Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Janeway Children's Health and Rehabilitation Centre, Saint John's, Newfoundland, Canada.
JAMA Pediatr. 2016 Dec 1;170(12):1181-1187. doi: 10.1001/jamapediatrics.2016.2132.
Excessive antibiotic use has been associated with altered bacterial colonization and may result in antibiotic resistance, fungemia, necrotizing enterocolitis (NEC), and mortality. Exploring the association between antibiotic exposure and neonatal outcomes other than infection-related morbidities may provide insight on the importance of rational antibiotic use, especially in the setting of culture-negative neonatal sepsis.
To evaluate the trend of antibiotic use among all hospitalized very low-birth-weight (VLBW) infants across Canada and the association between antibiotic use rates (AURs) and mortality and morbidity among neonates without culture-proven sepsis or NEC.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted among VLBW infants (<1500 g) admitted to level III neonatal intensive care units between January 1, 2010, and December 31, 2014, using data obtained from the Canadian Neonatal Network database.
Duration of antibiotic use during the hospitalization period.
The AUR was defined as the number of days an infant was exposed to 1 or more antimicrobial agents divided by the total length of hospital stay. The composite primary outcome was defined as mortality or major morbidity, including any of the following: persistent periventricular echogenicity or echolucency on neuroimaging, chronic lung disease, and stage 3 or higher retinopathy of prematurity. Multivariable regression analysis was used to calculate adjusted odds ratios (aORs) and 95% CIs for the association between AURs and outcomes.
Among 13 738 eligible VLBW infants, 11 669 (84.9%) (mean [SD] gestational age, 27.7 [2.5] weeks; 47.4% female) received antibiotics during their hospital course and were included in the study. The annual AUR decreased from 0.29 in 2010 to 0.25 in 2014 (slope for the best-fit line, -0.011; 95% CI, -0.016 to -0.006; P < .01), which occurred in parallel with a reduction in the rate of late-onset sepsis from 19.0% in 2010 to 13.8% in 2014 during the same period. Of the 11 669 infants who were treated with antibiotics of varying duration during their hospital stay, 2845 were diagnosed as having sepsis-related complications. Among the remaining 8824 infants without early-onset sepsis, late-onset sepsis, or NEC, a 10% increase in the AUR was associated with an increased odds of the primary composite outcome (aOR, 1.18; 95% CI, 1.13-1.23), mortality (aOR, 2.04; 95% CI, 1.87-2.21), and stage 3 or higher retinopathy of prematurity (aOR, 1.18; 95% CI, 1.06-1.32).
Antibiotic use in VLBW infants decreased between 2010 and 2014 in Canada. However, among infants without culture-proven sepsis or without NEC, higher AURs were associated with adverse neonatal outcomes.
过度使用抗生素与细菌定植改变有关，并可能导致抗生素耐药性、真菌血症、坏死性小肠结肠炎（NEC）和死亡。探索抗生素暴露与感染相关发病率以外的新生儿结局之间的关系，可能有助于了解合理使用抗生素的重要性，尤其是在培养阴性新生儿败血症的情况下。
评估加拿大所有住院极低出生体重（VLBW）婴儿的抗生素使用趋势，以及抗生素使用率（AUR）与无培养阳性败血症或 NEC 的新生儿死亡率和发病率之间的关系。
设计、设置和参与者：对 2010 年 1 月 1 日至 2014 年 12 月 31 日期间在加拿大新生儿网络数据库中住院的胎龄<1500 g 的 VLBW 婴儿进行了回顾性队列研究。
住院期间抗生素使用的持续时间。
AUR 定义为婴儿接受 1 种或多种抗菌药物治疗的天数除以总住院天数。主要复合结局定义为死亡率或主要发病率，包括以下任何一种情况：神经影像学上持续存在脑室周围回声增强或回声减弱、慢性肺病和 3 期或更高的早产儿视网膜病变。使用多变量回归分析计算 AUR 与结局之间的调整后比值比（aOR）和 95%CI。
在 13738 名符合条件的 VLBW 婴儿中，11669 名（84.9%）（平均[SD]胎龄 27.7[2.5]周；47.4%为女性）在住院期间接受了抗生素治疗，并纳入了研究。2010 年至 2014 年期间，年 AUR 从 0.29 降至 0.25（最佳拟合线斜率，-0.011；95%CI，-0.016 至-0.006；P<.01），同时晚期发病败血症的发生率从同期的 19.0%降至 13.8%。在接受不同时间抗生素治疗的 11669 名婴儿中，有 2845 名被诊断为与败血症相关的并发症。在其余 8824 名无早发性败血症、晚发性败血症或 NEC 的婴儿中，AUR 增加 10%，则主要复合结局的发生几率增加（aOR，1.18；95%CI，1.13-1.23）、死亡率（aOR，2.04；95%CI，1.87-2.21）和 3 期或更高的早产儿视网膜病变（aOR，1.18；95%CI，1.06-1.32）。
2010 年至 2014 年期间，加拿大 VLBW 婴儿的抗生素使用量有所下降。然而，在无培养阳性败血症或无 NEC 的婴儿中，较高的 AUR 与新生儿不良结局相关。
