Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofloxacin has been licensed for use in various mammalian species, but not as yet for turkeys, although its kinetic properties distinguish it from other fluoroquinolones. For example, the longer half-life of marbofloxacin in many animal species has been appreciated in veterinary practice. It is generally accepted that, for fluoroquinolones, the optimal dose should be estimated on the basis of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the drug under consideration. Knowledge of these specific data for the target animal species allows the establishment of an integrated PK-PD model that is of high predictive value. In the present study, the antibacterial efficacy (PD indices) against a field isolate of Escherichia coli O78/K80 was investigated ex vivo following oral and intravenous administration of marbofloxacin to turkeys (breed BUT 9; six animals per group) at a dose of 2 mg/kg of body weight (BW). At the same time, the serum concentrations of marbofloxacin were measured at different time intervals by a standardized high-performance liquid chromatography method, allowing the calculation of the most relevant kinetic parameters (PK parameters). The in vitro serum inhibitory activity of marbofloxacin against the selected E. coli strain, O78/K80, was 0.5 g/ml in the blood serum of turkeys, and the ratio of the maximum concentration of the drug in serum to the serum inhibitory activity was 1.34. The lowest ratio of the measured serum concentration multiplied by the incubation period of 24 h to the serum inhibitory activity required for bacterial elimination was lower than the ratio of the area under the serum concentration-time curve (AUC) to the serum inhibitory activity. These first results suggested that the recommended dose of 2 mg/kg BW of marbofloxacin is sufficient to achieve a therapeutic effect in diseased animals. However, considering the risk of resistance induction, the applied dose should be equal to an AUC/MIC of >125, the generally recommended dose for all fluoroquinolones. According to the PK-PD results presented here, a dose of 3.0 to 12.0 mg/kg BW per day would be needed to meet this criterion. In conclusion, the results of the present study provide the rationale for an optimal dose regimen for marbofloxacin in turkeys and hence should form the basis for dose selection in forthcoming clinical trials.Marbofloxacin is a synthetic fluoroquinolone, developed for veterinary use only (47). It has a broad spectrum of activity (58), and bactericidal concentration-dependent killing is observed against many gram-negative bacteria (12, 49, 51, 52). The pharmacokinetic (PK) properties of marbofloxacin have been studied in several mammalian species, and some advantages over other fluoroquinolones, such as a longer elimination half-life, have been described (2,43,47,48). In practice, this would e...

The hepatitis C virus (HCV) is a major human pathogen. Genetically related viruses in animals suggest a zoonotic origin of HCV. The closest relative of HCV is found in horses (termed equine hepacivirus [EqHV]). However, low EqHV genetic diversity implies relatively recent acquisition of EqHV by horses, making a derivation of HCV from EqHV unlikely. To unravel the EqHV evolutionary history within equid sister species, we analyzed 829 donkeys and 53 mules sampled in nine European, Asian, African, and American countries by molecular and serologic tools for EqHV infection. Antibodies were found in 278 animals (31.5%), and viral RNA was found in 3 animals (0.3%), all of which were simultaneously seropositive. A low RNA prevalence in spite of high seroprevalence suggests a predominance of acute infection, a possible difference from the mostly chronic hepacivirus infection pattern seen in horses and humans. Limitation of transmission due to short courses of infection may explain the existence of entirely seronegative groups of animals. Donkey and horse EqHV strains were paraphyletic and 97.5 to 98.2% identical in their translated polyprotein sequences, making virus/host cospeciation unlikely. Evolutionary reconstructions supported host switches of EqHV between horses and donkeys without the involvement of adaptive evolution. Global admixture of donkey and horse hepaciviruses was compatible with anthropogenic alterations of EqHV ecology. In summary, our findings do not support EqHV as the origin of the significantly more diversified HCV. Identification of a host system with predominantly

Colibacillosis is a systemic disease responsible for important economic losses in poultry breeding; fluoroquinolones, including danofloxacin, are used to treat diseased animals. The purpose of the present study was to estimate pharmacokinetic-pharmacodynamic (PK-PD) surrogates for bacteriostasis, bactericidal activity and bacterial elimination against Escherichia coli O78/K80, using a PK-PD approach, for danofloxacin in turkeys after oral administration. Eight healthy turkeys, breed BUT 9, were included in a two-way crossover study. The drug was administered intravenously (i.v.) and orally at a dose rate of 6 mg/kg bw. The values of the elimination half-life and the total body clearance after i.v. administration were 8.64 +/- 2.35 h and 586.76 +/- 136.67 ml kg(-1)h(-1), respectively. After oral administration, the values of the absolute bioavailability and the elimination half-life were 78.37+/- 17.35% and 9.74+/- 2.93 h, respectively. The minimum inhibitory concentration against the investigated strain in turkey serum was 0.25 microg/ml, four times higher than in broth. The lowest effective ex vivo AUC(24)/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coli O78/K80 were 0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the present study could be interpreted as being sufficient to eliminate E. coli with an MIC 0.25 microg/ml. However, considering the demand that antimicrobial resistance should be avoided by complete bacterial elimination, PK-PD considerations suggest that an even higher dose of 32 mg/kg per day or 0.7 mg/kcal per day should be evaluated in clinical trials.

Systemic therapy with oxytetracycline is often used for treatment of clinical metritis although data about its penetration into the uterus and uterine secretion are lacking. Uterine secretions and milk from six cows with clinical metritis were collected for microbiological assay. The animals were treated intramuscularly with long-acting oxytetracycline (20 mg/kg) and samples of plasma, milk and uterine secretions were collected for determination of the antibiotic concentrations by HPLC-PDA analysis. Pharmacokinetics of the antibiotic and in silico prediction of its penetration into the uterus were described. Trueperella pyogenes with MIC values of 16–64 µg mL−1 was isolated (n of cows = 4) from uterine secretions. Oxytetracycline showed fast absorption and penetration in the uterine secretions and milk. No change of withdrawal time for milk was necessitated in cows with clinical metritis. Maximum levels in uterine secretions and predicted concentrations of oxytetracycline in the uterus were lower than MIC values. Systemic administration of long-acting oxytetracycline did not guarantee clinical cure and was not a suitable choice for treatment of clinical metritis associated with Trueperella pyogenes. The appropriate approach to antibiotic treatment of uterine infections of cows requires knowledge on penetration of the antibiotics at the site of infection and sensitivity of pathogens.

Staphylococcus warneri and Shewanella putrefaciens Coinfection in Siberian Sturgeon (Acipenser baerii) and Hybrid Sturgeon (Huso huso x Acipenser baerii)Submit Manuscript | http://medcraveonline.com IntroductionFish are in continuous contact with microorganisms in the water and sediment, which influences the microbial species diversity on their skin, gills and alimentary tract [1]. Although all microorganisms are part of the normal aquatic environment, some opportunistic pathogens cause bacterial diseases in fish with high mortality rates [2]. Examples are several Gram-positive and Gram-negative bacteria including Staphylococcus warneri (S. warneri) and Shewanella putrefaciens (S. putrefaciens) [3].From pond water samples at a fish farm, Newaj-Fyzul et al. [4] isolated Gram-positive bacteria identified as Staphylococcus spp. In the belief of Musharrafieh et al. [5] S. warneri is a part of the normal fish microflora, but Gil et al. [6] were the first to describe a disease on rainbow trouts caused by S. warneri, which makes it an opportunistic pathogen. Thereafter, Metin et al. [7] also reported S. warneri infection in rainbow trouts.S. putrefaciens is a Gram-negative facultatively anaerobic bacterium from the Shewanellaceae family. It is usually isolated from sea water, sediment and marine fish [8,9]. The first outbreak of disease caused by S. putrefaciens was described by Saeed et al. [10]. Kozinska & Pekala [8] and Pekala et al.[11] also reported S. putrefaciens infection in fish.The present study describes the first case of S. warneri and S. putrefaciens co-infection in Siberian sturgeons (Acipenser baerii) and hybrid sturgeons (Huso huso x Acipenser baerii). Case PresentationOn a sturgeon farm with recirculation aquaculture systems in North Bulgaria, an average daily mortality of 30 fish has occurred in September 2015 among fish weighing 200-800 g. In this study, a total of 10 fish were used (5 Siberian and 5 hybrid sturgeons).Gross anatomy findings consisted in ulcerations, 1 to 1.5cm in diameter (Figure 1) on the skin and multiple haemorrhages on the ventral part of the body. After dissection of the abdominal cavity, yellow-tinted muscles with multiple haemorrhages were observed (Figure 2). The spleen was hyperemic. The liver was of yellow ochre colour, frail consistency and surface petechial haemorrhages. Small gray-yellowish nodules were detected in some areas. Mesenteric blood vessels were hyperemic, and intestines were filled with bloody liquid content.The specimens for histopathological examination were fixed in 10% neutral formalin and processed by routine histology techniques [12,13]. Cross sections (4 μm) were stained with haematoxylin-eosin (H/E).For microbiology examination, samples from skin lesions, liver, spleen and intestines were collected and cultured on tryptic soy agar (Fluca, India) supplemented with 5% defibrinated ovine blood (TSBA), MacConkey agar (NCIPD, Bulgaria) and GSP agar (Merck, Germany). Plates were incubated aerobically at 37 °C for 24-48 h. In addition, the samples were cul...