The prospects and challenge of pathogen diagnosis of lower respiratory tract infections in grassroots hospitals: The clinical practicality of targeted nextgeneration sequencing

virus, fungi, chlamydia and mycoplasma.In addition, for some immunocompromised patients, almost all bacteria or fungi can be considered potential pathogens in LRTIs 3 .Currently, conventional microbiological test methods (CMTs) including microscopy, pathogen culture and isolation, biochemical testing, enzyme-linked immunosorbent assay (ELSA), and polymerase chain reaction (PCR) testing, are applied to identify LRTIs pathogens.However, these methods have ABSTRACT INTRODUCTIONEarly effective detection and confirmation of infectious pathogens in patients with lower respiratory tract infections (LRTIs) is very difficult, especially in grassroots hospitals.This study aims to evaluate the clinical practicality of targeted next-generation sequencing (t-NGS) detection of pathogens.METHODS A retrospective observational study was conducted in 140case final enrolled patients with LRTIs.We comprehensively analyzed the interrelationships between the distributions of positive pathogens and related factors such as age, disease type and underlying diseases by different distribution maps made by Graph-board Template Chooser.The accuracy and agreement tests were conducted separately using Pearson chi-squared test and qualitative data consistency test.RESULTS Among enrolled patients, the potential pathogens detectable by t-NGS in the bronchoalveolar lavage fluid (BALF) were bacteria, with the highest proportion 57.86%, followed by viruses 45.0% and fungi 44.29%.The vast majority of patients showed co-infected pathogens, among those in advanced age (aged ≥80 years), with multiple underlying diseases, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD); the joint infection was the most significant, followed by CAP/P in 2-type DM.The accuracy of detecting positive pathogens by t-NGS method was significantly higher than that of CMTs method (all p≤0.001).The consistency between the detection results of various pathogens and final clinical confirmed pathogen (FCCP) was significant (all κ coefficients ≥0.80).Early use of t-NGS also reduced the antibiotic replacement rate in elderly patients after 3 days of admission (all p<0.001).CONCLUSIONS The t-NGS is a pathogen detection method with clinical prospects in grassroots hospitals because of higher positive detection rate, higher rate of accuracy and consistency, lower antibiotic replacement rate, especially for advanced age patients compared to the CMT method.Ιt is crucial and a challenge for clinical physicians on how to evaluate the results of t-NGS detection.