A Pharmacoepidemiologic Study of the Safety and Effectiveness of Clindamycin in Infants.
A Pharmacoepidemiologic Study of the Safety and Effectiveness of Clindamycin in Infants.
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克林霉素在婴儿中的安全性和有效性的药物流行病学研究。
DOI：
10.1097/inf.0000000000002524
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Walter,EmmanuelB
中科院分区：
文献类型：
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作者：
Greenberg,RachelG;Wu,Huali;Maharaj,Anil;Cohen-Wolkowiez,Michael;Tomashek,KayM;Osborn,BlaireL;Clark,ReeseH;Walter,EmmanuelB
背景：尽管缺乏足够的安全性或有效性数据，克林霉素被广泛用于新生儿重症监护室。我们评估了克林霉素暴露和不良事件之间的关联，以及抗生素在infants.Methods中的有效性：这是一项回顾性队列研究，研究对象是出生后第121天从Pediatrix Medical Group新生儿重症监护室出院的接受克林霉素的婴儿（1997-2015）。使用以前开发的药代动力学模型，我们进行了模拟，以预测克林霉素暴露的基础上，现有的剂量数据。我们使用多变量逻辑回归来评估克林霉素暴露与克林霉素治疗期间和之后的安全性结局之间的关系。我们报告了耐甲氧西林金黄色葡萄球菌（MRSA）菌血症和MRSA菌血症清除率的婴儿比例。结果：共有4089名婴儿接受克林霉素的中位数（第25 - 75百分位数）剂量为15 mg/kg/d（12-16）。清除率随胎龄增加而增加。克林霉素总暴露量最高的婴儿在7天内发生坏死性小肠结肠炎的几率略有增加（调整后的比值比= 1.95 [1.04-3.63]），但暴露与死亡、败血症、癫痫发作、肠穿孔或肠狭窄无关。在25名患有MRSA菌血症的婴儿中，19名（76%）在克林霉素疗程结束时清除了感染。结论：克林霉素暴露量越高，死亡或非实验室不良事件的几率越高。当大规模试验不可行时，结合现有的电子健康记录数据使用药代动力学模型提供了一种有价值的、具有成本效益的方法来分析婴儿药物的安全性和有效性。
Background:Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and adverse events, as well as antibiotic effectiveness in infants.Methods:This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997–2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia.Results:A total of 4089 infants received clindamycin at a median (25th–75th percentile) dose of 15 mg/kg/d (12–16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio= 1.95 [1.04–3.63]), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course.Conclusions:Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.