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Objective

To evaluate pharmacokinetics of once daily IV administration of gentamicin sulfate to adult horses that had abdominal surgery.

Design

Prospective study.

Animals

28 adult horses that underwent abdominal surgery for colic.

Procedure

14 horses were treated with each dosage of gentamicin (ie, 6.6 or 4 mg/kg, IV, q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemic clearance. Treatment outcome, CBC, and serum creatinine concentrations were recorded.

Results

1 horse in the high-dosage group died. All other horses successfully recovered, and did not develop bacterial infection or have evidence of drug toxicosis resulting in renal injury. Mean pharmacokinetic variables for gentamicin administration at a high or low dosage (ie, 6.6 or 4 mg/kg, IV, q 24 h) were half-life of 1.47 and 1.61 hours, volume of distribution of 0.17 and 0.17 L/kg, and systemic clearance of 1.27 and 1.2 ml/kg/min, respectively. Mean serum creatinine concentration was 1.74 and 1.71 for the high and low dosages, respectively, and serum creatinine concentration was not correlated with gentamicin clearance.

Conclusions and Clinical Relevance

Gentamicin administration at a dosage of 4 mg/kg, IV, every 24 hours, will result in plasma concentrations that are adequate against susceptible bacteria with a minimum inhibitory concentration (MIC) of ≤ 2.0 μg/ml. Gentamicin administration at a calculated dosage of 6.8 mg/kg, IV, every 24 hours will result in optimum plasma concentrations against susceptible bacteria with a MIC of ≤ 4.0 μg/ml. (J Am Vet Med Assoc 1999;215:503–506)

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A.

Animals

6 healthy foals that were 2 to 4 months old.

Procedure

Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, and plasma was harvested for determination of erythromycin concentrations by microbiologic assay and a HPLC method. Pharmacokinetic analysis of plasma concentration-time data was performed, and results derived from each method were compared.

Results

Concentration-time profiles for IV administration were best described by a two-compartment open model. Comparing pharmacokinetic data obtained by the 2 methods revealed substantial differences in results. Values for area under the plasma concentration-time curve and area under the first moment of the curve were substantially higher when determined by the bioassay, indicating overestimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and Ke1) and mean residence time were significantly different, when determined by the bioassay. Systemic bioavailability of erythromycin base was low in all foals.

Conclusions and Clinical Relevance

The bioassay method overestimated plasma concentrations of erythromycin, compared with the HPLC method. Despite low systemic bioavailability of erythromycin base administered intragastrically, plasma concentrations of erythromycin exceeded, for at least 4 hours, the minimum inhibitory concentration of most Rhodococcus equi isolates. (Am J Vet Res 1999;60:414-419)

Free access
in American Journal of Veterinary Research

Abstract

Objectives

To determine tilmicosin concentrations in serum and tissues of rabbits given a single dose of 25 mg of tilmicosin/kg of body weight. To examine the effects of tilmicosin treatment (25 mg/kg, SC) in rabbits with pasteurellosis.

Procedure

After receipt of tilmicosin, healthy New Zealand White female rabbits (n = 3 at each time) were euthanatized at 2, 4, 8, 24, 48, and 72 hours for collection of blood samples and tissue specimens; 4 rabbits served as untreated controls. Rabbits (male and female) with pasteurellosis (n = 42) also were treated. Tilmicosin concentration was determined in serum, lung, and uterine tissues. Rabbits with pasteurellosis were treated with tilmicosin. Response was monitored, using bacteriologic culturing and antibiotic resistance and susceptibility testing, and by scoring clinical signs of disease.

Results

Serum tilmicosin concentration reached 1.91 ±0.18 μg/ml after 2 hours, decreased to 0.77 ± 0.07 μg/ml by 8 hours, and was below minimum inhibitory concentrations for Pasteurella multocida at 24 hours. Terminal half-life in serum was 5.97 hours. Lung and uterus concentrations were 14.43 ± 1.34 and 11.57 ± 0.09 ppm at 2 hours, and were 5.10 ± 1.05 and 8.87 ± 1.66 ppm at 24 hours, respectively. 69% (29/42) of rabbits with pasteurellosis responded favorably in 3 days. Second treatment was required in 31% (13/42), and 5 of these rabbits had clinical signs on day 6; 2 of these 5 had improved. Treatment success rate was 93% (39/42). Of the rabbits that were culture positive on day 0, 35% (6/17) remained positive on day 3. 1 of 6 rabbits was culture positive on day 6.

Conclusion

Tilmicosin (25 mg/kg, SC) was an effective treatment for pasteurellosis in New Zealand White rabbits.

Clinical Relevance

Tilmicosin treatment of pasteurellosis in rabbits is useful in research rabbits and in those destined for meat production. A single dose of antibiotic minimizes stress-associated handling. (Am J Vet Res 1996;57:1180-1184)

Free access
in American Journal of Veterinary Research

Abstract

Objectives

To compare cefazolin pharmacokinetics in serum and concentrations in tissues during total hip arthroplasty in dogs with and without hip dysplasia, and to calculate the optimal dosage of cefazolin for prophylactic use during total hip arthroplasty.

Animals

10 dogs with hip dysplasia and 3 clinically normal dogs.

Procedure

Blood samples and tissue specimens from the coxofemoral joint capsule, acetabulum, and femur were obtained during unilateral total hip arthroplasty. Cefazolin concentrations in serum and tissue specimen supernatant were determined, using high-performance liquid chromatography, for use in pharmacokinetic analysis. Mathematical simulation of serum cefazolin concentrations was used to to predict the optimal dose.

Results

Mean pharmacokinetic constants (SEM) were 0.146 (0.013) mm-1 for α, 4.74 min for t1/2α,, 0.015 (0.004) min-1 for ß, and 46.83 min for t1/2ß. Significant difference was not detected for cefazolin distribution and elimination between dogs with and without hip dysplasia. Additionally, significant difference was not observed in pharmacokinetic parameters describing distribution and elimination between the first and second doses of cefazolin. The predicted optimal dosage regimen was 8 mg/ kg of body weight, IV, every hour or 22 mg/kg, IV, every 2 hours.

Clinical Relevance

For prophylactic IV treatment during total hip arthroplasty, use of cefazolin at a dosage of 8 mg/kg every hour or 22 mg/kg every 2 hours should maintain serum cefazolin concentrations at least 10× the minimum inhibitory concentration for 3 to 4 hours. (Am J Vet Res 1996; 57:720–723)

Free access
in American Journal of Veterinary Research

SUMMARY

Objectives

To evaluate in vitro susceptibility to topical antifungal medications, as measured by minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50%), of fungal isolates from horses with ulcerative keratomycosis in Florida; to compare results with those of other studies to identify differences in susceptibility patterns among fungi isolated from horses in different geographic regions; and to note indications of fungal resistance to drugs tested in other studies.

Sample Population

Corneal fungal cultures from client-owned horses from Florida with ulcerative keratomycosis (n = 22).

Procedure

Fungal cultures were plated on Emmons modified Sabouraud dextrose agar and mycobiotic agar, examined weekly for growth, and kept for a total of 30 days. In vitro MIC and IC50% of fluconazole, itraconazole, ketoconazole, miconazole, and natamycin were measured for each fungal isolate.

Results

Aspergillus (n = 9; 41%), Fusarium (7; 32%), Penicillium (2; 9%), Cylindrocarpon (1; 4%), Scytalidium (1; 4%), and Torulopsis (1; 4%) spp and an unidentified yeast (1; 4%) were isolated. Fungi were most susceptible to antifungal drugs in the following order: natamycin and miconazole equally, itraconazole, and ketoconazole, although no significant difference was found among drugs. Fungi were significantly less susceptible to fluconazole (P < 0.0001) than to the other 4 drugs.

Conclusions

Initial antifungal therapy with topically applied natamycin, miconazole, itraconazole, or ketoconazole is recommended for ulcerative keratomycosis in horses in the subtropical environment of Florida.

Clinical Relevance

Specific antifungal treatment of horses with ulcerative keratomycosis should be based on history, results of ophthalmic examination, cytologic findings, isolation of the pathogenic fungus, and known prevalence of unique ocular fungi in specific geographic areas. In vitro antifungal susceptibility testing may be most beneficial in aiding documentation of pharmacologic susceptibility patterns of fungi in specific geographic regions. (Am J Vet Res 1998; 59:138–142)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine whether methicillin-resistant staphylococci from dogs expressed the mecA gene and to determine what proportion of canine staphylococcal isolates positive for the mecA gene were resistant to oxacillin and other antibiotics.

Sample Population

25 methicillin-resistant (10 coagulase-positive and 15 coagulase-negative) and 15 methicillin-susceptible (8 coagulase-positive and 7 coagulase-negative) staphylococci isolated from dogs.

Procedure

All strains were tested for methicillin resistance by use of oxacillin agar screening and identified by use of standard techniques. Minimum inhibitory concentrations of 16 antibiotics were determined for all 40 isolates. A polymerase chain reaction method targeting a 533-basepair fragment of the mecA gene was used to detect mecA gene expression.

Results

23 of the 25 methicillin-resistant isolates and none of the methicillin-susceptible isolates possessed the mecA gene. For 10 of 16 antibiotics, the proportion of mecA-positive isolates that were resistant or of intermediate susceptibility was significantly higher than the proportion of mecA-negative isolates that were resistant or of intermediate susceptibility. Only 1 methicillin-resistant coagulase-positive isolate was identified as Staphylococcus intermedius; the other 9 were identified as S aureus.

Conclusions and Clinical Relevance

Results confirm that staphylococci isolated from dogs may have methicillin resistance mediated by the mecA gene. Isolates positive for the mecA gene were more likely to be resistant to various antibiotics than were isolates negative for the mecA gene. Results suggest that in dogs, infections caused by staphylococci that have the mecA gene may be difficult to treat because of resistance to antibiotics. (Am J Vet Res 1999;60:1526–1530)

Free access
in American Journal of Veterinary Research

Abstract

Eight Holstein cows, 4 inoculated intracistemally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean ± SEM peak log10 bacterial concentration in milk of 5.03 ± 0.69 colonyforming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 ± 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 ± 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 ± 27.5 hours) than noninfected cows (1.3 ± 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 p.g/ml, and was 0.20 jig/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 ± 0.3 μg/ml and 0.7 ± 0.1 μg/ml for infected and noninfected cows, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows. Ceftiofur was not detected in serum (< 0.05 μg/ml) of any cow at or after 120 hours following inoculation of infected cows.

Storage of serum samples at —20 C for 3 weeks resulted in a 98.8% decrease in ceftiofur activity, compared with that in fresh serum samples. Eightyseven percent of this loss occurred 30 minutes after mixing serum and ceftiofur; thus, about 13% of the original activity was lost in storage. Storage of milk samples under similar conditions did not result in loss of ceftiofur activity.

Despite acute inflammation, the dosage of ceftiofur used in this trial would not result in drug concentrations in milk above FDA safe concentrations, or above the reported minimum inhibitory concentration for coliform bacteria.

Free access
in American Journal of Veterinary Research

SUMMARY

Cortical bone concentrations of enrofloxacin were determined over time in dogs after sc administration of the drug. Nineteen healthy adult dogs were anesthetized and were given 2.5 or 5.0 mg of enrofloxacin/kg of body weight, sc. Serial serum and bone samples were obtained for determination of enrofloxacin concentrations at intervals until 8 hours after drug administration. Cortical bone samples were procured by surgical disarticulation of successive second phalanges. Additional cortical bone samples were taken from long bones in 4 dogs. Mean ± sd peak serum enrofloxacin concentration was 0.54 ± 0.10 μg/ml for the 2.5-mg/kg dosage and 0.97 ± 0.34 μg/ml for the 5.0-mg/kg dosage. Serum concentration was significantly higher than bone concentration for each dosage. Mean peak bone concentrations reached 29% of peak serum values: 0.15 ± 0.09 μg/g and 0.29 ± 0.09 μg/g for 2.5-mg/kg and 5.0-mg/kg dosages, respectively. Serum concentration for the 5.0-mg/kg dosage was significantly greater than that for the 2.5-mg/kg dosage for all times, whereas bone concentrations for the 5.0-mg/kg dosage were significantly higher at all times after 180 minutes. For the duration of the study, cortical bone concentrations of enrofloxacin at either dosage exceeded the minimum inhibitory concentration (mic) for the Enterobacteriaceae, but reliably exceeded the mic for Staphylococcus sp only at the 5.0-mg/kg dosage. At no time did cortical bone concentrations of enrofloxacin exceed the mic for Pseudomonas aeruginosa at either dosage.

To validate extrapolation of data from the second phalanx to long bones and from anesthetized to awake dogs, 16 healthy dogs being euthanatized in unrelated studies were given 2.5 or 5.0 mg of enrofloxacin/kg, sc. These dogs were not anesthetized but were euthanatized at 60, 120, or 240 minutes after drug administration, and multiple cortical bone samples were taken. Antibiotic concentrations in the second phalanx were not significantly different from those in long bones. Comparison of enrofloxacin concentrations in cortical bone of awake and anesthetized dogs suggested no differences between groups. We concluded that general anesthesia and use of the antibiotic concentrations in the second phalanx as representative of those in long bones did not affect results of this study.

Free access
in American Journal of Veterinary Research

isolates with susceptibility testing from cats described in Table 1 with their associated minimum inhibitory concentrations (MICs) for the classes of antibiotic used in the treatment of this cohort. All urine samples were collected via cystocentesis, and

Free access
in Journal of the American Veterinary Medical Association

-type Enterobacterales typically test resistant to these agents, and comparison of reported median minimum inhibitory concentrations to approved breakpoints 4 suggests that the reported values overestimate the percentage susceptible. Additionally, ceftiofur and

Full access
in Journal of the American Veterinary Medical Association