基于TRAIL、IP-10和CRP的宿主标志物用于区分儿童细菌感染与病毒感染以减少抗生素过度使用：一项前瞻性、多中心队列研究
A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study.
作者信息
Papan Cihan, Argentiero Alberto, Porwoll Marian, Hakim Ummaya, Farinelli Edoardo, Testa Ilaria, Pasticci Maria Bruna, Mezzetti Daniele, Perruccio Katia, Etshtein Liat, Mastboim Niv, Moscoviz Einat, Ber Tahel Ilan, Cohen Asi, Simon Einav, Boico Olga, Shani Liran, Gottlieb Tanya M, Navon Roy, Barash Eran, Oved Kfir, Eden Eran, Simon Arne, Liese Johannes G, Knuf Markus, Stein Michal, Yacobov Renata, Bamberger Ellen, Schneider Sven, Esposito Susanna, Tenenbaum Tobias
机构信息
University Children's Hospital Mannheim, Heidelberg University, Paediatric Infectious Diseases, Mannheim, Germany; Centre for Infectious Diseases, Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany.
Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy.
出版信息
Clin Microbiol Infect. 2022 May;28(5):723-730. doi: 10.1016/j.cmi.2021.10.019. Epub 2021 Nov 10.
OBJECTIVES
Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections.
METHODS
This prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data.
RESULTS
In total, 1140 patients were recruited (February 2017-December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7-98.7), a specificity of 94.2% (92.2-96.1), positive predictive value of 73.0% (65.0-81.0), and negative predictive value of 98.9% (98.0-99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients.
CONCLUSIONS
The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.
目的
确定感染病因对于合理使用抗生素至关重要。先前的研究表明，由肿瘤坏死因子相关凋亡诱导配体（TRAIL）、干扰素γ诱导蛋白10（IP-10）和C反应蛋白（CRP）组成的宿主蛋白特征可准确区分细菌感染和病毒感染。
方法
这项名为AutoPilot-Dx的前瞻性多中心队列研究旨在验证该特征的性能，并评估其对意大利和德国急诊科及病房中患有呼吸道感染或不明原因发热的广泛儿科人群（90天以上至18岁）抗生素使用的潜在影响。感染病因由专家根据临床和实验室检查（包括多重PCR和随访数据）进行判定。
结果
共招募了1140名患者（2017年2月至2018年12月），其中1008名符合纳入标准（平均年龄3.5岁，41.9%为女性）。分别对628名（85.8%）儿童和104名（14.2%）儿童的病毒和细菌感染进行了判定；276名患者被判定为参考标准结果不确定。对于732名有参考标准病因的儿童，该特征区分细菌感染和病毒感染的敏感性为93.7%（95%CI 88.7-98.7），特异性为94.2%（92.2-96.1），阳性预测值为73.0%（65.0-81.0），阴性预测值为98.9%（98.0-99.8）；9.8%的检测结果不明确。该特征在不同患者亚组中表现一致，并在病毒PCR阳性患者中检测到细菌免疫反应。
结论
这些发现验证了TRAIL/IP-10/CRP特征在广泛儿科队列中的高诊断性能，并支持其在减少病毒感染儿童抗生素过度使用方面的潜力。
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