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  • Author or Editor: Harry W. Boothe x
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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).

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in American Journal of Veterinary Research

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)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of treatment approach on outcome and the appropriateness of initial empirical antimicrobial treatment in dogs with pyothorax.

Design—Retrospective case series.

Animals—46 dogs with pyothorax confirmed by either (n = 15) or both (31) of the following: intracellular bacteria in pleural fluid or tissue (41) and bacteria recovered via culture of pleural fluid (36).

Procedures—Medical records of dogs treated for pyothorax from 1983 through 2001 were reviewed. Data on signalment, history, clinical signs, and treatment and results of diagnostic imaging and cytologic and microbiological evaluations were obtained. Follow-up was performed via reexamination (n = 15) and contact with referring veterinarians (26) and owners (24).

Results—46 dogs were treated with at least 1 antimicrobial and thoracocentesis (n = 7; noninvasive group), a thoracostomy tube (26; invasive group) with or without pleural lavage and heparin, or a thoracotomy (13; surgical group) and thoracostomy tube with or without pleural lavage and heparin. Pyothorax recurred in 7 dogs, and 5 of the 7 died or were euthanatized. In the respective groups, the short-term survival rate was 29%, 77%, and 92% and the long-term survival rate was 29%, 71%, and 70%. Pleural lavage and heparin treatment increased the likelihood of short- and long-term survival. Results of antimicrobial susceptibility testing suggested empirical antimicrobial selection was associated with a 35% risk of inefficacy.

Conclusions and Clinical Relevance—In the dogs with pyothorax in this study, favorable treatment effects were achieved with surgery (for short-term survival) and pleural lavage and heparin treatment (for short- and long-term survival). Findings failed to support the hypothesis that invasive (surgical) versus noninvasive treatment of pyothorax in dogs leads to a better long-term outcome.

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in Journal of the American Veterinary Medical Association

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)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy.

Design—Randomized controlled clinical trial.

Animals—45 client-owned cats weighing ≥ 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration.

Procedure—Cats were randomly assigned to be treated with a TFP (25 µg/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery.

Results—Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean ± SD serum fentanyl concentrations were 1.56 ± 1.08, 4.85 ± 2.38, 4.87 ± 1.56, and 4.35 ± 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement.

Conclusion and Clinical Relevance—Results suggest that use of a TFP (25 µg/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective. (J Am Vet Med Assoc 2000;217:1013–1020)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate differences in bacterial numbers, identity, and susceptibility in samples obtained from the tympanic cavity on entry (preflush) and after evacuation and lavage (postflush) and assess perioperative and empiric antimicrobial selection in dogs that underwent total ear canal ablation (TECA) with lateral bulla osteotomy (LBO) or reoperation LBO.

Design—Prospective clinical study.

Animals—34 dogs.

Procedure—TECA with LBO or reoperation LBO was performed on 47 ears. Pre- and postflush aerobic and anaerobic samples were obtained from the tympanic cavity. Isolates and antimicrobial susceptibility patterns were compared.

Results—Different isolates (31/44 [70%] ears) and susceptibility patterns of isolate pairs (6/44 [14%] ears) were detected in pre- and postflush samples from 84% of ears. Evacuation and lavage of the tympanic cavity decreased the number of bacterial isolates by 33%. In 26% of ears, bacteria were isolated from postflush samples but not preflush samples. Only 26% of isolates tested were susceptible to cefazolin. At least 1 isolate from 53% of dogs that received empirically chosen antimicrobials postoperatively was resistant to the selected drugs. Anaerobic bacteria were recovered from 6 ears.

Conclusions and Clinical Relevance—Accurate microbiologic assessment of the tympanic cavity should be the basis for selection of antimicrobials in dogs undergoing TECA with LBO. Bacteria remain in the tympanic cavity after evacuation and lavage. Cefazolin was a poor choice for dogs that underwent TECA with LBO, as judged on the basis of culture and susceptibility testing results. (J Am Vet Med Assoc 2005;227:748–755)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine long-term results and complications of gonadectomy performed at an early age (prepubertal) or at the traditional age in cats.

Design—Cohort study.

Animals—263 cats from animal shelters.

Procedure—Cats that underwent gonadectomy were allotted to 2 groups on the basis of estimated age at surgery (traditional age, ≥ 24 weeks old; prepubertal, < 24 weeks old). Adoptive owner information was obtained from shelter records, and telephone interviews were conducted with owners to determine physical or behavioral problems observed in the cats after adoption. Follow-up information was obtained from attending veterinarians for cats with complex problems or when owners were uncertain regarding the exact nature of their cat's problem.

Results—Compared with traditional-age gonadectomy, prepubertal gonadectomy did not result in an increased incidence of infectious disease, behavioral problems, or problems associated with any body system during a median follow-up period of 37 months. Additionally, the rate of retention in the original adoptive household was the same for cats that underwent prepubertal gonadectomy as those that underwent traditional-age gonadectomy.

Conclusions and Clinical Relevance—Prepubertal gonadectomy may be performed safely in cats without concern for increased incidence of physical or behavioral problems for at least a 3-year period after gonadectomy. (J Am Vet Med Assoc 2000;217: 1661–1665)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine long-term results and complications of gonadectomy performed at an early age (prepubertal) or at the traditional age in dogs.

Design—Cohort study.

Animals—269 dogs from animal shelters.

Procedure—Dogs that underwent gonadectomy were allotted to 2 groups on the basis of estimated age at surgery (traditional age, ≥ 24 weeks old; prepubertal, < 24 weeks old). Adoptive owner information was obtained from shelter records, and telephone interviews were conducted with owners to determine physical or behavioral problems observed in the dogs since adoption. Follow-up information was obtained from attending veterinarians for dogs with complex problems or when owners were uncertain regarding the exact nature of their dog's problem.

Results—Prepubertal gonadectomy did not result in an increased incidence of behavioral problems or problems associated with any body system, compared with traditional-age gonadectomy, during a median follow-up period of 48 months after gonadectomy. Rate of retention in the original adoptive household was the same for dogs that underwent prepubertal gonadectomy as those that underwent traditional- age gonadectomy. Infectious diseases, however, were more common in dogs that underwent prepubertal gonadectomy.

Conclusions and Clinical Implications—With the exception of infectious diseases, prepubertal gonadectomy may be safely performed in dogs without concern for increased incidence of physical or behavioral problems during at least a 4-year period after gonadectomy. (J Am Vet Med Assoc 2001;218: 217–221)

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in Journal of the American Veterinary Medical Association