Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
PLoS Pathog. 2013 May;9(5):e1003311. doi: 10.1371/journal.ppat.1003311. Epub 2013 May 9.
Ideally, invading bacteria are detected as early as possible in critically ill patients: the strain of morbific pathogens is identified rapidly, and antimicrobial sensitivity is known well before the start of new antimicrobial therapy. Bacteria have a distinct metabolism, part of which results in the production of bacteria-specific volatile organic compounds (VOCs), which might be used for diagnostic purposes. Volatile metabolites can be investigated directly in exhaled air, allowing for noninvasive monitoring. The aim of this review is to provide an overview of VOCs produced by the six most abundant and pathogenic bacteria in sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Such VOCs could be used as biological markers in the diagnostic approach of critically ill patients. A systematic review of existing literature revealed 31 articles. All six bacteria of interest produce isopentanol, formaldehyde, methyl mercaptan, and trimethylamine. Since humans do not produce these VOCs, they could serve as biological markers for presence of these pathogens. The following volatile biomarkers were found for identification of specific strains: isovaleric acid and 2-methyl-butanal for Staphylococcus aureus; 1-undecene, 2,4-dimethyl-1-heptane, 2-butanone, 4-methyl-quinazoline, hydrogen cyanide, and methyl thiocyanide for Pseudomonas aeruginosa; and methanol, pentanol, ethyl acetate, and indole for Escherichia coli. Notably, several factors that may effect VOC production were not controlled for, including used culture media, bacterial growth phase, and genomic variation within bacterial strains. In conclusion, VOCs produced by bacteria may serve as biological markers for their presence. Goal-targeted studies should be performed to identify potential sets of volatile biological markers and evaluate the diagnostic accuracy of these markers in critically ill patients.
理想情况下，应尽早在危重病患者中检测到入侵细菌：快速鉴定致病病原体的菌株，并在开始新的抗菌治疗之前，就充分了解抗菌药物敏感性。细菌具有独特的代谢方式，其中一部分会导致产生细菌特异性挥发性有机化合物（VOC），这些化合物可能用于诊断目的。可以直接研究挥发性代谢物，从而进行非侵入性监测。本综述的目的是概述脓毒症中六种最丰富和致病性细菌（金黄色葡萄球菌、肺炎链球菌、粪肠球菌、铜绿假单胞菌、肺炎克雷伯菌和大肠杆菌）产生的 VOC。此类 VOC 可作为危重病患者诊断方法中的生物标志物。对现有文献进行系统回顾，共发现 31 篇文章。所有六种感兴趣的细菌均产生异戊醇、甲醛、甲硫醇和三甲胺。由于人类不产生这些 VOC，因此它们可作为这些病原体存在的生物标志物。还发现了以下挥发性生物标志物可用于鉴定特定菌株：金黄色葡萄球菌的异戊酸和 2-甲基丁醛；铜绿假单胞菌的 1-十一烯、2,4-二甲基-1-庚烷、2-丁酮、4-甲基喹唑啉、氢氰酸和甲基硫氰酸；大肠杆菌的甲醇、戊醇、乙酸乙酯和吲哚。值得注意的是，有几个可能影响 VOC 产生的因素未得到控制，包括使用的培养基、细菌生长阶段和菌株内的基因组变异。总之，细菌产生的 VOC 可以作为其存在的生物标志物。应开展目标明确的研究，以确定潜在的挥发性生物标志物组合，并评估这些标志物在危重病患者中的诊断准确性。
