Impact of time to antibiotics on clinical outcome in paediatric febrile neutropenia: a target trial emulation of 1685 episodes

IF 7.6 1区医学 Q1 HEALTH CARE SCIENCES & SERVICES

The Lancet Regional Health: Western Pacific Pub Date : 2024-11-02 DOI:10.1016/j.lanwpc.2024.101226

Gabrielle M. Haeusler , S Ghazaleh Dashti , Fiona James , Franz E. Babl , Meredith L. Borland , Julia E. Clark , Bhavna Padhye , Heather Tapp , Frank Alvaro , Trisha Soosay Raj , Thomas Walwyn , David S. Ziegler , Leanne Super , Lisa Hall , Daniel K. Yeoh , Coen Butters , Brendan McMullan , Diane M.T. Hanna , Richard De Abreu Lourenco , Monica A. Slavin , Karin A. Thursky

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引用次数: 0

Abstract

Background

Prompt antibiotic administration for febrile neutropenia (FN) is standard of care, and targets of time to antibiotics (TTA) <60 min are common. We sought to determine the effect of TTA ≥60 versus <60 min on adverse outcomes (intensive care unit (ICU) admission or death) in children with cancer and FN. Effect modification by a decision rule that predicts infection (AUS-rule) and bacteraemia were also investigated.

Methods

The prospective, multi-centre (n = 8), Australian PICNICC study dataset was analysed. To control for confounding, we used outcome regression adjusted for propensity score modelled as restricted cubic spline with two degrees of freedom. The propensity score was estimated from a logistic regression model for the exposure on the confounders, identified a priori (age, sex, severely unwell, disease, chemotherapy intensity and site). TTA was defined as time from from emergency triage to first antibiotic dose.

Findings

1685 FN episodes in 976 patients were included. Median TTA was 53 min (IQR 37–77 min, 1542 (92%) <120 min). An adverse outcome occurred in 43 (2.6%) episodes (39 ICU; 5 deaths). The confounder-adjusted point estimate suggested a lower risk for adverse outcome associated with TTA ≥60 min (RR 0.62, 95% CI 0.32–1.21), but the wide 95% CI precluded definitive judgement about strength and direction of the effect (unadjusted RR 0.52; 95% CI 0.26, 1.05). Similarly, although the point estimates were suggestive of a null association or reduced risk for adverse outcome associated with TTA ≥60 min for all comparisons across bacteraemia or AUS-rule strata, the 95% CIs were imprecise.

Interpretation

For children with FN, there was no definite evidence that TTA ≥60 min from hospital triage (but within 2 h), increased risk of adverse outcome or prolonged hospital admission. This study has important implications for FN TTA mandates, suggesting a more nuanced approach is required.

Funding

National Health and Medical Research Council and Medical Research Future Fund.

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使用抗生素的时间对儿科发热性中性粒细胞减少症临床结果的影响：1685 例病例的目标试验模拟

背景发热性中性粒细胞减少症（FN）的及时抗生素应用是标准护理，抗生素应用时间（TTA）为 60 分钟的目标很常见。我们试图确定TTA≥60分钟与<60分钟对癌症和FN患儿不良结局（入住重症监护室或死亡）的影响。方法分析了澳大利亚 PICNICC 研究的前瞻性多中心（n = 8）数据集。为控制混杂因素，我们使用了根据倾向得分调整的结果回归，以两个自由度的受限立方样条为模型。倾向得分是根据事先确定的混杂因素（年龄、性别、严重不适、疾病、化疗强度和部位）暴露的逻辑回归模型估算得出的。TTA定义为从急诊分诊到首次服用抗生素的时间。中位 TTA 为 53 分钟（IQR 为 37-77 分钟，1542 (92%) <120 分钟）。43例（2.6%）发生不良后果（39例重症监护室；5例死亡）。混杂因素调整后的点估计值表明，TTA ≥60 分钟的不良结局风险较低（RR 0.62，95% CI 0.32-1.21），但 95% CI 较宽，无法明确判断影响的强度和方向（未调整 RR 0.52；95% CI 0.26，1.05）。同样，尽管在菌血症或 AUS 规则分层的所有比较中，点估计值均提示与 TTA ≥60 分钟相关的无效关联或不良结局风险降低，但 95% CI 不精确。这项研究对FN TTA规定具有重要意义，表明需要采取更细致的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

The Lancet Regional Health: Western Pacific Medicine-Pediatrics, Perinatology and Child Health

CiteScore

8.80

自引率

2.80%

发文量

305

审稿时长

11 weeks

期刊介绍： The Lancet Regional Health – Western Pacific, a gold open access journal, is an integral part of The Lancet's global initiative advocating for healthcare quality and access worldwide. It aims to advance clinical practice and health policy in the Western Pacific region, contributing to enhanced health outcomes. The journal publishes high-quality original research shedding light on clinical practice and health policy in the region. It also includes reviews, commentaries, and opinion pieces covering diverse regional health topics, such as infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, aging health, mental health, the health workforce and systems, and health policy.