Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
Philips Research, Royal Philips B.V., Eindhoven, The Netherlands.
J Breath Res. 2018 Jan 3;12(2):026002. doi: 10.1088/1752-7163/aa8efc.
Ventilator-associated pneumonia (VAP) is a healthcare-acquired infection arising from the invasion of the lower respiratory tract by opportunistic pathogens in ventilated patients. The current method of diagnosis requires the culture of an airway sample such as bronchoalveolar lavage, which is invasive to obtain and may take up to seven days to identify a causal pathogen, or indeed rule out infection. While awaiting results, patients are administered empirical antibiotics; risks of this approach include lack of effect on the causal pathogen, contribution to the development of antibiotic resistance and downstream effects such as increased length of intensive care stay, cost, morbidity and mortality. Specific biomarkers which could identify causal pathogens in a timely manner are needed as they would allow judicious use of the most appropriate antimicrobial therapy. Volatile organic compound (VOC) analysis in exhaled breath is proposed as an alternative due to its non-invasive nature and its potential to provide rapid diagnosis at the patient's bedside. VOCs in exhaled breath originate from exogenous, endogenous, as well as microbial sources. To identify potential markers, VAP-associated pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were cultured in both artificial sputum medium and nutrient broth, and their headspaces were sampled and analysed for VOCs. Previously reported volatile markers were identified in this study, including indole and 1-undecene, alongside compounds that are novel to this investigation, cyclopentanone and 1-hexanol. We further investigated media components (substrates) to identify those that are essential for indole and cyclopentanone production, with potential implications for understanding microbial metabolism in the lung.
呼吸机相关性肺炎（VAP）是一种医源性感染，由呼吸机患者下呼吸道机会致病菌入侵引起。目前的诊断方法需要对气道样本（如支气管肺泡灌洗）进行培养，这种方法具有侵入性，可能需要长达 7 天的时间才能确定致病病原体，或者实际上排除感染。在等待结果的同时，患者会接受经验性抗生素治疗；这种方法的风险包括对致病病原体无效、导致抗生素耐药性的产生以及增加重症监护停留时间、成本、发病率和死亡率等下游影响。需要寻找能够及时识别致病病原体的特定生物标志物，因为它们可以合理地使用最合适的抗菌治疗。呼气中挥发性有机化合物（VOC）分析由于其非侵入性和在患者床边提供快速诊断的潜力而被提议作为替代方法。呼气中的 VOC 源自外源性、内源性和微生物源。为了识别潜在的标志物，将与 VAP 相关的病原体大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和金黄色葡萄球菌分别在人工痰培养基和营养肉汤中进行培养，并对其腔室进行采样和 VOC 分析。本研究鉴定了先前报道的挥发性标志物，包括吲哚和 1-十一烯，以及该研究中发现的新型化合物环戊酮和 1-己醇。我们进一步研究了培养基成分（底物），以确定对吲哚和环戊酮产生必不可少的成分，这可能对理解肺部微生物代谢有重要意义。
