Department of Pharmacy, University of Colorado Hospital, Aurora, CO, USA.
Department of Pharmacy, Kaiser Permanente, Los Angeles, CA, USA.
J Clin Pharmacol. 2019 Jul;59(7):997-1005. doi: 10.1002/jcph.1392. Epub 2019 Feb 18.
Concern for bacterial resistance and treatment failure with vancomycin trough concentrations < 10 μg/mL have led guidelines to increase goal concentrations. There is a paucity of data evaluating vancomycin dosage necessary to achieve goals in the neonatal intensive care unit (NICU). We aimed to evaluate the implementation of a new vancomycin dosing guideline in improving trough target attainment. This retrospective study evaluated neonates in the NICU treated with vancomycin between January 2009 and December 2015. Therapeutic trough concentration attainment (10-20 μg/mL) was compared between neonates receiving vancomycin per old versus new dosing guidelines. Vancomycin trough concentrations, modeled pharmacodynamic target attainment, and nephrotoxicity were compared between groups. A total of 212 vancomycin trough concentrations (n = 91 old and n = 121 new guideline) were evaluated in 182 unique neonates. The mean ± standard deviation trough concentration achieved was 18.0 ± 7.3 μg/mL vs 8.9 ± 4.8 μg/mL in the new and old guidelines, respectively (P < .01). The new guideline resulted in a higher percentage of neonates achieving trough concentrations of 10 to 20 μg/mL (62% vs 29%; P < .01) and decreased the percentage of neonates with subtherapeutic trough concentrations (9% vs 69%; P < .01). Pharmacokinetic modeling identified postmenstrual age, days of life, and urine output as predictors of vancomycin clearance and resultant trough and area under the curve values (P < .01 for all). Trough concentrations >10 μg/mL ensured area under the curve /minimum inhibitory concentration >400 in >90% of neonates when bacteria minimum inhibitory concentration was ≤ 1 μg/mL. Nephrotoxicity was similar between groups (8.3% vs 7.7%; P = .99). In conclusion, a vancomycin nomogram designed to achieve trough concentration of 10 to 20 μg/mL improves pharmacodynamic target attainment in neonates in the NICU.
由于对万古霉素谷浓度 < 10μg/mL 时出现细菌耐药和治疗失败的担忧，指南建议提高目标浓度。在新生儿重症监护病房（NICU）中，评估达到目标所需的万古霉素剂量的数据很少。我们旨在评估新的万古霉素剂量指南的实施情况，以提高谷值目标的实现。这项回顾性研究评估了 2009 年 1 月至 2015 年 12 月期间在 NICU 接受万古霉素治疗的新生儿。比较了接受旧和新剂量指南的万古霉素治疗的新生儿的治疗性谷浓度达标情况（10-20μg/mL）。比较了两组的万古霉素谷浓度、模型药代动力学目标达标情况和肾毒性。共评估了 182 例接受万古霉素治疗的 182 例独特新生儿的 212 个万古霉素谷浓度（n=91 个旧和 n=121 个新指南）。新指南组的平均±标准差谷浓度分别为 18.0±7.3μg/mL 和 8.9±4.8μg/mL（P<.01）。新指南使更多的新生儿达到 10-20μg/mL 的谷浓度（62% vs 29%；P<.01），并减少了亚治疗性谷浓度的新生儿比例（9% vs 69%；P<.01）。药代动力学模型确定胎龄、生命天数和尿量为万古霉素清除率及相应的谷浓度和曲线下面积值的预测因子（所有 P<.01）。当细菌最小抑菌浓度≤1μg/mL 时，>10μg/mL 的万古霉素谷浓度可确保>90%的新生儿的 AUC/MIC 比值>400。两组的肾毒性相似（8.3% vs 7.7%；P=0.99）。总之，设计达到 10-20μg/mL 谷浓度的万古霉素列线图可提高 NICU 新生儿的药效学目标实现。
