Wakimoto Yuji, Okamoto Koh, Yamamoto Takehito, Akamatsu Nobuhisa, Kariya Taro, Hoshino Yoko, Harada Sohei, Hashimoto Hideki, Jubishi Daisuke, Tanaka Takehiro, Yamaguchi Ryo, Kaneko Junichi, Okugawa Shu, Takada Tappei, Hasegawa Kiyoshi, Uchida Kanji, Tsutsumi Takeya
Department of Infectious Diseases, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Department of Pharmacy, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
JAC Antimicrob Resist. 2025 Aug 26;7(4):dlaf149. doi: 10.1093/jacamr/dlaf149. eCollection 2025 Aug.
Guidelines recommend redosing with intravenous prophylactic antibiotics when excessive bleeding exceeds 1500 mL during surgery based on the pharmacokinetics data of cefazolin. However, the necessity for redosing of other antibiotics and the threshold volume of blood loss necessitating such supplementation remain undefined. We investigated plasma antibiotic concentrations during liver transplant surgery in patients with frequent excessive bleeding.
A single-centre, prospective, observational pharmacokinetic study was conducted. Adult liver transplant recipients who received 2 g of ampicillin and 1 g of sulbactam every 3 h during surgery were included. Blood samples were collected hourly during surgery, and intraoperative bleeding amounts were reviewed from anaesthesia records. Plasma concentrations of ampicillin and sulbactam were determined using validated liquid chromatography-tandem mass spectrometry. The probability of target attainment was set at 80% free time above the MIC (fT > MIC).
Twenty participants were included. Of these, 11 participants (55%) were female. The median age, body weight, and bleeding volume were 52 years, 62.1 kg, and 11 158 mL, respectively. The intraoperative clearance of ampicillin was 80.28 mL/min, and sulbactam was 77.23 mL/min. The fT > MIC for both ampicillin and sulbactam tended to be lower with bleeding > 20 000 mL than with less bleeding. Plasma concentrations of ampicillin and sulbactam were maintained during surgery without redosing, even after bleeding exceeded 1500 mL.
Even with excessive bleeding, administering 3 g of ampicillin/sulbactam every 3 h maintained sufficient plasma concentration. Redosing may be unnecessary unless total bleeding exceeds 20 000 mL.
根据头孢唑林的药代动力学数据，指南建议在手术期间出血超过1500 mL时静脉补充预防性抗生素。然而，其他抗生素再给药的必要性以及需要补充抗生素的失血阈值仍不明确。我们调查了频繁出现大量出血的肝移植手术患者的血浆抗生素浓度。
进行了一项单中心、前瞻性、观察性药代动力学研究。纳入手术期间每3小时接受2 g氨苄西林和1 g舒巴坦的成年肝移植受者。手术期间每小时采集血样，并从麻醉记录中查看术中出血量。使用经过验证的液相色谱 - 串联质谱法测定氨苄西林和舒巴坦的血浆浓度。目标达成概率设定为游离时间高于最低抑菌浓度（fT > MIC）的概率为80%。
纳入20名参与者。其中，11名参与者（55%）为女性。中位年龄、体重和出血量分别为52岁、62.1 kg和11158 mL。氨苄西林的术中清除率为80.28 mL/min，舒巴坦为77.23 mL/min。出血>20000 mL时，氨苄西林和舒巴坦的fT>MIC往往低于出血量较少时。即使出血超过1500 mL，手术期间氨苄西林和舒巴坦的血浆浓度在未再次给药的情况下仍能维持。
即使出血过多，每3小时给予3 g氨苄西林/舒巴坦仍可维持足够的血浆浓度。除非总出血量超过20000 mL，否则可能无需再次给药。
