{"title":"Impact of time to antibiotics on clinical outcome in paediatric febrile neutropenia: a target trial emulation of 1685 episodes","authors":"","doi":"10.1016/j.lanwpc.2024.101226","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>a priori</em> (age, sex, severely unwell, disease, chemotherapy intensity and site). TTA was defined as time from from emergency triage to first antibiotic dose.</div></div><div><h3>Findings</h3><div>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.</div></div><div><h3>Interpretation</h3><div>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.</div></div><div><h3>Funding</h3><div><span>National Health and Medical Research Council</span> and <span>Medical Research Future Fund</span>.</div></div>","PeriodicalId":22792,"journal":{"name":"The Lancet Regional Health: Western Pacific","volume":null,"pages":null},"PeriodicalIF":7.6000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Lancet Regional Health: Western Pacific","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666606524002207","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEALTH CARE SCIENCES & SERVICES","Score":null,"Total":0}
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.
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.