Whether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections. The PROMPT trial is a prospective, non-interventional, multi-center clinical study that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status. Subject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90–0.99) and 0.90 (95% CI 0.83–0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95% CI 0.79–0.96) for PCT, 0.80 (95% CI 0.72–89) for CRP and 0.78 (95% CI 0.69–0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (> 0.5 µg/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out). InSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship. Registration number at Clinicaltrials.gov NCT 03295825.

中文翻译：

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来自血液的 29-mRNA 宿主反应测试可准确区分急诊科患者的细菌和病毒感染

对于到急诊科 (ED) 就诊的疑似感染患者，是否使用抗生素是一项常见且具有挑战性的临床决定。我们前瞻性地验证了 InSep，这是一种基于 29-mRNA 血液的宿主反应测试，用于预测细菌和病毒感染。PROMPT 试验是一项前瞻性、非干预性、多中心临床研究，招募了 397 名到 ED 就诊的成年患者，这些患者有急性感染的迹象和至少一个生命体征改变。感染状态由三位对 InSep 结果不知情的传染病医生使用图表审查（包括综合征分子呼吸小组、降钙素原和 C 反应蛋白）来判断。InSep（BVN-2 版）使用在 NanoString nCounter SPRINT 上处理和定量的 PAXgene Blood RNA 进行。InSep 结果（细菌和病毒感染的可能性）与判定的感染状态进行了比较。受试者平均年龄为 64 岁，糖尿病 (17.1%)、慢性阻塞性肺病 (13.6%) 和严重神经系统疾病 (6.8%) 的合并症显着；16.9% 的受试者免疫功能低下。感染被判定为细菌 (14.1%)、病毒 (11.3%) 和非感染 (0.25%)：74.1% 的受试者被判定为不确定。InSep 使用 AUROC 分别为 0.94 (95% CI 0.90–0.99) 和 0.90 (95% CI 0.83–0.96) 的共识来区分细菌与病毒/非感染患者和病毒与细菌/非感染患者。细菌与病毒/非感染患者的 AUROC PCT 为 0.88（95% CI 0.79–0.96），CRP 为 0.80（95% CI 0.72–89）和 0.78（95% CI 0.69–0）。87）用于白细胞计数（值得注意的是，后者的生物标志物是作为临床裁决的一部分提供的）。为了实现临床可操作性，InSep 结合了分数临界值以将患者分配到解释带中。非常可能（规则）InSep 细菌条带显示出 98% 的特异性，而相应 PCT 条带的特异性为 94%（> 0.5 µg/L）；非常不可能（排除）波段显示 InSep 的灵敏度为 95%，而 PCT 的灵敏度为 86%。对于病毒感染的检测，InSep 对非常可能带（排除）的特异性为 93%，对非常不可能带（排除）的灵敏度为 96%。InSep 在预测疑似急性感染或疑似败血症的 ED 患者中是否存在细菌和病毒感染方面表现出很高的准确性。当转化为快速的即时检验时，InSep 将为 ED 医生提供可操作的结果，支持早期知情的治疗决策，以改善患者的治疗效果，同时坚持抗菌药物管理。Clinicaltrials.gov NCT 03295825 上的注册号。