High‐throughput sequencing of cerebrospinal fluid for diagnosis of chronic <i><scp>P</scp>ropionibacterium acnes</i> meningitis in an allogeneic stem cell transplant recipient

Wylie, Kristine M.; Blanco-Guzman, Merilda; Wylie, Todd; Lawrence, Steven J.; Ghobadi, Armin; DiPersio, John F.; Storch, Gregory A.

doi:10.1111/tid.12512

Cited by 22 publications

(14 citation statements)

References 13 publications

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“…Metagenomics to screen for unclear or unknown infectious etiologies has been recently applied in several clinical cases to support routine diagnostics (Cordey et al, 2014 ; Naccache et al, 2015 ; Ortiz Alcántara et al, 2015 ; Kawada et al, 2016 ; Wylie et al, 2016 ; Lewandowska et al, 2017 ; Ruppé et al, 2017 ). Like for every eukaryotic sample, NGS analyses in clinical samples are greatly affected by a very low pathogen-to-host genome ratio.…”

Section: Discussionmentioning

confidence: 99%

“…For adequate patient management, improved identification of CNS infection etiologies to enable targeted therapy is indispensable. Metagenomics was recently used to assist infectious disease diagnostics, also for meningo-/encephalitis (Cordey et al, 2014 ; Naccache et al, 2015 ; Ortiz Alcántara et al, 2015 ; Kawada et al, 2016 ; Wylie et al, 2016 ; Lewandowska et al, 2017 ; Ruppé et al, 2017 ). Shotgun metagenomics, that sequences all nucleic acids (NA) in a given sample, has the potential to identify known but mutated (evading qPCR detection), unexpected, and previously undetected pathogens or mixed infections (Palacios et al, 2008 ; Basmaci et al, 2011 ; Smits et al, 2013 ; Tan le et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Limited Correlation of Shotgun Metagenomics Following Host Depletion and Routine Diagnostics for Viruses and Bacteria in Low Concentrated Surrogate and Clinical Samples

Oechslin

Lenz

Liechti

et al. 2018

Front. Cell. Infect. Microbiol.

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The etiologic cause of encephalitis, meningitis or meningo-encephalitis is unknown in up to 70% of cases. Clinical shotgun metagenomics combined with host depletion is a promising technique to identify infectious etiologies of central nervous system (CNS) infections. We developed a straightforward eukaryotic host nucleic acid depletion method that preserves intact viruses and bacteria for subsequent shotgun metagenomics screening of clinical samples, focusing on cerebrospinal fluid (CSF). A surrogate CSF sample for a CNS infection paradigm was used to evaluate the proposed depletion method consisting of selective host cell lysis, followed by enzymatic degradation of the liberated genomic DNA for final depletion with paramagnetic beads. Extractives were subjected to reverse transcription, followed by whole genome amplification and next generation sequencing. The effectiveness of the host depletion method was demonstrated in surrogate CSF samples spiked with three 1:100 dilutions of Influenza A H3N2 virus (qPCR Ct-values 20.7, 28.8, >42/negative). Compared to the native samples, host depletion increased the amount of the virus subtype reads by factor 7127 and 132, respectively, while in the qPCR negative sample zero vs. 31 (1.4E-4 %) virus subtype reads were detected (native vs. depleted). The workflow was applied to thirteen CSF samples of patients with meningo-/encephalitis (two bacterial, eleven viral etiologies), a serum of an Andes virus infection and a nose swab of a common cold patient. Unlike surrogate samples, host depletion of the thirteen human CSF samples and the nose swab did not result in more reads indicating presence of damaged pathogens due to, e.g., host immune response. Nevertheless, previously diagnosed pathogens in the human CSF samples (six viruses, two bacteria), the serum, and the nose swab (Human rhinovirus A31) were detected in the depleted and/or the native samples. Unbiased evaluation of the taxonomic profiles supported the diagnosed pathogen in two native CSF samples and the native and depleted serum and nose swab, while detecting various contaminations that interfered with pathogen identification at low concentration levels. In summary, damaged pathogens and contaminations complicated analysis and interpretation of clinical shotgun metagenomics data. Still, proper consideration of these issues may enable future application of metagenomics for clinical diagnostics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Limited Correlation of Shotgun Metagenomics Following Host Depletion and Routine Diagnostics for Viruses and Bacteria in Low Concentrated Surrogate and Clinical Samples

Oechslin

Lenz

Liechti

et al. 2018

Front. Cell. Infect. Microbiol.

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show abstract

“…Despite some advantages, WMGS is not routinely used in clinical microbiology. Few clinical single-patient studies investigated with metagenomics have been reported in the literature and they mostly concern viral acute encephalitis [ 5 ], infective endocarditis [ 6 ], or bacterial meningitis [ 7 , 8 ]. There are several reasons why WMGS has not yet been extensively used in routine analyses.…”

Section: Introductionmentioning

confidence: 99%

Detection of Bacterial Pathogens from Broncho-Alveolar Lavage by Next-Generation Sequencing

Leo

Gaïa

Ruppé

et al. 2017

IJMS

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The applications of whole-metagenome shotgun sequencing (WMGS) in routine clinical analysis are still limited. A combination of a DNA extraction procedure, sequencing, and bioinformatics tools is essential for the removal of human DNA and for improving bacterial species identification in a timely manner. We tackled these issues with a broncho-alveolar lavage (BAL) sample from an immunocompromised patient who had developed severe chronic pneumonia. We extracted DNA from the BAL sample with protocols based either on sequential lysis of human and bacterial cells or on the mechanical disruption of all cells. Metagenomic libraries were sequenced on Illumina HiSeq platforms. Microbial community composition was determined by k-mer analysis or by mapping to taxonomic markers. Results were compared to those obtained by conventional clinical culture and molecular methods. Compared to mechanical cell disruption, a sequential lysis protocol resulted in a significantly increased proportion of bacterial DNA over human DNA and higher sequence coverage of Mycobacterium abscessus, Corynebacterium jeikeium and Rothia dentocariosa, the bacteria reported by clinical microbiology tests. In addition, we identified anaerobic bacteria not searched for by the clinical laboratory. Our results further support the implementation of WMGS in clinical routine diagnosis for bacterial identification.

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“…Brain abscess, subdural or epidural empyema, and shunt meningitis are common P. acnes-related CNS infections that are successfully treated by antibiotics, sometimes in combination with surgical interventions such as drainage and debridement [7][8][9]. By contrast, P. acnes causes meningitis without neurosurgical procedures in both immunocompromised [22] and immunocompetent patients [10][11][12][13][14]. In P. acnes infection cases without trauma or surgical procedures, the paths by which P. acnes invades the CNS putatively include (1) hematogenous routes via the diploic veins from the hair follicles or sebaceous glands of the scalp or (2) invasion from adjacent inflammation such as sinusitis, orbititis, and otitis media [4].…”

Section: Discussionmentioning

confidence: 99%

Propionibacterium acnes-associated chronic hypertrophic pachymeningitis followed by refractory otitis media: a case report

et al. 2020

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Background: Hypertrophic pachymeningitis (HP) is a rare disorder that involves localized or diffuse thickening of the dura mater. HP is associated with various inflammatory, infectious, and malignant diseases, such as rheumatic arthritis, sarcoidosis, anti-neutrophil cytoplasmic antibody-associated vasculitis, IgG4-related disorders, syphilis, tuberculosis, bacterial and fungal infections, cancer, and idiopathic diseases, when evaluation fails to reveal a cause. Among them, chronic infection with Propionibacterium acnes is a rare etiology of HP, and its pathology remains unclear. Case presentation: An 80-year-old man having refractory otitis media with effusion of the right ear presented with progressive right-sided headache and nausea. Post-contrast brain magnetic resonance imaging revealed right mastoiditis and remarkable thickening of the dura mater and enhancement of pia mater extending from the right middle cranial fossa to the temporal lobe. HP secondary to middle ear infection was suspected, and a biopsy of the right mastoid was performed. An anaerobic culture of the biopsied right mastoid showed the growth of P. acnes, and histopathological examination using P. acnes-specific monoclonal antibody (PAB antibody) revealed the infiltration of inflammatory cells with P. acnes. Moreover, using PAB antibody, P. acnes was detected in the biopsy specimen of the thickening dura mater. No granulomas were identified in either specimen. HP was resolved with long-term administration of antibiotics and steroids. Conclusion: This is the first documentation of pathologically demonstrated chronic HP associated with P. acnes infection followed by refractory otitis media. This report showed that chronic latent P. acnes infection induces chronic inflammation.

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High‐throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient

Abstract: High-throughput metagenomic shotgun sequencing revealed P. acnes as the cause of chronic meningitis that had eluded conventional attempts at diagnosis. Treatment directed at this organism resulted in cure of the infection and clinical improvement.

Cited by 22 publications

References 13 publications

Limited Correlation of Shotgun Metagenomics Following Host Depletion and Routine Diagnostics for Viruses and Bacteria in Low Concentrated Surrogate and Clinical Samples

Limited Correlation of Shotgun Metagenomics Following Host Depletion and Routine Diagnostics for Viruses and Bacteria in Low Concentrated Surrogate and Clinical Samples

Detection of Bacterial Pathogens from Broncho-Alveolar Lavage by Next-Generation Sequencing

Propionibacterium acnes-associated chronic hypertrophic pachymeningitis followed by refractory otitis media: a case report

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