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.     

Medical Management of Right Dorsal Colitis in 5 Horses: A Retrospective Study (1987–1993)

Right dorsal colitis in horses has been associated with administration of phenylbutazone. Although reports of right dorsal colitis in this species have described surgical treatment associated with a poor prognosis, we have had success treating this condition medically. This report describes 5 horses with right dorsal colitis confirmed during celiotomy that were initially managed medically. All horses had a history of intermittent abdominal pain; weight loss was noted in only 1 horse. The doses (2.0 to 4.6 mg/kg PO bid) and duration (5 to 30 days) of administration of phenylbutazone were not unusually high relative to those recommended (4.4 mg/kg PO bid). Hypoproteinemia and hypoalbuminemia were observed in all horses at the time of admission; packed cell volume was low in 4 horses, and hypocalcemia was also observed in 4 horses. Three of 5 horses (60%) appeared to respond to dietary management and discontinuation of administration of nonsteroidal anti-inflammatory drugs. Dietary management consisted of feeding pelleted feed, and restricting or eliminating roughage for a period of at least 3 months. Two horses developed strictures of the right dorsal colon. One horse that developed a colonic stricture, possibly because its owners did not comply with recommendations for management, was subsequently treated surgically. The remaining horse that developed a stricture of the right dorsal colon was euthanized. These data indicate that some horses with right dorsal colitis can be successfully managed with medical treatment.     

Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses

OBJECTIVE: To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. ANIMALS: 6 healthy horses. PROCEDURE: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods. RESULTS: Itraconazole reached higher mean +/- SD plasma concentrations after administration of the solution (0.41 +/- 0.13 microg/mL) versus the capsules (0.15 +/- 0.12 microg/mL). Bioavailability after administration of capsules relative to solution was 33.83 +/- 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 +/- 0.94 L/kg) and a long half-life (11.3 +/- 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 +/- 0.17%. CONCLUSIONS AND CLINICAL RELEVANCE: Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses.     

A Case of Equine Aspergillosis: A Novel Sampling Procedure for Diagnosis

Aspergillus spp. may induce equine respiratory infections such as fungal pneumonia, guttural pouch mycosis, and systemic infection in immunocompromised individuals. This study describes a case of probable respiratory aspergillosis in a horse presenting clinical signs of the upper airway disease different from those previously reported. Nasopharyngeal swabs and guttural pouch centesis were performed, and Aspergillus flavus was isolated and identified. Following 30 days of pharmaceutical treatment with itraconazole, clinical signs resolved. Results suggested that aspergillosis should be included in the differential diagnosis of upper airway infections, guttural pouch centesis may be useful to make a correct diagnosis, and itraconazole is efficacious in the treatment of A flavus infection.     

Delayed recurrence of nasal aspergillosis in a dog

A two-year-old, female spayed Australian cattle dog was diagnosed with nasal aspergillosis. The dog was treated topically with clotrimazole. Clinical signs recurred two months later and the clotrimazole treatment was repeated and 5 mg/kg itraconazole twice daily was added to it. The recommended dose of itraconazole for nasal aspergillosis is 5 mg/kg twice daily administered orally. The dog's symptoms completely resolved, but it developed an adverse febrile reaction to the Itraconazole. The Itraconazole was discontinued and the dog remained asymptomatic for four years. The dog then developed mucopurulent discharge from the right nostril and was diagnosed as having recurrent nasal aspergillosis. Itraconazole at 5 mg/kg twice daily was prescribed, which again induced a fever. When the itraconazole was decreased to 5 mg/kg once daily there were no fever episodes, but the nasal discharge was not completely resolved. The dog was then treated with topical clotrimazole Infusion, and maintained on 5 mg/kg itraconazole daily. To the authors' knowledge, this case is unique because of the delayed recurrence of nasal aspergillosis. Additionally, the idiosyncratic febrile reaction to the itraconazole has not previously been reported in the veterinary literature, but is similar to reports of drug-induced fever in humans.     

The first case of feline sinonasal aspergillosis due to Aspergillus fischeri in Japan

Feline upper respiratory tract infection due to Aspergillus spp. is considered an emerging disease, with the number of reported cases continuing to rise. In this study, we report the first case of feline sinonasal aspergillosis caused by Aspergillus fischeri in Japan. The patient presented after 2 months of progressive facial deformity around the nose and nasal discharge. The isolate from this case was susceptible to itraconazole (ITZ), voriconazole and micafungin, but was resistant to amphotericine B. However, the infected cat died approximately 1 month after referral, despite treatment for 12 days ITZ administered orally at 10 mg/kg.     

Cimetidine for treatment of melanomas in three horses

Cimetidine, an H2 histamine antagonist, was used in the clinical management of progressive, multifocal melanomatosis in 3 adult gray horses. Prior to treatment, the tumors had increased rapidly in size and number in 2 horses (duration of 6 and 27 months, respectively) and slowly in the third horse (duration of 48 months). All 3 horses were treated with cimetidine (2.5 mg/kg of body weight, PO, q 8 h) for 2 months to 1 year. During treatment, the number and size of the melanomas decreased substantially (50 to 90%). The progression of the disease was halted in 2 horses and controlled in the third horse, which is still being treated with cimetidine (1.6 mg/kg, PO, q 24 h). The horses in which treatment was terminated have not been treated for 31 and 41 months, respectively, during which time the melanomas have not increased in number or size.     

Itraconazole for the Treatment of Histoplasmosis in Cats

Eight cats with histoplasmosis were treated with itraconazole at 5 mg/kg per dose PO bid. There were multiple sites of infection, and 2 of the cats had hypercalcemia that was attributed to the histoplasmosis. All 8 cats were eventually cured, but 2 cats experienced recurrences of disease after completion of therapy, requiring 2 to 3 additional months of itraconazole. There were no clinically relevant adverse effects during treatment. Although a limited number of cats were treated, the study suggests that itraconazole is a well-tolerated and effective drug for the treatment of histoplasmosis in the cat.     

Intralesional administration of formalin for treatment of epidermal inclusion cysts in five horses

Five horses with unilateral epidermal inclusion cysts located in the nasal diverticula were sedated and treated with intralesional injection of neutral-buffered 10% formalin (volume range, 2 to 4.5 mL). After aspiration of the cyst, formalin was injected intralesionally until leakage of fluid around the needle was observed. After several weeks, desiccation of the cyst was evident; it was excised 2 weeks after treatment in 3 horses, digitally removed by the owner of 1 horse, and never removed in 1 horse, because the owner declined further treatment after resolution of the original swelling of the nasal diverticulum. Swelling of the cyst after treatment was observed in all horses; nasal discharge (2 horses) and a mild episode of epistaxis (1 horse) were the only other complications of the treatment. Intralesional administration of formalin appears to be a simple and effective treatment for epidermal inclusion cysts in the nasal diverticula of horses.     

Fungal rhinitis and sinusitis in three cats

Localized infection of the nasal or paranasal cavities caused by Aspergillus spp or Penicillium spp was diagnosed in 3 cats. Clinical signs included chronic mucopurulent nasal discharge, epistaxis, and mandibular lymphadenopathy. Rhinoscopic and diagnostic imaging findings were compatible with severe inflammation of the nasal mucosa and destruction of the turbinates. Fungal plaques were observed rhinoscopically in 2 cats, and histologic examination of biopsy specimens revealed fungal colonies with surrounding inflammatory infiltrates in all 3. Results of fungal culture were negative for all 3 cats. Results of serum immunoelectrophoresis for antibodies against Aspergillus spp were positive in 2 cats. Treatment with itraconazole was effective in controlling clinical signs in 1 cat, but hepatotoxicosis developed. A single intranasal infusion of clotrimazole subsequently led to long-term resolution of clinical signs in this cat. Localized aspergillosis-penicilliosis is clinically indistinguishable from other pathologic conditions of the nasal and paranasal cavities in cats and should be considered when examining cats with chronic nasal discharge.     

In vitro susceptibility patterns of Aspergillus and Fusarium species isolated from equine ulcerative keratomycosis cases in the midwestern and southern United States with inclusion of the new antifungal agent voriconazole

Objective  To evaluate and compare the in vitro susceptibility of Aspergillus and Fusarium spp. isolated from horses with ulcerative keratomycosis, address regional differences in equine keratomycosis isolates, and provide susceptibility data to update prior studies.
Animal studied  Fourteen horses with ulcerative keratomycosis.
Procedures  Banked fungal isolates from equine corneal ulcers (eight Aspergillus spp. and six Fusarium spp.) were identified at The University of Texas Health Science Center at San Antonio. In vitro minimum inhibitory concentration and susceptibility to natamycin, fluconazole, itraconazole, voriconazole, ketoconazole, and miconazole were determined for each isolate.
Results  Fungi were significantly more susceptible to voriconazole than to natamycin, itraconazole, fluconazole, and ketoconazole, but miconazole susceptibility did not differ significantly from voriconazole. Aspergillus spp. were most susceptible to voriconazole, miconazole, and itraconazole, which were significantly better to fluconazole and ketoconazole. Fusarium spp. susceptibility was greatest to natamycin and voriconazole and lowest to itraconazole and ketoconazole. Fusarium spp. were significantly less susceptible to itraconazole and ketoconazole compared to natamycin. No significant differences in susceptibility were found when isolates from Florida were compared with isolates from other states.
Conclusions and clinical relevance  Based on in vitro evidence, voriconazole appears to be the most effective antifungal for initial treatment of equine keratomycosis in the midwestern and southern United States. Results are comparable with previous studies in that isolated fungi from equine keratomycosis cases showed consistently poor susceptibility to fluconazole. Organisms isolated in different geographic locations of the midwestern and southern United States appeared to have similar patterns of antifungal susceptibility.     

Anaerobic bacterial pneumonia with septicemia in two racehorses

Anaerobic bacterial pneumonia with septicemia was diagnosed in 2 Thoroughbred racehorses referred with respiratory tract disease that had failed to respond to initial treatment with various antibiotics including penicillin and trimethoprim-sulfamethoxazole. Multiple anaerobic organisms, including Bacteroides spp and Fusobacterium spp, were isolated from blood and transtracheal aspirates obtained from both horses and from aspirates of cutaneous nodules obtained from 1 horse. The latter horse responded to metronidazole treatment followed by procaine penicillin G administration and regained its health over the following 6 months. The other horse did not respond as favorably to a similar antibiotic regimen and died following an acute episode of pulmonary hemorrhage after remaining intermittently febrile for 7 weeks. Although in vitro antimicrobial susceptibility tests indicated that all anaerobic organisms isolated from both horses were susceptible to penicillin, the infection in these horses responded poorly to initial treatments with this drug. We speculated that adequate penicillin concentration was not attained in the deep foci of infection in the lungs. Animals with anaerobic bacterial infections that fail to respond to penicillin or from which penicillin-resistant anaerobes are isolated may benefit from treatment with metronidazole.     

Pyrantel pamoate resistance in horses receiving daily administration of pyrantel tartrate

CASE DESCRIPTIONS: 16 horses treated daily with pyrantel tartrate (2.64 mg/kg [1.2 mg/lb], PO) as part of a prophylactic anthelmintic program. CLINICAL FINDINGS: Fecal worm egg counts (FWECs) were obtained on all 16 horses. Mean FWEC was 478 eggs/g (epg; range, 0 to 4,075 epg). Three of the 16 horses were responsible for 85% of the total fecal egg output for the herd on the day of sampling. Six horses had FWECs < 200 epg. Three horses that had arrived within 4 months of the sampling date had FWECs < 100 epg. TREATMENT AND OUTCOME: An FWEC reduction test was initiated the day after FWECs were obtained; all horses with FWECs > 100 epg (9 horses) were treated with pyrantel pamoate (6.6 mg/kg [3 mg/lb], PO), and 14 days later, the FWEC was repeated. During the 14-day period, all horses received pyrantel tartrate (2.64 mg/kg, PO) daily. Fecal worm egg count reduction was calculated for each horse. Mean FWEC reduction for the group was 28.5% (range, increase of 21% in FWECs 14 days after treatment to a decrease of 100% in FWEC 14 days after treatment). CLINICAL RELEVANCE: Farms should be monitored for cyathostomes resistant to pyrantel pamoate prior to use of pyrantel tartrate. Fecal worm egg counts should be monitored routinely in horses before and after treatment to ensure efficacy of cyathostome control measures.     

Retropharyngeal infections in five horses

Five horses with retropharyngeal (RP) infections had clinical signs of dysphagia and/or dyspnea. Diagnosis was confirmed, using pharyngeal endoscopy and lateral radiography of the pharynx. One horse responded to surgical drainage of a RP abscess and was sound at light work. One horse responded to medical management after the site of infection was surgically explored. Two horses recovered after medical management; the RP abscess of 1 of these 2 horses ruptured spontaneously into the pharynx and the other horse became racing sound. The fifth horse remained dysphagic and had left laryngeal hemiplegia after medical treatment.     

Evaluation of clinical signs of disease, bronchoalveolar and tracheal wash analysis, and arterial blood gas tensions in 13 horses with chronic obstructive pulmonary disease treated with prednisone, methyl sulfonmethane, and clenbuterol hydrochloride.

We evaluated the efficacy of 3 treatments for chronic obstructive pulmonary disease in horses: prednisone (400 mg/horse, PO, daily; n = 7), methyl sulfonmethane (10 g/horse, PO, q 12 h; n = 6), and clenbuterol hydrochloride (0.4 mg/horse, PO, q 12 h; n = 7). A fourth group acted as controls (n = 6) and was not treated. The treatment period lasted 10 days. Each horse was a member of 2 different groups for 10 days, separated by an 18-day interval of no treatment. All horses were housed together in an outdoor pen without bedding. Horses were fed alfalfa/grass hay mix ad libitum from a large feeder. The same batch of hay was fed throughout the study. Multiple physical and laboratory variables were monitored prior to, during, and at the end of each 10-day trial period. Changes in lung sounds, respiratory effort, degree of anal movement, nasal discharge, temperature, respiratory rate, or heart rate were not significant. Changes in arterial blood gas tensions, tracheal wash or bronchoalveolar lavage cytologic findings, or phagocyte function were not significant. All horses were tachypneic and most were tachycardic. The median value for PaO2 was below normal for all horses. All tracheal wash and most bronchoalveolar lavage cytologic findings represented a suppurative response. Negative linear correlation was observed between PaO2 and degree of respiratory effort in these horses (eg, as PaO2 decreased, the degree of respiratory effort increased).     

Entomophthoramycosis conidiobolae in a llama.

A 9-year-old female llama was evaluated for chronic dermatosis involving the external nares. The condition had been diagnosed as a fungal infection. Examination of punch biopsy specimens confirmed the diagnosis of Conidiobolus coronatus. Because of the chronicity of the disease and history of ineffective drug treatment, excision of infected tissue was attempted. Permanent nasal openings were created by suturing the nasal mucosa to the skin after debulking of infected tissue. Excision of most of the infected tissue enabled the llama to breathe easily for 3 years. Because C coronatus does not usually induce deep infections, it may continue to remain dormant in this llama.     

Anthelmintic resistance in cyathostomins of brood horses in Ukraine and influence of anthelmintic treatments on strongylid community structure

In 2004-2006, 322 brood horses from 11 horse farms were examined using the faecal egg count reduction test (FECRT) to determine the presence and distribution of anthelmintic resistance in strongylids in Ukraine. The anthelmintic drugs "Albendazole-7.5" (7.5mg of albenazole, Ukraine) at a dose of 5mg per kg body weight and "Univerm" (0.2% aversectin C, Russia) at a dose of 0.5mg per kg body weight were used. Seventy-one horses from six farms were examined in vivo to investigate the influence of anthelmintic treatment on the gastrointestinal strongylid community structure. Horses were treated with anthelmintics; faecal sampling (200 g in each sample) for strongylid expulsion was performed 24, 36, 48 and 60 h after treatment; and all strongylids expelled (25,292 specimens) were collected and identified. Fourteen horses from the Dubrovsky horse farm were also examined to determine the benzimidazole-resistant cyathostomin species; 5208 specimens of benzimidazole-resistant cyathostomins were collected and identified. According to the FECRT data, benzimidazole resistance in strongylids was observed only at the Dubrovsky horse farm (FECRT=68.7%). No resistance to macrocyclic lactones in strongylids or in Parascaris equorum was observed. Twenty-nine strongylid species were found in horses from six horse farms. The number of species per horse ranged from 4-9 (5.8+/-1.5) to 10-20 (14.4+/-2.9) and depended on horse anthelmintic treatment strategies. From 4 to 13 strongylid species predominated (prevalence>66.7%) in the strongylid community. Eleven cyathostomin species (Cylicocyclus nassatus, C. ashworthi, C. leptostomum, Cyathostomum catinatum, C. pateratum, Cylicostephanus calicatus, C. longibursatus, C. goldi, C. minutus, Coronocyclus coronatus and C. labiatus) were found to be resistant to benzimidazoles at the Dubrovsky horse farm. Ten of these were the dominant species in the strongylid community; only C. labiatus was a rare species (prevalence 29.4%). Species richness and species diversity were significantly higher in horses from farms without treatment or with occasional treatments than from farms with regular treatments. The shape of the prevalence frequency distribution of strongylid species from farms with regular treatments was bimodal ("core" and "satellite" mode). This distribution was multimodal at farms without treatment or with occasional anthelmintic treatments. The results of the current study indicated the possibility of the further spread of anthelmintic resistance on horse farms in Ukraine and the necessity of monitoring the development of resistance in horse parasitic nematodes.     

P-83 Intradermal testing in cattle: evaluation of sensitization to Dermatophagoides extracts in healthy cattle and cattle infected with Psoroptes or Chorioptes

The purpose of this retrospective study was to evaluate six cases of equine sarcoidosis for initial presenting symptoms, response to therapy and actual outcome. Dermatologists and dermatopathologists from Europe, the United States, Australia and Canada were contacted to obtain these six cases, as this is a rare disease. Signalment, clinical signs, histological findings, clinical management and outcome were determined via a questionnaire and compared to former reports. There was no age or breed predilection, and four of six horses were geldings. Age of onset ranged from 3 months to 17 years. Onset of the disease was insidious or rapid. Interestingly, in five of six cases, scaling began on the trunk (girth and shoulder). Scaling, crusting and alopecia were seen in all six horses. In one horse, clinical signs of systemic disease were reported and included intermittent fever, prescapular lymphadenopathy, depression, poor body condition and nasal discharge. Treatment included phenylbutazone, deworming agents, antibiotics, short-term low-dose corticosteroids, and 1–1.5 mg/kg of prednisolone. One horse showed a partial response to trimethoprim and sulfonamide, and five of six went into clinical remission with corticosteroid treatment. Five of six horses were still alive 1 year after diagnosis; one horse was diagnosed <12 months ago. Two horses are in complete remission 4 and 8 years after diagnosis. In both horses, clinical signs recurred after cessation of therapy and went into remission again with reintroduction of treatment. Both of these horses have been in remission for several years without therapy.
Funding: Self-funded.     

P‐81 A retrospective study of equine sarcoidosis

The purpose of this retrospective study was to evaluate six cases of equine sarcoidosis for initial presenting symptoms, response to therapy and actual outcome. Dermatologists and dermatopathologists from Europe, the United States, Australia and Canada were contacted to obtain these six cases, as this is a rare disease. Signalment, clinical signs, histological findings, clinical management and outcome were determined via a questionnaire and compared to former reports. There was no age or breed predilection, and four of six horses were geldings. Age of onset ranged from 3 months to 17 years. Onset of the disease was insidious or rapid. Interestingly, in five of six cases, scaling began on the trunk (girth and shoulder). Scaling, crusting and alopecia were seen in all six horses. In one horse, clinical signs of systemic disease were reported and included intermittent fever, prescapular lymphadenopathy, depression, poor body condition and nasal discharge. Treatment included phenylbutazone, deworming agents, antibiotics, short‐term low‐dose corticosteroids, and 1–1.5 mg/kg of prednisolone. One horse showed a partial response to trimethoprim and sulfonamide, and five of six went into clinical remission with corticosteroid treatment. Five of six horses were still alive 1 year after diagnosis; one horse was diagnosed <12 months ago. Two horses are in complete remission 4 and 8 years after diagnosis. In both horses, clinical signs recurred after cessation of therapy and went into remission again with reintroduction of treatment. Both of these horses have been in remission for several years without therapy. Funding: Self‐funded.     

Cutaneous paecilomycosis in a cat

A cat was presented for a 2-year history of a recurrent, soft-tissue swelling of the left metacarpal region. The mass was excised and submitted for aerobic and anaerobic bacterial culture, fungal culture, and histopathological examination. Cultures revealed the organism Paecilomyces lilacinus, and histopathological examination showed a nodular mycotic granuloma. Itraconazole (10 mg/kg body weight, per os [PO], q 24 hours) was administered and continued for a total of 60 days, with a swelling of the upper lip occurring 3 months after the initial presentation. Subsequent surgical excisions and debridements along with treatment with itraconazole (20 mg/kg body weight, PO, q 24 hours) for a total of 4 months were curative.