los valores sanguineos correspondientes. Lufénuron no tuvo efecto como tratamiento de la demodicosis generalizada en estos perros a pesar de los altos niveles farmacológicos alcanzados a nivel cutáneo. [Schwassmann, M., Kunkle, G. A., Hepler, D. I., Lewis, D. T. Use of lufénuron for treatment of generalized demodicosis in dogs. (Uso de lufénuron para el tratamiento de la demodicosis generalizada en perros.) Veterinary Dermatology 1997; 8 : 11–18.] Zusammenfassung— Die Wirksamkeit von Luferunon in der Behandlung von generalisierter Demodikose wurde untersucht. Elf Hunde mit generalisierter Demodikose erhielten entweder eine niedrige (durchschnittlich 13.3 mg kg^-1 täglich an den ersten fünf Monatstagen) oder hohe Dosis Lufénuron (durchschnittlich 15.8 mg kg^-1 dreimal wöchentlich) oral für 2–3 Monate. Bei keinem Hund zeigte die monatliche Untersuchung von tiefen Hautgeschabseln eine Verminderung der Milbenanzahl. Um den Hautspiegel (Epidermis und Dermis) des oral verabreichten Lufénurons zu bestimmen, erhielten drei Hunde jeweils oral Lufénuron in einer Durchschnittsdosis von 19.3 mg kg^-1 täglich für 5 Tage. Lufénuron wurde in Serum-und Hautproben gemessen die vor und 1, 6, 16, 30, 44 und 60 Tage nach Beginn der Medikamenteneinnahme genommen wurden. Durchschnittliche Hautspiegel von Lufénuron waren zehn Mai so hoch wie die korrespondierenden Blutspiegel. Die Behandlung der generalisierten Demodikose mit Lufénuron war trotz der hohen Medikamentenkonzentration in der Haul unwirksam. [Schwassmann, M., Kunkle, G. A., Hepler, D. I., Lewis, D. T. Use of lufénuron for treatment of generalized demodicosis in dogs. (Die Verwendung von Lufénuron für die Behandlung der generalisierten Demodikose beim Hund.) Veterinary Dermatology 1997; 8 : 11–18.]     

Use of lufenuron as a treatment for fungal endometritis in four mares

Lufenuron, a benzoylphenyl urea derivative, was evaluated as a treatment for endometrial fungal infections in 4 mares. Intrauterine lavage was performed with lufenuron suspended in sterile saline (0.9% NaCl) solution. Cytologic evaluation and fungal culture of the endometrium, as well as subsequent reproductive performance, were used to monitor efficacy of this treatment. Fungal endometritis in mares is associated with infertility. Treatment is often ineffective and costly, and recurrence following treatment is not uncommon. Intrauterine infusions of lufenuron were effective in eliminating fungal endometritis in the 4 mares of this report.