Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study

Shi et al. Journal of Orthopaedic Surgery and Research https://doi.org/10.1186/s13018-024-04745-5 (2024) 19:301 RESEARCH ARTICLE Journal of Orthopaedic Surgery and Research Open Access Clinical applications of metagenomic next‑generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study Tengfei Shi1†, Huiyu Chen2†, Yinhuan Liu1, Yexin Wu1 and Feitai Lin3* Abstract Background This study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI). Methods A retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed. Results mNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37). † Tengfei Shi and Huiyu Chen contributed equally to this work and were the co-first author. *Correspondence: Feitai Lin Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Shi et al. Journal of Orthopaedic Surgery and Research (2024) 19:301 Page 2 of 11 Conclusions Metagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies. Keywords Periprosthetic joint infection, Metagenomic next-generation sequencing, Microbial culture, Staphylococcus aureus, Sinus tract Introduction Periprosthetic joint infection (PJI) is a serious complication of joint replacement surgery, with an incidence rate ranging from 2.0 to 2.7% [1]. The complexity of the treatment and management of PJI persists and remains a clinical focus [2, 3]. With the popularization of artificial joint replacement surgery, the incidence of PJI has increased, and PJI poses a significant burden on patients and the health care system [4, 5]. Traditional microbiological culture methods have long been regarded as the “gold standard” for the diagnosis of infection. However, this method has significant limitations, such as a lengthy turnaround time, dependence on viable pathogens, and high standards for culture conditions [6]. Especially in PJI patients requiring urgent intervention, the time required for culture results may lead to delays in clinical treatment and severe adverse outcomes [7, 8]. In recent years, molecular diagnostic techniques have been widely used in the diagnosis of PJI due to their speed, avoidance of antibiotic interference, and minimal sample requirements. However, these techniques, such as multiplex polymerase chain reaction (PCR) and 16S rRNA gene sequencing [9, 10], can only identify a limited number of microorganisms and potentially miss some uncommon pathogens or even fail to detect fungal or polymicrobial infections. Additionally, while matrixassisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been widely used in clinical bacterial identification, this method is primarily used for the identification of cultured strains. Although there have been researchers that have attempted to use MALDI-TOF MS to directly assess synovial specimens from blood culture bottles for PJI diagnosis, the sensitivity and specificity of this method are still unable to meet the requirements for PJI diagnosis [11, 12]. To overcome these limitations, metagenomic nextgeneration sequencing (mNGS) has garnered significant attention. This technology possesses high-throughput detection capabilities, thereby enabling the simultaneous analysis of thousands of DNA fragments and allowing for the comprehensive detection of pathogens such as bacteria, fungi, viruses, and parasites. Diagnostic results are typically available within 48 h [13]. Metagenomic nextgeneration sequencing has been applied in the detection of pathogens in various infectious diseases, including those affecting the nervous, urinary, and respiratory systems [14–16]. Studies have shown that mNGS exhibits high overall diagnostic sensitivity and specificity in diagnosin (...truncated)