Clinical Application of Metagenomic Next-Generation Sequencing in Patients with Hematologic Malignancies Suffering from Sepsis

Liu, Wang-Da; Yen, Ting‐Yu; Liu, Po-Yo; Wu, Un‐In; Bhan, Prerana; Li, Yuchi; Chi, Chih-Hung; Sheng, Wang‐Huei

doi:10.3390/microorganisms9112309

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…The detected fungi include Marneffei basket fungus, Aspergillus , and Candida albicans . 17 There were viruses detected from both the clinical concordance group and nonconcordance group, including human γ Herpes virus type 4 (EBV), 18 human α Herpes virus type 1 (HSV1), human β Herpesvirus 6B, human β Herpes virus type 5 (CMV), and various subtypes of the macrocyclic virus, 19 which were detected in both groups. Combined with clinical information, sepsis was not considered.…”

Section: Resultsmentioning

confidence: 99%

Clinical Diagnosis Application of Metagenomic Next-Generation Sequencing of Plasma in Suspected Sepsis

Wang¹,

Qin²,

Tang³

et al. 2023

IDR

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Purpose We analyzed the clinical concordance of mNGS test results from blood samples and improved the clinical efficiency of mNGS in the diagnosis of suspected sepsis pathogens. Patients and Methods In this study, 99 samples of suspected blood flow infection were included for plasma mNGS, and the correlation between mNGS results and blood culture results, serum inflammatory indices, clinical symptoms and antibiotic treatment was analyzed, as well as the comparison with the detection rate of BALF pathogens, as well as the classification of different pathogens in the mNGS results were analyzed. Results The mNGS pathogen detection rate was higher than that of traditional blood culture (83.02% vs 35.82%). The rate of the mNGS results being consistent with the clinical diagnosis was also higher than that of traditional blood culture (58.49% vs 20.75%). This study shows that bacteria and fungi are the main pathogens in sepsis, and viral sepsis is very rare. In this study, 32% of sepsis patients were secondary to pneumonia. Compared with the pathogen detection rate using alveolar lavage fluid, the detection rate from plasma mNGS was 62.5%. Samples were also easy to sample, noninvasive, and more convenient for clinical application. Conclusion This study shows that compared with blood culture, the detection rate of mNGS pathogen that meets the diagnosis of sepsis is higher. We need a combination of multiple indicators to monitor the early diagnosis and treatment of sepsis.

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Section: Resultsmentioning

confidence: 99%

Clinical Diagnosis Application of Metagenomic Next-Generation Sequencing of Plasma in Suspected Sepsis

Wang¹,

Qin²,

Tang³

et al. 2023

IDR

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“…27 mNGS can detect microorganisms from samples like BLAF, cavity effusion, biopsy tissue, cerebrospinal fluid, urine, blood and sputum. 26,[28][29][30] The application of mNGS for immunocompromised CAP patients could provide a wide range of potential pathogens and improve the prognosis. 30 Haibing Liu and his colleagues found that several antibiotic resistance genes of bacteria by mNGS were consistent with drug sensitivity test.…”

Section: Discussionmentioning

confidence: 99%

“…26,[28][29][30] The application of mNGS for immunocompromised CAP patients could provide a wide range of potential pathogens and improve the prognosis. 30 Haibing Liu and his colleagues found that several antibiotic resistance genes of bacteria by mNGS were consistent with drug sensitivity test. 12 Nowadays, mNGS provide a new insight for a promising pathogenic identification for various infectious disease and is further likely to evaluate immunological competence to offending agents, virulence genes and more antimicrobial genes.…”

Section: Discussionmentioning

confidence: 99%

“…A study showed that CAP patients' overall microbial detection rate was 90.3% for mNGS versus 39.5% for conventional tests 27 . mNGS can detect microorganisms from samples like BLAF, cavity effusion, biopsy tissue, cerebrospinal fluid, urine, blood and sputum 26,28–30 . The application of mNGS for immunocompromised CAP patients could provide a wide range of potential pathogens and improve the prognosis 30 .…”

Section: Discussionmentioning

confidence: 99%

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Identification and comparison of Chlamydia psittaci, Legionella and Mycoplasma pneumonia infection

Ning

Zhou

Yuan

et al. 2023

Clinical Respiratory J

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Introduction Conventional etiological detection and pathogenic antibody methods make it challenging to identify the atypical pathogens among the community‐acquired pneumonia (CAP). Metagenomic next‐generation sequencing (mNGS) could rapidly detect all potentially infectious diseases and identifies novel or potential pathogens. Methods Eighteen patients diagnosed with atypical CAP were enrolled in this retrospective study, including nine Chlamydia psittaci pneumonia (C. p), four Legionella pneumonia (L. p) and five Mycoplasma pneumonia (M. p). We simultaneously tested bronchoalveolar lavage fluid (BALF) samples for conventional microbiological methods and mNGS, and blood specimens were analysed. We also collected and compared baseline and clinical characteristics and treatment responses. Results Patients with C. p and L. p had similar symptoms, including fever, cough, headache, dyspnoea, asthenia, shivering and headache, compared with M. p, whose symptoms were slight. C. p and L. p usually showed multiple lobar distributions with pleural effusion. Serologic testing indicated that L. p had higher levels of white blood cells (WBCs), neutrophils, C‐reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine compared with M. p and L. p (p < 0.05). However, patients with C. p had lower levels of albumin (p < 0.05), and M. p had a minimum risk of cardiac volume loads (p < 0.05). CD4/CD8 ratio, lymphocytes, aspartate aminotransferase (AST), creatine kinase (CK), cell counting of BALF and coagulation had no difference (p < 0.05). Pathogenic IgM assay showed that 4/5 cases were positive for M. p and no positive detection for C. p and L. p infection. We timely adjusted the antibiotics according to the final mNGS results. Eventually, 16/18 patients recovered fully. Conditions of L. p patients were worse than those of C. p patients, and those of M. p patients were the least. Conclusion Early application of mNGS detection increased the atypical pathogenic identification, improved the prognosis and made up for the deficiency of conventional detection methods.

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“…Working on pathogen detection in cerebrospinal fluid (CSF) by mNGS, Miller et al [16] reported a claimed sensitivity of 73% and a claimed specificity of 99%. In some study [17], sensitivity and specificity were not explicitly stated. In this study, a sensitivity of 81.8% was reported.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Metagenomic Next-Generation Sequencing Assay With a Novel Host Depletion Method for Pathogen Identification in Septic Patients

Chen

Liao

Chen

et al. 2023

Preprint

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Background The traditional diagnosis of sepsis has always been based on microbial blood culture (BC). However, BC suffers from (1) long culture cycle, leading to delay in results, and (2) low diagnostic yields. Metagenomic next-generation sequencing (mNGS) has been proposed as an efficient and agnostic option that potentially overcomes these issues. In this study, a mNGS workflow utilizing a novel filter to specifically capture white blood cells and deplete host DNA background, was evaluated against BC results, as well as mNGS without host depletion, for pathogen identification. Materials and Methods Patients admitted to Taipei Veterans General Hospital (TVGH) with suspected sepsis were recruited to the study approved by the IRB. Blood sample was taken for BC (designated as BC1) before any antibiotic exposure. Upon patient enrolment, blood was taken again and divided in 3 portions with one used for the 2nd BC (BC2). The other two were used for mNGS with one processed with the filter and the other without filtering, to assess the effectiveness of host-depletion by the filter. Results A total of 50 patients were recruited among which 45 had results for all 4 tests. mNGS with filter had the highest positive rate of 74.4%, followed by mNGS without filter and BC1 (51.1% and 50.0% respectively), while the 2nd BC had the lowest positive rate of 22.0%. Further, mNGS was less sensitive to antibiotics exposure as compared to BC. The overall correlation between samples with vs without filtration (R2=0.96) confirmed that filtration does not affect microbial composition in a sample. For the BC positive samples, the effect of host depletion by filtration increased microbial target reads/million QC reads from 46 reads to 243 reads on average. Microbial reads enrichment by the filter appeared to be more effective for the samples with lower microbial concentration, thus increasing the test sensitivity over mNGS without filter. Using the 2nd BC results as reference, mNGS with filter and mNGS without filter exhibited sensitivities of 81.8% and 63.6%. Conclusion The mNGS with filter was able to recover most of the pathogens identified by clinical BC and achieved the highest diagnostic yield. With the clinical implementation to complete the workflow within 24 hours, it has the potential to overcome slow turnaround and low diagnostic yield issues of traditional BC.

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Clinical Application of Metagenomic Next-Generation Sequencing in Patients with Hematologic Malignancies Suffering from Sepsis

Cited by 16 publications

References 32 publications

Clinical Diagnosis Application of Metagenomic Next-Generation Sequencing of Plasma in Suspected Sepsis

Clinical Diagnosis Application of Metagenomic Next-Generation Sequencing of Plasma in Suspected Sepsis

Identification and comparison of Chlamydia psittaci, Legionella and Mycoplasma pneumonia infection

Evaluation of a Metagenomic Next-Generation Sequencing Assay With a Novel Host Depletion Method for Pathogen Identification in Septic Patients

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