Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Eur J Clin Microbiol Infect Dis. 2019 Oct;38(10):1829-1836. doi: 10.1007/s10096-019-03616-w. Epub 2019 Jun 26.
A novel multiplex real-time PCR for bloodstream infections (BSI-PCR) detects pathogens directly in blood. This study aimed at determining the positive predictive value (PPV) of BSI-PCR in critically ill patients with sepsis. We included consecutive patients with presumed sepsis upon admission to the intensive care unit (ICU). The multiplexed BSI-PCR included 17 individual PCRs for a broad panel of species- and genus-specific DNA targets. BSI-PCR results were compared with a reference diagnosis for which plausibility of infection and causative pathogen(s) had been prospectively assessed by trained observers, based on available clinical and microbiological evidence. PPV and false positive proportion (FPP) were calculated. Clinical plausibility of discordant positive results was adjudicated by an expert panel. Among 325 patients, infection likelihood was categorized as confirmed, uncertain, and ruled out in 210 (65%), 88 (27%), and 27 (8%) subjects, respectively. BSI-PCR identified one or more microorganisms in 169 (52%) patients, of whom 104 (61%) had at least one detection in accordance with the reference diagnosis. Discordant positive PCR results were observed in 95 patients, including 30 subjects categorized as having an "unknown" pathogen. Based on 5525 individual PCRs yielding 295 positive results, PPV was 167/295 (57%) and FPP was 128/5525 (2%). Expert adjudication of the 128 discordant PCR findings resulted in an adjusted PPV of 68% and FPP of 2%. BSI-PCR was all-negative in 156 patients, including 79 (51%) patients in whom infection was considered ruled out. BSI-PCR may complement conventional cultures and expedite the microbiological diagnosis of sepsis in ICU patients, but improvements in positive predictive value of the test are warranted before its implementation in clinical practice can be considered.
一种新的血流感染（BSI-PCR）多重实时 PCR 可直接检测血液中的病原体。本研究旨在确定重症监护病房（ICU）中疑似败血症患者的 BSI-PCR 的阳性预测值（PPV）。我们纳入了 ICU 入院时被认为患有败血症的连续患者。该多重 BSI-PCR 包括 17 种针对广泛物种和属特异性 DNA 靶标的个体 PCR。BSI-PCR 结果与参考诊断进行了比较，参考诊断是由经过培训的观察者根据可用的临床和微生物学证据，前瞻性评估感染的可能性和病原体。计算了 PPV 和假阳性比例（FPP）。通过专家小组对不一致的阳性结果的临床可能性进行了裁决。在 325 名患者中，感染可能性被归类为确诊、不确定和排除，分别为 210 名（65%）、88 名（27%）和 27 名（8%）患者。BSI-PCR 在 169 名（52%）患者中鉴定出一种或多种微生物，其中 104 名（61%）患者至少有一种检测结果与参考诊断一致。在 95 名患者中观察到不一致的阳性 PCR 结果，包括 30 名被归类为具有“未知”病原体的患者。基于产生 295 个阳性结果的 5525 个单独 PCR，PPV 为 167/295（57%），FPP 为 128/5525（2%）。对 128 个不一致的 PCR 结果进行专家裁决后，调整后的 PPV 为 68%，FPP 为 2%。BSI-PCR 在 156 名患者中均为阴性，其中 79 名（51%）患者被认为感染已排除。BSI-PCR 可能补充常规培养并加速 ICU 患者败血症的微生物学诊断，但在考虑将其应用于临床实践之前，需要提高该测试的阳性预测值。
