Division of Pediatric General and Thoracic Surgery, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Rangos Research Center 6th Floor, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
Division of Pediatrics, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA, 92123, USA.
Trials. 2022 May 23;23(1):428. doi: 10.1186/s13063-022-06352-3.
Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants.
The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity.
The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery.
Trial registration data: June 25, 2019 NCT03997266 .
早发性败血症是早产儿发病率和死亡率的重要原因。尽管极低出生体重儿（ELBW）中早发性败血症的总体发病率为 2-3%，但被认为有早发性败血症风险的婴儿通常在等待确认性血液培养的同时，经验性地接受广谱抗生素治疗。最近的观察性研究表明，围产期使用抗生素与 ELBW 婴儿中坏死性小肠结肠炎、晚发性败血症和死亡率的发生率增加有关。鉴于目前可用的数据和临床实践中的变异性，我们设计了一项前瞻性多机构随机对照试验，以确定 ELBW 婴儿早期使用抗生素的安全性。
NICU 抗生素和结局（NANO）试验是一项多中心、双盲、随机对照试验。将 802 名 ELBW 早产儿进行基于网络的分层分组随机分组，以在常规评估早发性败血症时接受经验性抗生素（EA；氨苄西林和庆大霉素）或安慰剂。参与的站点将使用预先存在的机构抗生素剂量和持续时间方案。在参与站点出生的胎龄为 29 周或更小的婴儿有资格入组。排除标准包括母体宫内感染、血流动力学或呼吸不稳定、无劳动或延长胎膜破裂的母体指征行剖宫产、以及之前使用过抗生素。主要结局是参与者指数住院期间坏死性小肠结肠炎、晚发性败血症或死亡的复合发生率。将纵向收集母婴样本并评估微生物组组成和多样性的差异。
NANO 试验旨在比较出生时使用 EA 与安慰剂在 ELBW 早产儿中的不良结局发生率。如果出生时使用 EA 恶化临床结局，则试验结果可能有助于提供者减少 NICU 中的抗生素使用，从而降低与 ELBW 婴儿早期使用抗生素相关的并发症发生率。如果我们发现 EA 改善结局，那么试验将验证一种长期存在的临床实践，而这种实践以前没有得到高质量数据的支持。未来的研究将评估接受经验性抗生素治疗后婴儿的长期临床和微生物结局。
试验注册数据：2019 年 6 月 25 日 NCT03997266 。
