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Diagnosis and Treatment of Periprosthetic Joint Infections

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Diagnostic Microbiology and Infectious Disease".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 23914

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Dr. Giovanni Balato

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Department of Public Health, University of Naples “Federico II”, 80131 Napoli, Italy
Interests: TKA; revision TKA; periprosthetic joint infection; diagnosis; one-stage revision; two-stage revision; 3D printing
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Special Issue Information

Dear Colleagues,

Periprosthetic joint infection represents a huge complication after total joint replacement which influences the patient's quality of life and mortality. Once the septic process occurs, the diagnosis and treatment need a multidisciplinary approach, including orthopedic surgeons, microbiologists, and infectious disease specialists. The scientific community's interest in new serum and synovial biomarkers and biosensors has recently increased, intending to increase the sensibility of diagnostic tests to identify patients affected by deep infections. Furthermore, the treatment approach includes the mechanical and chemical removal of all infected tissues associated with antibiotic administration. The joint prosthesis removal in one or two surgical stages is the gold standard technique, facing chronic infections. Although the one-stage approach has shown promising results at specific institutions, the two-stage protocol remains the most widely applied. The treatment in two stages comprises double debridement and a bone cement (PMMA) device, the objective of which is to facilitate the healing process from the infection locally and grant joint activity. The effort to intraoperatively identify infected tissue and contaminated implant and the use of 3D printing to customize mobile spacers represent future strategies to increase the efficacy as well as clinical and functional outcomes of surgical procedures.

This Special Issue titled "Diagnosis and Treatment of Periprosthetic Joint Infections" will cover all aspects of the diagnostic and treatment approach, highlighting the new strategies, including the role of biological receptors, biosensors, biomarkers, organic dyes, and customization using 3D printing technologies, as well as their applications in the management of biofilm infections.

Dr. Giovanni Balato
Guest Editor

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Keywords

PJI
diagnosis
biomarkers
disclosing agents
3D printing
biosensors

Published Papers (13 papers)

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Research

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11 pages, 857 KiB

Open AccessArticle

Direct Prosthetic Joint Infection Diagnosis from Sonication Fluid Inoculated in Blood Culture Bottles by Direct MALDI-TOF Mass Spectrometry

by Iñaki Beguiristain, Lucia Henriquez, Ignacio Sancho, Carmen Martin, Angel Hidalgo-Ovejero, Carmen Ezpeleta and Maria Eugenia Portillo

Diagnostics 2023, 13(5), 942; https://doi.org/10.3390/diagnostics13050942 - 02 Mar 2023

Cited by 2 | Viewed by 1457

Abstract

An accurate and fast microbiological diagnosis is key for a proper management and results when facing prosthetic joint infection (PJI). The purpose of this study is to assess the role of direct Matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS) for early identification of the pathogens causing PJI from sonication fluid inoculated in blood culture bottles (BCB-SF). This prospective multicentric study included 107 consecutive patients from February 2016 to February 2017. Among them, 71 prosthetic joint revision surgeries were undergone for aseptic and 36 for septic reasons. Prostheses were sonicated and the resulting fluid inoculated into blood culture bottles, regardless the suspicion for infection. We assessed the diagnostic performance of direct MALDI-TOF MS identification of the pathogens in BCB-SF and compared it with periprosthetic tissue and conventional sonication fluid cultures. The sensitivity of direct MALDI-TOF MS of BCB-SF (69%) was higher compared to conventional sonication fluid (69% vs. 64%, p > 0.05) or intraoperative tissue cultures (69% vs. 53%, p = 0.04), especially for patients receiving antimicrobial treatment. This approach also reduced the time for identification but the specificity was compromised (100% vs. 94%) and polymicrobial infections were missed. In conclusion, BCB-SF improves the sensitivity and reduces the time of PJI diagnosis when used in combination with conventional cultures under strict sterility conditions. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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10 pages, 1115 KiB

Open AccessArticle

Evaluation of Synovial Calprotectin by Using a Lateral Flow Test for the Diagnosis of Prosthetic Joint Infections

by Marta Bottagisio, Marco Viganò, Antonio Pellegrini, Nicola Logoluso, Luigi Zagra, Andrea Prina, Laura de Girolamo and Elena De Vecchi

Diagnostics 2023, 13(4), 741; https://doi.org/10.3390/diagnostics13040741 - 15 Feb 2023

Cited by 1 | Viewed by 1123

Abstract

The analysis of synovial fluid is a crucial step in the diagnosis of prosthetic joint infections (PJIs). Recently several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI. In this study, synovial calprotectin was analyzed by a commercial stool test to explore whether it might accurately predict PJIs. The synovial fluids of 55 patients were analyzed and calprotectin levels were compared to other synovial biomarkers of PJI. Of the 55 synovial flu-ids, 12 patients were diagnosed with PJI and 43 with an aseptic failure of the implant. Specificity, sensitivity, and AUC of calprotectin resulted in 0.944, 0.80, and 0.852 (95%CI: 0.971–1.00), respectively, with a set threshold of 529.5 µg/g. Calprotectin had a statistically relevant correlation with the synovial leucocyte counts (rs = 0.69, p < 0.001) and the percentage of synovial neutrophils (rs = 0.61, p < 0.001). From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicators of local infection, and the use of a commercial lateral flow stool test could be a cost-effective strategy delivering rapid and reliable results and supporting the diagnostic process of PJI. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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13 pages, 907 KiB

Open AccessArticle

Accuracy of a Novel Preoperative Failure Risk Model for Debridement Antibiotics and Implant Retention (DAIR) in Acute Prosthetic Joint Infection

by Ignacio Sancho, Iñaki Otermin-Maya, Jorge Gutiérrez-Dubois, Ignacio Aláez, Ángel Hidalgo-Ovejero, Julián Librero and María Eugenia Portillo

Diagnostics 2022, 12(9), 2097; https://doi.org/10.3390/diagnostics12092097 - 29 Aug 2022

Viewed by 1474

Abstract

Given the variable success of the debridement, antibiotics and implant retention (DAIR) procedure in patients with acute prosthetic joint infection (PJI), an accurate selection of candidates is critical. In this study, we set about calculating the predictive value of a novel algorithm for predicting outcome following DAIR developed by Shohat et al. Sixty-four patients who underwent debridement for (early and late) acute PJI in a tertiary-level university hospital were selected, and the aforementioned algorithm was retrospectively applied. Patients with model scores of 40–50%, 50–60%, 60–70%, 70–80% and 80–90% displayed success rates of 33.34%, 41.18%, 57.9%, 78.27% and 100%, respectively. The receiver operating characteristic curve showed an area under the curve of 0.69. The calibration intercept value was 0, and the calibration slope value was 1. Failure rates were significantly higher for the following variables: revision surgery (p = 0.012) index surgery for reasons other than osteoarthritis (p = 0.01), and C-reactive protein level >30 mg/L (p = 0.042). This analysis demonstrated that the Shohat algorithm is associated with an optimal calibration value and a moderate predictive value for failure of a DAIR procedure in patients with acute PJI. Its validation is recommended before it can be routinely applied in daily practice. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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9 pages, 399 KiB

Open AccessArticle

Cell Toxicity Study of Antiseptic Solutions Containing Povidone–Iodine and Hydrogen Peroxide

by Veronica Romano, Donato Di Gennaro, Anna Maria Sacco, Enrico Festa, Emanuela Roscetto, Morena Anna Basso, Tiziana Ascione and Giovanni Balato

Diagnostics 2022, 12(8), 2021; https://doi.org/10.3390/diagnostics12082021 - 21 Aug 2022

Cited by 10 | Viewed by 1967

Abstract

The increasing incidence of periprosthetic joint infections (PJIs) has led to a growing interest in developing strategies to prevent and treat this severe complication. The surgical site’s application of antiseptic solutions to eliminate contaminating bacteria and eradicate the bacterial biofilm has been increasing over time. Even though it has been proven that combining antimicrobials could enhance their activities and help overcome acquired microbial resistance related to the topical use of antibiotics, the toxicity of integrated solutions is not well described. This study aimed to evaluate the cytotoxicity of solutions containing povidone–iodine (PI) and hydrogen peroxide (H

_{2}

_{2}

), alone or in combination, after 1.3 and 5 min of exposure. Chondrocytes, tenocytes, and fibroblast-like synoviocytes were used for cytotoxicity analysis. Trypan blue stain (0.4% in PBS) was applied to evaluate the dead cells. All solutions tested showed a progressive increase in toxicity as exposure time increased except for PI at 0.3%, which exhibited the lowest toxicity. The combined solutions reported a reduced cellular killing at 3 and 5 min than H

_{2}

_{2}

at equal concentrations, similar results to PI solutions. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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11 pages, 257 KiB

Open AccessArticle

Microbiological Profiles of Patients with Periprosthetic Joint Infection of the Hip or Knee

by Frank Sebastian Fröschen, Thomas Martin Randau, Alexander Franz, Ernst Molitor and Gunnar Thorben Rembert Hischebeth

Diagnostics 2022, 12(7), 1654; https://doi.org/10.3390/diagnostics12071654 - 07 Jul 2022

Cited by 6 | Viewed by 1658

Abstract

Periprosthetic joint infections (PJI) are one of the most devastating consequences after total joint arthroplasty. We sought to analyze the causative pathogens of patients with PJI to get better insights and improve treatment. We performed a retrospective study of all patients with PJI of the hip and knee with microbiological detection of a causative pathogen at a tertiary endoprothetic referral center between January 2016 and March 2021. A total of 432 cases with PJI (hip: n = 250; knee: n = 182) were included. The most common causative pathogen were coagulase-negative staphylococci (n = 240; 44.2%), of which Staphylococcus epidermidis (n = 144; 26.7%) was the most frequently detected, followed by S. aureus (n = 77; 14.3%) and enterococci (n = 49; 9%). Gram-negative pathogens and fungi could be detected in 21% (n = 136) and 2.4% (n = 13) of all cases. Overall, 60% of all coagulase-negative staphylococci were oxacillin-resistant, while none of these displayed to be vancomycin-resistant. In summary, the majority of pathogens in cases of PJI could be identified as coagulase-negative staphylococci. For empirical therapy vancomycin might provide the highest antimicrobial coverage in case of an unknown pathogen. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

8 pages, 1676 KiB

Open AccessArticle

Synovial Fluid Interleukin Levels Cannot Distinguish between Prosthetic Joint Infection and Active Rheumatoid Arthritis after Hip or Knee Arthroplasty

by Leilei Qin, Chengcheng Du, Jianye Yang, Hai Wang, Xudong Su, Li Wei, Chen Zhao, Cheng Chen, Hong Chen, Ning Hu and Wei Huang

Diagnostics 2022, 12(5), 1196; https://doi.org/10.3390/diagnostics12051196 - 11 May 2022

Cited by 5 | Viewed by 1608

Abstract

Inflammatory arthritis affects the level of synovial inflammatory factors, which makes it more difficult to diagnose prosthetic joint infection (PJI) patients with inflammatory arthritis. The aim of this study was to analyze synovial interleukin levels to distinguish between PJI and active rheumatoid arthritis (RA) after a hip or knee arthroplasty. From September 2019 to September 2021, we prospectively enrolled patients with joint pain after arthroplasty due to aseptic prosthesis loosening (n = 39), acute RA (n = 26), and PJI (n = 37). Synovial fluid from the affected joint is obtained and tested with a standard enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was analyzed for each biomarker. Interleukin (IL)-1β, IL-6, and IL-8 showed promising value in differentiating of aseptic loosening from PJI, with areas under the curves (AUCs) of 0.9590, 0.9506, and 0.9616, respectively. Synovial IL-1β, IL-6, and IL-8 showed limited value in distinguishing between PJI and acute episodes of RA after arthroplasty, with AUCs of 0.7507, 0.7069, and 0.7034, respectively. Interleukins showed satisfactory efficacy in differentiating aseptic loosening from PJI. However, when pain after arthroplasty results from an acute episode of RA, current synovial interleukin levels do not accurately rule out the presence of PJI. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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11 pages, 1262 KiB

Open AccessArticle

Do Serum C-Reactive Protein Trends Predict Treatment Outcome in Patients with Knee Periprosthetic Joint Infection Undergoing Two-Stage Exchange Arthroplasty?

by Sheng-Hsun Lee, Chun-Ting Chu, Chih-Hsiang Chang, Chih-Chien Hu, Szu-Yuan Chen, Tung-Wu Lu and Yu-Chih Lin

Diagnostics 2022, 12(5), 1030; https://doi.org/10.3390/diagnostics12051030 - 20 Apr 2022

Cited by 3 | Viewed by 1775

Abstract

Two-stage exchange arthroplasty is the standard treatment for knee periprosthetic joint infection (PJI). This study aimed to determine whether serial changes in C-reactive protein (CRP) values can predict the prognosis in patients with knee PJI. We retrospectively enrolled 101 patients with knee PJI treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. We excluded patients with spacer complications and confounding factors affecting CRP levels. We tested the association between treatment outcomes and qualitative CRP patterns or quantitative CRP levels. Of the 101 patients, 24 (23.8%) had recurrent PJI and received surgical intervention after two-stage reimplantation. Patients with a fluctuating CRP pattern were more likely to receive antibiotics for a longer period (p < 0.001). There was greater risk of treatment failure if the CRP levels were higher when antibiotics were switched from an intravenous to oral form (p = 0.023). The patients who received antibiotics for longer than six weeks (p = 0.017) were at greater risk of treatment failure after two-stage arthroplasty. Although CRP patterns cannot predict treatment outcomes, CRP fluctuation in the interim period was associated with longer antibiotic duration, which was related to a higher treatment failure rate. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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Review

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14 pages, 336 KiB

Open AccessReview

Advances in the Microbiological Diagnosis of Prosthetic Joint Infections

by Maria Eugenia Portillo and Ignacio Sancho

Diagnostics 2023, 13(4), 809; https://doi.org/10.3390/diagnostics13040809 - 20 Feb 2023

Cited by 8 | Viewed by 2314

Abstract

A significant number of prosthetic joint infections (PJI) are culture-negative and/or misinterpreted as aseptic failures in spite of the correct implementation of diagnostic culture techniques, such as tissue sample processing in a bead mill, prolonged incubation time, or sonication of removed implants. Misinterpretation may lead to unnecessary surgery and needless antimicrobial treatment. The diagnostic value of non-culture techniques has been investigated in synovial fluid, periprosthetic tissues, and sonication fluid. Different feasible improvements, such as real-time technology, automated systems and commercial kits are now available to support microbiologists. In this review, we describe non-culture techniques based on nucleic acid amplification and sequencing methods. Polymerase chain reaction (PCR) is a frequently used technique in most microbiology laboratories which allows the detection of a nucleic acid fragment by sequence amplification. Different PCR types can be used to diagnose PJI, each one requiring the selection of appropriate primers. Henceforward, thanks to the reduced cost of sequencing and the availability of next-generation sequencing (NGS), it will be possible to identify the whole pathogen genome sequence and, additionally, to detect all the pathogen sequences present in the joint. Although these new techniques have proved helpful, strict conditions need to be observed in order to detect fastidious microorganisms and rule out contaminants. Specialized microbiologists should assist clinicians in interpreting the result of the analyses at interdisciplinary meetings. New technologies will gradually be made available to improve the etiologic diagnoses of PJI, which will remain an important cornerstone of treatment. Strong collaboration among all specialists involved is essential for the correct diagnosis of PJI. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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Graphical abstract

11 pages, 296 KiB

Open AccessReview

Role of Biomarkers in Periprosthetic Joint Infections

by Serhat Akcaalan, Halil Ibrahim Ozaslan, Ceyhun Caglar, Mehmet Emin Şimşek, Mustafa Citak and Mustafa Akkaya

Diagnostics 2022, 12(12), 2958; https://doi.org/10.3390/diagnostics12122958 - 25 Nov 2022

Cited by 2 | Viewed by 1586

Abstract

Periprosthetic joint infection (PJI) is one of the most serious complications after joint arthroplasty. The incidence rate of PJI after total joint replacement is 1–3%. Although there are different guidelines and diagnostic criteria used to diagnose PJI, diagnosing PJI is a highly difficult process for orthopedists. The current Musculoskeletal Infection Society (MSIS) criteria are widely used for the diagnosis of PJI. These criteria include results from blood/synovial fluid tests, physical examination, and histological and microbiological analyses of intra-operative samples. However, there is currently no blood or synovial test that can definitively diagnose PJI. To make a more effective diagnosis of PJI, a large number of studies have explored and continue to investigate biomarkers. This review aims to provide general information about serum and synovial markers used for the diagnosis of PJI that may be used to create a database to guide researchers in new studies. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

Other

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10 pages, 474 KiB

Open AccessSystematic Review

The Role of Single Positive Cultures in Presumed Aseptic Total Hip and Knee Revision Surgery—A Systematic Review of the Literature

by Jan Schwarze, Burkhard Moellenbeck, Georg Gosheger, Jan Puetzler, Niklas Deventer, Tobias Kalisch, Kristian Nikolaus Schneider, Sebastian Klingebiel and Christoph Theil

Diagnostics 2023, 13(9), 1655; https://doi.org/10.3390/diagnostics13091655 - 08 May 2023

Cited by 1 | Viewed by 1286

Abstract

(1) Background: Prior to revision hip (THA) or knee arthroplasty (TKA), periprosthetic low-grade infection (PJI) should be ruled out. Despite advances in preoperative diagnosis, unsuspected positive cultures (UPCs) may occur in initially planned aseptic revisions. Particularly, single UPCs pose a diagnostic and therapeutic dilemma, as their impact on outcome is unclear and recommendations are heterogeneous. This review investigates the frequency of single UPCs and their impact on implant survivorship. (2) Methods: In July 2022, a comprehensive literature search was performed using PubMed and Cochrane Library search. In total, 197 articles were screened. Seven retrospective studies with a total of 5821 cases were able to be included in this review. (3) Results: Based on the cases included, UPCs were found in 794/5821 cases (14%). In 530/794 cases (67%), the majority of the UPCs were single positive. The most commonly isolated pathogens were coagulase negative Staphylococci and Cutibacterium acnes. Five of seven studies reported no influence on revision- or infection-free survival following a single positive culture. In two studies, single UPCs following THA revision were correlated with subsequent re-revision for PJI. (4) Conclusions: Single UPCs of a non-virulent pathogen following presumed aseptic TKA revision may be interpreted as contaminants. A single UPC following THA revision may be a risk factor for subsequent PJI. The role of systemic antibiotic treatment remains unclear, but it should be considered if other risk factors for PJI are present. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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9 pages, 1721 KiB

Open AccessCase Report

by Cristiano De Franco, Gabriele Colò, Marco Melato, Alberto Battini, Simone Cambursano, Giuseppe Pietro Logrieco, Giovanni Balato and Kristijan Zoccola

Diagnostics 2022, 12(10), 2476; https://doi.org/10.3390/diagnostics12102476 - 13 Oct 2022

Cited by 2 | Viewed by 3081

Abstract

Case: A 51-year-old man was affected by a fracture-related infection after a bicolumnar acetabular fracture. A significant alteration of the anatomy was present; thus, a 3D-printed model was useful for planning. A two-stage treatment was planned: in the first stage, implant removal with irrigation and debridement was performed, while in the second stage, a new osteosynthesis and implant of a THA were planned. During the second stage, the patient suffered a cardiogenic shock, so a third surgical procedure was necessary to implant THA. Targeted antibiotic therapy was administered eight weeks after the first stage, with the resolution of the infection. Conclusions: The infection was resolved following the recent guidelines and treating it like a periprosthetic infection with a two-stage revision. A collaboration between specialists in orthopaedics and infectious disease, respectively, and using multidisciplinary approach, were mandatory. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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12 pages, 567 KiB

Open AccessSystematic Review

Diagnostic Performance of Neutrophil to Lymphocyte Ratio, Monocyte to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Platelet to Mean Platelet Volume Ratio in Periprosthetic Hip and Knee Infections: A Systematic Review and Meta-Analysis

by Enrico Festa, Tiziana Ascione, Alessio Bernasconi, Donato Di Gennaro, Morena Anna Basso, Amedeo Guarino and Giovanni Balato

Diagnostics 2022, 12(9), 2033; https://doi.org/10.3390/diagnostics12092033 - 23 Aug 2022

Cited by 13 | Viewed by 2154

Abstract

The current literature on the diagnosis of periprosthetic joint infection provides controversial evidence on the diagnostic accuracy of MLR, NLR, PVR, and PLR. Therefore, this critical literature search and meta-analysis was aimed to summarize the diagnostic accuracy of these biomarkers for the diagnosis of hip and knee prosthetic infection. According to the PRISMA flowchart, we searched MEDLINE, Scopus, and Web of Science, for studies on these ratios for diagnosing PJI. Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and AUC were analyzed. We included 11 articles in our meta-analysis, including 7537 patients who underwent total hip and knee arthroplasties; among these, 1974 (26%) patients reported a joint infection. The pooled sensitivity and specificity were 0.72 and 0.74, respectively, for NLR, 0.72 and 0.77 for PVR, and 0.77 and 0.75 for PLR. The sensitivity of MLR ranges from 0.54 to 0.81, while the specificity ranges from 0.78 to 0.81. Regarding the evaluation of AUCs, the best diagnostic performance was achieved by MLR (AUC = 0.77) followed by PLR (AUC = 0.75), NLR (AUC = 0.73), and PVR (AUC = 0.70). This meta-analysis demonstrates a fair diagnostic accuracy of these ratios, thus not being useful as a screening tool. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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9 pages, 610 KiB

Open AccessOpinion

Synchronous Periprosthetic Joint Infections: A Scoping Review of the Literature

by Andrea Sambri, Emilia Caldari, Michele Fiore, Claudio Giannini, Matteo Filippini, Lorenzo Morante, Claudia Rondinella, Eleonora Zamparini, Sara Tedeschi, Pierluigi Viale and Massimiliano De Paolis

Diagnostics 2022, 12(8), 1841; https://doi.org/10.3390/diagnostics12081841 - 30 Jul 2022

Cited by 2 | Viewed by 1313

Abstract

Prosthetic joint infections (PJIs) occurring in multiple joints at the same time (synchronous PJI) are an extremely rare complication, frequently associated with bacteremia, and are associated with high mortality rates. The presence of three or more prosthetic joints, rheumatoid arthritis, neoplasia, bacteremia and immune-modulating therapy seem to be the recurring risk factors for synchronous PJI. In case of PJIs, all other replaced joints should be considered as potentially infected and investigated if PJI is suspected. Treatments of synchronous multiple PJIs vary and must be decided on a case-by-case basis. However, the advantages of one-stage exchange seem to outweigh the two-stage protocol, as it decreases the number of necessary surgical procedures. Nonetheless, too few studies have been conducted to allow firm conclusions about the best handling of synchronous PJI. Thus, additional studies are needed to understand this devastating complication and to design the most appropriate diagnostic and therapeutic path. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Periprosthetic Joint Infections)

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