Verlaan Diede, Derde Lennie P G, van der Poll Tom, Bonten Marc J M, Cremer Olaf L
Department of Intensive Care Medicine, University Medical Centre Utrecht, Utrecht University, Heidelberglaan 100, F06.149, P.O. Box 85500, 3508, GA, Utrecht, The Netherlands.
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Intensive Care Med Exp. 2024 May 28;12(1):50. doi: 10.1186/s40635-024-00634-7.
BACKGROUND: Pancreatic stone protein (PSP) exhibits potential as a plasma biomarker for infection diagnosis and risk stratification in critically ill patients, but its significance in nosocomial infection and intensive care unit (ICU)-acquired bloodstream infection (BSI) remains unclear. This study explores the temporal responses of PSP in ICU-acquired BSI caused by different pathogens. METHODS: From a large cohort of ICU patients, we selected episodes of ICU-acquired BSI caused by Gram-negative rods (GNRs), enterococci, or Candida species. Events were matched on length of ICU stay at infection onset, Severe Organ Failure Assessment (SOFA) score, presence of immune deficiency, and use of renal replacement therapy. PSP concentrations were measured at infection onset (T0) and at 24, 48 and 72 h prior to infection onset as defined by the first occurrence of a positive blood culture. Absolute and trend differences in PSP levels between pathogen groups were analysed using one-way analysis of variance. Sensitivity analyses were performed in events with a new or worsening systematic inflammatory response based on C-reactive protein, white cell count and fever. RESULTS: We analysed 30 BSI cases per pathogen group. Median (IQR) BSI onset was on day 9 (6-12). Overall, PSP levels were high (381 (237-539) ng/ml), with 18% of values exceeding the assay's measurement range. Across all 90 BSI cases, there was no clear trend over time (median change 34 (- 75-189) ng/ml from T-72 to T0). PSP concentrations at infection onset were 406 (229-497), 350 (223-608), and 480 (327-965) ng/ml, for GNR, enterococci, and Candida species, respectively (p = 0.32). At every time point, absolute PSP levels and trends did not differ significantly between pathogens. PSP values at T0 correlated with SOFA scores. Eighteen (20%) of 90 BSI events did not exhibit a systemic inflammatory response, primarily in Candida species. No clear change in PSP concentration before BSI onset or between-group differences were found in sensitivity analyses of 72 cases. CONCLUSIONS: Against a background of overall (very) high plasma PSP levels in critically ill patients, we did not find clear temporal patterns or any pathogen-specific differences in PSP response in the days preceding onset of ICU-acquired BSI.
背景：胰石蛋白（PSP）有潜力作为重症患者感染诊断和风险分层的血浆生物标志物，但其在医院感染及重症监护病房（ICU）获得性血流感染（BSI）中的意义仍不明确。本研究探讨了PSP在不同病原体所致ICU获得性BSI中的时间反应。 方法：从一大群ICU患者中，我们选取了由革兰氏阴性杆菌（GNRs）、肠球菌或念珠菌属引起的ICU获得性BSI病例。根据感染发作时的ICU住院时间、严重器官功能衰竭评估（SOFA）评分、免疫缺陷的存在情况以及肾脏替代治疗的使用情况对病例进行匹配。在感染发作时（T0）以及首次血培养阳性所定义的感染发作前24、48和72小时测量PSP浓度。使用单因素方差分析分析病原体组之间PSP水平的绝对差异和趋势差异。基于C反应蛋白、白细胞计数和发热，对有新的或加重的全身炎症反应的病例进行敏感性分析。 结果：我们对每个病原体组的30例BSI病例进行了分析。BSI发作的中位时间（四分位间距）为第9天（6 - 12天）。总体而言，PSP水平较高（381（237 - 539）ng/ml），18%的值超过了检测范围。在所有90例BSI病例中，随时间没有明显趋势（从T - 72到T0的中位变化为34（-75 - 189）ng/ml）。GNR、肠球菌和念珠菌属感染发作时的PSP浓度分别为406（229 - 497）、350（223 - 608）和480（327 - 965）ng/ml（p = 0.32）。在每个时间点，病原体之间的PSP绝对水平和趋势没有显著差异。T0时的PSP值与SOFA评分相关。90例BSI事件中有18例（20%）未表现出全身炎症反应，主要见于念珠菌属。在72例病例的敏感性分析中，未发现BSI发作前PSP浓度有明显变化或组间差异。 结论：在重症患者血浆PSP总体（非常）高水平的背景下，我们未发现ICU获得性BSI发作前数天PSP反应有明确的时间模式或任何病原体特异性差异。
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