Reed R L, Wu A H, Miller-Crotchett P, Crotchett J, Fischer R P
Department of Surgery, University of Texas Medical School, Houston 77030.
J Trauma. 1989 Nov;29(11):1462-8; discussion 1468-70. doi: 10.1097/00005373-198911000-00002.
An assessment of the dosage regimens prescribed for potentially nephrotoxic antibiotics (amikacin, gentamicin, tobramycin, and vancomycin) was undertaken on surgical intensive care unit patients. In 166 patients, 224 series of blood antibiotic level determinations were obtained. Using individualized pharmacokinetic determinations, the regimens were revised as necessary to provide optimal blood levels. Because of variable volumes of distribution and elimination rates, dosing according to standard clinical guidelines produced significantly lower peaks than did pharmacokinetically determined regimens for gentamicin (p less than 0.005), tobramycin (p less than 0.0001), and vancomycin (p less than 0.05). Importantly, fewer patients achieved therapeutic levels with the original regimens than with the revised regimens for gentamicin (9% vs. 91%, p less than 0.0005), tobramycin (27% vs. 92%, p less than 0.0001), and vancomycin (30% vs. 69%, p less than 0.0001). Individualized pharmacokinetic analysis of potentially nephrotoxic antibiotics in critically ill patients is essential if therapeutic, non-toxic levels are to be maintained.
对手术重症监护病房患者使用的可能具有肾毒性的抗生素(阿米卡星、庆大霉素、妥布霉素和万古霉素)的给药方案进行了评估。在166例患者中,共进行了224次血液抗生素水平测定。根据个体化药代动力学测定结果,必要时对给药方案进行调整,以达到最佳血药浓度。由于分布容积和消除率存在差异,按照标准临床指南给药时,庆大霉素(p<0.005)、妥布霉素(p<0.0001)和万古霉素(p<0.05)的血药峰浓度显著低于根据药代动力学确定的给药方案。重要的是,与调整后的给药方案相比,使用原给药方案达到治疗浓度的患者更少,庆大霉素(9%对91%,p<0.0005)、妥布霉素(27%对92%,p<0.0001)和万古霉素(30%对69%,p<0.0001)。如果要维持治疗性、无毒的血药浓度,对重症患者进行可能具有肾毒性抗生素的个体化药代动力学分析至关重要。