Disposition of norfloxacin in broiler chickens and turkeys after different methods of oral administration.

Norfloxacin was administered orally to chickens and turkeys at 15 mg/kg body weight by pulse dosing at 24 h intervals and by continuous dosing at 100 mg/L in drinking water for five days. Blood samples were taken serially. Plasma norfloxacin concentrations were determined by high-performance liquid chromatography. The plasma norfloxacin concentrations increased slowly during continuous dosing and reached the MIC(90) (250 ng/mL) for Gram-negative pathogens by 12 h in chickens and 18 h in turkeys. The steady-state plasma concentration was attained in 36 h and remained at approximately 776.67+/-33.23 ng/mL in chickens and 682.50+/-28.55 ng/mL in turkeys. After pulse dosing, the plasma norfloxacin concentrations increased rapidly and exceeded the MIC(90) at 2 h in both species and remained above MIC(90) for 8 h in chickens and 6 h in turkeys. Pulse dosing provided half the steady-state concentration that was achieved by continuous dosing, 365.32+/-39.31 ng/mL in chickens and 306.03+/-32.26 ng/mL in turkeys, during the dosing interval of 24 h. Data for daily pulse dosing suggested that every administration corresponded to a single, daily repeated bolus administration although pulse dosing produced higher plasma concentrations more readily. Continuous and pulse dosing are both rational for the administration of norfloxacin to flocks of chickens and turkeys. We recommend that treatment be commenced with a pulse oral dose administered over a 4 h period and maintained by continuous oral medication for three to five consecutive days.

Antibiotic resistance of staphylococci from humans, food and different animal species according to data of the Hungarian resistance monitoring system in 2001.

Based on data of the Hungarian resistance monitoring system the antibiotic resistance of Staphylococcus strains of human and animal origin was studied. No methicillin-resistant staphylococci harbouring mecA gene were isolated from animals in 2001. Penicillin resistance, mediated by penicillinase production, was the most frequent among Staphylococcus aureus strains isolated from humans (96%), from bovine mastitis (55%), from foods (45%) and from dogs. In staphylococci isolated from animals low resistance percentages to aminoglycosides (0-2%), fluoroquinolones (0.5-3%) and sulphonamides (0.5-4%) were found but in strains isolated humans these figures were higher (1-14%, 5-18% and 3-31%, respectively). The most frequent antibiotic resistance profiles of strains isolated from animals and food were penicillin/tetracycline, penicillin/lincomycin and penicillin/lincomycin/tetracycline. Penicillin/tetracycline resistance was exhibited by strains from mastitis (3), samples from the meat industry (31), poultry flocks (1), poultry industry (1), noodle (1) and horses (2). Penicillin/lincomycin resistance was found in 10 Staphylococcus strains from mastitis, 1 from the dairy industry, 1 from the meat industry and 6 from dogs. Isolates from mastitis (2), from the dairy industry (2), from pigs (1), from the meat industry (1) and from poultry (1) harboured penicillin/lincomycin/tetracycline resistance pattern. Multiresistant strains were usually isolated only from one and sometimes from two animal species; therefore, the spread of defined resistant strains (clones) among different animal species could not be demonstrated. These results also suggest that the transfer of antibiotic resistance of S. aureus from animals to humans probably occurs less frequently than is generally assumed.

Comparative study of beta-tricalcium phosphate mixed with platelet-rich plasma versus beta-tricalcium phosphate, a bone substitute material in dentistry.

Animal experiments were carried out with osteoconductive bone substitute beta-tricalcium phosphate (beta-TCP), with the aim of assessing the effects of the growth factors synthesised by thrombocytes on the speed of beta-TCP incorporation and on the quality of newly formed bone. The question to be answered was the extent to which platelet-rich plasma (PRP) accelerated the resorption of beta-TCP and the formation of new bone. Two teeth were removed symmetrically from each side of the mandible of 12 Beagle dogs; the resulting cavities were filled on one side with beta-TCP alone, and on the other side with a mixture of beta-TCP + PRP (obtained from autologous blood). The quality of the newly formed bone and the effects of this PRP were studied by histological and histomorphometric methods. In week 6, bone formation was already more effective when PRP was applied in comparison with beta-TCP alone, and in week 12 the growth was significantly greater. The results demonstrate that the use of PRP accelerates the remodelling of new bone created by beta-TCP.

Development of an antibiotic resistance monitoring system in Hungary.

Because of the rapid development and spread of antimicrobial resistance it is important that a system be established to monitor antimicrobial resistance in pathogenic zoonotic and commensal bacteria of animal origin. Susceptibility testing of bacteria from carcasses and different samples of animal origin has been carried out in veterinary institutes for a long time but by an inconsistent methodology. The disc diffusion method proposed by the National Committee for Clinical Laboratory Standards (NCCLS) was introduced in all institutes in 1997. In order to obtain a coherent view of the antimicrobial resistance of bacteria a computer system was consulted, consisting of a central computer to store all data and some local computers attached to it through the network. At these local measuring stations computers are connected to a video camera, which displays the picture of Petri dishes on the monitor, and inhibition zone diameters of bacteria can be drawn with the mouse by the inspector. The software measures the diameters, evaluates whether or not the bacteria are sensitive, and stores the data. The evaluation is based upon the data of the NCCLS. The central computer can be connected to as many local computers with measuring stations as we wish, so it is suitable for an integrated system for monitoring trends in antimicrobial resistance of bacteria from animals, food and humans, facilitating comparison of the occurrence of resistance for each circumstance in the chain. It depends on the examiners which antibiotics they want to examine. Thirty-two different antibiotic panels were compiled, taking into consideration the active ingredients of medicinal products permitted for veterinary use in Hungary, natural resistance and cross-resistance, the mechanism of resistance and the animal species, i.e. which drugs were recommended for treatment in the given animal species, and the recommendations of the OIE Expert Group on Antimicrobial Resistance. The members of the panels can be changed any time, even during the measuring process. In addition to the inhibition zone diameters of bacteria the database also includes information about bacterial and animal species, the age of animals and the sample or organ where the bacteria are from. Since January 2001 the antibiotic susceptibility of E. coli, Salmonella, Campylobacter and Enterococcus strains isolated from the colons of slaughter cows, pigs and broiler chickens has also been examined. Each of the 19 counties of Hungary submits to the laboratory three tied colon samples from a herd of the above-mentioned animals every month.

Pulse and continuous oral norfloxacin treatment of experimentally induced Escherichia coli infection in broiler chicks and turkey poults.

Experimental colibacillosis was produced in 40 healthy, 7-day-old broiler chickens and turkeys by intratracheal injection of 1 x 10(8) CFU/chick and 1.23 x 10(9) CFU/poult bacteria of an O1:F11 strain of Escherichia coli, respectively. Two days before E. coli challenge all chicks were vaccinated with a live attenuated strain of infectious bronchitis virus (H-52). This model of infection--at least in chicken--proved to be useful for evaluating the efficacy of antimicrobial medication, by recording mortality, body weight gain, pathological alterations and frequency of reisolation of E. coli. Using this model, the efficacy of two different dosing methods of norfloxacin (continuous and pulse dosing) was evaluated. The once-per-day pulse dosing of norfloxacin administered via the drinking water at 15 mg/kg body weight proved to be more efficacious than the continuous dosing method of 100 mg/L for 5 days in chickens, while there were no convincing differences between the two treatment regimens in turkeys. The results confirmed earlier observations on the pharmacokinetic properties of norfloxacin in chicks and turkeys (Laczay et al., 1998).

Treatment of experimentally induced Pasteurella multocida infections in broilers and turkeys: comparative studies of different oral treatment regimens.

Experimental fowl cholera was induced in 60 healthy 10-week-old broiler chickens and 8-week-old turkeys by intramuscular inoculation with approximately 80 colony-forming units (cfu) of Pasteurella multocida X-73 strain and with approximately 70 cfu of P. multocida P-1059 strain, respectively. This method of infection proved to be useful for evaluating the efficacy of anti-microbial medication, by measuring mortality, weight gain, pathological responses and frequency of re-isolation of P. multocida. The efficacies of two different dosing methods, continuous and pulse dosing, were compared. Using the continuous-dosing method, norfloxacin was administered to drinking water at 100 mg/l for 5 days in chickens. Efficacies were slightly improved compared with pulse dosing at 15 mg/kg bodyweight for the same length of time. The opposite was observed in turkeys, to the degree of control of mortality and maintenance of weight gain.

Pharmacokinetics and bioavailability of doxycycline in fasted and nonfasted broiler chickens.

The pharmacokinetics and the influence of food on the kinetic profile and bioavailability of doxycycline was studied after a single intravenous (i.v.) and oral dose of 10.0 mg/kg body weight in 7-week-old broiler chickens. Following i.v. administration the drug was rapidly distributed in the body with a distribution half-life of 0.21 +/- 0.01 h. The elimination half-life of 6.78 +/- 0.06 h was relatively long and resulted from both a low total body clearance of 0.139 +/- 0.007 L/h.kg and a large volume of distribution of 1.36 +/- 0.06 L/kg. After oral administration to fasted chickens, the absorption of doxycycline was quite fast and substantial as shown by the absorption half-life of 0.39 +/- 0.03 h, the maximal plasma concentration of 4.47 +/- 0.16 micrograms/mL and the time to reach the Cmax of 1.73 +/- 0.06 h. The distribution and the final elimination of the drug were slower than after i.v. administration. The absolute bioavailability was 73.4 +/- 2.5%. The presence of food in the intestinal tract reduced and extended the absorption (t1/2a = 1.23 +/- 0.21 h; Cmax = 3.07 +/- 0.23 micrograms/mL; tmax = 3.34 +/- 0.21 h). The absolute bioavailability was reduced to 61.1% +/- 4.4%.

Therapeutic efficacy of doxycycline against experimental Pasteurella multocida infection in broiler chickens.

The efficacy of doxycycline was investigated in two sets of experiments. In the first experiment 40, in the second experiment 60, hence altogether 100 five-week-old Ross broilers of both sexes were used. The birds were randomly allocated into groups (A and B in experiment 1; A, B and C in experiment 2) of 20 birds in each. All birds were infected intramuscularly with approx. 2 x 10(3) colony forming units of Pasteurella multocida strain X-73 (serotype A:1). Birds in groups A were non-medicated controls. Chickens in groups B were given doxycycline via the drinking water at a dose of 10 mg/kg body weight for 5 days, while group C was treated with chlortetracycline at a dose of 20 mg/kg body weight for 5 days. The trial lasted for 9 days, then the surviving chickens were sacrificed. Clinical symptoms, number of deaths, post mortem lesions and bacteriological findings were recorded using a special score system. Acute fowl cholera developed in broilers within a few hours after infection, as evidenced by the clinical symptoms, the high mortality rate (90% of the birds died within 4 days after infection), the pathological lesions and the recovery of P. multocida from the challenged birds. Doxycycline reduced the number of deaths (30% and 5% of birds died in experiments 1 and 2, respectively) and the severity of the clinical symptoms, and P. multocida could be re-isolated only from one of the survivors. In contrast, chlortetracycline slightly influenced the mortality; however, it delayed death and reduced the severity of clinical symptoms. These data indicate that doxycycline is highly effective for the treatment of experimental pasteurellosis in chickens.

Attachment of different Escherichia coli strains to cultured rumen epithelial cells.

The attachment to fully characterized primary rumen epithelial cell cultures of Escherichia coli strains isolated from different animal species and expressing F1-F4 or F17 fimbriae was examined. As the cell cultures contained stratified (keratinized) and non-stratified (non-keratinized) cells which grew either confluently or non-confluently, the strength of attachment of the different bacterial strains was assessed in relation to the differentiation state of the cells. Thus, strains having F1 fimbriae attached to all types of cultured cells, while strains with F2 and F3 fimbriae did not bind at all. E. coli strains having F4 or F17 fimbriae attached only to non-keratinized cells, particularly to confluent areas. As membrane glycosylation is known to change with differentiation (keratinization), our results suggest that the attachment of fimbriated E. coli strains which were capable of binding to rumen cells was more likely to be dependent on differentiation than the host specificity of the bacteria.

Oral bioavailability of sulphonamides in ruminants: a comparison between sulphamethoxazole, sulphatroxazole, and sulphamerazine, using the dwarf goat as animal model.

The various sulphonamides show marked differences in disposition characteristics after administration to ruminants. For use in combination with a diaminopyrimidine derivative such as trimethoprim or baquiloprim, it is essential that a sulphonamide has similar pharmacokinetic properties in order to obtain optimal synergy. In the present study the pharmacokinetics of sulphamethoxazole, sulphatroxazole, and sulphamerazine were investigated in dwarf goats (n = 6) after IV and intraruminal administration at a dose of 30 mg/kg bodyweight. In addition, the in vitro binding of sulphamerazine to ruminal contents was studied as a possible explanation for a reduced absorption rate. Sulphamethoxazole showed the most rapid absorption after intraruminal administration (mean tmax +/- SD : 0.8 +/- 0.2h). However, the drug was rapidly eliminated from the plasma (t1/2 beta : 2.4 +/- 1.5 h) and the bioavailability was only 12.4 +/- 4.7%, most likely due to an extensive 'first-pass' effect. The bioavailability of orally administered sulphamerazine and sulphatroxazole was much higher (67.6 +/- 13.5% and 70.2 +/- 32.3%, respectively). After intraruminal administration, sulphatroxazole showed the highest plasma peak concentration (26.1 +/- 6.3 mg/l) and the longest plasma half-life (4.7 +/- 1.8h) and mean residence time (13.9 +/- 4.5 h). Sulphamerazine showed considerable binding to rumen contents in vitro. Based on its pharmacokinetic properties sulphatroxazole appears to be a suitable candidate to be used in combination with the more recently developed diaminopyrimidines such as baquiloprim.

Comparative studies on the efficacy of sulphachlorpyrazine and toltrazuril for the treatment of caecal coccidiosis in chickens.

The therapeutic efficacy of sulphachlorpyrazine and toltrazuril against experimentally induced Eimeria tenella infection was compared in battery and floor pen raised broiler chickens. In the battery studies, both drugs prevented coccidiosis-related mortality and decrease of weight gain to a similar degree, but toltrazuril was more effective in reducing intestinal lesions and faecal scores, when treatments were initiated 24 h postinfection. When medication was delayed until 72 h after inoculation, the sulphonamide proved to be more effective in preventing reduction of weight gain and intestinal lesions caused by the parasites. Under simulated use conditions both drugs showed an appropriate anticoccidial efficacy without major differences between them.

Toxicological studies on potentiated ionophores in chickens. I. Tolerance study.

The tolerance of chickens to monensin (12.5 mg/kg of feed) and maduramicin (3.0 mg/kg of feed) fed at a reduced dose in the presence of the antioxidant duokvin was studied in two experiments including 2 x 200 Tetra-82 broiler chickens. Tolerance was assessed by the appearance of clinical signs indicative of a toxic effect, the number of deaths, the groups' body weight gain, feed and drinking water intake, the aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities, calcium ion, inorganic phosphate and total protein content of the blood plasma, the haematocrit value, and haemoglobin concentration. When applied at a dose that had proved to be optimum in the efficacy studies, neither the monensin-duokvin combination (12.5 mg monensin per kg of feed + 120 mg duokvin per kg of feed) nor the maduramicin-duokvin combination (3.0 mg maduramicin per kg of feed + 120 mg duokvin per kg of feed) exerted a statistically significant influence on the parameters tested.

Toxicological studies on potentiated ionophores in chickens. II. Compatibility study.

Two trials were carried out on a total of 2 x 360 Tetra-82 broiler chickens to study how the presence of the antioxidant duokvin as potentiating agent influenced the compatibility of reduced doses of monensin (12.5 mg/kg of feed) or maduramicin (3.0 mg/kg of feed) with other chemotherapeutic agents (tiamulin, erythromycin, sulfaquinoxaline, sulfachlorpyrazine, flumequine, tylosin, kitasamycin) widely used in broiler rearing. Compatibility was assessed on the basis of the appearance of clinical signs suggestive of toxic interaction, the mortality rate, body mass gain, feed consumption and drinking water intake, and changes in AST and LDH activities of the blood plasma. The monensin-duokvin combination (12.5 mg monensin/kg of feed + 120 mg duokvin/kg of feed) was found to be compatible with erythromycin, sulfaquinoxaline, sulfachlorpyrazine, flumequine, tylosin and kitasamycin. For tiamulin, a slight incompatibility was observed; however, this was much less severe than that found for monensin administered at a dose of 100 mg/kg of feed. The maduramicin-duokvin combination (3.0 mg maduramicin/kg of feed + 120 mg duokvin/kg of feed) was compatible with all the compounds tested; thus, it can be safely applied also in combination with tiamulin.

Potentiation of ionophorous anticoccidials with dihydroquinolines: reduction of adverse interactions with antimicrobials.

In two experiments, the compatibility of the anticoccidial combinations of monensin and duokvin, as well as that of maduramicin and duokvin, with some antimicrobials widely used in the broiler production was studied in cockerels. The monensin-duokvin combination was found to be fully compatible with erythromycin, sulphachlorpyrazine, and sulphaquinoxaline. With tiamulin, a slight interaction was observed, but it was far less severe than the toxic interaction between monensin and the diterpene antibiotic. The maduramicin-duokvin combination proved to be compatible with all of the chemotherapeutics tested, including tiamulin. The results of the studies indicate that the adverse interactions of monensin and maduramicin with certain antimicrobials can be considerably diminished or even abolished by using them in reduced doses in combination with the dihydroquinoline compound duokvin.