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宏基因组下一代测序在混合性肺部感染诊断中的应用。

Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis.

机构信息

Respiratory Department, Tianjin Medical University General Hospital, Tianjin, 300052, China.

出版信息

BMC Pulm Med. 2019 Dec 19;19(1):252. doi: 10.1186/s12890-019-1022-4.

Abstract

BACKGROUND

Metagenomic next-generation sequencing (mNGS) is emerging as a promising technique for pathogens detection. However, reports on the application of mNGS in mixed pulmonary infection remain scarce.

METHODS

From July 2018 to March 2019, 55 cases were enrolled in this retrospective analysis. Cases were classified into mixed pulmonary infection (36 [65.5%]) and non-mixed pulmonary infection (19 [34.5%]) according to primary diagnoses. The performances of mNGS and conventional test on mixed pulmonary infection diagnosis and pathogen identification were compared.

RESULTS

The sensitivity of mNGS in mixed pulmonary infection diagnosis was much higher than that of conventional test (97.2% vs 13.9%; P < 0.01), but the specificity was the opposite (63.2% vs 94.7%; P = 0.07). The positive predictive value of mNGS was 83.3% (95% CI, 68.0-92.5%), and the negative predictive value was 92.3% (95% CI, 62.1-99.6%). A total of 5 (9.1%) cases were identified as mixed pulmonary infection by both conventional tests and mNGS, however, the pathogens identification results were consistent between these two methods in only 1 (1.8%) case. In summary, the pathogens detected by mNGS in 3 (5.5%) cases were consistent with those by conventional test, and only 1 (1.8%) case was mixed pulmonary infection. According to our data, mNGS had a broader spectrum for pathogen detection than conventional tests. In particular, application of mNGS improved the diagnosis of pulmonary fungal infections. Within the 55 cases, mNGS detected and identified fungi in 31 (56.4%) cases, of which only 10 (18.2%) cases were positive for the same fungi by conventional test. The most common pathogen detected by mNGS was Human cytomegalovirus in our study, which was identified in 19 (34.5%) cases of mixed pulmonary infection. Human cytomegalovirus and Pneumocystis jirovecii, which were detected in 7 (12.7%) cases, were the most common co-pathogens in the group of mixed pulmonary infection.

CONCLUSIONS

mNGS is a promising technique to detect co-pathogens in mixed pulmonary infection, with potential benefits in speed and sensitivity.

TRIAL REGISTRATION

(retrospectively registered): ChiCTR1900023727. Registrated 9 JUNE 2019.

摘要

背景

宏基因组下一代测序(mNGS)作为一种有前途的病原体检测技术正在兴起。然而,关于 mNGS 在混合性肺部感染中的应用的报告仍然很少。

方法

本回顾性分析于 2018 年 7 月至 2019 年 3 月纳入 55 例患者。根据主要诊断,将病例分为混合性肺部感染(36 例[65.5%])和非混合性肺部感染(19 例[34.5%])。比较 mNGS 和常规检测对混合性肺部感染诊断和病原体鉴定的性能。

结果

mNGS 对混合性肺部感染诊断的敏感性明显高于常规检测(97.2%比 13.9%;P<0.01),但特异性相反(63.2%比 94.7%;P=0.07)。mNGS 的阳性预测值为 83.3%(95%可信区间,68.0-92.5%),阴性预测值为 92.3%(95%可信区间,62.1-99.6%)。5 例(9.1%)通过常规检测和 mNGS 均被确认为混合性肺部感染,然而,这两种方法的病原体鉴定结果仅在 1 例(1.8%)中一致。总之,mNGS 在 3 例(5.5%)病例中检测到的病原体与常规检测一致,仅 1 例(1.8%)为混合性肺部感染。根据我们的数据,mNGS 比常规检测具有更广泛的病原体检测谱。特别是,mNGS 的应用提高了肺部真菌感染的诊断。在这 55 例患者中,mNGS 检测并鉴定出 31 例(56.4%)真菌,其中只有 10 例(18.2%)通过常规检测呈同一真菌阳性。本研究中最常见的病原体是人类巨细胞病毒,在 19 例(34.5%)混合性肺部感染病例中被检测到。人类巨细胞病毒和卡氏肺孢子虫,在 7 例(12.7%)中被检测到,是混合性肺部感染组中最常见的共病原体。

结论

mNGS 是一种有前途的检测混合性肺部感染共病原体的技术,具有速度和敏感性方面的潜在优势。

试验注册

(回顾性注册):ChiCTR1900023727。注册于 2019 年 6 月 9 日。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ae/6921575/94a4a9326bc8/12890_2019_1022_Fig1_HTML.jpg

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