Safety of florfenicol administered in feed to tilapia (Oreochromis sp.).

The safety of Aquaflor(®) (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2× the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5× the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

In vitro and in vivo efficacy of florfenicol for treatment of Francisella asiatica infection in tilapia.

Francisella asiatica is a recently described, Gram-negative, facultative intracellular fish pathogen, known to be the causative agent of francisellosis in warm-water fish. Francisellosis outbreaks have increased in frequency among commercial aquaculture operations and have caused severe economic losses in every case reported. The lack of effective treatments for piscine francisellosis led us to investigate the potential efficacy of florfenicol for inhibition of F. asiatica in vitro and as an oral therapeutic agent in vivo. The MIC of florfenicol for F. asiatica, as determined by the broth dilution method, was 2 µg/ml, which indicates its potential efficacy as a therapeutic agent for treatment of francisellosis. The intracellular susceptibility of the bacterium to florfenicol in tilapia head kidney-derived macrophages (THKDM) was also investigated. Addition of florfenicol to the medium at 10 µg/ml was sufficient to significantly reduce bacterial loads in the THKDM in vitro. Cytotoxicity assays done in infected THKDM also demonstrated drug efficacy in vivo, as determined by lactate dehydrogenase (LDH) release. Levels of LDH released from infected THKDM were significantly lower in macrophages treated with florfenicol (P < 0.001) than in untreated cells. In medicated-feed trials, fish were fed 15 mg of florfenicol/kg of fish body weight for 10 days, and the feeding was initiated at either 1, 3, or 6 days postchallenge. Immersion challenges resulted in 30% mean percent survival in nontreated fish, and fish receiving medicated feed administered at 1 and 3 days postinfection showed higher mean percent survival (100% and 86.7%, respectively). A significant decrease (P < 0.001) in bacterial numbers (number of CFU/g of spleen tissue) was observed in treated groups compared to nontreated infected fish at both 1 and 3 days postchallenge. There were no differences in bacterial burden in the spleens between fish treated 6 days postchallenge and untreated controls. In conclusion, if florfenicol is administered during early stages of infection, it has the potential for effectively treating piscine francisellosis, including the capacity for intracellular penetration and bacterial clearance.

Safety of Aquaflor (florfenicol, 50% type A medicated article), administered in feed to channel catfish, Ictalurus punctatus.

Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.

Repellency and efficacy of a 65% permethrin spot-on formulation for dogs against Aedes aegypti (Diptera: Culicidae) mosquitoes.

A topically applied 65% permethrin spot-on (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health) used for flea and tick control on dogs was evaluated for repellency and efficacy against the yellow fever mosquito, Aedes aegypti, a vector of canine filariasis. Six dogs were randomly assigned to receive a single application of 65% permethrin on Day 0 (n=3) or to remain untreated as controls (n=3). Dogs were anesthetized and exposed to 100 unfed, female mosquitoes in screened cages for 2 hours on Days -6, -4, -1, 0, 1, 7, 14, 21, and 28. Mosquito landing rates, engorgement rates, and mortality were determined for each mosquito challenge. Cages were thoroughly cleaned after each mosquito challenge. Treatment of dogs with 65% permethrin reduced the mosquito landing rates by 96.3% 6 hours after treatment and by 82.5% on Day 1. Mosquito mortality, relative to the control group, was 28.2% 6 hours after treatment, ranged from 84.0% to 90.9% through Day 21, and declined to 50.3% 28 days after treatment. Successful feeding by mosquitoes was significantly (P=.05) reduced on Days 1 through 28. The 65% permethrin spot-on treatment killed and repelled significantly (P =.05) more mosquitoes on treated dogs versus untreated dogs for 28 days after treatment.

Efficacy of two 65% permethrin spot-on formulations against induced infestations of Ctenocephalides felis (Insecta: Siphonaptera) and Amblyomma americanum (Acari: Ixodidae) on beagles.

The efficacy of two formulations of a topically applied 65% permethrin spot-on (Defend Exspot Treatment for Dogs, Schering-Plough Animal Health) was evaluated against experimental infestations of the cat flea Ctenocephalides felis and the lone star tick Amblyomma americanum in dogs. Eighteen dogs were randomly assigned to treatment with 65% permethrin in either diethylene glycol monomethyl ether (DGME; original formulation) or propylene glycol monomethyl ether (PGME) or to be untreated as a control. Treated dogs received either 1 (body weight < 15 kg) or 2 ml (body weight > or =15 kg) of the assigned formulation on Day 0. One hundred unfed, adult C. felis were placed on each dog on Days -6, -1, 4, 11, 18, 25, and 32. Fifty unfed, adult ticks were placed on each dog on Days -1, 3, 9, 16, 23, and 30. Live fleas and ticks were counted and removed on Days 3, 7, 14, 21, and 28. Treatment of dogs with the 65% permethrin in DGME reduced flea numbers by 90.4% to 99.9% from Days 3 through 21 (P < or =.05) and by 48.2% 28 days after treatment. Treatment of dogs with 65% permethrin in PGME reduced flea numbers by 93.7% to 99.7% from Days 3 through 28 and by 78.4% 35 days after treatment (P < or =.05). Treatment with 65% permethrin in DGME reduced tick numbers by 90% or more only on Day 7, whereas treatment with 65% permethrin in PGME reduced the number of live ticks by 90%or more on Days 7 and 14 and approached 90%(87.9%) on Day 21. Efficacy against fleas and ticks for the PGME formulation was significantly better (P < or =.05) than for the DGME formulation on Day 28. Findings in this study indicate that both the DGME and PGME formulations of 65% permethrin performed well in reducing numbers of live C. felis and A. americanum on laboratory beagles; however, the PGME formulation was effective approximately 1 to 2 weeks longer than the DGME formulation.

Efficacy of two 65 % permethrin spot-on formulations against canine infestations of Ctenocephalides felis and Rhipicephalus sanguineus.

The efficacy of two formulations of a topically applied 65% permethrin spot-on for dogs (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp.) was evaluated against experimental infestations of the cat flea, Ctenocephalides felis, and the brown dog tick, Rhipicephalus sanguineus. Thirty dogs were randomly allocated to treatment with 65 % permethrin in diethylene glycol monomethyl ether (original formulation), 65 % permethrin in propylene glycol monomethyl ether (test formulation), or to an untreated control group. Dogs assigned to treatment with a permethrin formulation received either 1 or 2 ml of the formulation in accordance with label directions on Day 0. One hundred unfed, adult cat fleas and 50 unfed, adult ticks were placed on each dog on Days -1, 5, 12, 19, 26, 33, and 40. Live fleas and ticks were counted on each dog on Days 2, 7, 14, 21, 28, 35, and 42. Treatment of dogs with either formulation of 65 % permethrin significantly (P <.05) reduced the number of live fleas and ticks from Days 2 through 42. No statistical differences were noted between the formulations regarding efficacy against C. felis or R. sanguineus.

Repellency and efficacy of 65% permethrin and selamectin spot-on formulations against Ixodes ricinus ticks on dogs.

Two topically applied spot-on products used for flea and tick control on dogs, 65% permethrin (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp., Union, NJ) and selamectin (Revolution [United States] or Stronghold [Europe], Pfizer Animal Health, New York, NY), were evaluated for repellency and efficacy against Ixodes ricinus, the primary vector of Lyme disease in Europe. Eighteen dogs were evenly and randomly allocated to the following treatments: 1) 65% permethrin, 2) selamectin, 3) untreated control. Dogs were treated by topical application of the assigned product in accordance with product label directions on Day 0. At 7, 14, 21, 28, and 35 days after treatment, each dog was exposed for 2 hours to 50 unfed, adult ticks in a cage with a carpet that covered approximately 70% of the floor area. After the exposure period, dogs were removed from the cages and live and dead ticks were counted on the dogs and in the cages. The number of live ticks recovered was reduced by 90.3% to 99.5% for dogs treated with 65% permethrin (P <.0001 versus controls and selamectin), compared with 10.9% to 31.1% for dogs treated with selamectin (P >.05 versus controls). The repellency of 65% permethrin was 63.4% to 80.2% against I. ricinus ticks (P <.0001 versus controls, P <.0007 versus selamectin), compared with 0% to 10.9% repellency for selamectin (P >.05 versus controls).

Efficacy of a 1% lambdacyhalothrin cattle Pour-on (Saber) against sucking and biting lice infesting beef cattle.

Four studies were conducted to determine the efficacy of a 1% lambdacyhalothrin pour-on (Saber Pour-on, Schering-Plough Animal Health) for control of sucking lice (Linognathus vituli, Haematopinus eurysternus, Solenopotes capillatus) and biting lice (Damalinia bovis) on beef cattle. Seventy-four mixed-breed cattle naturally infested with one or more species of lice at locations in Wisconsin, Nebraska, Oklahoma, and North Dakota were included in the study. Pretreatment lice samples were taken and identified by genus with the exception that sucking lice were not identified by genus at the North Dakota site. In January or February, half of the cattle at each location received a single application of 1% lambdacyhalothrin pour-on at 10 ml per head for cattle weighing less than 273 kg (600 lb) or 15 ml per head for cattle weighing 273 kg or more. The other cattle at each site served as untreated controls. Lice on designated body areas were counted 2, 4, 6, and 8 weeks after treatment, and the sum of all lice observed on each counting area was reported for each animal. The collective efficacy 6 weeks after treatment against three species of sucking lice (L. vituli, H. eurysternus, S. capillatus) was 88.4% at the Wisconsin site, 92.0% at the North Dakota site, and 100% at the Nebraska and Oklahoma sites. The 1% lambdacyhalothrin pour-on eliminated all biting lice within 2 weeks after treatment, and no biting lice were detected 8 weeks after treatment. A single treatment of 1% lambdacyhalothrin pour-on administered when lice populations were highest (January or February) provided effective season-long control of both biting and sucking lice on cattle.

Efficacy of three dose volumes of topically applied 65% permethrin against Ctenocephalides felis and Rhipicephalus sanguineus on dogs weighing 30 kg or more.

Twenty-five dogs were evenly and randomly allocated by weight to five treatment groups: untreated control, 2 ml 65% permethrin (dogs weighing 15 to 29 kg, "average dogs"), and 2, 3, or 4 ml 65% permethrin (dogs weighing > or = 30 kg, "big dogs"). Each dog was infested with 125 unfed, adult cat fleas, Ctenocephalides felis, and 50 unfed, adult brown dog ticks, Rhipicephalus sanguineus, on Days -3 (ticks only), -2 (fleas only), 3, 7, 14, 17, 21, 24, and 28. Fleas and ticks were counted 1 and 3 or 4 days after each infestation. The duration of efficacy (defined as >90%) against C. felis was 28 to 31 days. The efficacy against fleas 31 days after application of 2, 3, or 4 ml on big dogs ranged from 79.1% (2 ml) to 100% (4 ml). Big dogs that received either 3 or 4 ml of 65% permethrin had significantly (P < or = .05) fewer fleas at several evaluations between 15 and 31 days after treatment. The duration of efficacy against R. sanguineus was 15 (2 ml for big dogs) to 28 (2 ml for average dogs) days. The efficacy against R. sanguineus 28 days after treatment ranged from 79.1% (2 ml on big dogs) to 94.1% (2 ml on average dogs). Significantly (P < or = .05) fewer ticks were present at several evaluations after treatment on big dogs that received 3 or 4 ml than were present on big dogs treated with 2 ml. No significant differences were detected between the 3- and 4-ml groups from Days 10 to 31; however, the geometric mean number of ticks in the group treated with 4 ml was numerically lower than that for dogs treated with 3 ml on several occasions. These data indicate that a dose volume of 3 or 4 ml of 65% permethrin is needed to obtain an adequate level and duration of efficacy against both C. felis and R. sanguineus on dogs weighing 30 kg or more.