Identification of Potential Urinary Metabolite Biomarkers of Pseudomonas aeruginosa Ventilator-Associated Pneumonia

IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Biomarker Insights Pub Date : 2022-01-01 DOI:10.1177/11772719221099131
B. Jongers, A. Hotterbeekx, Kenny Bielen, P. Vervliet, J. Boddaert, C. Lammens, E. Fransen, G. Baggerman, A. Covaci, H. Goossens, S. Malhotra-Kumar, P. Jorens, S. Kumar-Singh
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Abstract

Introduction: Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of P. aeruginosa-derived markers in easily accessible patients’ samples can enable an early detection of P. aeruginosa VAP (VAP-PA), thereby stewarding antibiotic use and improving clinical outcomes. Methods: Metabolites were analysed using liquid chromatography-mass spectrometry (LC-MS) in prospectively collected urine samples from mechanically ventilated patients admitted to the Antwerp University Hospital ICU. Patients were followed from the start of mechanical ventilation (n = 100 patients) till the time of clinical diagnosis of VAP (n = 13). Patients (n = 8) in whom diagnosis of VAP was further confirmed by culturing respiratory samples and urine samples were studied for semi-quantitative metabolomics. Results: We first show that multivariate analyses highly discriminated VAP-PA from VAP–non-PA as well as from the pre-infection groups (R2 = .97 and .98, respectively). A further univariate analysis identified 58 metabolites that were significantly elevated or uniquely present in VAP-PA compared to the VAP–non-PA and pre-infection groups (P < .05). These comprised both a known metabolite of histidine as well as a novel nicotine metabolite. Most interestingly, we identified 3 metabolites that were not only highly upregulated for, but were also highly specific to, VAP-PA, as these metabolites were completely absent in all pre-infection timepoints and in VAP–non-PA group. Conclusions: Considerable differences exist between urine metabolites in VAP-PA compared to VAP due to other bacterial aetiologies as well to non-VAP (pre-infection) timepoints. The unique urinary metabolic biomarkers we describe here, if further validated, could serve as highly specific diagnostic biomarkers of VAP-PA.
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铜绿假单胞菌呼吸机相关性肺炎潜在尿液代谢物生物标志物的鉴定
由铜绿假单胞菌引起的呼吸机相关性肺炎(VAP)是医院重症监护病房(ICU)发病和死亡的主要原因。在易于获取的患者样本中快速鉴定铜绿假单胞菌衍生的标记物可以早期发现铜绿假单胞菌VAP (VAP- pa),从而管理抗生素的使用并改善临床结果。方法:采用液相色谱-质谱联用(LC-MS)对安特卫普大学医院ICU收治的机械通气患者前瞻性尿液样本进行代谢物分析。随访患者从机械通气开始(n = 100例)至临床诊断为VAP时(n = 13例)。通过培养呼吸样本和尿液样本进一步证实VAP诊断的患者(n = 8)进行半定量代谢组学研究。结果:我们首先发现多变量分析高度区分了VAP-PA与vap -非pa以及感染前组(R2 =。分别为97和0.98)。进一步的单变量分析发现,与vap -非pa组和感染前组相比,VAP-PA组中58种代谢物显著升高或仅存在(P < 0.05)。这包括一种已知的组氨酸代谢物和一种新的尼古丁代谢物。最有趣的是,我们发现了3种代谢物,它们不仅对VAP-PA高度上调,而且对VAP-PA高度特异性,因为这些代谢物在所有感染前时间点和vap -非pa组中完全不存在。结论:与VAP相比,由于其他细菌病因以及非VAP(感染前)时间点,VAP- pa尿液代谢物存在相当大的差异。我们在这里描述的独特的尿液代谢生物标志物,如果进一步验证,可以作为高度特异性的VAP-PA诊断生物标志物。
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来源期刊
Biomarker Insights
Biomarker Insights MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.00
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: An open access, peer reviewed electronic journal that covers all aspects of biomarker research and clinical applications.
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