Metagenomic Next-Generation Sequencing for the Diagnosis of Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients: A Retrospective Study

Jiang, Juan; Bai, Lijun; Yang, Wei; Peng, Wenzhong; An, Jian; Wu, Yanhao; Pan, Pinhua; Li, Yuanyuan

doi:10.1007/s40121-021-00482-y

Cited by 60 publications

(78 citation statements)

References 31 publications

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“…mNGS showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in mixed infection. Moreover, Pneumocystis jirovecii was found to be the most common pathogen in pulmonary mixed infection, which was similar to the previous study (22). Compare to CMTs, mNGS have identi ed much more co-pathogens of PJP.…”

Section: Discussionsupporting

confidence: 87%

Diagnostic Value of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid for the Diagnosis of Suspected Pneumonia in Immunocompromised Patients

Lin

Chen

et al. 2022

Preprint

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Background: To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparation to that of conventional microbiological tests (CMTs).Methods: Sixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard. Results: Sixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 54%, P＜0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P＜0.05). Among fifty-two patients with definite pathogens, nineteen patients (37%) were identified as pulmonary mixed infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in mixed infection. Moreover, Pneumocystis jirovecii was the most common pathogen in mix infection and mNGS have identified much more co-pathogens of PJP than CMTs.Conclusions: mNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying mixed infections in immunocompromised patients.

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Section: Discussionsupporting

confidence: 87%

Diagnostic Value of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid for the Diagnosis of Suspected Pneumonia in Immunocompromised Patients

Lin

Chen

et al. 2022

Preprint

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“…Again, data from several recent studies supported its advantages in detecting opportunistic pathogens and mixed infections, especially in detecting uncultivable pathogens, such as P. jirovecii ( 17 – 19 ). More importantly, in a retrospective study of evaluating the utility of mNGS for the diagnosis of PCP, their research data revealed that the sensitivity of mNGS was 100% in non-HIV infected PCP patients, which was dramatically higher than GMS staining and serum BDG ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Characteristics and Prognostic Factors of Non-HIV Immunocompromised Patients With Pneumocystis Pneumonia Diagnosed by Metagenomics Next-Generation Sequencing

et al. 2022

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ObjectiveThe aim of this study was to evaluate the potential of metagenomic next-generation sequencing (mNGS) for the diagnosis of pneumocystis pneumonia (PCP) in patients with non-human immunodeficiency virus-infection and to discuss the clinical characteristics and identify prognostic factors associated with patients with non-HIV PCP.MethodsForty-six patients with PCP who were admitted in respiratory intensive care unit (ICU) between May 2018 and May 2020 were retrospectively reviewed. The subjects were divided into survivor and non-survivor groups according to the patients' outcome. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were analyzed. The patients' demographics, comorbidities, laboratory parameters, and treatments were compared and evaluated in both groups to identify risk factors for mortality by using univariate and multivariate logistic regression.ResultsMetagenomic next-generation sequencing (mNGS) showed a satisfying diagnostic performance of 100% positive of detecting P. jirovecii from bronchoalveolar lavage (BAL) specimens in forty-six patients with non-HIV PCP, compared to only 15.2% for Gomori Methenamine silver (GMS) staining and 84.8% for Serum 1,3-beta-D-glucan (BDG). Among them, the mean age was 46.4-year-old (range 18–79-year-old) and mortality rate was 43.5%. The dominant underlying conditions were connective tissue diseases (34.8%), autoimmune kidney diseases (30.4%), followed by hematologic malignancies (10.9%), and solid organ transplantation (6.5%). A total of 38 cases (82.6%) received glucocorticoid and 19 cases (41.3%) used immunosuppressant within 3 months before diagnosed PCP. Multiple infections were very common, over two thirds' cases had mixed infections. Compared with survivors, non-survivors had a higher acute physiology and chronic health evaluation II (APACHE II) score (14.4 ± 4.8 vs. 10 ± 3.4), Procalcitonin (PCT) [ng/ml: 0.737 (0.122–1.6) vs. 0.23 (0.095–0.35)], lactic dehydrogenase (LDH) [U/L: 1372 (825.5–2150) vs. 739 (490.5–956)], and neutrophil-lymphocyte ratio (NLR) [21.6 (15.67–38.2) vs. 11.75 (5.1–15.52)], but had a lower PaO2/FiO2 ratio (mmHg:108.8 ± 42.4 vs. 150.5 ± 47.5), lymphocytes [×109/L: 0.33 (0.135–0.615) vs. 0.69 (0.325–1.07)] and CD4+ T cells [cell/μl: 112 (53.5–264) vs. 255 (145–303.5)], all P < 0.05. Furthermore, we found non-survivors' PaO2/FiO2 ratio of day 3 and day 7 had not improved when compared with that of day one, and platelet level and NLR became worse. Multivariate analysis showed that other pathogens' co-infection (OR = 9.011, 95% CI was 1.052–77.161, P = 0.045) and NLR (OR = 1.283, 95% CI was 1.046–1.547, P = 0.017) were the independent risk factors of poor prognosis.ConclusionmNGS is a very sensitive diagnostic tool for identifying P. jirovecii in patients who are non-HIV immunocompromised. PCP in patients who are non-HIV infected is associated with a high rate of multiple infections and severe condition. Mixed infection and elevation of NLR were the independent risk factors of poor prognosis.

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“…The proportion of mixed pulmonary infections in patients with PJP was much higher than originally predicted ( Jiang et al., 2021 ). The main reason for this is incomplete immunity.…”

Section: Discussionmentioning

confidence: 74%

“…Therefore, mNGS requires standardisation. mNGS is a highly sensitive method for detecting Pneumocystis ( Chen et al., 2020 ; Jiang et al., 2021 ; Zhang et al., 2021 ). However, it is difficult to differentiate between colonisation and true infections.…”

Section: Discussionmentioning

confidence: 99%

“…With the rapid development of molecular biology, metagenomic next-generation sequencing (mNGS) tests of respiratory samples are used to directly detect target organisms ( Gu et al., 2019 ). Jiang et al. (2021) found that mNGS had a remarkably higher sensitivity of 100% compared to Gomori methenamine silver staining (25.0%) and serum (1,3)-β-D-glucan (BDG) (67.4%) for diagnosing PJP.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonisation

Liu

Yuan

Shi

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundDifferentiating Pneumocystis jirovecii infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage fluid (BAL) metagenomic next-generation sequencing (mNGS) and serum 1,3-β-D-glucan (BDG) tests in differentiating colonisation and infection with P. jirovecii.MethodsFrom January 2018 to March 2021, 47 patients were enrolled in this study at the Hunan Provincial People’s Hospital. The final diagnosis was used as a reference, and cases were classified into the P. jirovecii pneumonia (PJP) group or the P. jirovecii colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.ResultThe fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 vs. 5.61 ± 0.88 in the PJP and PJC groups, respectively (P < 0.0001). BDG also significantly differed between the two groups, with a median titre of 233.60 ± 39.65 pg/ml in the PJP group and 68.48 ± 19.21 pg/ml in the PJC group (P = 0.0006). The area under the curve was 0.973 (95%CI: 0.868–1.007) for mNGS of the BAL and 0.879 (95%CI: 0.769–0.989) for the serum BDG. The optimal threshold value for discriminating P. jirovecii infection from colonisation appeared to be 14 reads (sensitivity, 83.3%; specificity, 95.7%; positive likelihood ratio, 19.2) and BDG = 88.6 pg/ml (sensitivity, 79.2%; specificity, 92.9%; positive likelihood ratio, 18.2). No correlation between mNGS reads and the BDG titre was found in mNGS-positive patients (r2 = 0.0076, P = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.ConclusionBAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of P. jirovecii.

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Metagenomic Next-Generation Sequencing for the Diagnosis of Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients: A Retrospective Study

Cited by 60 publications

References 31 publications

Diagnostic Value of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid for the Diagnosis of Suspected Pneumonia in Immunocompromised Patients

Diagnostic Value of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid for the Diagnosis of Suspected Pneumonia in Immunocompromised Patients

Characteristics and Prognostic Factors of Non-HIV Immunocompromised Patients With Pneumocystis Pneumonia Diagnosed by Metagenomics Next-Generation Sequencing

Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonisation

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