Laine Niina, Kaukonen Ann Marie, Hoppu Kalle, Airaksinen Marja, Saxen Harri
Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 11, 00029 HUS, Helsinki, PL 281, Finland.
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 9, 00014, Helsinki, Finland.
Eur J Clin Pharmacol. 2017 May;73(5):609-614. doi: 10.1007/s00228-017-2200-z. Epub 2017 Jan 18.
Off-label (OL) use of drugs for hospitalized children is very common. OL use occurs especially in the youngest patients, neonates. This study focused on the OL use of antimicrobials in neonates. To our knowledge, only few studies have focused on the prevalence of OL use of antimicrobials in neonates.
We investigated the OL use of antimicrobials in neonates in a tertiary children's hospital. First, we investigated what were the most consumed OL antimicrobials in defined daily doses according to hospital's registry data from neonatal intensive care unit (NICU) during 2009-2014. Second, we conducted a targeted retrospective study of premature neonates (400-2000 g) with blood culture-positive infections and receiving antimicrobial therapy between 2005 and 2014 (N = 282). The data were obtained from the electronic patient records and from the hospital's electronic infection registry. Statistical analysis was conducted by using a univariate logistic regression model fitted for OL usage.
In NICU, 35% (7/20) of antimicrobials used were OL. Eighteen percent (51/282) of premature neonates with blood culture-positive infections received at least one antimicrobial OL. The most commonly used OL antimicrobials in neonates were meropenem 88% (45/51), rifampicin 18% (9/51), and ciprofloxacin 8% (4/51). The odds for OL use were significantly higher the smaller the neonate birth weight was. An increase in birth weight was found to statistically significantly decrease the probability of OL usage (odds ratio = 0.85 for 100 g increase in birth weight, p value <0.001).
More studies in neonates on especially dosing and pharmacokinetics of antimicrobials are urgently needed.
药物在住院儿童中的超说明书（OL）使用非常普遍。OL使用尤其发生在最年幼的患者，即新生儿中。本研究聚焦于新生儿抗菌药物的OL使用。据我们所知，仅有少数研究关注新生儿抗菌药物OL使用的患病率。
我们调查了一家三级儿童医院中新生儿抗菌药物的OL使用情况。首先，根据2009 - 2014年新生儿重症监护病房（NICU）的医院登记数据，我们调查了按限定日剂量计算消耗最多的OL抗菌药物有哪些。其次，我们对2005年至2014年间血培养阳性感染且接受抗菌治疗的早产新生儿（400 - 2000克）进行了针对性回顾性研究（N = 282）。数据从电子病历和医院的电子感染登记处获取。使用适合OL使用情况的单因素逻辑回归模型进行统计分析。
在NICU中，使用的抗菌药物有35%（7/20）为OL。血培养阳性感染的早产新生儿中有18%（51/282）至少接受了一种抗菌药物的OL使用。新生儿中最常用的OL抗菌药物为美罗培南88%（45/51）、利福平18%（9/51）和环丙沙星8%（4/51）。新生儿出生体重越小，OL使用的几率显著越高。发现出生体重增加在统计学上显著降低了OL使用的概率（出生体重每增加100克，优势比 = 0.85，p值<0.001）。
迫切需要针对新生儿开展更多关于抗菌药物特别是给药剂量和药代动力学的研究。
