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Etiologic Diagnosis of Lower Respiratory Tract Bacterial Infections Using Sputum Samples and Quantitative Loop-Mediated Isothermal Amplification

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机构: [1]Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China; [2]Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China; [3]Peking Univ, Peoples Hosp, Dept Resp & Crit Care Med, Beijing 100871, Peoples R China; [4]Chinese Acad Sci, Beijing Inst Genom, Key Lab Genome Sci & Informat, Beijing, Peoples R China; [5]Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China; [6]Capitalbio Corp, Dept Assay Dev, Beijing, Peoples R China; [7]Fujian Prov Hosp, Dept Resp Med, Fuzhou, Peoples R China; [8]Capital Med Univ, Beijing Childrens Hosp, Dept Resp Med, Beijing, Peoples R China; [9]Capital Med Univ, Beijing Childrens Hosp, Dept Emergency Med, Beijing, Peoples R China; [10]Cent S Univ, Xiangya Hosp, Dept Resp Med, Changsha, Hunan, Peoples R China; [11]Nanchang Univ, Affiliated Hosp 1, Dept Resp Med, Nanchang, Peoples R China; [12]Inner Mongolia Med Coll, Affiliated Hosp 3, Dept Resp & Crit Care Med, Baotou, Peoples R China; [13]Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Resp Med, Shanghai 200030, Peoples R China; [14]Lanzhou Univ, Hosp 1, Dept Resp Med, Lanzhou 730000, Peoples R China; [15]Guangzhou Med Univ, Affiliated Hosp 3, Dept Resp Med, Guangzhou, Guangdong, Peoples R China; [16]Xuzhou Med Coll, Lianyungang Peoples Hosp 1, Dept Resp Med, Lianyungang, Peoples R China; [17]Mil Gen Hosp Beijing, Clin Sect 263, Dept Resp Med, Beijing, Peoples R China; [18]China Med Univ, Affiliated Hosp 1, Inst Resp Dis, Shenyang, Peoples R China; [19]Wuhan Univ, Renmin Hosp, Dept Resp Med, Wuhan 430072, Peoples R China; [20]Henan Prov People Hosp, Dept Resp Med, Zhengzhou, Peoples R China; [21]Tsinghua Univ, Affiliated Hosp 1, Dept Resp Med, Beijing 100084, Peoples R China; [22]GuiYang Med Coll, Affiliated Hosp, Dept Resp Med, Guiyang, Peoples R China; [23]Peking Univ, Hosp 3, Dept Resp Med, Beijing 100871, Peoples R China; [24]Lanzhou Pulm Hosp, Dept Resp Med, Lanzhou, Peoples R China; [25]Guangxi Med Univ, Affiliated Hosp 1, Dept Resp Med, Nanning, Peoples R China; [26]Peking Univ, Space Cent Hosp, Dept Resp Med, Beijing 100871, Peoples R China; [27]So Med Univ, Nanfang Hosp, Dept Resp Med, Guangzhou, Guangdong, Peoples R China; [28]Univ Chicago, Dept Med, Sect Pulm & Crit Care Med MC 6076, Chicago, IL 60637 USA
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Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship.

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出版当年[2011]版:
大类 | 2 区 生物
小类 | 2 区 生物学
最新[2023]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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出版当年[2010]版:
Q1 BIOLOGY
最新[2023]版:
Q1 MULTIDISCIPLINARY SCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2010版] 出版当年五年平均 出版前一年[2009版] 出版后一年[2011版]

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第一作者机构: [3]Peking Univ, Peoples Hosp, Dept Resp & Crit Care Med, Beijing 100871, Peoples R China; [4]Chinese Acad Sci, Beijing Inst Genom, Key Lab Genome Sci & Informat, Beijing, Peoples R China;
通讯作者:
通讯机构: [1]Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China; [2]Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China;
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