Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Sci Rep. 2022 Aug 18;12(1):14028. doi: 10.1038/s41598-022-18168-x.
Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. We analyzed the association between time from recognition of fever to start of antibiotics (TTA) and SRE (death, admission to intensive care unit, severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation with FN. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. TTA (median, 120 min; interquartile range, 49-180 min) was not associated with SRE, with a trend for less SREs in episodes with longer TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. In conclusion, TTA was unrelated to poor clinical outcome in pediatric patients with FN presenting without severe disease. We saw strong evidence for triage bias which could only be partially adjusted.
中性粒细胞减少症（FN）并发发热是化疗不可避免的、潜在致命的并发症。及时给予经验性广谱静脉内抗生素治疗已成为常规护理。但抗生素治疗时间（TTA），即从发热或到达医院开始使用抗生素的时间到开始使用抗生素的时间之间的时间差，其影响仍不清楚。在这里，我们旨在分析前瞻性多中心研究数据中 TTA 与安全相关事件（SRE）之间的关联。我们使用三级混合逻辑回归分析了从发热识别到开始使用抗生素（TTA）的时间与 SRE（死亡、入住重症监护病房、严重败血症和菌血症）之间的关联。我们使用倾向评分调整了可能的分诊偏倚，并根据 FN 时疾病的严重程度对分析进行分层。我们分析了 266 例 FN 发作，包括 140 例 269 例患者中报告的 53 例（20%）有 SRE。从 2016 年 4 月至 2018 年 8 月招募的 FN 患者中报告的 53 例（20%）有 SRE。TTA（中位数 120 分钟；四分位距 49-180 分钟）与 SRE 无关，TTA 较长的发作 SRE 较少。应用倾向评分的分析表明存在相关的分诊偏倚。仅在首发疾病严重的患者中，较长的 TTA 与更多的 SRE 呈趋势相关。总之，在没有严重疾病的 FN 儿科患者中，TTA 与不良临床结局无关。我们看到了强烈的分诊偏倚证据，只能部分调整。
