title: High-throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient.
abstract: BACKGROUND
  A 40-year-old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide-based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities.
  
  
  METHODS
  We used high-throughput metagenomic shotgun sequencing to identify microbes in 2 CSF samples collected from the patient during his illness. These results were compared to sequence data from 1 CSF sample collected during treatment and 5 control CSF samples from other patients.
  
  
  RESULTS
  We found sequences representing 53% and 67% of the Propionibacterium acnes genome in 2 CSF samples collected from the patient during his illness. Directed antimicrobial therapy was administered for 6 weeks with resolution of CSF and neuroimaging abnormalities. Sequencing of a sample obtained during treatment demonstrated that the P. acnes levels were decreased to background levels. After insertion of a ventriculo-peritoneal shunt, the patient returned to baseline status.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.|The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Wylie
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: M
authors.initials: M
authors.lastname: Blanco-Guzman
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.|The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Wylie
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lawrence
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ghobadi
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: DiPersio
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Storch
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002443:Ceftriaxone / Q000627:therapeutic use; D002908:Chronic Disease; D016908:Gram-Positive Bacterial Infections / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000382:microbiology*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D016867:Immunocompromised Host; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000382:microbiology*; D011425:Propionibacterium acnes / Q000302:isolation & purification*; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014184:Transplantation, Homologous
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone
keywords: Propionibacterium acnes; high-throughput sequencing; meningitis; metagenomic sequencing