Objective—To determine the effects of enteral administration of doxycycline, amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical duration on hemostatic variables in healthy dogs.
Procedure—Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h), cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were administered in random order to 10 healthy dogs at standard therapeutic dosages for 7 days, with a 7-day washout period between subsequent antimicrobials. In addition, 4 Beagles served as control dogs. Variables were evaluated before and after antimicrobial administration; they included platelet count, Hct, 1-stage prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen concentration, and platelet function. Platelet function was assessed via buccal mucosal bleeding time, aggregation, and a platelet-function analyzer.
Results—Administration of all antimicrobials caused a slight prolongation of 1-stage PT and activated PTT and slight decrease in fibrinogen concentration. Cephalexin caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused a significant increase in activated PTT, and enrofloxacin caused a significant decrease in fibrinogen concentration. Platelet count or function did not differ significantly after administration of any antimicrobial.
Conclusions and Clinical Relevance—Oral administration of commonly used antimicrobials in healthy dogs resulted in minor secondary hemostatic abnormalities, with no change in platelet count or function. Although these changes were clinically irrelevant in healthy dogs, additional studies of the effects of antimicrobial administration on hemostasis in animals with underlying disease processes are warranted.
Objective—To determine whether a novel third-generation chelating agent (8mM disodium EDTA dehydrate and 20mM 2-amino-2-hydroxymethyl-1, 3-propanediol) would act as an antimicrobial potentiator to enhance in vitro activity of antifungal medications against fungal isolates obtained from horses with mycotic keratitis.
Sample Population—Fungal isolates (3 Aspergillus isolates, 5 Fusarium isolates, 1 Penicillium isolate, 1 Cladosporium isolate, and 1 Curvularia isolate) obtained from horses with mycotic keratitis and 2 quality-control strains obtained from the American Type Culture Collection (ATCC; Candida albicans ATCC 90028 and Paecilomyces variotii ATCC 36257).
Procedure—Minimum inhibitory concentrations (MICs) against fungal isolates for 4 antifungal drugs (miconazole, ketoconazole, itraconazole, and natamycin) were compared with MICs against fungal isolates for the combinations of each of the 4 antifungal drugs and the chelating agent. The Clinical and Laboratory Standards Institute microdilution assay method was performed by use of reference-grade antifungal powders against the fungal isolates and quality-control strains of fungi.
Results—Values for the MIC at which the antifungal drugs decreased the growth of an organism by 50% (MIC50) and 90% (MIC90) were decreased for the control strains and ophthalmic fungal isolates by 50% to 100% when the drugs were used in combination with the chelating agent at a concentration of up to 540 μg/mL.
Conclusions and Clinical Relevance—The chelating agent increased in vitro activity of antifungal drugs against common fungal pathogens isolated from eyes of horses with mycotic keratitis.
Objective—To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses.
Animals—18 horses with clinically normal tarsocrural joints.
Procedure—Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentamicin at various time points during and 73 hours after initiation of treatment. Gentamicin concentrations were compared by use of a Kruskal-Wallis ANOVA.
Results—At 73 hours, mean ± SE gentamicin concentrations in synovial fluid, synovial membrane, joint capsule, subchondral bone, and collateral ligament of group 1 horses were 11.5 ± 1.5 μg/mL, 21.1 ± 3.0 μg/g, 17.1 ± 1.4 μg/g, 9.8 ± 2.0 μg/g, and 5.9 ± 0.7 μg/g, respectively. Corresponding concentrations in group 2 horses were 458.7 ± 130.3 μg/mL, 496.8 ± 126.5 μg/g, 128.5 ± 74.2 μg/g, 99.4 ± 47.3 μg/g, and 13.5 ± 7.6 μg/g, respectively. Gentamicin concentrations in synovial fluid, synovial membrane, and joint capsule of group 1 horses were significantly lower than concentrations in those samples for horses in groups 2 and 3.
Conclusions and Clinical Relevance—Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.
Objective—To determine the pharmacokinetics and effects of orally administered fluconazole in African grey parrots.
Animals—40 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).
Procedure—In single-dose trials, parrots were placed into groups of 4 to 5 birds each and fluconazole was administered orally at 10 and 20 mg/kg. Blood samples for determination of plasma fluconazole concentrations were collected from each group at 2 or 3 of the following time points: 1, 3, 6, 9, 12, 24, 31, 48, and 72 hours. In multiple-dose trials, fluconazole was administered orally to groups of 5 birds each at doses of 10 and 20 mg/kg every 48 hours for 12 days. Trough plasma concentrations were measured 3 times during treatment. Groups receiving 20 mg/kg were monitored for changes in plasma biochemical analytes, and blood samples were collected on days 1 and 13 of treatment to allow comparison of terminal half-life.
Results—Peak plasma concentrations of fluconazole were 7.45 and 18.59 μg/mL, and elimination half-lives were 9.22 and 10.19 hours for oral administration of 10 and 20 mg/kg, respectively. Oral administration of fluconazole for 12 days at 10 or 20 mg/kg every 48 hours did not cause identifiable adverse effects or change the disposition of fluconazole.
Conclusions and Clinical Relevance—Oral administration of fluconazole to parrots at 10 to 20 mg/kg every 24 to 48 hours maintains plasma concentrations above the minimum inhibitory concentration for several common yeast species. The prolonged dosing interval is an advantage of this treatment regimen.
Objective—To determine the cause of persistent resistance to chloramphenicol (CP) after the ban on its use in food-producing animals in several countries.
Sample Population—71 CP-resistant and 104 CP-susceptible Escherichia coli strains isolated from sick cattle and pigs in Japan.
Procedure—Susceptibility of all bacterial strains to thiamphenicol (TP) and florfenicol (FFC) was tested by use of an agar dilution method. The CP-resistance genes and variable region within class 1 integrons in CP-resistant strains were identified by use of a PCR assay.
Results—The CP acetyltransferase gene (ie, cat1) was identified as the predominant CP-resistance gene in strains isolated from cattle, and the cat1and nonenzymatic CP-resistance gene (ie, cmlA) were the predominant CP-resistance genes in strains isolated from pigs. Additionally, strains with cat1 isolated from cattle often were resistant to ampicillin, dihydrostreptomycin (DSM), oxytetracycline, and trimethoprim (TMP), whereas strains with cat1 or cmlA isolated from pigs often were resistant to DSM and TMP. Class 1 integrons were significantly more prevalent in strains with CP-resistance genes, compared with prevalence in strains without CP-resistance genes. All gene cassettes within the integrons were involved in resistance to DSM, TMP, or both.
Conclusions and Clinical Relevance—Coresistance that develops because of the use of DSM and TMP in cattle and pigs apparently contributes to the selection of CP-resistant strains of E coli. Thus, it is possible that bacterial resistance to CP in animals would persist despite a ban on the use of CP in cattle and pigs.