Oreff Gil L, Tatz Amos J, Dahan Roee, Segev Gilad, Haberman Shelley, Britzi Malka, Kelmer Gal
Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Department of Small Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Vet Surg. 2017 Nov;46(8):1120-1125. doi: 10.1111/vsu.12720. Epub 2017 Sep 27.
To determine the metacarpophalangeal joint fluid concentrations of ceftazidime administered via regional limb perfusion (RLP).
Eight healthy horses.
RLP was performed by injecting 2 g of ceftazidime and 60 mL of perfusate volume in the cephalic vein of standing, sedated horses. Serum and synovial fluid from the metacarpophalangeal joint were collected before perfusion and at 0.5, 2, 6, 12, 24 hours postperfusion. Ceftazidime concentrations were measured via liquid chromatography. Maximal concentration (C ), area under the curve (AUC), half-life of the drug (T ½), and the timing of C (T ) were determined to assess ceftazidime as a candidate drug for RLP. Continuous parameters were compared with the Mann-Whitney U test. P value ≤ .05 was considered statistically significant.
The C of ceftazidime in synovial fluid (235 µg/mL) was 15 times higher than the minimal inhibitory concentration (MIC) for most bacteria involved in orthopedic infections, including resistant pathogens such as Pseudomonas aeruginosa (MIC = 16 µg/mL). However, synovial concentrations decreased quickly and remained above the MIC in only 1 horse by 6 hours postperfusion.
RLP generated high synovial fluid concentrations of ceftazidime in the distal limb, but these concentrations decreased rapidly below the deliberately high MIC selected.
Once daily RLP, as applied in our study, with 2 g ceftazidime in standing horses, cannot be recommended for use in a clinical setting.
测定通过肢体区域灌注（RLP）给予的头孢他啶在掌指关节液中的浓度。
8匹健康马。
对站立、镇静的马，通过在头静脉注射2 g头孢他啶和60 mL灌注液进行RLP。在灌注前以及灌注后0.5、2、6、12、24小时采集掌指关节的血清和滑液。通过液相色谱法测定头孢他啶浓度。确定最大浓度（C）、曲线下面积（AUC）、药物半衰期（T½）以及C出现的时间（T），以评估头孢他啶作为RLP候选药物的情况。连续参数采用曼-惠特尼U检验进行比较。P值≤0.05被认为具有统计学意义。
滑液中头孢他啶的C（235 µg/mL）比大多数骨科感染相关细菌的最低抑菌浓度（MIC）高15倍，包括铜绿假单胞菌等耐药病原体（MIC = 16 µg/mL）。然而，滑液浓度迅速下降，灌注后6小时只有1匹马的滑液浓度保持在MIC以上。
RLP在肢体远端产生了高浓度的头孢他啶滑液，但这些浓度迅速下降至选定的刻意设定的高MIC以下。
在我们的研究中，对站立的马每日一次应用2 g头孢他啶进行RLP，不推荐在临床环境中使用。
