Hansen Anne, Forbes Peter, Arnold Alana, O'Rourke Edward
Division of Newborn Medicine, Children's Hospital, Boston, MA, USA.
J Perinatol. 2003 Dec;23(8):635-9. doi: 10.1038/sj.jp.7210996.
Based on recent safety and efficacy data, combined with the known pharmacokinetic parameters of aminoglycosides in the newborn, once-daily gentamicin should be preferable to the many other dosing regimens currently in use. Although there are growing data to support its use in term newborns, experience with preterm infants is more limited. In our Neonatal Intensive Care Unit, we experienced difficulties regarding complicated dosing regimens, actual dosing errors, and the tendency to check trough and peak levels around the third dose for infants receiving only a 48 hour course. Therefore, we conducted a quality improvement initiative in which we developed and tested a clinical practice guideline for the use of once-daily gentamicin for preterm and term infants that we hoped would yield trough and peak levels in our target range.
We combined a review of the published English language literature with pharmacokinetic analysis of our own data prior to initiation of this new regimen to design the following dosing regimen: <35 weeks gestation: 3 mg/kg q 24 hours, > or =35 weeks gestation: 4 mg/kg q 24 hours. Our goal serum levels were a trough < or =2 microg/ml and a peak between 6 and 12 microg/ml. We collected and analyzed trough and peak levels from all infants receiving this dosing regimen in the first week of life for at least 72 hours between 3/1/99 and 12/31/00.
In total, 214 babies met our inclusion criteria, 75 of whom were <35 weeks gestation. 100% of babies of all gestational ages had a nontoxic trough level. For infants <35 weeks gestation, 79% had a therapeutic peak level, with a mean value of 6.8 microg/ml. For infants of at least 35 weeks gestation, 93% had a therapeutic peak level, with a mean value of 8.4 microg/ml. 92% of nontherapeutic peaks were too low.
This study of once-daily gentamicin represents the largest sample size of pre-term infants published to date. The proposed regimen is simple and yields a high proportion of desirable levels. We recommend it for use in preterm and term newborns.
基于近期的安全性和有效性数据，结合新生儿氨基糖苷类药物已知的药代动力学参数，每日一次的庆大霉素给药方案应优于目前使用的许多其他给药方案。尽管有越来越多的数据支持其在足月儿中的应用，但在早产儿中的经验更为有限。在我们的新生儿重症监护病房，我们在复杂的给药方案、实际给药错误以及对仅接受48小时疗程的婴儿在第三次给药前后检查谷值和峰值水平的倾向方面遇到了困难。因此，我们开展了一项质量改进计划，制定并测试了一项针对早产儿和足月儿每日一次使用庆大霉素的临床实践指南，我们希望该指南能使谷值和峰值水平达到我们的目标范围。
在启动这一新方案之前，我们将已发表的英文文献回顾与我们自己的数据的药代动力学分析相结合，以设计以下给药方案：妊娠<35周：3mg/kg，每24小时一次；妊娠≥35周：4mg/kg，每24小时一次。我们的目标血清水平为谷值≤2μg/ml，峰值在6至12μg/ml之间。我们收集并分析了1999年3月1日至2000年12月31日期间所有接受该给药方案的婴儿在出生后第一周内至少72小时的谷值和峰值水平。
总共有214名婴儿符合我们的纳入标准，其中75名妊娠<35周。所有孕周的婴儿100%谷值水平无毒。对于妊娠<35周的婴儿，79%的峰值水平处于治疗范围，平均值为6.8μg/ml。对于妊娠至少35周的婴儿，93%的峰值水平处于治疗范围，平均值为8.4μg/ml。92%的非治疗性峰值过低。
这项关于每日一次庆大霉素的研究是迄今为止发表的早产儿样本量最大的研究。所提出的方案简单，且能产生较高比例的理想水平。我们建议将其用于早产儿和足月儿。
