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Identification of Prosthetic Joint Infection Pathogens Using a Shotgun Metagenomics Approach

Matthew J Thoendel1, Patricio R Jeraldo2, Kerryl E Greenwood-Quaintance3

  • 1Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|April 13, 2018
PubMed
Abstract

Insights

Metagenomic shotgun sequencing accurately detects pathogens in prosthetic joint infections (PJIs), even in culture-negative cases. This advanced method offers a powerful new diagnostic tool for challenging infections.

Area of Science:

  • Microbiology
  • Genomics
  • Infectious Diseases

Background:

  • Metagenomic shotgun sequencing offers a novel approach for diagnosing infections, especially those caused by organisms resistant to culturing.
  • Prosthetic joint infections (PJIs) present diagnostic challenges, making advanced molecular techniques valuable.

Purpose of the Study:

  • To evaluate the efficacy of metagenomic shotgun sequencing in identifying pathogens in prosthetic joint infections (PJIs).
  • To compare metagenomic sequencing with traditional culture methods for PJI diagnosis.

Main Methods:

  • Analyzed 408 sonicate fluid samples from hip and knee arthroplasties (213 infected, 195 non-infected).
  • Enriched microbial DNA, performed whole-genome amplification, and utilized Illumina HiSeq 2500 for sequencing.
  • Developed a bioinformatics pipeline (Livermore Metagenomics Analysis Toolkit, MetaPhlAn2) to analyze microbial content and filter human reads.

Main Results:

  • Metagenomics identified known pathogens in 94.8% of culture-positive PJIs, with additional potential pathogens found in 9.6%.
  • Detected novel pathogens in 43.9% of culture-negative PJIs, with 21 cases showing unique microbial signatures.
  • Microorganism detection in aseptic failure cases was low (3.6%), indicating high specificity.

Conclusions:

  • Metagenomic shotgun sequencing is highly effective for identifying a broad spectrum of PJI pathogens.
  • This technique is particularly valuable for detecting difficult-to-culture organisms in culture-negative PJIs, improving diagnostic capabilities.

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