Metsvaht Tuuli, Nellis Georgi, Varendi Heili, Nunn Anthony J, Graham Susan, Rieutord Andre, Storme Thomas, McElnay James, Mulla Hussain, Turner Mark A, Lutsar Irja
Institute of Microbiology, Tartu University, Tartu, Estonia.
Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.
BMC Pediatr. 2015 Apr 16;15:41. doi: 10.1186/s12887-015-0359-y.
Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement.
A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis.
In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations.
The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.
新生儿抗生素给药剂量在不同国家和医疗中心存在差异，这表明部分新生儿的药物暴露情况未达最佳。我们旨在描述欧洲新生儿重症监护病房（NICU）常用抗生素给药剂量的差异及影响变异性的因素，以帮助制定改进策略。
对欧洲新生儿辅料暴露点患病率研究进行了一项子分析。记录了2012年1月至6月三个两周时间段之一内，在研究日接受任何抗生素治疗的新生儿的人口统计学数据、每张处方的剂量、给药间隔和给药途径。使用《英国国家儿童处方集》（BNFC）和《新生儿用药手册》作为参考资料。通过多因素逻辑回归分析确定超过相关BNFC剂量推荐±25%偏差的危险因素。
来自21个国家的89个NICU报告了342例婴儿的586份抗生素处方。12种最常用的抗生素——庆大霉素、青霉素G、氨苄西林、万古霉素、阿米卡星、头孢噻肟、头孢他啶、美罗培南、阿莫西林、甲硝唑、替考拉宁和氟氯西林——涵盖了92%的全身处方。糖肽类、胎龄小于32周、第5分钟阿氏评分小于5以及地理区域与偏离BNFC剂量推荐有关。虽然青霉素类药物的剂量超过了推荐值，但随后是有安全问题的抗生素（庆大霉素）或低于推荐剂量给药的抗生素（万古霉素）。
目前新生儿现有给药推荐的依从性欠佳，需要通过开展针对少数几种抗生素的精心设计的临床试验来确定该人群的药代动力学/药效学、疗效和安全性，并有效传播研究结果来加以克服。
