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.     

单诺沙星对人工诱发鸡大肠肝菌病的药效试验

根据试管 2倍稀释法测定的单诺沙星及氯霉素对鸡大肠杆菌的最小抑菌浓度 ,对实验性大肠杆菌病鸡进行内服给药 (每隔 12h给药 1次 ,连续 3d)治疗试验。结果表明 ,单诺沙星及氯霉素对鸡大肠杆菌的最小抑菌浓度分别是 0 0 5及 1 6mg/L。单诺沙星以 5mg/kg、氯霉素以40mg/kg的剂量给鸡内服后 ,对大肠杆菌病的治愈率分别为 87 5%及 55 0 %。     

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.     

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 ht 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.     

Pathology of experimental chlamydiosis in chicks

Twelve one-day-old chicks were experimentally inoculated with Chlamydia psittaci derived from turkeys. Acute chlamydial septicemic lesions were induced by the inoculation into the air sac and trachea. No lesions were produced by the esophageal injection. Clinically, the affected chicks showed emaciation and mouth breathing, and were inactive while some birds died. Grossly, they had hepatomegaly, splenomegaly and airsacculitis. Histopathologically, fibrinopurulent airsacculitis, pneumonia and bronchitis, multiple fibrinous serositis in the hepatic and splenic capsules, peri- and epicardium, and mesenterium, focal endoarteritis in the aortae, activation of reticuloendothelial cells in the spleen, and hepatic necrosis were noted. Immunohistochemically, chlamydial antigen granules were present in the cytoplasm of epithelial cells of the respiratory system, hepatocytes, macrophages in the air sac, lung, serous membrane, liver, spleen, aortae, reticuloendothelial cells in the spleen, and mesothelial cells in various organs or tissues. Chlamydial multiplication in the cells of the organs or tissues involved was preceded to form the lesions.     

Efficacy of maternal Salmonella antibodies and experimental oral infection of chicks with Salmonella enteritidis

Distribution of maternally transmitted Salmonella antibodies and their protective effects were studied in the progeny of broiler breeder birds which had been vaccinated with live S. Typhimurium and inactivated S. Enteritidis vaccines. Vaccination resulted in a significant increase of the antibody concentration in yolk of hatching eggs and in serum and jejunum of the progeny of immunized breeder birds. Higher antibody titres for isotypes IgG and IgA were still seen on day 21 of age. Antibody production of isotypes IgA and IgM by the chickens themselves was found between 14 and 21 days of age. Two challenge models (10(2) cfu/bird on day 1 of age and a seeder bird model, respectively) were used to evaluate the efficacy of maternal antibodies against challenge with S. Enteritidis. Using both models numbers of challenge organisms were lower in the caeca of the progeny of immunized parent birds between day 7 and day 21 of age (maximum about 1.5 log10 units) compared with control chicks. The results indicate the efficacy of maternally transferred antibodies but it remains the question of their practical relevance. The effects of acquired maternal antibodies on an active immunization of the progeny of immunized breeder birds with live Salmonella vaccines are discussed.     

Successful treatment of mycoplasmosis in layer chickens with single dose therapy

The efficacy of treatment with single dose administration of 5 drugs at different dosages to layer hens naturally infected with Mycoplasma gallisepticum was studied. The drugs were tiamulin, which was administered orally, tylosin (parenterally and orally), spiramycin (orally), long-acting oxytetracycline (parenterally) and tylosindihydrostreptomycin (parenterally). Cure was assessed by the absence of nasal discharge. The cure rate was significantly higher (P less than 0.05) in treated hens than in untreated hens, as early as 1 day after treatment. Remission for 33 days was achieved in 60% of hens treated with 100 mg oxytetracycline, in 100% of hens treated with 100 mg or 200 mg spiramycin, in 92% and 85% of hens treated with 100 mg tylosin, parenterally and orally, and in 89% and 88% of birds given 100 mg tiamulin and tylosin-dihydrostreptomycin, respectively.     

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.     

Pharmacokinetic-pharmacodynamic integration of danofloxacin in the calf

The pharmacokinetics and pharmacodynamics of danofloxacin were studied in calves after intravenous (IV) and intramuscular (IM) administration, at a dose of 1.25 mg/kg in a two period cross-over study, using tissue cages to monitor aspects of extravascular distribution. Danofloxacin had a high volume of distribution (3.90 L/kg) and relatively rapid clearance (1.02 L/kgh) after IV dosing. Terminal half-life was 2.65 and 4.03 h, respectively, after IV and IM administration. Danofloxacin penetrated slowly into and was cleared slowly from tissue cage fluid (transudate), elimination half-life (10.2 h after IV and 8.9 h after IM dosing) being greater than for serum. The antibacterial actions of danofloxacin against the pathogen Mannheimia haemolytica 3575 were established in vitro in Mueller Hinton Broth, serum and transudate. These data were used together with in vivo pharmacokinetic parameters, C(max) and AUC to determine the surrogate markers of antimicrobial activity, C(max)/MIC, AUC/MIC and T>MIC.The antibacterial actions of danofloxacin were also determined ex vivo in serum and transudate samples harvested at pre-determined times after IM danofloxacin dosing. Ex vivo AUC/MIC data were integrated with ex vivo bacterial count to establish values producing a bacteriostatic action, inhibition of bacterial count by 50%, reduction in bacterial count by 99.9% (bactericidal action) and elimination of bacteria. Mean values were, respectively, 15.9, 16.7, 18.15 and 33.5h for serum and 15.0, 16.34, 17.8 and 30.7 h for transudate. The AUC/MIC-effect relationships for serum may be regarded as representative of a shallow compartment of blood and well perfused tissues, whilst AUC/MIC-effect relationships for transudate may be considered to represent a deep peripheral compartment of poorly perfused tissues. A novel approach to selecting antimicrobial drug dosage for evaluation in clinical trials, using AUC/MIC values producing either bactericidal activity or elimination of bacteria together with MIC(90) values for calf pathogens, is proposed. This approach can be expected to optimise efficacy and minimise the development of resistance.     

Pharmacokinetic study of danofloxacin in cattle and swine.

Pharmacokinetic values of a new quinolone antimicrobial, danofloxacin, were studied in cattle and swine. Plasma concentration was detected within 15 minutes after IM administration, peaked by 1 hour, and subsequently decreased, with half-life of 2.9 and 6.8 hours for cattle and swine, respectively. In swine, danofloxacin was absorbed, whether orally administered by gavage, in feed, or in drinking water. Danofloxacin concentrated in lung tissue at 4 to 7 times the plasma concentration. Lung tissue concentration exceeded the minimal inhibitory concentrations for im90portant respiratory tract pathogens for extended periods after administration of the drug by any of the routes studied. The major routes of excretion were in urine and bile.     

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.     

Disposition kinetics of danofloxacin and ciprofloxacin in broiler chickens.

Disposition kinetics of danofloxacin and ciprofloxacin were studied in broiler chickens following intravenous, intramuscular and oral administration in a single dose of 5 and 10 mg/kg-1 body weight respectively. In addition, tissue distribution and residual pattern of both drugs were determined. The maximum serum concentration (Cmax) after intramuscular and oral administration were 1.03 and 0.55 mu/ml for danofloxacin and 2.92 and 1.24 mu/ml for ciprofloxacin attained at 0.8 and 2.43 and 0.55 and 1.27 hours for danofloxacin and ciprofloxacin respectively. The volume of distribution and systemic bioavailability were higher for danofloxacin (Vdss 2.21 L/kg and F% 96.56 and 81.4%) as compared with ciprofloxacin (Vdss 1.41 L/kg and F% 75.5 and 29.4%). Data relating to intravenous injection for both drugs were analyzed using a two compartment open model curve fit. Danofloxacin and ciprofloxacin were not detected in the serum of broilers at the 5th and 3rd day respectively following the drugs withdrawal while were detected in liver, kidneys, spleen and lungs. Danofloxacin completely disappeared from all tissues at the 13th day after stopping of the drug medication but ciprofloxacin disappeared after 5 days only.     

单诺沙星在健康与支原体-大肠杆菌合并感染鸡体内的药动学研究

以高压液相色谱 (HPLC)法为定量手段研究了单诺沙星在健康和支原体与大肠杆菌合并感染鸡体内的药动学特征。 60只健康鸡和 60只合并感染鸡内服单诺沙星 (5mg/kg)后 ,血浆的药时数据均符合一级吸收二室模型。健康和合并感染鸡的主要动力学参数分别如下 :t1 /2ka为 0 2 4 2 8和 0 31 82h,t1 /2α为 0 891 7和 1 550 2h ,t1 /2 β为 8 793 6和 1 2 62 0 0h ,Tp为 0 9377和 1 1 1 0 7h ,Cmax为 0 5487和 0 51 0 6μg/mL ,每小时为3 0 52 3和 3 660 2mg/L ,Tcp为 31 1 1 5和 39 1 8h。单诺沙星在鸡体内的药动学特征是吸收迅速且完全 ,体内分布广泛 ,但消除缓慢 ,有效浓度维持时间长。合并感染使单诺沙星在感染鸡体内的吸收、分布和消除均减慢 ,达峰时间、有效浓度维持时间延长