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Abstract

OBJECTIVE To determine whether target values for pharmacokinetic-pharmacodynamic (PK-PD) indices against selected canine pathogens were achievable for pradofloxacin in various canine fluids and leukocytes.

ANIMALS 8 healthy adult hounds (experiments 1 and 2) and 6 healthy adult dogs (experiment 3).

PROCEDURES In 3 experiments, pradofloxacin (3, 6, or 12 mg/kg) and enrofloxacin (5 or 10 mg/kg) were orally administered once a day for 5 days, and blood, interstitial fluid (ISF), and other fluid samples were collected at various points. Sample drug concentrations were measured, and noncompartmental pharmacokinetic analysis was performed; then, PK-PD indices (ratios between maximum observed concentration [Cmax] and minimum inhibitory or mutant prevention concentrations) were determined for 7 bacterial species.

RESULTS PK-PD values for pradofloxacin at 3 mg/kg were approximately 5 times as high in leukocyte versus plasma and were lowest in CSF, synovial fluid, and aqueous humor. No significant differences were noted between serum and ISF. Value ratios for serum versus other body fluids were numerically higher for pradofloxacin (vs enrofloxacin) for all fluid types except CSF and aqueous humor. Target PK-PD values were exceeded for pradofloxacin against all 7 bacterial species in leukocytes and against all species except Bacteroides spp in serum and ISF. Enrofloxacin achieved the target Cmax-to-minimum inhibitory concentration ratio against Pasteurella multocida in serum, ISF, and leukocytes and for Staphylococcus pseudintermedius in serum and leukocytes. A Cmax-to-mutant prevention concentration ratio ≥ 1 against Eschericha coli was achieved for pradofloxacin at 6 mg/kg.

CONCLUSIONS AND CLINICAL RELEVANCE These findings supported once-daily oral administration of pradofloxacin to dogs at the currently recommended dose (7.5 mg/kg).

Full access
in American Journal of Veterinary Research

Abstract

Objective

To determine existence of portal and systemic bacteremia in dogs with induced severe hepatic disease, compared with clinically normal dogs, before and after vena caval banding.

Animals

6 control dogs and 10 dogs with induced severe hepatic disease and multiple portosystemic shunts (PSS).

Procedure

Dogs of the diseased group were given dimethylnitrosamine (2 mg/kg of body weight, PO) twice weekly until multiple PSS developed. Surgery was performed on dogs of both groups, and blood for baseline aerobic and anaerobic bacterial culture was collected from catheters placed in the portal and hepatic veins and caudal vena cava. All dogs underwent vena caval banding, and blood for aerobic and anaerobic bacterial culture was collected from the portal and hepatic venous catheters at 120, 240, and 360 minutes after banding.

Results

Compared with control dogs (16% gram-positive and 84% gram-negative bacteria), diseased dogs had significantly higher percentage of gram-positive bacteria (42% of positive culture results, P ≤ 0.01) and significantly lower percentage of gram-negative bacteria (58% of positive culture results, P ≤ 0.01) isolated. Pseudomonas aeruginosa was isolated most frequently from dogs of both groups; more than 1 organism was isolated from 5 dogs of each group. Antimicrobial susceptibility included that to aminoglycosides (particularly amikacin), fluorinated quinolones, and imipenem.

Conclusions

Portal and systemic, predominantly gram-negative, bacteremia is present in catheterized, clinically normal dogs and dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS. (Am J Vet Res 1999;60:181-185)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To document presence of endotoxin in portal and systemic blood in a model of canine multiple portosystemic shunts (PSS), and compare values in clinically normal dogs, before and after vena caval banding.

Animals

6 control dogs and 10 dogs with dimethylnitrosamine-induced multiple PSS that were subjected to vena caval banding.

Procedure

Dimethylnitrosamine was administered orally (2 mg/kg of body weight, twice weekly) to the 10 dogs in the diseased group until multiple PSS developed. Surgery was then performed on all 16 dogs (both groups), and shunts were confirmed in the diseased dogs. Blood was collected from the portal vein, hepatic vein, and caudal vena cava for baseline endotoxin determination and aerobic and anaerobic blood culturing. Baseline pressure measurements were taken from the portal venous catheter; then vena caval banding was performed. Blood for endotoxin determinations was taken from all vessels 20, 40, 60, 120, 240, and 360 minutes after banding; portal pressure measurements were taken at the same time as sample acquisition. Blood for culturing was taken from the portal and hepatic venous catheters at 120, 240, and 360 minutes after banding.

Results

Dogs in the diseased group had significantly greater overall presence of endotoxin in the portal vein (P ≤ 0.0002), hepatic vein (P ≤ 0.0001), and caudal vena cava (P ≤ 0.0004) than did control dogs. With respect to time, endotoxin presence was greater in the diseased group before banding (P ≤ 0.0002), and at 20 (P ≤ 0.0008), 40 (P ≤ 0.002), 60 (P ≤ 0.006), and 120 (P ≤ 0.01) minutes after banding.

Conclusions

Endotoxemia is more frequently present in catheterized dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS, compared with clinically normal dogs. Additionally, portal pressure changes induced by vena caval banding did not affect endotoxemia.

Clinical Relevance

Endotoxemia may exist in dogs with hepatic disease and multiple PSS, and should be kept in mind when formulating treatment (particularly antimicrobial selection) for dogs with suspected endotoxemia. (Am J Vet Res 1997;58:83–88)

Free access
in American Journal of Veterinary Research

Summary

Twenty-five animals (21 dogs and 4 cats) in which hepatobiliary scintigraphy (hbs) was performed between 1982 and 1989 were included in a retrospective study to determine the utility of hbs for diagnosis of extrahepatic biliary obstruction. Final diagnoses, which were based on liver biopsy results and surgical findings in all animals, were hepatocellular disease alone (n = 17), hepatocellular disease and extrahepatic biliary obstruction (n = 7), and normal liver (n = 1). Hepatobiliary scintigraphy was performed by use of 99mTc-diisopropyl iminodiacetic acid in all cases. All 7 cases of extrahepatic biliary obstruction were confirmed at surgery. In animals with biliary obstruction, hbs failed to demonstrate radiolabel within either the gallbladder or intestine at any time. Using nonvisualization of the intestine by 180 minutes as the scintigraphic criterion for diagnosis of biliary obstruction, sensitivity was 83% and specificity was 94% in this series. Hepatobiliary scintigraphy was concluded to be an accurate indicator of extrahepatic biliary obstruction in this group of animals. High serum bilirubin concentration at the time hbs was performed did not appear to reduce the diagnostic usefulness of the scintigraphic findings.

Free access
in Journal of the American Veterinary Medical Association

Objective

To describe the long-term outcome in dogs with naturally developing multiple extrahepatic portosystemic shunts (PSS).

Design

Retrospective case series.

Animals

30 dogs with multiple PSS.

Procedure

Medical records of dogs with multiple PSS were reviewed. Follow-up data were obtained by 1 or more of the following methods: recheck at the veterinary teaching hospital (n = 6) or telephone contact with the referring veterinarian (n = 18) or owner (n = 10). The χ 2 or Mann-Whitney rank sum test was used to determine the association of clinical factors with long-term outcome. Survival curves were generated by the Kaplan-Meier product limit method.

Results

Median age at diagnosis was 1 year. Findings on exploratory surgery in 25 dogs included ascites; numerous tortuous vessels connecting the portal vein with systemic veins; a small, misshapen liver; and an enlarged portal vein. The most common lesions on histologic evaluation of hepatic tissue specimens were hepatocellular atrophy, portal vascular duplication, cirrhosis, inflammation, and bile duct proliferation. Twelve dogs were treated surgically with vena caval banding, whereas 13 dogs were treated conservatively with dietary restriction of protein and administration of antibiotics, diuretics, and other drugs. Long-term survival and quality of life were similar in dogs from both treatment groups. Median follow-up interval in dogs that survived hospitalization was 24 months (range, 1 to 54 months).

Clinical Implications

On the basis of these findings, vena caval banding in dogs with multiple PSS is not superior to medical and nutritional treatment. (J Am Vet Med Assoc 1996;208:1849-1854)

Free access
in Journal of the American Veterinary Medical Association

Objective—

To determine factors associated with long-term outcome in dogs with tracheal collapse treated with extraluminal polypropylene C-shaped stents.

Design—

Retrospective case series.

Animals—

90 dogs.

Procedure—

Medical records of dogs with surgically treated tracheal collapse were reviewed. Follow-up was obtained either by recheck at the veterinary teaching hospital only (n = 10) or by telephone interviews with referring veterinarians and owners (n = 35), referring veterinarians alone (n = 23), or owners alone (n = 16). The χ2 test was used to determine which factors were associated with long-term outcome.

Results—

11 breeds were represented. Yorkshire Terriers, Poodles, and Pomeranians were most common. Median age at the time of surgery was 6.8 years. Median weight was 2.9 kg. Severity of collapse ranged from grade II to grade IV. Dogs < 6 years old had more severe collapse than did dogs ≥ 6 years old. Dogs ≥ 6 years old had more postoperative complications and a poorer long-term outcome than did dogs < 6 years old. 17 dogs required permanent tracheostomy, 10 within 24 hours after surgery.

Clinical Implications—

Surgical placement of extraluminal polypropylene C-shaped stents was an effective method of attenuating clinical signs of tracheal collapse. Dogs < 6 years old had more severe tracheal collapse but did better after surgery than did dogs ≥ 6 years old. U Am Vet Med Assoc 1996;208:380-384)

Free access
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs.

Animals—12 adult mixed-breed and purebred hounds.

Procedure—10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence.

Results—Mean ± SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 ± 0.52 µg/mL and 1.81 ± 0.21 µg/mL, respectively. Mean ± SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 ± 24.61 µg/mL) was significantly greater than that in plasma (1.81 ± 0.21 µg/mL) and ELF (0.82 ± 0.34 µg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs.

Conclusions and Clinical Relevance—Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF. The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration. (Am J Vet Res 2005;66:1770–1774)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To document blood nitric oxide concentrations in the portal vein and systemic circulation in a rat model of acute portal hypertension and compare values with a control group and a sham surgical group.

Animals—30 rats; 10 controls (group 1), 10 sham surgical (group 2), and 10 rats with surgically induced acute portal hypertension (group 3).

Procedure—Following induction of anesthesia, catheters were placed surgically in the carotid artery, jugular, and portal veins of group 2 and 3 rats and in the carotid artery and jugular vein of group 1 rats. Baseline heart and respiratory rates, rectal temperature, and vascular pressure measurements were obtained, and blood was drawn from all catheters for baseline nitric oxide (NO) concentrations. Acute portal hypertension was induced in the group 3 rats by tying a partially occluding suture around the portal vein and a 22-gauge catheter. The catheter was then removed, resulting in a repeatable degree of portal vein impingement. After catheter placement, all variables were remeasured at 15-minute intervals for 3 hours.

Results—Blood nitric oxide concentrations were greater in all vessels tested in group 3 than in group 2 rats.

Conclusions and Clinical Relevance—Acute portal hypertension in this experimental model results in increased concentrations of NO in the systemic and portal circulation. On the basis of information in the rat, it is possible that increased NO concentrations may develop in dogs following surgical treatment of congenital portosystemic shunts if acute life-threatening portal hypertension develops. Increased NO concentrations may contribute to the shock syndrome that develops in these dogs. (Am J Vet Res 2000;61:1173–1177)

Full access
in American Journal of Veterinary Research