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Pradofloxacin is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria. The minimal bactericidal concentrations have been determined against clinical isolates of Staphylococcus pseudintermedius, Staphylococcus aureus, Escherichia coli, Pasteurella multocida, Streptococcus canis, Proteus spp., Fusobacterium spp., Porphyromonas gingivalis and Prevotella species. A subset of these species was selected, and the in vitro rate of kill by pradofloxacin was determined. For 27 of the 30 tested aerobic strains the pradofloxacin MBC was within two doubling dilutions of the MIC. For the remaining strains, the MIC and MBC were within three to four doubling dilutions. Pradofloxacin also demonstrated bactericidal activity against all anaerobic strains, and the MBC was equal to the MIC for four of the strains, within 1 doubling dilution for three strains, within 2 dilutions for a further 3 strains and within 3 dilutions for the remaining five strains. As pradofloxacin concentration was increased, a faster rate of killing was observed; bactericidal effects were seen in all cases at concentrations ≤ 0.25 μg/mL. The bactericidal activity against the anaerobic strains was marked, of particular relevance was the complete absence of regrowth even at 48 h at concentrations as low as 0.125 μg/mL. In conclusion, pradofloxacin exhibits clear bactericidal activity in terms of MBC and kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats at concentrations that are greatly exceeded within the systemic circulation after administration of the recommended therapeutic doses to the target animals. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy. These data demonstrate the complete and rapid killing of anaerobic bacteria by a veterinary 8-cyano-fluoroquinolone., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of < or =0.016 to 1 microg/ml, the overall MIC(50) was 0.062, and the overall MIC(90) was 0.25 microg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of < or =8 microg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 microg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 microg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.

Objectives: To compare the intrinsic activity of pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats., Methods: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology., Results: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC(50), MIC(90) and mode MIC values, pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones., Conclusions: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.

In a balance trial with 10 pigs (mean body mass 50 kg) the influence of a bacterial protein supplement (Alcaligenes eutrophus) on N-metabolism was investigated. The bacteria were included into the diet at levels of 7 and 14% at the expense of extracted soyabean meal. Thus bacterial "pure protein" (bacterial non-nucleic acid N X X 6.25) amounted to 30 and 60% of the protein of the ration. Consuming 2 kg of feed dry matter per day the animals of the control group (I) and the experimental groups (II and III) ingested 48 g, 52 g and 55 g of total N respectively. The difference in N-intake is explained by the additional nucleic acid-N, amounting to 19,8% of total bacterial N. Daily weight gain (on average 1054 g) and feed conversion efficiency (feed ingested/weight gain; on average 1,9) were relatively improved at the highest dietary level of bacterial cell mass. Faecal N-excretion was increased significantly, whereas renal N-excretion remained unchanged. Mean apparent N-digestibility was 87,4% showing no significant difference between the experimental groups. N-balance values were noticibly increased following the intake of the bacterial protein supplement. The excretion of urinary urea-N was slightly reduced whereas 4-6 times as much allantoin-N was excreted when bacteria were fed. It is calculated that about 80% of the bacterial purines are renally excreted as allantoin and uric acid.

In a 4 X 4 Latin square experiment four cows were given, twice daily, diets consisting of (g/kg dry matter (DM)) 500 barley, 400 grass silage and 100 soya-bean meal. The diets were given at either 1.15 (L) or 2.3 (H) times maintenance energy requirements and the soya-bean meal was either untreated (U) or formaldehyde (HCHO)-treated (T). The passage of digesta to the duodenum was estimated using chromic oxide as a flow marker; 35S was used to estimate the amount of microbial protein entering the small intestine. A microbial fraction was prepared by differential centrifugation from duodenal digesta. Samples of bacteria and of protozoa from rumen digesta were also prepared. The total amino acid contents of feedingstuffs, duodenal digesta, duodenal microbial material, rumen bacteria and rumen protozoa were determined by ion-exchange chromatography. The D-alanine and D-glutamic acid contents of the samples were determined by gas-liquid chromatography. The quantity of each amino acid entering the small intestine was significantly (P less than 0.001) increased by increasing DM intake and tended to be increased by formaldehyde-treatment of the soya-bean meal. There were net losses of all amino acids across the forestomachs except for lysine, methione, D-alanine and D-glutamic acid for which there were net gains. There were significant (P less than 0.05) differences in amino acid composition between rumen bacteria and duodenal microbial material; differences in amino acid composition between rumen bacteria and rumen protozoa were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

In a 4 X 4 Latin square experiment four cattle were given in two meals per d diets consisting of (g/kg dry matter (DM)) 500 barley, 400 grass silage and 100 soya-bean meal. The diets were given at either 1.15 (L) or 2.3 times (H) maintenance energy requirements and the soya-bean meal was either untreated (U) or formaldehyde-treated (T). A 24 h collection of duodenal digesta and a 7 d collection of faeces were made using chromium sesquioxide for flow estimation and 35S as a marker of microbial nitrogen entering the small intestine. Samples of rumen fluid were also taken for estimation of rumen pH, ammonia and volatile fatty acid concentrations. Spot samples of duodenal digesta were obtained after administration of Cr2O3-mordanted silage-fibre and soya-bean meal, to determine the rates of outflow of these markers from the rumen. Similar samples were also obtained after cessation of a continuous intraruminal infusion of ruthenium phenanthroline, 35S and CoEDTA. Incubations of each feedingstuff in porous synthetic fibre (psf) bags were carried out in the rumen and the rates of N disappearance from the bags determined. Increasing DM intake significantly (P less than 0.001) increased the quantities of organic matter (OM), total N and amino acid-N entering the small intestine and amounts subsequently voided in the faeces. Apparent digestibilities of OM and N were unaffected by DM intake; the proportions of total digestible OM digested in the rumen were significantly lower (P less than 0.01) at the higher level of DM intake. Formaldehyde treatment of the soya-bean meal increased the quantities of N entering the small intestine; these increases were not significant. Increased DM intake increased the quantities of both microbial N (P less than 0.001) and undegraded feed N (P less than 0.01) entering the small intestine; HCHO-treatment also significantly (P less than 0.05) increased the quantities of undegraded feed N entering the small intestine. The efficiency of microbial N synthesis within the rumen was not significantly affected by dietary treatments whereas apparent feed N degradability was reduced significantly (P less than 0.05) both by increasing DM intake and by HCHO-treatment of the soya-bean meal. Rates of disappearance of N from psf bags in the rumen were different for different feedingstuffs. However, for a given feedingstuff, the rate of N disappearance was not affected by the diets fed.(ABSTRACT TRUNCATED AT 400 WORDS)

In a balance trial with growing rats the influence of dietary ribonucleic acid (RNA) on N-metabolism was tested. Yeast-RNA was supplied at four levels ranging from 7.8% to 31.2% of diets nitrogen (1.64% in DM from casein + DL-methionine). The mean apparent digestibility of the RNA-N ingested was determined as 95%. Of the RNA-N consumed 16.6% were retained as measured by N-balance technique, whereas no retention of the RNA-N was observed by body-N analysis. This discrepancy in RNA-N retention was attributed to the relatively increased N-losses with higher N-intake when using the N-balance method. By regression analysis it was found that 80.2% of the RNA-N consumed were excreted via kidneys. Of the RNA-N intake 45.5% appeared in urea, 30.9% in allantion, only 1.1% and 0.3% in uric acid and creatinine respectively.

In a feeding trial with growing rats the influence of dietary ribonucleic acid on the composition of body gain was investigated. To a control ration with casein + 50% DL-methionine as the sole protein source (1,64 N% in DM) ribonucleic acid (RNA) from yeast was supplemented at four levels ranging from 7,8% to 31,2% of diets nitrogen. The portion of daily feed and nitrogen intake derived from the basal diet was designed to be equal for all the animals. RNA was ingested in addition. Gain of body fresh and dry matter slightly increased with the dietary RNA-level, due to an increased deposition of body fat. Protein efficiency ratio as well as productive protein value decreased linearly with increasing N-intake. It may be concluded that RNA-N has slightly contributed to body mass gain but was not utilised for protein deposition.