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Pharmacokinetics of ceftazidime in dogs following subcutaneous administration and continuous infusion and the association with in vitro susceptibility of Pseudomonas aeruginosa

Kenneth W. MooreDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.
Present address is Coral Springs Animal Hospital, Coral Springs, FL 33065.

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Lauren A. TrepanierDepartment of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Sarah J. LautzenhiserDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.
Present address is Michigan Veterinary Specialists, Southfield, MI 48037.

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James P. FialkowskiDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Eberhard RosinDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Abstract

Objective—To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa.

Animals—10 healthy adult dogs.

Procedure—MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs.

Results—The MIC of ceftazidime for P aeruginosa was ≤ 8 µg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean β disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 µg/ml during continuous IV infusion. None of the dogs developed adverse effects.

Conclusions and Clinical Relevance—Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P aeruginosa. (Am J Vet Res 2000;61:1204–1208)

Abstract

Objective—To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa.

Animals—10 healthy adult dogs.

Procedure—MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs.

Results—The MIC of ceftazidime for P aeruginosa was ≤ 8 µg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean β disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 µg/ml during continuous IV infusion. None of the dogs developed adverse effects.

Conclusions and Clinical Relevance—Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P aeruginosa. (Am J Vet Res 2000;61:1204–1208)