Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections

Diao, Zhenli; Han, Dongsheng; Zhang, Rui; Li, Jinming

doi:10.1016/j.jare.2021.09.012

Cited by 105 publications

(92 citation statements)

References 79 publications

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“…Because mNGS is culture-independent, ex vivo pathogen viability has no effect on assay results, making it easier to assess slow-growing, difficult-to-cultivate pathogens, and pathogens that are lethal due to antibiotic exposure. This is also the advantage of mNGS over whole genome sequencing (WGS) ( Wang et al., 2020 ; Diao et al., 2022 ). Despite the appeal of culture-independent mNGS, many issues remain to be addressed.…”

Section: Discussionmentioning

confidence: 99%

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis

Zhang

Gui

Wang

et al. 2022

Front. Cell. Infect. Microbiol.

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Rapid and accurate pathogen identification is essential for timely and effective treatment of pneumonia. Here, we describe the use of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage (BALF) fluid to identify pathogens in patients with hematologic comorbid respiratory symptoms in a retrospective study with 84 patients. In the transplantation group, 8 cases (19.5%) and 47 cases (97.9%) were positive for BALF by conventional method detection and mNGS detection, respectively, and 6 cases (14.0%) and 41 cases (91.1%) in chemotherapy group, respectively. The detection rate of mNGS in both groups was significantly higher than that of conventional detection methods (all P<0.05). Pseudomonas aeruginosa and Streptococcus pneumoniae were the most common bacterial infections in the transplantation and chemotherapy groups, respectively. Aspergillus was the most common fungal infection in both groups. Human betaherpesvirus 5 (HHV-5), torque teno virus and human betaherpesvirus 7 (HHV-7) were the most common pathogen species in both groups. The most common type of infection in patients in the transplantation and chemotherapy groups was the mixed infection of bacteria-virus. Most patients in the transplantation group had mixed infections based on multiple viruses, with 42 cases of viral infections in the transplantation group and 30 cases of viral infections in the chemotherapy group, which were significantly higher in the transplantation group than in the chemotherapy group (χ2 = 5.766, P=0.016). and the mixed infection of virus-virus in the transplantation group was significantly higher than that in the chemotherapy group (27.1% vs 4.4%, P=0.003). The proportion of death due to pulmonary infection was significantly higher in the transplantation group than in the chemotherapy group (76.9% vs 16.7%, χ2 = 9.077, P=0.003). This study demonstrated the value of mNGS of BALF in improving the diagnosis and prognosis of hematologic comorbid pneumonia, helping patients to obtain timely and effective treatment, and giving guidance on the overall treatment plan for patients, with particular benefit for patients with hematologic chemotherapy comorbid pneumonia.

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Section: Discussionmentioning

confidence: 99%

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis

Zhang

Gui

Wang

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Immunocompromised patients have a more complex microbial etiology and are susceptible to uncommon pathogens or coexisting infections ( Di Pasquale et al, 2019 ; Peng et al, 2021 ; Zhan et al, 2021 ). mNGS has advantages in detecting pathogens because of its high-throughput capacity, fast turnaround time (usually within 24 h) and ability to simultaneously detect a wide array of bacteria, viruses, and fungi in an unbiased way ( Diao et al, 2022 ). Among the patients with community-acquired pneumonia or undefined pneumonia, mNGS using lower respiratory tract samples has a distinct advantage in the field of fungi or viral identification (such as Pneumocystis jirovecii , cytomegalovirus, et al) and co-infection (such as Acinetobacter baumannii co-infected with pneumocystis jirovecii or cytomegalovirus, Aspergillus co-infected with cytomegalovirus), when comparing with the conventional microbiologist testing (CMT) ( Pan et al, 2018 ; Sun et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although mNGS is usually used as a tool to detect pathogens in the infectious disease, it can also be used to discover the drug resistance genes by analyzing the microbial nucleic acid sequence messages, which will help clinicians to choose precise antimicrobial agents ( Chiu and Miller, 2019 ; Casto et al, 2021 ). However, mNGS diagnosis platforms are based on short read sequencing, it is challenging to determine the detected antibiotic resistance genes originated from the genome of the causative pathogen rather than normal flora, or contaminations in environment ( Diao et al, 2022 ). In this study, the antibiotic resistance genes detected by mNGS are for the reference of independent multidisciplinary panel after the initial evaluation on the risk factors of multidrug-resistant bacteria infection.…”

Section: Discussionmentioning

confidence: 99%

Metagenomic next-generation sequencing-guided antimicrobial treatment versus conventional antimicrobial treatment in early severe community-acquired pneumonia among immunocompromised patients (MATESHIP): A study protocol

Fan

et al. 2022

Front. Microbiol.

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BackgroundSevere community-acquired pneumonia (SCAP) is the main cause of mortality in immunocompromised patients. Compared with conventional microbiological tests (CMT), metagenomic next-generation sequencing (mNGS) can quickly and simultaneously detect a wide array of bacteria, viruses, and fungi in an unbiased manner. It is increasingly used for severe respiratory infectious diseases, especially for immunocompromised patients. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes in immunocompromised patients with SCAP have not been evaluated.Methods/DesignThe MATESHIP study is a prospective, multicenter, parallel-group, open-label, randomized controlled trial from 20 ICUs in university hospitals and academic teaching hospitals across Shandong Province, China. We will enroll 342 immunocompromised patients with early onset SCAP who are admitted to an intensive care unit (ICU). Participants will be randomly allocated to an mNGS-guided treatment group or a conventional treatment group (guided by CMT), according to centrally computer-based block randomization stratified by participating centers. Participants will undergo CMT tests using appropriate lower respiratory tract (LRT) and other necessary specimens, with or without mNGS tests using LRT specimens. The primary outcomes will be: (1) The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death; and (2) the consumption of antimicrobial agents during ICU stay (expressed as defined daily doses). The secondary outcome measures will be: days from randomization to initiation of definitive antimicrobial treatment; overall antimicrobial agent use and cost; total cost of hospitalization; length of ICU stay; 28- and 90-day mortality; and clinical cure rate. This study hypothesizes that mNGS-guided treatment will decrease the degree of organ dysfunction/failure, the consumption of antimicrobial agents, and mortality, while the cure rate will be increased, and the time to initiation of appropriate therapy will be advanced.DiscussionThe MATESHIP study will evaluate for the first time whether mNGS-guided antimicrobial therapy improves the outcomes of SCAP in an immunocompromised population, and provide high-level evidence on the application of mNGS in the management of this population.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT05290454].

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“…Metagenomic sequencing has been the cornerstone of many studies of the bowel microbiota, but non-purulent sputa (airway secretions) typically contain <5% microbial DNA 65 and cellular samples such as brushings and biopsies will contain even less. Abundant pathogens and commensals may nevertheless be identified by sequencing, albeit at great depth 65,66 . Our results will greatly improve metagenome assembly and allow assays of individual microbial activities through metatranscriptomics.…”

Section: Discussionmentioning

confidence: 99%

Genomic and ecologic characteristics of the airway microbial-mucosal complex

Cuthbertson

Löber

Ish-Horowicz

et al. 2022

Preprint

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Lung diseases due to infection and dysbiosis affect hundreds of millions of people world-wide. Microbial communities at the airway mucosal barrier are conserved and highly ordered, reflecting symbiosis and co-evolution with human host factors. Freed of selection to digest nutrients for the host, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the results of the first systematic culture and whole-genome sequencing of the principal airway bacterial species, identifying abundant novel organisms within the genera Streptococcus, Pauljensenia, Neisseria and Gemella. Bacterial genomes were enriched for genes encoding antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. RNA-targeting CRISPR elements in some taxa suggest the potential to prevent or treat specific viral infections. Homologues of human RO60 present in Neisseria spp. provide a possible respiratory primer for autoimmunity in systemic lupus erythematosus (SLE) and Sjogren syndrome. We interpret the structure and biogeography of airway microbial communities from clinical surveys in the context of whole-genome content, identifying features of airway dysbiosis that may presage breakdown of homeostasis during acute attacks of asthma and chronic obstructive pulmonary disease (COPD). We match the gene content of isolates to human transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways that can sustain host interactions with the microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosal immunity in lung diseases of global significance.

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Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections

Cited by 105 publications

References 79 publications

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis

Metagenomic next-generation sequencing-guided antimicrobial treatment versus conventional antimicrobial treatment in early severe community-acquired pneumonia among immunocompromised patients (MATESHIP): A study protocol

Genomic and ecologic characteristics of the airway microbial-mucosal complex

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