Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep

The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.     

Morphologic and physiologic changes induced by Clostridium perfringens type A alpha toxin in the intestine of sheep

OBJECTIVE: To evaluate the morphologic and physiologic changes induced by Clostridium perfringens type A (alpha toxin in the ileum and colon of sheep. SAMPLE POPULATION: 16 ligated intestinal loops in 4 Merino lambs and 18 explants of ileum and colon from slaughtered lambs. PROCEDURE: alpha Toxin-induced fluid accumulation was evaluated in ligated ileal and colonic loops of sheep. Tissues were evaluated morphologically by use of gross and histologic examination. Effects of toxin on in vitro intestinal net water transport were tested in modified Ussing chambers. RESULTS: Ovine ileal and colonic loops incubated with C perfringens type A alpha toxin retained more fluid than control loops. Histologically, in the ileum of lambs inoculated with 300 LD50 of alpha toxin/mL, there was a mild to moderate multifocal infiltration of neutrophils in the lamina propria and submucosa. The colonic loops of lambs inoculated with 30 or 300 LD50 of alpha toxin/mL had excessive mucus in the lumen, a moderate amount of neutrophils mixed with mucus in the intestinal lumen, and moderate multifocal infiltration of the lamina propria and submucosa with neutrophils; the blood vessels of these layers were engorged with neutrophils. In vitro measurements of water transport also revealed inhibition of net epithelial water absorption in ileum and colon incubated with alpha toxin on the mucosal side. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that alpha toxin induces alterations in sheep intestine. Clostridium perfringens type A organisms that produce alpha toxin could be responsible for diseases of intestinal origin in some ruminants.     

Comparison and standardisation of serological methods for the diagnosis of Neospora caninum infection in bovines

Various existing serological tests were compared with a standard panel of 523 sera in a multicentred study across Europe. Well characterised sera from animals that were experimentally or naturally infected with Neospora caninum as well as sera from cattle deemed uninfected with N. caninum were provided by the participants of the study and analysed in several commercial (CHEKIT Dr. Bommeli/Intervet, CIVTEST BOVIS NEOSPORA Hipra, Cypress Diagnostics C.V., Herd Check IDEXX, Mastazyme MAST Diagnostics, P38-ELISA Animal Welfare and Food Safety GmbH (AFOSA)) as well as in-house assays (five ELISAs and one IFAT). Most tests showed a high level of agreement in the interpretation of the test results (positive or negative). A further distinct increase in agreement between tests was obtained after the application of standardised cut-offs offered by a two-graph receiver operating characteristic analysis. This procedure allows a standardised interpretation of results obtained with different tests used in independent, parallel seroepidemiological studies.     

Anaplasma infection in free-ranging Iberian red deer in the region of Castilla-La Mancha, Spain

Organisms in the genus Anaplasma are obligate intracellular pathogens that multiply in both vertebrate and invertebrate hosts. The type species, Anaplasma marginale, causes bovine anaplasmosis and infects erythrocytes of the vertebrate host and undergoes a complex developmental cycle in ticks which serve as biological vectors. Infected cattle, wild ruminants and ticks can all serve as reservoirs of A. marginale. In this study, hunter killed Iberian red deer (Cervus elaphus hispanicus) from the region of Castilla-La Mancha in southwestern Spain were tested for Anaplasma infection. We found that 10% of the deer examined were seropositive for Anaplasma. Three A. marginale strains were subsequently obtained from salivary glands of Hyalomma marginatum that were removed from these deer, and the sequence of the major surface protein (msp)4 gene was determined for each strain and used for phylogenetic studies. Maximum parsimony analyses of msp4 sequences from H. marginatum ticks in comparison with New World cattle and bison isolates reported previously, suggested different origins for these Spanish A. marginale strains. The results of this study demonstrated that Iberian red deer are naturally infected with Anaplasma, and may therefore serve as a wildlife reservoir of the pathogen. Although the link between deer infection and the strains of A. marginale identified in ticks was not established, H. marginatum and Rhipicephalus bursa were identified as potential biological vectors for A. marginale in this region and may effect transmission of A. marginale between deer and cattle populations.     

Pharmacokinetics of a combination preparation of ampicillin and sulbactam in turkeys

OBJECTIVE: To investigate the disposition kinetics of ampicillin and sulbactam after IV and IM administration of an ampicillin-sulbactam (2:1) preparation and determine the bioavailability of the combined preparation after IM administration in turkeys. ANIMALS: 10 healthy large white turkeys. PROCEDURE: In a crossover study, turkeys were administered the combined preparation IV (20 mg/kg) and IM (30 mg/kg). Blood samples were collected before and at intervals after drug administrations. Plasma ampicillin and sulbactam concentrations were measured by use of high-performance liquid chromatography; plasma concentration-time curves were analyzed via compartmental pharmacokinetics and noncompartmental methods. RESULTS: The drugs were distributed according to an open 2-compartment model after IV administration and a 1-compartment model (first-order absorption) after IM administration. For ampicillin and sulbactam, the apparent volumes of distribution were 0.75+/-0.11 L/kg and 0.74+/-0.10 L/kg, respectively, and the total body clearances were 0.67+/-0.07 L x kg(-1) x h(-1) and 0.56+/-0.06 L x kg(-1) x h(-), respectively. The elimination half-lives of ampicillin after IV and IM administration were 0.78+/-0.12 hours and 0.89+/-0.17 hours, respectively, whereas the corresponding half-lives of sulbactam were 0.91+/-0.12 hours and 0.99+/-0.16 hours, respectively. Bioavailability after IM injection was 58.87+/-765% for ampicillin and 53.75+/-5.35% for sulbactam. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that a regimen of loading and maintenance doses of 300 mg of the ampicillin-sulbactam (2:1) combination/kg every 8 hours could be clinically useful in turkeys. This dosage regimen maintained plasma concentrations of ampicillin > 0.45 microg/mL in turkeys.     

Ovine Pulmonary Adenomatosis in Patagonia,Argentina

An outbreak of pulmonary adenomatosis (OPA) occurred in sheep in Patagonia, Argentina's southernmost region. On the affected farm, nine animals died over a 6-month period with pulmonary lesions of OPA. In all cases, the histology of the lungs was characterized by proliferation of cuboideal and prismatic cells lining the alveoli. Inflammatory exudates and accumulation of alveolar macrophages were marked in most cases, but in six of the cases there was no excess fluid in the airways. The presence of the Jaagsiekte retrovirus was demonstrated in the lungs by immunocytochemistry and PCR. To the best of our knowledge, this is the first report of OPA in Patagonia.     

Pharmacokinetics of danofloxacin in horses after intravenous, intramuscular and intragastric administration

REASONS FOR PERFORMING STUDY: Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. OBJECTIVE: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. METHODS: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared and administered via nasogastric tube. Danofloxacin concentrations were determined by HPLC assay with fluorescence detection. Tolerability at the the site of i.m. injection was monitored by creatine kinase (CK) activity. RESULTS: Danofloxacin plasma concentration vs. time data after i.v. and i.g. administration could best be described by a 2-compartment open model. The disposition of i.m. administered danofloxacin was best described by a one-compartment model. The terminal half-lives for i.v., i.m. and i.g. routes were 6.31, 5.36 and 4.74 h, respectively. Clearance value after i.v. dosing was 0.34 l/kg bwt/h. After i.m. administration, absolute bioavailability was mean +/- s.d. 88.48 +/- 11.10% and Cmax was 0.35 +/- 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 +/- 6.84% and Cmax 0.21 +/- 0.07 mg/l. CK activity following i.m. dosing increased 3-fold over pre-injection levels 12 h after dosing and subsequently approached (but did not reach) normal values at 72 h post dose. CONCLUSIONS: Systemic danofloxacin exposure achieved in horses following i.m. administration was consistent with the predicted blood levels needed for a positive therapeutic outcome for many equine infections. Conversely, danofloxacin utility by the i.g. route was limited by low bioavailability. Tolerability associated with i.m. administration was high. POTENTIAL RELEVANCE: Pharmacokinetics, blood levels and good tolerability of i.v. and i.m. administration of danofloxacin in horses indicates that it is likely to be effective for treating sensitive bacterial infections.     

Pharmacokinetics of moxifloxacin in rabbits after intravenous, subcutaneous and a long-acting poloxamer 407 gel formulation administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long-acting poloxamer 407 gel formulation (SC-P407). Moxifloxacin concentrations were determined by high-performance liquid chromatography assay with fluorescence detection. Mean half-life for IV, SC and SC-P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C(max) was 1.61 +/- 0.49 mg/l. After SC-P407 administration, the bioavailability was 44% and the C(max) 1.83 was +/-0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC-P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC-P407 formulation and the favourable PK behaviour such as the long half-life, acceptable bioavailability and excellent PK-PD ratios achieved indicate that it is likely to be effective in rabbits.     

Pharmacokinetics and milk penetration of moxifloxacin after intravenous and subcutaneous administration to lactating goats

The pharmacokinetics of moxifloxacin was studied following intravenous (IV) and subcutaneous (SC) administration of 5 mg/kg to healthy lactating goats (n = 6). Moxifloxacin concentrations were determined by high performance liquid chromatography assay with fluorescence detection. The moxifloxacin plasma concentration versus time data after IV administration could best be described by a two compartment open model. The disposition of SC administered moxifloxacin was best described by a one-compartment model. The plasma moxifloxacin clearance (Cl) for the IV route was 0.43 +/- 0.02 L/kg (mean +/- SE). The steady-state volume of distribution (Vss) was 0.79 +/- 0.08 L/kg. The terminal half-life (t1/2lambdaz) was 1.94 +/- 0.41 and 2.98 +/- 0.48 h after IV and SC administration, respectively. The absolute bioavailability was 96.87 +/- 10.27% after SC administration. Moxifloxacin penetration from blood to milk was quick for both routes of administration and the high AUCmilk/AUCplasma and Cmax-milk/Cmax-plasma ratios reached indicated a wide penetration of moxifloxacin into the milk. From these data, it appears that a 5 mg/kg SC dose of moxifloxacin would be effective in lactating goats against bacterial isolates with MIC < or = 0.20 microg/mL in plasma and MIC < or = 0.40 microg/mL in milk.     

Susceptibility of common herbaceous crops to Phytophthora cinnamomi and its influence on Quercus root rot in rangelands

The susceptibility to Phytophthora cinnamomi of four crops (wheat, oat, vetch, and yellow lupin) commonly planted in rangeland ecosystems in southern Spain was evaluated. By means of in vitro infection experiments, the presence of the pathogen into the roots of yellow lupin (symptomatic) and vetch (asymptomatic) was observed, but never into wheat and oat roots (asymptomatic). It was also demonstrated that yellow lupin stimulated the production of zoospores of P. cinnamomi. Vetch, wheat and oat did not stimulate zoospore production. Under controlled conditions, only yellow lupin induced an increase in the number of viable chlamydospores in the soil. We concluded that the culture of wheat, oat, and vetch in rangelands did not influence the epidemiology of the Quercus root disease, even when asymptomatically-infected vetch is grown, and these crops can constitute an alternative to the culture of yellow lupin in rangeland ecosystems affected by Quercus root rot.