TY - JOUR
T1 - Direct detection and identification of prosthetic joint infection pathogens in synovial fluid by metagenomic shotgun sequencing
AU - Ivy, Morgan I.
AU - Thoendel, Matthew J.
AU - Jeraldo, Patricio R.
AU - Greenwood-Quaintance, Kerryl E.
AU - Hanssen, Arlen D.
AU - Abdel, Matthew P.
AU - Chia, Nicholas
AU - Yao, Janet Z.
AU - Tande, Aaron J.
AU - Mandrekar, Jayawant N.
AU - Patel, Robin
N1 - Publisher Copyright:
© 2018 American Society for Microbiology. All Rights Reserved.
PY - 2018/9
Y1 - 2018/9
N2 - Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Genus- and species-level analyses of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analyses yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analyses of the 60 culture-negative aseptic failure cases yielded 53 (88%) and 56 (93%) cases with insignificant findings and 7 (12%) and 4 (7%) with potential clinically significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases.
AB - Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Genus- and species-level analyses of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analyses yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analyses of the 60 culture-negative aseptic failure cases yielded 53 (88%) and 56 (93%) cases with insignificant findings and 7 (12%) and 4 (7%) with potential clinically significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases.
KW - (molecular) diagnostics
KW - (peri)prosthetic joint infection/joint infection
KW - Metagenomics
KW - Next-generation sequencing
KW - Synovial fluid
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U2 - 10.1128/JCM.00402-18
DO - 10.1128/JCM.00402-18
M3 - Article
C2 - 29848568
AN - SCOPUS:85052533069
SN - 0095-1137
VL - 56
JO - Journal of clinical microbiology
JF - Journal of clinical microbiology
IS - 9
M1 - e00402
ER -