OBJECTIVES: 

Sepsis remains a leading and preventable cause of hospital utilization and mortality in the United States. Despite updated guidelines, the optimal definition of sepsis as well as optimal timing of bundled treatment remain uncertain. Identifying patients with infection who benefit from early treatment is a necessary step for tailored interventions. In this study, we aimed to illustrate clinical predictors of time-to-antibiotics among patients with severe bacterial infection and model the effect of delay on risk-adjusted outcomes across different sepsis definitions.

DESIGN: 

A multicenter retrospective observational study.

SETTING: 

A seven-hospital network including academic tertiary care center.

PATIENTS: 

Eighteen thousand three hundred fifteen patients admitted with severe bacterial illness with or without sepsis by either acute organ dysfunction (AOD) or systemic inflammatory response syndrome positivity.

MEASUREMENTS AND MAIN RESULTS: 

The primary exposure was time to antibiotics. We identified patient predictors of time-to-antibiotics including demographics, chronic diagnoses, vitals, and laboratory results and determined the impact of delay on a composite of inhospital death or length of stay over 10 days. Distribution of time-to-antibiotics was similar across patients with and without sepsis. For all patients, a J-curve relationship between time-to-antibiotics and outcomes was observed, primarily driven by length of stay among patients without AOD. Patient characteristics provided good to excellent prediction of time-to-antibiotics irrespective of the presence of sepsis. Reduced time-to-antibiotics was associated with improved outcomes for all time points beyond 2.5 hours from presentation across sepsis definitions.

CONCLUSIONS: 

Antibiotic timing is a function of patient factors regardless of sepsis criteria. Similarly, we show that early administration of antibiotics is associated with improved outcomes in all patients with severe bacterial illness. Our findings suggest identifying infection is a rate-limiting and actionable step that can improve outcomes in septic and nonseptic patients.

中文翻译：

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患者异质性以及抗生素使用时间与入院细菌感染患者结果之间的 J 曲线关系*

目标： 

脓毒症仍然是美国医院利用率和死亡率的主要原因，且是可预防的。尽管更新了指南，脓毒症的最佳定义以及捆绑治疗的最佳时机仍然不确定。确定可从早期治疗中受益的感染患者是量身定制干预措施的必要步骤。在这项研究中，我们的目的是阐明严重细菌感染患者使用抗生素时间的临床预测因素，并模拟延迟对不同脓毒症定义的风险调整结果的影响。

设计： 

一项多中心回顾性观察研究。

环境： 

七家医院网络，包括学术三级护理中心。

患者： 

18,315 名患者因急性器官功能障碍 (AOD) 或全身炎症反应综合征阳性而患有严重细菌性疾病，伴有或不伴有脓毒症。

测量和主要结果： 

主要接触时间是抗生素的使用时间。我们确定了患者使用抗生素时间的预测因素，包括人口统计、慢性诊断、生命体征和实验室结果，并确定了延迟对住院死亡或超过 10 天住院时间的综合影响。患有和不患有脓毒症的患者的抗生素使用时间分布相似。对于所有患者，观察到抗生素使用时间与结果之间存在 J 曲线关系，这主要是由无 AOD 患者的住院时间决定的。无论是否存在脓毒症，患者特征都可以很好地预测抗生素使用时间。在脓毒症定义中，抗生素使用时间的缩短与就诊后 2.5 小时以上的所有时间点的结果改善相关。

结论： 

无论脓毒症标准如何，抗生素使用时机都是患者因素的函数。同样，我们表明，早期使用抗生素与所有患有严重细菌性疾病的患者的预后改善相关。我们的研究结果表明，识别感染是一个限速且可行的步骤，可以改善脓毒症和非脓毒症患者的预后。