Use of a Rapid Test of Pneumococcal Colonization Density to Diagnose Pneumococcal Pneumonia

Use of a Rapid Test of Pneumococcal Colonization Density to Diagnose Pneumococcal Pneumonia
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DOI:
10.1093/cid/cir859
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发表时间:
2012-03-01
影响因子:
11.8
通讯作者:
Klugman, K. P.
Klugman, K. P.
中科院分区:
医学1区
文献类型:
--
作者:
Albrich, W. C.;Madhi, S. A.;Klugman, K. P.

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背景主要需要一种更敏感的检测方法来诊断肺炎球菌社区获得性肺炎(CAP)。我们假设,肺炎球菌鼻咽(NP)增殖可能会导致微吸入肺炎。因此,我们对肺炎患者和对照组的NP拭子样本进行了定量lytA实时聚合酶链反应(rtPCR)检测。在一项前瞻性研究中,通过实时聚合酶链反应(rtPCR)测定,人类免疫缺陷病毒(HIV)感染的肺炎球菌肺炎患者的鼻咽定植密度比同时确定的HIV感染的无症状对照组高5 log(10)。鼻咽lytA密度>= 8000拷贝/mL在rtPCR可能是一个有用的诊断标志物肺炎球菌肺炎。在缺乏敏感性参考标准的情况下,如果血液培养、诱导的高质量痰培养、革兰氏染色或尿Binax显示肺炎球菌,则认为南非人类免疫缺陷病毒(HIV)感染的成人住院放射学确诊CAP患者的肺炎球菌肺炎复合诊断标准为阳性。将肺炎支原体肺炎患者和300例HIV感染者的NP拭子样本中lytA定量RTPCR结果与菌落计数结果进行比较。肺炎球菌是280例CAP患者中76例(27.1%)的主要病原体。通过lytA rtPCR测量的NP定殖密度与定量培养物相关(r = 0.67; P < .001)。肺炎球菌性肺炎患者的平均lytA rtPCR拷贝数为6.0 log(10)copies/mL,而CAP患者超出复合标准(2.7 log(10)copies/mL; P <0.001)和无症状对照(0.8 log(10)copies/mL; P <0.001)。lytA rtPCR密度>= 8000拷贝/mL区分肺炎球菌CAP与无症状定植的敏感性为82.2%,特异性为92.0%。使用该临界值,肺炎球菌引起的CAP病例比例从27.1%增加到52.5%。在容易获得的标本上进行NP肺炎球菌密度的快速分子测定可显著增加成人肺炎球菌肺炎的诊断。
Background. There is major need for a more sensitive assay for the diagnosis of pneumococcal community-acquired pneumonia ( CAP). We hypothesized that pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration followed by pneumonia. We therefore tested a quantitative lytA real-time polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia and controls.In a prospective study, human immunodeficiency virus (HIV)-infected patients with pneumococcal pneumonia had nasopharyngeal colonization densities 5 log(10) higher than those in concurrently identified HIV-infected asymptomatic controls, as measured by real-time polymerase chain reaction (rtPCR). A nasopharyngeal lytA density of >= 8000 copies/mL at rtPCR may be a useful diagnostic marker for pneumococcal pneumonia.Methods. In the absence of a sensitive reference standard, a composite diagnostic standard for pneumococcal pneumonia was considered positive in South African human immunodeficiency virus (HIV)-infected adults hospitalized with radiographically confirmed CAP, if blood culture, induced good-quality sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of quantitative lytA rtPCR in NP swab samples were compared with quantitative colony counts in patients with CAP and 300 HIV-infected asymptomatic controls.Results. Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP (27.1%) using the composite diagnostic standard. NP colonization density measured by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0 log(10) copies/mL, compared with patients with CAP outside the composite standard (2.7 log(10) copies/mL; P < .001) and asymptomatic controls (0.8 log(10) copies/mL; P < .001). A lytA rtPCR density >= 8000 copies/mL had a sensitivity of 82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from asymptomatic colonization. The proportion of CAP cases attributable to pneumococcus increased from 27.1% to 52.5% using that cutoff.Conclusions. A rapid molecular assay of NP pneumococcal density performed on an easily available specimen may significantly increase pneumococcal pneumonia diagnoses in adults.