Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Lancet Microbe. 2022 Apr;3(4):e294-e302. doi: 10.1016/S2666-5247(21)00327-X. Epub 2022 Mar 11.
Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients.
We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection.
Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24-0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19-0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37-14·21, p<0·0001) or dominance (3·97, 1·20-13·08, p=0·024) of Staphylococcus aureus was linked with lower survival. Moreover, dominance of Enterobacteriaceae was associated with higher risk of death (2·26, 1·03-4·93, p=0·041).
Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies.
UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund.
胸膜感染是一种常见且严重的疾病，在全球范围内具有较高的发病率和死亡率。由于基于培养的病原体检测方法灵敏度不足且偏向于选择特定的微生物，胸膜感染的细菌学知识仍不完整。我们设计了一项研究，旨在发现和研究胸膜感染的全微生物组，并评估细菌模式与患者 1 年生存率之间的相关性。
我们评估了 PILOT 研究中的 243 份胸膜液样本，该研究是一项关于胸膜感染的前瞻性观察性研究，采用了 16S rRNA 下一代测序技术。20 份来自非感染性胸腔积液患者的胸膜液样本和 10 份 PCR 级水样本作为对照。下游分析采用 DADA2 管道进行。我们应用多变量 Cox 回归分析来研究胸膜感染患者的细菌模式与 1 年生存率之间的关联。
胸膜感染主要为多微生物感染（243 份样本中的 192 份），在单微生物和多微生物疾病以及社区获得性和医院获得性感染中观察到不同的细菌频率。混合厌氧菌和其他革兰氏阴性菌在社区获得性多微生物感染中占主导地位，而肺炎链球菌则在单微生物病例中占主导地位。厌氧菌的存在（风险比 0.46，95%CI 0.24-0.86，p=0.015）或酿脓链球菌组细菌的存在（0.43，0.19-0.97，p=0.043）与患者生存状况较好相关，而金黄色葡萄球菌的存在（5.80，2.37-14.21，p<0.0001）或优势（3.97，1.20-13.08，p=0.024）与较低的生存率相关。此外，肠杆菌科的优势与死亡风险增加相关（2.26，1.03-4.93，p=0.041）。
胸膜感染主要为多微生物感染，这解释了大多数个体需要广谱抗生素覆盖的原因。高死亡率感染与金黄色葡萄球菌和肠杆菌科相关，支持更积极、更窄谱的抗生素策略。
英国医学研究理事会、国家卫生研究院牛津生物医学研究中心、惠康信托基金会、牛津郡卫生服务研究委员会、中国医学科学院和约翰·费尔基金会。
