Abstract
Background: The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming. Methods: We enrolled 292 consecutively hospitalized patients suspected to have LRI between November 2018 and June 2019 in a single-center, prospective cohort study. Rapid clinical metagenomics test was performed on-site, and the results were compared with those of routine microbiology tests and evaluated for potential clinical benefit. Results: 171 bronchoalveolar lavage fluid (BAL) and 121 sputum samples were collected from patients with six kinds of LRI. The turn around-time (from sample registration to result) for the rapid metagenomics test was 6.4 ± 1.4 hours, compared to 94.8 ± 34.9 hours for routine culture. Compared with culture and real-time PCR tests, rapid metagenomics achieved 96.6% sensitivity and 88.0% specificity and identified pathogens in 63 out of 161 (39.1%) culture-negative samples. Correlation of anaerobes enrichment with lung abscess was demonstrated as 38 anaerobic species failed in culture but identified by metagenomics sequencing. The hypothetical impact of metagenomics test proposed antibiotic de-escalation in 34 patients compared to 1 using routine culture. Conclusions: Rapid clinical metagenomics test increased pathogen detection yield in the diagnosis of LRI. Empirical antimicrobial therapy could be de-escalated if rapid metagenomics test results were hypothetically applied to clinical management. Funding: The funder of the study had no role in study design, data collection,data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Declaration of Interest: None to declare Ethical Approval: The study was carried out in China-Japan Friendship Hospital, Beijing, China. Ethical approval was obtained from the China-Japan Friendship Hospital Ethics Committee(2018-145-k102). All subjects provided written consents.
Highlights
Lower respiratory tract infection (LRI) is one of the top four causes of mortality worldwide (Naghavi et al, 2017)
Each collected sample was divided into two aliquots for simultaneous routine microbiological testing and on-site rapid metagenomic sequencing
bronchoalveolar lavage (BAL) samples were collected from 171 subjects (59%), and qualified sputum samples were collected from the remaining subjects (Figure 1A)
Summary
Lower respiratory tract infection (LRI) is one of the top four causes of mortality worldwide (Naghavi et al, 2017). The identification of causative agents of LRI remains challenging due to the limitations of the current methodology. Conventional methods for diagnosing LRI, mainly using culture and serological tests, are insensitive and time-consuming (Holter et al, 2015). The abuse of broad-spectrum antibiotics has made it even harder to identify pathogens, as patients may have already received antibiotics before the tests. A delayed diagnosis leads to inappropriate empiric, broad-spectrum antibiotic therapy, which causes poor therapy outcomes, longer hospital stays, and higher costs (Vaughn et al, 2019; Webb et al, 2019). The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming
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