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Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_11 | Pages 32 - 32
1 Oct 2019
Goswami K Parvizi J
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Introduction

Next generation sequencing (NGS) has been shown to facilitate detection of microbes in a clinical sample, particularly in the setting of culture-negative periprosthetic joint infection (PJI). However, it is unknown whether every microbial DNA signal detected by NGS is clinically relevant. This multi-institutional study was conceived to 1) identify species detected by NGS that may predict PJI, then 2) build a predictive model for PJI in a developmental cohort; and 3) validate the predictive utility of the model in a separate multi-institutional cohort.

Methods

This multicenter investigation involving 15 academic institutions prospectively collected samples from 194 revision total knee arthroplasties (TKA) and 184 revision hip arthroplasties (THA) between 2017–2019. Patients undergoing reimplantation or spacer exchange procedures were excluded. Synovial fluid, deep tissue and swabs were obtained at the time of surgery and shipped to MicrogenDx (Lubbock, TX) for NGS analysis. Deep tissue specimens were also sent to the institutional labs for culture. All patients were classified per the 2018 Consensus definition of PJI. Microbial DNA analysis of community similarities (ANCOM) was used to identify 17 candidate bacterial species out of 294 (W-value >50) for differentiating infected vs. noninfected cases. Logistic Regression with LASSO model selection and random forest algorithms were then used to build a model for predicting PJI. For this analysis, ICM classification was the response variable (gold standard) and the species identified through ANCOM were the predictor variables. Recruited cases were randomly split in half, with one half designated as the training set, and the other half as the validation set. Using the training set, a model for PJI diagnosis was generated. The optimal resulting model was then tested for prediction ability with the validation set. The entire model-building procedure and validation was iterated 1000 times. From the model set, distributions of overall assignment rate, specificity, sensitivity, positive predictive value (PPV) and negative predicative value (NPV) were assessed.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_11 | Pages 33 - 33
1 Oct 2019
Jiranek WA Kildow BJ Danilkowicz RM Bolognesi MP Seyler TM
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Introduction

Recent focus has queried whether of deoxyribonucleic acid (DNA) sequencing modalities of bacterial DNA found in periarticular fluid and tissues will improve in periprosthetic joint infection (PJI) diagnosis and organism identification diagnostic accuracy for periprosthetic joint infection The purpose of this study was to compare the diagnostic accuracy of next generation sequencing (NGS) to polymerase chain reaction (PCR) multiplex, and culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al. [1] in the diagnosis of periprosthetic knee infections.

Methods

In this retrospective study, aspirate or tissue samples were collected in 70 revision and 58 primary knee arthroplasties for routine diagnostic workup for PJI and sent to the laboratory for NGS and PCR multiplex. Concordance along with statistical differences between diagnostic studies were calculated using Chi-squared test for categorical data.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_9 | Pages 7 - 7
1 Oct 2020
Goswami K Clarkson S Dennis DA Klatt BA O'Malley M Smith EL Pelt CE Gililland J Peters C Malkani AL Palumbo B Minter J Goyal N Cross M Prieto H Lee G Hansen E Ward D Bini S Higuera C Levine B Nam D Della Valle CJ Parvizi J
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Introduction. Surgical management of PJI remains challenging with patients failing treatment despite the best efforts. An important question is whether these later failures reflect reinfection or the persistence of infection. Proponents of reinfection believe hosts are vulnerable to developing infection and new organisms emerge. The alternative hypothesis is that later failure is a result of an organism that was present in the joint but was not picked up by initial culture or was not a pathogen initially but became so under antibiotic pressure. This multicenter study explores the above dilemma. Utilizing next-generation sequencing (NGS), we hypothesize that failures after two stage exchange arthroplasty can be caused by an organism that was present at the time of initial surgery but not isolated by culture. Methods. This prospective study involving 15 institutions collected samples from 635 revision total hip (n=310) and knee (n=325) arthroplasties. Synovial fluid, tissue and swabs were obtained intraoperatively for NGS analysis. Patients were classified per 2018 Consensus definition of PJI. Treatment failure was defined as reoperation for infection that yielded positive cultures, during minimum 1-year follow-up. Concordance of the infecting pathogen cultured at failure with NGS analysis at initial revision was determined. Results. Among the total cohort, 203 revisions were considered infected and 432 were aseptic (based on ICM-criteria). Of the infected cases, 157 were NGS-positive and 46 NGS-negative. Twenty-nine ICM-positive patients (29/157;18.5%) failed by reoperation with an organism confirmed on culture. In 23 of these (23/29;79.3%), the organism at failure was present on NGS at initial revision. The remaining 6 cases detected discordant organisms between initial NGS and culture at failure. Of the 432 ICM-negative patients, NGS identified microbes in 48.1% (208/432) of “aseptic” revisions, and 17 of these failed. Thirteen of the 17 failures (76.5%) were due to an organism previously detected by NGS at initial revision. Conclusion. Our collaborative findings suggest that most failures (79.3%) by infection recurrence could be attributed to an organism previously detected by NGS at index revision surgery. For any figures or tables, please contact the authors directly


Bone & Joint Open
Vol. 2, Issue 8 | Pages 576 - 582
2 Aug 2021
Fuchs M Kirchhoff F Reichel H Perka C Faschingbauer M Gwinner C

Aims

Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA).

Methods

We conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11).


Bone & Joint Open
Vol. 2, Issue 5 | Pages 305 - 313
3 May 2021
Razii N Clutton JM Kakar R Morgan-Jones R

Aims

Periprosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA). Two-stage revision has traditionally been considered the gold standard of treatment for established infection, but increasing evidence is emerging in support of one-stage exchange for selected patients. The objective of this study was to determine the outcomes of single-stage revision TKA for PJI, with mid-term follow-up.

Methods

A total of 84 patients, with a mean age of 68 years (36 to 92), underwent single-stage revision TKA for confirmed PJI at a single institution between 2006 and 2016. In all, 37 patients (44%) were treated for an infected primary TKA, while the majority presented with infected revisions: 31 had undergone one previous revision (36.9%) and 16 had multiple prior revisions (19.1%). Contraindications to single-stage exchange included systemic sepsis, extensive bone or soft-tissue loss, extensor mechanism failure, or if primary wound closure was unlikely to be achievable. Patients were not excluded for culture-negative PJI or the presence of a sinus.