Heylen R M, Wilson A P, Hichens M, Felmingham D, Webb A, Pattison C W, Pugsley W
Department of Pharmacy, University College and Middlesex Hospital, London, UK.
J Antimicrob Chemother. 1995 May;35(5):649-55. doi: 10.1093/jac/35.5.649.
Treatment with an aminoglycoside plus flucloxacillin is commonly used to prevent wound infection and endocarditis after cardiac surgery. Cardiopulmonary bypass, blood transfusion and the lack of a steady state greatly affect handling of gentamicin. Urinary gentamicin excretion is not predictable in terms of preoperative risk factors possibly because there is no clear relationship between serum levels and gentamicin clearance. A study was performed to determine whether the existing prophylactic regimen gave adequate serum levels during surgery and to compare renal excretion of gentamicin and the trough serum levels. Ten patients received gentamicin (1.5 mg/kg at the start of surgery followed by 80 mg tds for 2 days) and flucloxacillin 500 mg qds for 2 days. Serum and urinary concentrations of gentamicin were assayed during surgery and in the early postoperative period. The median apparent serum half-life during the first 8 h was 2.5 h (95%CI 1.7-3.2 h). The median gentamicin clearance was 37 mL/min(95%CI 23-64 mL/min) and the creatinine clearance 85 mL/min (95%CI 72-210 mL/min). Serum levels remained above 1 mg/L during surgery but urinary concentrations varied between 0.4 and 364 mg/L (median 70 mg/L). At 24 h (but not 8 or 16 h), trough serum levels appeared to be related to the amount of gentamicin excreted but the relationship was not quite statistically significant (P = 0.057). Despite the effects of cardiopulmonary bypass, therapeutic serum gentamicin levels were maintained during surgery and reduced renal excretion in the postoperative period was associated with raised levels.
氨基糖苷类药物联合氟氯西林治疗常用于预防心脏手术后的伤口感染和心内膜炎。体外循环、输血以及缺乏稳态会极大地影响庆大霉素的处理。根据术前危险因素无法预测尿中庆大霉素的排泄情况,这可能是因为血清水平与庆大霉素清除率之间没有明确的关系。本研究旨在确定现有的预防性治疗方案在手术期间是否能使血清水平达到足够浓度,并比较庆大霉素的肾排泄情况和谷浓度血清水平。10例患者接受庆大霉素治疗(手术开始时1.5mg/kg,随后80mg每日3次,共2天)和氟氯西林500mg每日4次,共2天。在手术期间和术后早期测定血清和尿液中的庆大霉素浓度。最初8小时内的中位表观血清半衰期为2.5小时(95%可信区间1.7 - 3.2小时)。庆大霉素的中位清除率为37mL/min(95%可信区间23 - 64mL/min),肌酐清除率为85mL/min(95%可信区间72 - 210mL/min)。手术期间血清水平保持在1mg/L以上,但尿液浓度在0.4至364mg/L之间变化(中位数为70mg/L)。在24小时(而非8或16小时)时,谷浓度血清水平似乎与庆大霉素排泄量有关,但这种关系在统计学上并不十分显著(P = 0.057)。尽管体外循环有影响,但手术期间仍维持了治疗性血清庆大霉素水平,术后肾排泄减少与水平升高有关。