Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs

Kumar, V., Madabushi, R., Lucchesi, M. B. B., Derendorf, H. Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs. J. vet. Pharmacol. Therap. 34 , 130–135. Pharmacokinetics of cefpodoxime in plasma (total concentration) and subcutaneous fluid (free concentration using microdialysis) was investigated in dogs following single oral administration of prodrug cefpodoxime proxetil (equivalent to 5 and 10 mg/kg of cefpodoxime). In a cross over study design, six dogs per dose were utilized after a 1 week washout period. Plasma, microdialysate, and urine samples were collected upto 24 h and analyzed using high performance liquid chromatography. The average maximum concentration (C_max) of cefpodoxime in plasma was 13.66 (±6.30) and 27.14 (±4.56) μg/mL with elimination half‐life (t_1/2) of 3.01 (±0.49) and 4.72 (±1.46) h following 5 and 10 mg/kg dose, respectively. The respective average area under the curve (AUC_0–∞) was 82.94 (±30.17) and 107.71 (±30.79) μg·h/mL. Cefpodoxime was readily distributed to skin and average free C_max in subcutaneous fluid was 1.70 (±0.55) and 3.06 (±0.93) μg/mL at the two doses. Urinary excretion (unchanged cefpodoxime) was the major elimination route. Comparison of subcutaneous fluid concentrations using pharmacokinetic/pharmacodynamic indices of fT_>MIC indicated that at 10 mg/kg dose; cefpodoxime would yield good therapeutic outcome in skin infections for bacteria with MIC₅₀ upto 0.5 μg/mL while higher doses (or more frequent dosing) may be needed for bacteria with higher MICs. High urine concentrations suggested cefpodoxime use for urinary infections in dogs.     

Synergistic effects of Miconazole and Polymyxin B on microbial pathogens

The therapeutic value of antibiotics depends on the susceptibility of the infecting microorganism and the pharmacological profile of the drugs. To assess the value of an antibiotic combination of polymyxin B and miconazole this study examined the in vitro synergistic potential of the two drugs on Gram-negative and Gram-positive bacteria and yeast. Antifungal and antibacterial activity was tested by minimum inhibitory concentration (MIC) of broth macrodilution and urea broth microdilution, by fluorescence microscopy and flow cytometry. Synergism was calculated using the fractional inhibitory concentration index (FICi). With Staphylococcus intermedius as target we found up to an eightfold reduction of the individual MICs when both drugs were combined. However, the FICi was 0.63 suggesting no real interaction between the two drugs. With Escherichia coli, Pseudomonas aeruginosa, and Malassezia pachydermatis as targets the antimicrobial drug combination reduced the MICs of polymyxin B and miconazole from fourfold to hundredfold resulting in FICi between 0.06 and 0.5 which defines a synergistic action. Thus, if polymyxin B and miconazole are combined their effect is greater than the sum of the effects observed with polymyxin B and miconazole independently, revealing bactericidal and fungicidal synergism. Our results indicate a strong therapeutic value for the combination of these antimicrobial agents against Gram-negative bacteria and yeast and a weaker value against Gram positive bacteria for clinical situations where these pathogens are involved.     

Cerebral phaeohyphomycosis in a dog

Cerebral phaeohyphomycosis was diagnosed in a 9-year-old spayed dog that had a series of epileptic convulsions a day before death. About 6 weeks before her death, she had been treated for severe demodectic mange. During this period, persistent leukopenia, lymphocytopenia, and thrombocytopenia were found by blood analyses. At necropsy, multiple large pyogranulomatous lesions were found in the cerebrum and meninges. Dematiaceous fungi with brown, branching, septate hyphae and budding yeasts were found within tissue cells and in the necrotic areas.     

Limiting amino acids in an 11% crude protein corn-soybean meal diet for growing pigs

Three experiments were conducted to test the hypothesis that methionine, isoleucine, valine or nitrogen either singly or in combination are limiting in an 11% crude protein, lysine-tryptophan-threonine-supplemented, corn-soybean meal diet for growing pigs. A 16% crude protein diet was used as a positive control in each experiment and all amino acid additions were made, at a minimum, to equal requirements. Average initial weights were 21.3 kg, 23.0 kg and 19.1 kg in Exp. 1, 2 and 3, respectively. The experiments averaged 4 wk in duration. In Exp. 1 and 2, neither the addition of glutamic acid as a source of nitrogen, nor methionine to the 11% diet resulted in any improvement (P greater than .20) in rate or efficiency of growth. Addition of the combination of isoleucine and valine to the 11% diet resulted in an increase (P less than .05) in both growth rate and feed efficiency to a level not different (P greater than .20) from that of the pigs consuming the positive control diet. The addition of valine to the 11% crude protein diet with supplemental lysine, tryptophan and threonine (Exp. 3) caused an improvement in daily gain (P less than .05) but not feed efficiency (P greater than .10). Isoleucine addition tended to reduce pig performance. The results of these experiments suggest that an 11% crude protein, corn-soybean meal diet fortified with lysine, tryptophan and threonine is not limiting in sulfur amino acids or nitrogen. Valine may be the only limiting amino acid.     

Antigenic relatedness and partial amino acid sequences of pili of Escherichia coli serotypes O1, O2, and O78 pathogenic to poultry

Pilus proteins from Escherichia coli serotypes O1, O2, and O78 pathogenic to poultry were compared with regard to their antigenic relatedness and partial amino acid sequences. Agglutination, immunodiffusion, and immunoblot assays with polyclonal antibodies to these pili showed that these pili not only share some common antigens but also contain antigens unique to each pilus. The partial amino-terminal amino acid sequences support our earlier findings that the pili are different but contain some structural homologies.