Miglioli P A, Merlo F, Fabbri A, Padrini R
Department of Pharmacology, University of Padova, Italy.
J Antimicrob Chemother. 1997 Feb;39(2):229-33. doi: 10.1093/jac/39.2.229.
The concentrations of teicoplanin in serum, pericardium, pericardial fluid and thoracic wall fat were measured in patients undergoing cardio-pulmonary bypass (CPB) after the administration of a single i.v. 12 mg/kg dose. Five minutes after the start of CPB, teicoplanin serum concentrations decreased by, on average, 35% (95% confidence interval (CI): 28-42%) and remained significantly lower than the expected values over the subsequent 60 min period. After aortic unclamping drug concentrations rebounded but remained significantly lower than the expected values in the next 60 min. Immediately before CPB, penetration of teicoplanin in pericardium and thoracic wall fat was 0.44 (95% CI: 0.23-0.65) and 0.05 (95% CI: 0.03-0.7), respectively, and increased at the end of CPB to 0.90 (95% CI: 0.55-1.25) and 0.17 (95% CI: 0.05-0.29), respectively. MICs for most staphylococcal strains were attained during CPB procedure in pericardium but not in thoracic wall fat. However, since staphylococcal infections involve the interstitial space it is likely that penetration into fat cells is not important for antimicrobial prophylaxis. In this respect, it is worth noting that drug concentration in pericardial fluid, which should reflect the interstitial concentration, was higher than the MIC for most staphylococcal strains. Although no infective complications were observed in our limited series of patients, larger clinical trials are needed to assess whether the dose regimen employed is effective in preventing post-CPB surgery infections.
在接受体外循环(CPB)的患者中,静脉注射单次12mg/kg剂量的替考拉宁后,测定其血清、心包、心包液和胸壁脂肪中的浓度。CPB开始后5分钟,替考拉宁血清浓度平均下降35%(95%置信区间(CI):28 - 42%),并在随后的60分钟内仍显著低于预期值。主动脉钳夹松开后,药物浓度反弹,但在接下来的60分钟内仍显著低于预期值。在CPB开始前,替考拉宁在心包和胸壁脂肪中的穿透率分别为0.44(95%CI:0.23 - 0.65)和0.05(95%CI:0.03 - 0.7),在CPB结束时分别增至0.90(95%CI:0.55 - 1.25)和0.17(95%CI:0.05 - 0.29)。大多数葡萄球菌菌株的最低抑菌浓度(MIC)在CPB过程中在心包中达到,但在胸壁脂肪中未达到。然而,由于葡萄球菌感染涉及间质间隙,因此药物渗透到脂肪细胞中对于抗菌预防可能并不重要。在这方面,值得注意的是,心包液中的药物浓度(应反映间质浓度)高于大多数葡萄球菌菌株的MIC。尽管在我们有限的患者系列中未观察到感染并发症,但需要更大规模的临床试验来评估所采用的剂量方案在预防CPB术后感染方面是否有效。