Metagenomic next-generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients

Jiang, Peng; Du, Bin; Qin, Hanyu; Wang, Qian; Shi, Yan

doi:10.1016/j.jinf.2021.01.029

Cited by 98 publications

(95 citation statements)

References 28 publications

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“…mNGS can be used to assist in the diagnosis of IPA. For example, a comparison of mNGS with traditional microbial diagnostic methods for diagnosing Aspergillus found that mNGS had an accuracy of 78.3%, owing chiefly to the difficulty of extracting nucleic acids from molds, but a specificity as high as 97.5% ( 20 ). A search of PubMed identified only six case reports describing patients with secondary invasive pulmonary Aspergillus infection after Legionella infection ( 21 – 26 ) ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

Early Detection of Legionella pneumophila and Aspergillus by mNGS in a Critically Ill Patient With Legionella Pneumonia After Extracorporeal Membrane Oxygenation Treatment: Case Report and Literature Review

Yue

et al. 2021

Front. Med.

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Legionella pneumophila can cause pneumonia, leading to severe acute respiratory distress syndrome (ARDS). Because of its harsh growth requirements, limited detection methods, and non-specific clinical manifestations, diagnosing Legionella pneumonia remains still challenging. Metagenomic next-generation sequencing (mNGS) technology has increased the rate of detection of Legionella. This study describes a patient who rapidly progressed to severe ARDS during the early stage of infection and was treated with extracorporeal membrane oxygenation (ECMO). Although his bronchoalveolar lavage fluid (BALF) was negative for infection and his serum was negative for anti-Legionella antibody, mNGS of his BALF and blood showed only the presence of Legionella pneumophila (blood mNGS reads 229, BALF reads 656). After antibiotic treatment and weaning from ECMO, however, he developed a secondary Aspergillus and Klebsiella pneumoniae infection as shown by mNGS. Mechanical ventilation and antibiotic treatment were effective. A search of PubMed showed few reports of secondary Aspergillus infections after Legionella infection. Severe pneumonia caused by any type of pathogenic bacteria may be followed by Aspergillus infection, sometimes during extremely early stages of infection. Patients with severe pneumonia caused by Legionella infection should undergo early screening for secondary infections using methods such as mNGS, enabling early and precise treatment, thereby simplifying the use of antibiotics and improving patient prognosis.

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Section: Discussionmentioning

confidence: 99%

Early Detection of Legionella pneumophila and Aspergillus by mNGS in a Critically Ill Patient With Legionella Pneumonia After Extracorporeal Membrane Oxygenation Treatment: Case Report and Literature Review

Yue

et al. 2021

Front. Med.

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“…Since then, up to the time of writing, a total of 319 cases of fungal infections diagnosed by NGS were described in the literature, with some in case reports and others in case series or cohorts . In 40 out of the 319 cases (12.5%), more than 1 fungus was detected by NGS [26][27][28]32,34,39,41,44,45,53,59,62,64,67,73,74]. Pneumocystis jirovecii is the predominant fungus reported (~25% of the fungi detected), followed by Aspergillus species (~22%), Candida species (~16%), Cryptococcus species (~7%), Rhizopus species (~6%), Fusarium species (~4%), Alternaria species, Talaromyces marneffei and other Sordariomycetes (~3% each), Histoplasma capsulatum, other yeasts and Mucor species (~2% each), as well as some other rare fungal species (collectively~5%) (Figure 2).…”

Section: Laboratory Diagnosis Of Fungal Infections By Ngsmentioning

confidence: 99%

“…Pneumocystis jirovecii is the predominant fungus reported (~25% of the fungi detected), followed by Aspergillus species (~22%), Candida species (~16%), Cryptococcus species (~7%), Rhizopus species (~6%), Fusarium species (~4%), Alternaria species, Talaromyces marneffei and other Sordariomycetes (~3% each), Histoplasma capsulatum, other yeasts and Mucor species (~2% each), as well as some other rare fungal species (collectively~5%) (Figure 2). Excluding P. jirovecii, which is generally unculturable, out of the remaining 274 fungi detected by NGS, only 105 (~38%) were recovered by fungal culture from the same or different specimens from the respective patients [26,[29][30][31][32][33][34][35][36][37][38][39]43,45,46,49,52,54,57,59,62,64,66,67,71,73,76,77]. cies (~22%), Candida species (~16%), Cryptococcus species (~7%), Rhizopus species (~6%), Fusarium species (~4%), Alternaria species, Talaromyces marneffei and other Sordariomycetes (~3% each), Histoplasma capsulatum, other yeasts and Mucor species (~2% each), as well as some other rare fungal species (collectively ~5%) (Figure 2).…”

Section: Laboratory Diagnosis Of Fungal Infections By Ngsmentioning

confidence: 99%

“…cies (~22%), Candida species (~16%), Cryptococcus species (~7%), Rhizopus species (~6%), Fusarium species (~4%), Alternaria species, Talaromyces marneffei and other Sordariomycetes (~3% each), Histoplasma capsulatum, other yeasts and Mucor species (~2% each), as well as some other rare fungal species (collectively ~5%) (Figure 2). Excluding P. jirovecii, which is generally unculturable, out of the remaining 274 fungi detected by NGS, only 105 (~38%) were recovered by fungal culture from the same or different specimens from the respective patients [26,[29][30][31][32][33][34][35][36][37][38][39]43,45,46,49,52,54,57,59,62,64,66,67,71,73,76,77]. The majority of P. jirovecii infections diagnosed by NGS were reported in case series [34,36,39,41,48,53,55,58,62,64,65,67,72,75].…”

Section: Laboratory Diagnosis Of Fungal Infections By Ngsmentioning

confidence: 99%

“…Excluding P. jirovecii, which is generally unculturable, out of the remaining 274 fungi detected by NGS, only 105 (~38%) were recovered by fungal culture from the same or different specimens from the respective patients [26,[29][30][31][32][33][34][35][36][37][38][39]43,45,46,49,52,54,57,59,62,64,66,67,71,73,76,77]. The majority of P. jirovecii infections diagnosed by NGS were reported in case series [34,36,39,41,48,53,55,58,62,64,65,67,72,75]. All the patients unanimously suffered from pneumonia.…”

Section: Laboratory Diagnosis Of Fungal Infections By Ngsmentioning

confidence: 99%

See 2 more Smart Citations

Rapid Genomic Diagnosis of Fungal Infections in the Age of Next-Generation Sequencing

Tsang

Teng

Lau

et al. 2021

JoF

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Next-generation sequencing (NGS) technologies have recently developed beyond the research realm and started to mature into clinical applications. Here, we review the current use of NGS for laboratory diagnosis of fungal infections. Since the first reported case in 2014, >300 cases of fungal infections diagnosed by NGS were described. Pneumocystis jirovecii is the predominant fungus reported, constituting ~25% of the fungi detected. In ~12.5% of the cases, more than one fungus was detected by NGS. For P. jirovecii infections diagnosed by NGS, all 91 patients suffered from pneumonia and only 1 was HIV-positive. This is very different from the general epidemiology of P. jirovecii infections, of which HIV infection is the most important risk factor. The epidemiology of Talaromyces marneffei infection diagnosed by NGS is also different from its general epidemiology, in that only 3/11 patients were HIV-positive. The major advantage of using NGS for laboratory diagnosis is that it can pick up all pathogens, particularly when initial microbiological investigations are unfruitful. When the cost of NGS is further reduced, expertise more widely available and other obstacles overcome, NGS would be a useful tool for laboratory diagnosis of fungal infections, particularly for difficult-to-grow fungi and cases with low fungal loads.

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Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study

Huang

Zhang

Pang

et al. 2022

Journal of Medical Virology

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Purpose: This study aims to assess the clinical features of virome in the early onset of severe pneumonia in ICU patients.Methods: A total of 97 patients' clinical data was collected retrospectively from intensive care units of ve teaching hospitals in China from June 2018 to July 2021 followed by metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage uid (BALF) at the onset of severe pneumonia.Results: Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition, viral reactivation resulted in an overall increase of 2.052 folds of 28-day all-cause mortality (95% CI: 1. 004-4.194).Conclusion: This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients in the ICU at the onset of severe pneumonia. Viral reactivation is common and associated with an increased risk of mortality.

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Metagenomic next-generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients

Cited by 98 publications

References 28 publications

Early Detection of Legionella pneumophila and Aspergillus by mNGS in a Critically Ill Patient With Legionella Pneumonia After Extracorporeal Membrane Oxygenation Treatment: Case Report and Literature Review

Early Detection of Legionella pneumophila and Aspergillus by mNGS in a Critically Ill Patient With Legionella Pneumonia After Extracorporeal Membrane Oxygenation Treatment: Case Report and Literature Review

Rapid Genomic Diagnosis of Fungal Infections in the Age of Next-Generation Sequencing

Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study

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