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[Lancet在线发表]:PCT指导治疗决策缩短疑似早发性全身性感染新生儿的抗生素疗程
2017年08月06日 时讯速递, 进展交流 暂无评论

Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns)

Martin Stocker, Wendy van Herk, Salhab el Helou, et al.

Lancet 2017 Published: 12 July 2017

DOI: http://dx.doi.org/10.1016/S0140-6736(17)31444-7

Summary

Background 背景

Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.

在高收入国家中,多达7%的足月或早产儿在出生后3天内,因早发性全身性感染接受抗生素治疗。早发性全身性感染中培养阳性率不足0.1%,提示存在过度治疗。对于疑似早发性全身性感染,我们评价降钙素原指导的治疗决策能否安全地缩短抗生素疗程。

Methods 方法

We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.

我们在德国(n = 11)、瑞士(n = 4)、加拿大(n = 2)及捷克(n = 1)的医院中进行了一项随机对照干预试验。孕周超过34周的新生儿一旦疑似早发性全身性感染需要抗生素治疗,由主治医师进行风险分层,并根据计算机产生的随机数字按照中心进行随机分组,即PCT指导决策组或标准治疗组。出生后一周内接受手术或因重大先天性畸形需要住院的新生儿被排除。分组情况仅对主要研究者隐藏。共同主要预后终点包括出生后一个月内再次感染或死亡(非劣效)及抗生素疗程(优效)。采用意向治疗分析及符合方案集分析。

Findings 结果

Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 [0·6%] of 866 neonates in the procalcitonin group vs 4 [0·5%] of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 [0·7%] of 745 neonates in the procalcitonin group vs 4 [0·6%] of 663 neonates in the standard group).

2009年5月21日至2015年2月14日间,我们筛查了2440名疑似早发性全身性感染新生儿,622名婴儿因父母不同意被排除,另有93名婴儿未能入选,原因包括原因未知(68),先天性畸形(22),或第一周内接受手术(3);还有14名患儿因无法进行完整的数据监测或收集排除;1名新生儿因无法进行PCT测定被排除。最终1710名新生儿入选并被随机分为PCT指导治疗(n = 866)或标准治疗组(n = 844)。1408名患儿进入符合方案集分析(PCT组745名,标准治疗组663名)。在PCT组中,抗生素疗程显著缩短(意向治疗分析:55·1 vs 65·0 h, p<0·0001;符合方案集分析:51·8 vs 64·0 h; p<0·0001)。未发生感染相关死亡,1710名新生儿中的9名(<1%)发生了可能的再次感染。意向治疗分析中,非劣效风险差异为 0·1% (95% CI −4·6 to 4·8)(PCT组866名新生儿中5名 [0·6%] vs 标准治疗组844名新生儿中4名 [0·5%]),符合方案集分析结果为0·1% (−5·2 to 5·3)(PCT组745名新生儿中5名 [0·7%] vs 标准治疗组663名新生儿中4名 [0·6%])。

Interpretation 结论

Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.

对于疑似早发性全身性感染的新生儿,PCT指导的治疗决策对于缩短抗生素疗程的影响优于标准治疗。由于再次感染率很低,且没有研究相关死亡病例,因此未能显示非劣效结果。

Funding

The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.

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