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

Transpl Infect Dis. 2016 Apr;18(2):227-33. doi: 10.1111/tid.12512. Epub 2016 Mar 31.

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.

Keywords: Propionibacterium acnes; high-throughput sequencing; meningitis; metagenomic sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Ceftriaxone / therapeutic use
  • Chronic Disease
  • Gram-Positive Bacterial Infections / cerebrospinal fluid*
  • Gram-Positive Bacterial Infections / diagnosis
  • Gram-Positive Bacterial Infections / microbiology*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Immunocompromised Host
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Male
  • Meningitis, Bacterial / cerebrospinal fluid*
  • Meningitis, Bacterial / diagnosis
  • Meningitis, Bacterial / microbiology*
  • Propionibacterium acnes / isolation & purification*
  • Stem Cell Transplantation / adverse effects
  • Transplantation, Homologous

Substances

  • Anti-Bacterial Agents
  • Ceftriaxone