Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats.

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).

Tissue-invading ciliates associated with chronic colitis in a horse.

Ciliates resembling Polymorphella ampulla (Dogiel, 1929) were found in large numbers in the crypts and lamina propria of the caecum and colon of a one-year-old Thoroughbred gelding that had shown recurring bouts of chronic diarrhoea and weight loss over a 5-month period. A heavy burden of helminths, mainly cyathostomes (trichonemes) was present at post-mortem examination and no significant bacterial pathogens were recovered. It was considered that the Polymorphella (which is normally a commensal organism) had in this case assumed a secondary pathogenic role.

Efficacy of danofloxacin 18% injectable solution in the treatment of Escherichia coli diarrhoea in young calves in Europe.

The efficacy of danofloxacin 18% against naturally occurring Escherichia coli diarrhoea was investigated in calves at seven European sites. Treatment commenced on day 0, with either a single subcutaneous injection of danofloxacin 18% (n=267) at 6 mg/kg repeated on day 2 if required, or reference product containing baquiloprim/sulphadimidine (n=37) or gentamicin (n=98) administered as recommended. E. coli was isolated from 90% to 100% of calves pre-treatment, and the prevalence of serotypes K99 and F41 was 8-46% and 46-92%, respectively. In both treatments, the majority of calves (93.2-93.9%) showed clinical improvement and completed the studies. There were significant reductions for both treatments, in severity of clinical signs on days 4 and 10 compared to day 0 (P<0.0001), and between days 4 and 10 (P<0.05), but no significant differences between treatments (P>0.05). Danofloxacin 18% was clinically safe, and as effective as the reference products in the treatment of E. coli diarrhoea in calves.

Outbreak of ragwort (Senecio jacobea) poisoning in horses.

Five out of 20 horses (25 per cent) on one farm died from an acute hepatic encephalopathy typical of ragwort toxicosis. Circumstantial evidence implicated pasture rather than hay as the principal source of the toxic alkaloids. Plasma levels of gamma glutamyl transferase (GGT) were determined on three occasions in all surviving ragwort-exposed horses. Elevated GGT levels were a useful early indicator of hepatic damage although not all horses with this biochemical sign developed clinical disease.

Larval cyathostomiasis (immature trichonema-induced enteropathy): a report of 15 clinical cases.

Clinical and laboratory findings are recorded from a series of 15 cases (aged one to 16 years) of sudden-onset chronic diarrhoea with weight loss, progressing in many cases to emaciation and death, associated with the emergence of fourth stage cyathostome (trichoneme) larvae in large numbers through the colonic and caecal mucosae. Apart from a single incident in mid-October, disease only occurred in winter and spring (January to May). Characteristic features included hypoalbuminaemia, increased alpha and beta plasma globulin levels and neutrophilia without left shift. Faecal egg counts were frequently negative and eosinophilia and anaemia were not features. Horses treated in the early stages responded well to larvicidal doses of fenbendazole (60 mg/kg bodyweight) but in cases where this therapy was delayed for weeks or months the prognosis was poor.

Clinical bacteriological and epidemiological observations on infectious atrophic rhinitis of pigs in southern England.

Three distinct patterns of infection with Bordetella (Alcaligenes) bronchiseptica were found in groups of 12 to 24 pigs born in 1977-78 in 12 herds in southern England. In five of these, heavy bordetella infection of a substantial proportion of unweaned piglets persisted to a variable extent until slaughter. Clinical disease and severely atrophied turbinates were most marked in these groups. In three other herds the infection first appeared soon after weaning and occasionally persisted until slaughter. Clinical disease occurred in only one of these other groups and conchal atrophy at slaughter was moderate. In the groups of the four remaining herds there was no clinical disease and conchal atrophy at slaughter was slight, infection appearing only late in the weaning, or even the fattening, stages. These varying patterns suggest that immunological phenomena were involved in the infection in the least affected herds and that such responses might, if reproducible artificially, provide a better means of control of this disease in badly affected herds than the available forms of chemotherapy.

The prevalence of Brodetella bronchiseptica and turbinate (conchal) atrophy in English pig herds in 1978-79.

Examination of pigs (eight to 10 per farm) slaughtered between December 1978 and March 1979 at abattoirs in southern England indicated that infection with Bordetella bronchiseptica was widespread. The organism was recovered from the nasal cavity of 424 out of 844 (50 per cent) of such pigs and these were distributed among 79 out of 86 (91 per cent) of the herds submitting animals. The sensitivity to sulphonamide or potentiated sulphonamide of 255 of these strains was determined: in 20 out of 70 (25 per cent) herds there was partial or complete resistance to the former drug and, in 16 out of 79 (20 per cent), to the latter also. Despite this general level of infection and bacterial resistance the prevalence and severity of turbinate atrophy was less than in a survey undertaken by others in 1974. Thus about 74 per cent of pigs had no or minor atrophy only and about 10 per cent severe lesions. Some 10 per cent of the farms sent groups in which the majority of the pigs had severe atrophy.

Immunisation of pigs against experimental infection with Bordetella bronchiseptica.

During pregnancy seven minimum-disease sows (group A) were infected intranasally with Bordetella bronchiseptica, fed with the killed bacterium periodically and inoculated parenterally with a dead vaccine eight, six and two weeks before parturition. Groups B and C, isolated from A until farrowing, contained respectively six sows given the vaccine parenterally and eight control sows. At parturition, group A had much higher average agglutinin titres in the serum and colostrum than B or C. Group A sows gave their piglets a better passive protection against infection with B bronchiseptica strain 293 and its effects in the respiratory tract during the first eight weeks of life, especially in those exposed to spontaneous infection with bordetellae from a littermate deliberately inoculated intranasally 24 hours after birth. Passive antibody strongly affected the capacity of piglets to respond actively to parenteral vaccination (when seven and 28 days old), marked humoral responses being noted only in those from group C sows. Vaccination of piglets exposed to infection by contact reduced neither the prevalence or intensity of the nasal infection, the amount of turbinate atrophy or pneumonia nor significantly improved weight gain compared with unvaccinated littermates. Unlike their eight-week-old littermates there was little hypoplasia and no pneumonia in infected pigs (whether vaccinated or not) when they reached five months of age.

Treatment of experimental Bordetella bronchiseptica infection in young pigs with potentiated sulphonamide in the drinking water.

Bordetella bronchiseptica was eliminated from the nasal cavity of experimentally infected piglets after about three weeks by trimethoprim and sulphadiazine (potentiated sulphonamide) in the drinking water in two experiments (at levels of 13.3 and 66.7 micrograms per ml, respectively). The rhinitis and turbinate damage associated with the infection was significantly less when the animals were examined at seven weeks of age but daily weight gain was not improved to a significant extent compared with controls. Smaller quantities of potentiated sulphonamide were less active but no amount induced resistance in the bordetellae during the one month period of treatment.

Suspected poisoning of a goat by giant hogweed.

A five-year-old male African pygmy goat became ill four weeks after transfer from a zoological garden to a municipal park. The animal was subdued, refused to eat and drink and showed profuse salivation. Examination of the mouth revealed severe ulceration. The condition gradually responded to nursing and supportive therapy. Circumstantial evidence suggested the possibility that the lesions were caused by giant hogweed (Heracleum mantegazzianum). Supportive evidence that the plant could produce lesions was provided by the application of a cut stem to the hard palate and a solution of various dilutions to clipped areas of the backs of two ewes. Both ewes produced reddened skin when the concentrated solution was applied and both showed marked reddening of the gingival mucosae and in one animal small ulcers developed in the rostral part of the mouth. It is suggested that H mantegazzianum may be a potential hazard for grazing ruminants.

Efficacy of danofloxacin in the therapy of acute bacterial pneumonia in housed beef cattle.

Danofloxacin, a novel fluoroquinolone antimicrobial drug was evaluated in the treatment of acute bacterial pneumonia in recently housed beef cattle of approximately 300 kg liveweight. The clinical responses of 67 pneumonic cattle treated with danofloxacin were compared with those of 65 cattle treated with oxytetracycline, both treatments being given by intramuscular injection for either three or five days, depending on clinical response. Both treatments resulted in a rapid fall in group mean rectal temperature and improved the clinical condition of the majority of cases. However, in comparison with oxytetracycline, danofloxacin therapy was characterised by significantly fewer treatment days, a higher response rate, significantly better reduction of pyrexia and fewer cattle requiring re-treatment.

Efficacy of danofloxacin in the treatment of respiratory disease in European cattle.

The efficacy of an injectable formulation of danofloxacin (180 mg/ml) in the treatment of naturally occurring bovine respiratory disease was evaluated in field studies on farms in France, Ireland and the United Kingdom. Cattle aged one week to 15 months with clinical respiratory disease were randomly allocated to treatment with 6 mg/kg danofloxacin or 10 mg/kg tilmicosin, administered by a single subcutaneous injection on day 0. A second injection of danofloxacin was administered on day 2, only if predefined clinical criteria were met. Mannheimia haemolytica, Pasteurella multocida and Haemophilus somnus were isolated from pretreatment nasopharyngeal swabs taken on all the farms. After the treatment, there was a more rapid improvement in the clinical response of the 178 animals treated with danofloxacin by day 2 (P < 0.01) than in the 90 treated with tilmicosin. For both treatments, there were similar significant (P < 0.001) reductions in the mean rectal temperature and severity of clinical signs of abnormal respiration and depression, on days 4 and 10 compared with day 0; 78.1 per cent of the animals treated with danofloxacin and 78.5 per cent of those treated with tilmicosin completed the studies. Danofloxacin 18 per cent was clinically safe and as effective as tilmicosin in the treatment of bovine respiratory disease.

The efficacy of danofloxacin in the therapy of pneumonia associated with Pasteurella species in housed calves.

The efficacy of danofloxacin, a novel third generation fluoroquinolone, was assessed in the treatment of pneumonia in housed calves on three farms in the FDR and Italy. Seventy three calves with clinical signs of acute pneumonia and rectal temperatures greater than 40 degrees C were treated with danofloxacin at a dose rate of 1.25 mg/kg for three or five days depending on response to treatment. The response in these calves was compared to that obtained in 77 calves treated with trimethoprim/sulpha. The clinical response achieved with danofloxacin was superior to that achieved with trimethoprim/sulpha and significantly fewer calves which received danofloxacin required five days treatment. Pasteurella haemolytica and, or P. multocida were isolated from the majority of calves prior to treatment. All isolates were sensitive to danofloxacin and over 90 percent were sensitive to trimethoprim/sulpha.

In vitro evaluation of various antimicrobials against Mycoplasma gallisepticum and Mycoplasma synoviae by the micro-broth method, and comparison with a commercially-prepared test system.

The efficacy of danofloxacin, a new quinolone antimicrobial agent, was tested in vitro by the micro-broth method with nine field strains of Mycoplasma gallisepticum (Mg) and eight of M. synoviae (Ms) and comparison was made with oxytetracycline and tylosin tartrate. The virulent S6 strain of Mg was also included for reference. All Mycoplasma strains, including a strain of Mg that was resistant to tylosin tartrate, were susceptible to danofloxacin with minimal inhibitory concentrations ranging from pound 0.008 to 0.5 microg/ml. A commercially produced test system (Sensititre), using micro-plates whose wells were predosed with antimicrobial agents and then dried, was also investigated. Results with the same three antimicrobials were in agreement with those obtained by the micro-broth method. With the exception of the tylosin resistant strain, the Mg strains were more susceptible to erythromycin than the Ms strains. Conversely, Ms strains were susceptible to apramycin, while the Mg strains appeared to be resistant.

A comparison of the efficacy of danofloxacin and tylosin in the control of Mycoplasma gallisepticum infection in broiler chicks.

Groups of chicks were infected with a virulent strain of Mycoplasma gallisepticum (MG) and treated with either danofloxacin or tylosin while one infected group was left untreated and a further group was uninfected and untreated. Control of clinical signs and mortality was better with danofloxacin than tylosin and there was significantly (P < 0.05) greater weight gain with danofloxacin at 21 days after infection. However at necropsy the prevalence of lesions of the airsac walls was similar in both groups. MG was recovered from fewer live chicks for the first week following treatment with danofloxacin, but at 2 weeks and at necropsy, at the termination of the experiment, it was recovered from a similar proportion of birds in both treated groups. This was reflected also in the serological results at the end of the trial.

Clinical pharmacokinetics of parenterally administered danofloxacin in cattle.

Danofloxacin is a new fluoroquinolone antibacterial, developed specifically for veterinary use. Its in vitro activity and pharmacokinetic properties have been investigated to assess its potential for use in the therapy of respiratory disease in cattle. The minimum inhibitory concentration of danofloxacin against 90% (MIC90) of contemporary European and North American field isolates of Pasteurella haemolytica, Pasteurella multocida and Haemophilus somnus, the most important bacterial respiratory pathogens of cattle, was 0.125 micrograms/ml. The plasma and lung kinetics of danofloxacin following parenteral administration of 1.25 mg/kg were evaluated in two studies. Danofloxacin was rapidly absorbed following intramuscular and subcutaneous injection and bioavailability was virtually complete (101% and 94% respectively). Plasma concentration profiles of danofloxacin were similar for intramuscular and subcutaneous routes with no significant differences in the area under the plasma concentration-time curves (AUC) following one, three or five consecutive daily doses, although slightly higher peak plasma concentrations were achieved by the intramuscular route. Following intramuscular administration, the mean peak lung concentration of danofloxacin was 4.1 times greater than that of plasma. Similarly, the AUC for lung tissue was 3.7 times greater than that for plasma. These data indicate that danofloxacin should be particularly appropriate for the therapy of bacterial respiratory disease in cattle.