Pharmacokinetics of cefazolin for prophylactic administration to dogs

Abstract

OBJECTIVE To evaluate pharmacokinetics of cefazolin after IV injection of cefazolin (22 mg/kg) and after simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg) to dogs. ANIMALS 12 adult Beagles. PROCEDURES Dogs (6/group) were assigned to receive a single injection of cefazolin (IV group; 22 mg/kg, IV) or simultaneous injections (IV + IM group; 22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period by use of ultrafiltration probes for pharmacokinetic analysis. RESULTS Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.2, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. Mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half-life, and time to maximum concentration was 74.99 and 154.16 h·μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, and 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Therefore, simultaneous IV and IM administration of cefazolin 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

A prospective, randomized, double‐blinded, placebo‐controlled clinical study on postoperative antibiotherapy in 150 arthroscopy‐assisted tibial plateau leveling osteotomies in dogs

“…This time frame was chosen to facilitate data collection considering that the majority of SSI occur within 6 weeks of surgery. 9,18 Another limitation of this study is that all surgeries were performed by a single surgeon at a single institution, limiting the extrapolation of our findings to other populations. This design was selected to minimize variables and potential differences between the study groups.…”

“…Surgical site infections have been documented to occur up to 1 year postoperatively, yet we chose a minimum follow‐up of 8 weeks (mean time to follow‐up was 13.1 months). This time frame was chosen to facilitate data collection considering that the majority of SSI occur within 6 weeks of surgery . Another limitation of this study is that all surgeries were performed by a single surgeon at a single institution, limiting the extrapolation of our findings to other populations.…”

“…Both groups received antibiotics perioperatively (cefazolin 22 mg/kg IV within 60 minutes of surgery start time and intraoperatively every 90 minutes). Antibiotics were recommended to be given 30‐60 minutes before beginning surgery in a study on pharmacokinetics on cefazolin . Thereafter, the placebo group received an oral placebo every 24 hours for 7 days, and the treatment group received oral antibiotics for 7 days (cefpodoxime at 5‐10 mg/kg orally every 24 hours).…”

“…Antibiotics were recommended to be given 30-60 minutes before beginning surgery in a study on pharmacokinetics on cefazolin. 18 Thereafter, the placebo group received an oral placebo every 24 hours for 7 days, and the treatment group received oral antibiotics for 7 days (cefpodoxime at 5-10 mg/kg orally every 24 hours). Dog weights were grouped for ease of cefpodoxime dosing, with each dog receiving the closest onehalf tablet equivalent to a dose of 5-10 mg/kg.…”

“…[7][8][9] Factors contributing to increased SSI are multifactorial, 8,[13][14][15] and many surgeons prophylactically prescribe antibiotics. Scientific studies evaluating SSI in TPLO procedures have produced conflicting results, [7][8][9]11,12,[14][15][16][17][18] and many are limited by their retrospective nature. Much debate focuses on the impact of antibiotics on SSI rates in TPLO patients and individual surgeons' protocols vary widely (Table 1).…”