Effects of lufenuron treatment in cats on the establishment and course of Microsporum canis infection following exposure to infected cats

OBJECTIVE: To determine effects of lufenuron treatment in cats on the establishment and course of Microsporum canis infection following exposure to infected cats. DESIGN: Experimental trial. ANIMALS: 24 healthy juvenile domestic shorthair cats. PROCEDURE: 8 cats were given lufenuron PO (133 mg/cat/mo, equivalent to a dose of 100 to 130 mg/kg [45 to 59 mg/lb] at the beginning of the study and 25 to 35 mg/kg [11 to 16 mg/lb] at the end of the study), and 8 were given lufenuron SC (40 mg every 6 months). The remaining 8 were used as untreated control cats. After 4 months, cats were challenged by the introduction of cats with mild, experimentally induced M canis infection into the rooms where cats were housed. Extent of resulting infections in the na?ve cats was monitored for 22 weeks by physical examination and fungal culture. RESULTS: All lufenuron-treated and control cats became infected with M canis. Cats treated with lufenuron had significantly lower infection scores, compared with control cats, during the early weeks following exposure, and there was a more prolonged initial progression phase of the infection. Once infections reached peak intensity, they resolved over similar periods in lufenuron-treated and control cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that oral or SC administration of lufenuron to cats, at the dosages used and under the conditions of this study, did not prevent establishment of dermatophytosis following exposure to infected cats. Infection was established more slowly among cats treated with lufenuron, but once established, infection resolved in approximately the same amount of time in lufenuron-treated as in control cats.     

P-15 Identification of Malassezia spp. isolated from a cat and cattle, including a new species, M. nana

Preliminary studies showed that lufenuron inhibits chitin synthesis, a dermatophyte cell wall constituent, and may be effective in the treatment of dermatophytosis. Our purpose was to evaluate the efficacy of lufenuron in the treatment of feline dermatophytosis. Forty-six cats (Persians and mixed-breed cats from 1-month to 4-years old) naturally infected with Microsporum canis were included in this study. Fifteen cats were treated isolated in cages in the veterinary hospital and 31 were treated in their home environment (some with access to the outdoors). Dermatophyte skin lesions were seen in 29 animals while 17 other cats were asymptomatic carriers. Wood's lamp, direct microscopic examination of hairs, fungal culture and skin biopsies were used for the diagnosis. Affected cats and all in-contact animals received lufenuron at a dose of 120 mg/kg every 21 days for four treatments. Of the 29 symptomatic cats treated with lufenuron, 70% recovered within 21 days and 28% within 42 days of initiation of therapy. One cat had only partial recovery and another was euthanized. Negative fungal culture was recorded only after the fourth dose of lufenuron in 98% of affected cats and 100% of asymptomatic carriers. There was no difference in clinical response to lufenuron between the cats treated in their home environment and those treated in the veterinary hospital. Side effects were not observed, thus the drug proved to be safe and effective for the treatment of dermatophytosis.
Funding: Novartis.     

P‐13 Dermatophytosis in domestic cats: treatment with lufenuron

Preliminary studies showed that lufenuron inhibits chitin synthesis, a dermatophyte cell wall constituent, and may be effective in the treatment of dermatophytosis. Our purpose was to evaluate the efficacy of lufenuron in the treatment of feline dermatophytosis. Forty‐six cats (Persians and mixed‐breed cats from 1‐month to 4‐years old) naturally infected with Microsporumcanis were included in this study. Fifteen cats were treated isolated in cages in the veterinary hospital and 31 were treated in their home environment (some with access to the outdoors). Dermatophyte skin lesions were seen in 29 animals while 17 other cats were asymptomatic carriers. Wood's lamp, direct microscopic examination of hairs, fungal culture and skin biopsies were used for the diagnosis. Affected cats and all in‐contact animals received lufenuron at a dose of 120 mg/kg every 21 days for four treatments. Of the 29 symptomatic cats treated with lufenuron, 70% recovered within 21 days and 28% within 42 days of initiation of therapy. One cat had only partial recovery and another was euthanized. Negative fungal culture was recorded only after the fourth dose of lufenuron in 98% of affected cats and 100% of asymptomatic carriers. There was no difference in clinical response to lufenuron between the cats treated in their home environment and those treated in the veterinary hospital. Side effects were not observed, thus the drug proved to be safe and effective for the treatment of dermatophytosis. Funding: Novartis.     

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.     

In vitro and in vivo Effects of Lufenuron on Dermatophytes Isolated from Cases of Canine and Feline Dermatophytoses*

Lufenuron is a benzyl‐urea phenol compound that inhibits chitin synthesis and is used as an insecticide. Its efficacy in the therapy of dermatophytosis in dogs and cats was evaluated in several clinical studies, with contradictory results. We assessed the in vitro susceptibility of dermatophytes isolated from dogs and cats to lufenuron, and the clinical response of skin lesions to the drug. Dermatophyte cultures isolated from clinical cases were exposed to lufenuron by three different methods: direct application and application of whole blood or subcutaneous tissue samples obtained from a lufenuron‐treated healthy dog. No inhibition of dermatophyte growth was observed in any of the samples after 1 week of incubation. Eight dogs and six cats with skin lesions were included in the in vivo survey. Results indicated that six of seven skin lesions that were diagnosed as being caused by dermatophytes did not respond to lufenuron whereas six of seven skin lesions that were not caused by dermatophytes improved. We concluded that lufenuron, in the way it was administered in this study, had no inhibitory activity on dermatophytes in vitro or in vivo and its clinical use as an anti‐fungal agent is questionable. An immunomodulatory effect of the drug is, however, possible.     

In vitro and in vivo effects of lufenuron on dermatophytes isolated from cases of canine and feline dermatophytoses

Lufenuron is a benzyl-urea phenol compound that inhibits chitin synthesis and is used as an insecticide. Its efficacy in the therapy of dermatophytosis in dogs and cats was evaluated in several clinical studies, with contradictory results. We assessed the in vitro susceptibility of dermatophytes isolated from dogs and cats to lufenuron, and the clinical response of skin lesions to the drug. Dermatophyte cultures isolated from clinical cases were exposed to lufenuron by three different methods: direct application and application of whole blood or subcutaneous tissue samples obtained from a lufenuron-treated healthy dog. No inhibition of dermatophyte growth was observed in any of the samples after 1 week of incubation. Eight dogs and six cats with skin lesions were included in the in vivo survey. Results indicated that six of seven skin lesions that were diagnosed as being caused by dermatophytes did not respond to lufenuron whereas six of seven skin lesions that were not caused by dermatophytes improved. We concluded that lufenuron, in the way it was administered in this study, had no inhibitory activity on dermatophytes in vitro or in vivo and its clinical use as an anti-fungal agent is questionable. An immunomodulatory effect of the drug is, however, possible.     

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.     

Evaluation of the comparative efficacy of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats in simulated home environments

The comparative efficacy of monthly administration of selamectin or lufenuron against Ctenocephalides felis felis on dogs and cats was evaluated over a 5-month period in flea-infested environments. Twenty-four dogs and 32 cats were randomly allocated to receiving a topical treatment with selamectin or an oral administration of tablets containing lufenuron/milbemycin oxime (for dogs) or lufenuron only (for cats). Each product was administered in accordance with the manufacturer's label recommendations. Eight dogs and four cats served as untreated sentinels. Treatments were administered on days 0, 30, 60, 90, and 120. Each animal received an application of 100 fleas on days -28 and -21, and then weekly applications of 20 fleas from days 91 through 147. Flea comb counts were performed on day -6, and every 2 weeks after day 0. From day 29 (dogs) or day 44 (cats) to day 150, geometric mean flea counts for selamectin were < or =0.4. Mean flea counts for animals assigned to treatment with selamectin were significantly lower (P=0.0001) than for animals assigned to treatment with lufenuron at all assessments after day 0.     

Eradication of feline dermatophytosis in a shelter: a field study

Enzootic dermatophytosis in a shelter with approximately 140 cats was treated according to a protocol combining identification, isolation and treatment of subclinical carrier and affected animals in accordance with a three‐area system: healthy animals (no lesions and negative cultures), subclinical carrier animals (no lesions but with positive cultures) and clinically affected animals (lesions and positive cultures). The cats were examined and inspected under a Wood’s lamp and had samples taken for fungal culture every 2 weeks. Thirty‐three per cent of the cats had a positive fungal culture at the start of the study. Clinically affected animals and carriers were treated with a 0.2% enilconazole lotion (Imaverol^®) twice a week and given itraconazole (Itrafungol^®) 5 mg/kg SID orally every other week. The environment was treated once a day with a 1% bleach solution and once a week with a 0.6% enilconazole (Clinafarm^®) solution. Treated animals were considered cured after two consecutive negative fungal cultures. All cats were cured within 56 days. Prophylactic measures against dermatophytosis were implemented for new arrivals consisting of individual quarantine and the systematic taking of fungal cultures. No relapses were observed based on the fungal cultures taken from the animals and the environment over the first 10 months.     

Evaluation of the efficacy of oral lufenuron combined with topical enilconazole for the management of dermatophytosis in catteries

The efficacy of oral lufenuron, a chitin synthetase inhibitor, combined with topical enilconazole, was evaluated for the management of Microsporum canis infection in 100 cats housed in two catteries in France. The cats were treated with weekly rinses with enilconazole (0.2 per cent) for four weeks and, in each cattery, one group (A) was also treated with micronised griseofulvin (25 mg/kg administered orally twice a day for five weeks) and a second group (B) was treated with 60 mg/kg lufenuron administered orally once on day 0 and again after 30 days. All the cats were examined individually for cutaneous lesions and mycological cultures were made when the treatment began and after 15, 30, 60 and 90 days. In the first cattery, the cats' clinical scores after 30 and 60 days were significantly lower in group B than in group A. In both catteries and both treatment groups, the mean number of fungal colonies decreased rapidly during the first 15 days of treatment, remained stable for the following 45 days but increased from day 60 to the end of the experiment on day 90.     

FC-3 Immunity to bovine trichophytosis

During the last few years, reports have appeared claiming that lufenuron diminished or even cured dermatophyte infections in cats and dogs. As these observations have a rather anecdotal character leading to some ambiguity in the literature, it was decided to test lufenuron in a generally accepted animal model for dermatomycotic infection. The test was carried out in guinea pigs artificially infected with Microsporum canis on scarified dorsal skin and orally treated with lufenuron (Program™). The efficacy of up to five doses of 80 mg/kg was assessed 7 and 14 days after the start of treatment. All animals failed to show any improvement in skin lesions as compared to the vehicle-only treated animals. Clinical symptoms taken into account were scaling, crust formation, erythema, and exudation. Neither the number of treatments (one or five) nor the dose range (40 or 80 mg/kg) made any difference. Itraconazole, tested earlier under identical circumstances, resulted in a clear and consistent improvement at day 7 of the infection at a dose of 15 mg/kg, given either in one dose or spread over several days. The absence of antimycotic activity of lufenuron in this established animal model constitutes a significant element in the discussion on the antifungal potency of lufenuron and supports the fact that there is, as yet, no evidence that benzoylphenyl urea derivative compounds have an effect on chitin synthesis in fungi.
Funding: J&J Pharmaceutical Research and Development, Janssen Animal Health.     

FC‐1 Comparative efficacy of lufenuron and itraconazole in a guinea pig model of cutaneous Microsporum canis

During the last few years, reports have appeared claiming that lufenuron diminished or even cured dermatophyte infections in cats and dogs. As these observations have a rather anecdotal character leading to some ambiguity in the literature, it was decided to test lufenuron in a generally accepted animal model for dermatomycotic infection. The test was carried out in guinea pigs artificially infected with Microsporum canis on scarified dorsal skin and orally treated with lufenuron (Program?). The efficacy of up to five doses of 80 mg/kg was assessed 7 and 14 days after the start of treatment. All animals failed to show any improvement in skin lesions as compared to the vehicle‐only treated animals. Clinical symptoms taken into account were scaling, crust formation, erythema, and exudation. Neither the number of treatments (one or five) nor the dose range (40 or 80 mg/kg) made any difference. Itraconazole, tested earlier under identical circumstances, resulted in a clear and consistent improvement at day 7 of the infection at a dose of 15 mg/kg, given either in one dose or spread over several days. The absence of antimycotic activity of lufenuron in this established animal model constitutes a significant element in the discussion on the antifungal potency of lufenuron and supports the fact that there is, as yet, no evidence that benzoylphenyl urea derivative compounds have an effect on chitin synthesis in fungi. Funding: J&J Pharmaceutical Research and Development, Janssen Animal Health.     

Evaluation of praziquantel for treatment of experimentally induced paragonimiasis in dogs and cats

Praziquantel was used successfully for treatment of a small number of dogs and 1 cat infected with Paragonimus kellicotti. To further evaluate the usefulness of this drug in treating such infections, 7 cats and 7 dogs were inoculated orally with metacercariae (12 and 20 to 22, respectively) obtained from crayfish, then were treated after the infections became patent; 2 cats and 2 dogs served as noninfected controls. Beginning 1 week before infection, and continuing weekly thereafter, physical, hematologic, and fecal examinations were performed on each animal; thoracic radiography was performed every other week. By postinoculation week 6, all dogs given metacercariae had patent infection diagnosed on the basis of positive results of fecal examination. By postinoculation week 7, 5 cats had confirmed patent infection, but 2 cats given metacercariae never had patent infection or had signs of infection. Clinical signs of infection were minor and included increased respiratory tract noise, slight inducible cough, or mild dyspnea. Transient eosinophilia was detected in dogs around postinoculation week 3. Pretreatment radiography revealed cavitated lesions in cats only; pleural lines and patchy infiltrates in cats and dogs; or pneumothorax in dogs only. The treatment regimen consisted of 23 mg of praziquantel/kg of body weight given every 8 hours for 3 days; 1 infected cat and dog were not treated. By 11 days after treatment, eggs had disappeared from the feces of infected animals, and marked resolution of lung lesions was evident radiographically.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of ketoconazole in treatment of dermatophytosis in a dog

Ketoconazole, an antifungal imidazole derivative, was used successfully to treat Tricophyton mentagrophytes infection in a dog. The drug was administered orally (11 mg/kg of body weight, q 24 h) and continued for 90 days. Though ketoconazole is not licensed currently for veterinary purposes, it has been used successfully to treat dermatophyte infections as well as intermediate and deep fungal diseases in both dogs and cats. In this case, ketoconazole was found to be nontoxic and less expensive than griseofulvin in the treatment of dermatophytosis.     

Use of lime sulphur and itraconazole to treat shelter cats naturally infected with Microsporum canis in an annex facility: an open field trial

Dermatophytosis is the most common contagious and infectious skin disease of cats. It is of particular importance in animal shelters because it is a known zoonosis, highly contagious, and easily transmitted. In this open clinical trial, 58 cats with confirmed Microsporum canis dermatophytosis and 32 uninfected bonded pairs or littermates were treated with a combination of 21 days of oral itraconazole (10 mg kg(-1)) and twice weekly lime sulphur rinses until cured. Cats were not clipped in this treatment programme. Fungal cultures were obtained once weekly on all cats, and cats were considered cured when they had two consecutive negative weekly fungal cultures. Cats were held in the facility and received continued topical treatment until the fungal cultures were finalized. None of the cats developed oral ulcerations as a result of grooming the lime sulphur rinses. Oral ulcerations only developed in cats with clinical signs associated with upper respiratory disease. None of the uninfected cats living in contact with infected cats became culture positive or developed skin lesions. When data were examined retrospectively and the number of days to finalize the cultures was subtracted (21 days) from the total number of days the cats were housed in the annex, the mean number of days of treatment required for cure was 18.4 +/- 9.5 SEM (range 10-49 days). Cats with more severe infections required longer therapy. In this shelter, the combination of oral itraconazole and topical lime sulphur rinses for the treatment of dermatophytosis was effective and safe.     

Dose titration of an injectable formulation of lufenuron in cats experimentally infested with fleas

OBJECTIVES: To identify the lowest single dose of lufenuron injected s.c. that results in a 90% disruption of the flea (Ctenocephalides felis) life cycle for 6 months in cats. ANIMALS: 40 domestic shorthair cats (20 males, 20 females) between 5 and 7 months old. PROCEDURE: Cats were randomly assigned to 1 of 5 eight-cat groups and experimentally infested with C. felis on days -8, -7, -6, and -4. On day 0, cats in the 4 treatment groups were treated with an injectable formulation of lufenuron at doses of 2.5, 5, 10, or 20 mg/kg of body weight, respectively. Control cats received the injectable formulation without lufenuron. Experimental infestations were repeated and flea eggs collected at various intervals for 196 days after treatment. Eggs were placed in media and incubated in an insectary for 28 days to determine effects of injectable lufenuron on egg and larval development. Number of adults that emerged from eggs were compared among groups. RESULTS: Lufenuron injected once at a dose of 10 or 20 mg/kg, but not at 2.5 or 5 mg/kg, resulted in a 90% decrease in number of adult fleas emerging from eggs for 196 days after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that control of flea egg and larval development for at least 6 months can be achieved in cats with a single s.c. injection of lufenuron (10 mg/kg). The injectable formulation may provide veterinarians and cat owners an alternative to the tablet formulation of lufenuron.     

Use of itraconazole and either lime sulphur or Malaseb Concentrate Rinse® to treat shelter cats naturally infected with Microsporum canis: an open field trial

In an open non‐randomized study, 90 cats with severe dermatophytosis were treated with 21 days of oral itraconazole at 10 mg/kg and one of three topical antifungal rinses applied twice weekly: lime sulphur (LSO); reformulated lime sulphur with an odour‐masking agent (LSR); or a 0.2% miconazole nitrate and 0.2% chlorhexidine gluconate rinse (MC). Weekly examinations and fungal cultures were used to monitor the cats’ response to therapy. If at day 42 of treatment cats were still strongly fungal culture positive and/or developing new lesions, they were retreated with oral itraconazole and LSO. Cats were not prevented from licking the solutions and none developed oral ulcerations. Thirty‐one cats were treated with LSO, 27 with LSR and 32 with MC. The median number of days to cure was 30 (range 10–69 days) and 34 (range 23–80 days) for LSO and LSR, respectively. Thirty‐two cats were treated with MC, and 13 of 32 cats required repeat treatment because of persistent culture‐positive status and development of new lesions. Median number of days of treatment for the 19 cats that cured with MC was 48 (range 14–93 days). When the number of days to cure was compared between the groups, there was a significant difference between cats treated with LSO and LSR (P = 0.029) and cats treated with LSO and MC (P = 0.031), but no significant difference between the number of days to cure for cats treated with LSR and MC (P = 0.91).     

Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases

This study evaluated the efficacy of itraconazole as a combined continuous/pulse therapy for feline dermatophytosis. Nine cats with dermatophytosis caused by Microsporum canis were treated with itraconazole at 10 mg kg(-1) orally once daily for 28 days and then on an alternate week regimen (1 week off, 1 week on) at the same dosage. Cats were re-evaluated by physical examination and fungal culture at days 28, 42, 56 and 70 if necessary. Treatment was stopped when two consecutive negative fungal cultures were obtained. Eight cats were cured after 56 days, with two negative cultures obtained at days 28 and 42. In one case, a positive culture was obtained at day 28, but negative cultures were achieved at days 42 and 56. This protocol appears to be effective in the treatment of feline dermatophytosis, although these preliminary results should be confirmed by a controlled study.     

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.     

Ketoconazole for treatment of dermatophytosis in cats.

Twelve cats with generalized dermatophytosis were treated with ketoconazole (10 mg/kg of body weight, PO, with food, q 24 h). This treatment was successful in 8 cats, with resolution of lesions and negative findings on mycologic evaluation after 2 to 10 weeks (median duration, 6 weeks). One additional cat failed to improve initially, but complete resolution was achieved after the dosage of ketoconazole was doubled. Adverse effects in 3 cats included anorexia, weight loss, vomiting, and diarrhea.