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Comparative meta-omics for identifying pathogens associated with prosthetic joint infection.

ABSTRACT: Prosthetic joint infections (PJI) are economically and personally costly, and their incidence has been increasing in the United States. Herein, we compared 16S rRNA amplicon sequencing (16S), shotgun metagenomics (MG) and metatranscriptomics (MT) in identifying pathogens causing PJI. Samples were collected from 30 patients, including 10 patients undergoing revision arthroplasty for infection, 10 patients receiving revision for aseptic failure, and 10 patients undergoing primary total joint arthroplasty. Synovial fluid and peripheral blood samples from the patients were obtained at time of surgery. Analysis revealed distinct microbial communities between primary, aseptic, and infected samples using MG, MT, (PERMANOVA p = 0.001), and 16S sequencing (PERMANOVA p < 0.01). MG and MT had higher concordance with culture (83%) compared to 0% concordance of 16S results. Supervised learning methods revealed MT datasets most clearly differentiated infected, primary, and aseptic sample groups. MT data also revealed more antibiotic resistance genes, with improved concordance results compared to MG. These data suggest that a differential and underlying microbial ecology exists within uninfected and infected joints. This study represents the first application of RNA-based sequencing (MT). Further work on larger cohorts will provide opportunities to employ deep learning approaches to improve accuracy, predictive power, and clinical utility.

SUBMITTER: Goswami K

PROVIDER: S-EPMC8660779 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe aims of this study were to (1) evaluate the efficacy and safety of targeted antibiotics for the treatment of culture-negative prosthetic joint infection based on metagenomic next-generation sequencing results and (2) verify the accuracy and reliability of metagenomic next-generation sequencing for identifying pathogens related to culture-negative prosthetic joint infection.MethodsNinety-seven consecutive PJI patients, including 27 patients with culture-negative prosthetic joint infection, were treated surgically at our center. Thirteen of the 27 culture-negative prosthetic joint infection patients, who were admitted before June 2017 and treated with empirical antibiotics, comprised the empirical antibiotic group (EA group), and the other 14 patients, who were admitted after June 2017 and treated with targeted antibiotics according to their metagenomic next-generation sequencing results, were classified as the targeted antibiotic group (TA group). The short-term infection control rate, incidence of antibiotic-related complications and costs were compared between the two groups.ResultsTwo of the patients in the EA group experienced debridement and prolonged antimicrobial therapy due to wound infection after the initial revision surgery. No recurrent infections were observed in the TA group; however, no significant difference in the infection control rate was found between the two groups (83.33% vs 100%, P = 0.217). More cases of antibiotic-related complications were recorded in the EA group (6 cases) than in the TA group (1 case), but the difference was not statistically significant (P = 0.0697). The cost of antibiotics obtained for the EA group was 20,168.37 Yuan (3236.38-45,297.16), which was higher than that found for the TA group (10,164.16 Yuan, 2959.54-16,661.04, P = 0.04).ConclusionsTargeted antibiotic treatment for culture-negative prosthetic joint infection based on metagenomic next-generation sequencing results is associated with a favorable outcome, and metagenomic next-generation sequencing is a reliable tool for identifying pathogens related to culture-negative prosthetic joint infection.

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Comparative meta-omics for identifying pathogens associated with prosthetic joint infection.

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