Articles | Volume 10, issue 5
https://doi.org/10.5194/jbji-10-363-2025
© Author(s) 2025. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
https://doi.org/10.5194/jbji-10-363-2025
© Author(s) 2025. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
Review
| 
10 Oct 2025
Review |
| 10 Oct 2025
| 10 Oct 2025
Serum inflammatory markers for the screening and diagnosis of periprosthetic joint infection: a systematic review and meta-analysis
Irene K. Sigmund
CORRESPONDING AUTHOR
Department of Orthopaedics, Medical University of Vienna, Vienna, Austria
Matthew J. Dietz
Department of Orthopaedics, Health Sciences Center, WVU School of Medicine, Morgantown, WV, USA
Marta Sabater-Martos
Orthopedic and Traumatology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Antony J. R. Palmer
Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, UK
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK
Nicolas Cortés-Penfield
Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA
A full list of authors appears at the end of the paper.
Related authors
Irene K. Sigmund, Marjan Wouthuyzen-Bakker, Tristan Ferry, Ricardo Sousa, Daniel Pérez-Prieto, Alex Soriano, Volker Alt, Willem J. Metsemakers, Martin Clauss, and Rihard Trebse
J. Bone Joint Infect., 11, 651–654, https://doi.org/10.5194/jbji-11-651-2026, https://doi.org/10.5194/jbji-11-651-2026, 2026
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Sinus tracts are currently classified as present or absent in PJI definitions. Although appropriate for diagnosis, this binary approach does not reflect the considerable heterogeneity encountered in clinical practice. This Viewpoint highlights characteristics that may determine sinus tract complexity and proposes a framework for future standardized characterization to better inform surgical decision-making and treatment outcomes.
Laura Bessems, Jolien Onsea, Marjan Wouthuyzen-Bakker, Irene K. Sigmund, Tristan Ferry, Richard Kuehl, Martin Clauss, Alex Soriano, Ricardo Sousa, Annette Schuermans, and Willem-Jan Metsemakers
J. Bone Joint Infect., 11, 489–492, https://doi.org/10.5194/jbji-11-489-2026, https://doi.org/10.5194/jbji-11-489-2026, 2026
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We examined whether patients with musculoskeletal infections need to be separated in hospital. A review of published studies found no support for routine isolation or dedicated wards for infections without multidrug-resistant organisms when standard precautions are applied. An international survey showed wide variation in clinician attitudes. These findings highlight a gap between evidence and perception and support a more risk-based approach.
Markus Luger, Martin McNally, Lukas Rabitsch, Reinhard Windhager, Richard Lass, and Irene Katharina Sigmund
J. Bone Joint Infect., 11, 305–313, https://doi.org/10.5194/jbji-11-305-2026, https://doi.org/10.5194/jbji-11-305-2026, 2026
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Sinus tracts communicating with the prosthesis demonstrated high specificity and support their use as a confirmatory criterion for periprosthetic joint infection (PJI). Purulence also showed high specificity but may be better considered to be a suggestive criterion due to challenges in clinical differentiation. Both findings were associated with distinct microbiological patterns and less favourable outcomes, highlighting their clinical relevance.
Goran Georgievski, Nike Walter, Ronald Man Yeung Wong, Irene Katharina Sigmund, Ashok Kanuri, Christian Heiss, and Markus Rupp
J. Bone Joint Infect., 11, 219–228, https://doi.org/10.5194/jbji-11-219-2026, https://doi.org/10.5194/jbji-11-219-2026, 2026
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This article outlines 20 common errors in the prevention, diagnosis, and management of fracture-related infection (FRI), highlighting their clinical consequences and providing practical recommendations for avoiding them. By addressing typical pitfalls and emphasizing standardized procedures and interdisciplinary collaboration, the article aims to improve patient safety and treatment outcomes.
Laura Bessems, Jolien Onsea, Baixing Chen, Marjan Wouthuyzen-Bakker, Irene K. Sigmund, Tristan Ferry, Richard Kuehl, Martin Clauss, Alex Soriano, Ricardo Sousa, Annette Schuermans, and Willem-Jan Metsemakers
J. Bone Joint Infect., 10, 489–500, https://doi.org/10.5194/jbji-10-489-2025, https://doi.org/10.5194/jbji-10-489-2025, 2025
Short summary
Short summary
Isolation of patients with musculoskeletal infections in orthopedic care is controversial. Evidence supports selective isolation for certain resistant pathogens but not for non-resistant pathogens, nor does it support the routine use of septic wards. Effective infection control depends on hospital-wide strategies and adherence to standard precautions, with specialized centres offering better care than dedicated isolation units.
Lukas Rabitsch, Markus Luger, Felix Lötsch, Peter Starzengruber, Florian Thalhammer, Reinhard Windhager, Birgit Willinger, and Irene Katharina Sigmund
J. Bone Joint Infect., 10, 437–446, https://doi.org/10.5194/jbji-10-437-2025, https://doi.org/10.5194/jbji-10-437-2025, 2025
Short summary
Short summary
The novel multiplex polymerase chain reaction (mPCR), BioFire® Joint Infection Panel (BF-JIP; bioMérieux, Marcy-l’Étoile, France), demonstrated similar diagnostic accuracy to conventional synovial fluid culture and can therefore serve as a valuable adjunct in diagnosing septic arthritis in adults, particularly in patients with prior antimicrobial therapy.
Laura K. Certain and Irene K. Sigmund
J. Bone Joint Infect., 10, 397–402, https://doi.org/10.5194/jbji-10-397-2025, https://doi.org/10.5194/jbji-10-397-2025, 2025
Short summary
Short summary
The Musculoskeletal Infection Society (MSIS) and the European Bone and Joint Infection Society (EBJIS) are comprised of experts in preventing, diagnosing, and managing orthopedic infections. In 2023, MSIS and EBJIS surveyed their membership about their approach to various clinical aspects of these challenging conditions. The results indicate that, even among experts, there remains substantial variability of practice. This variability reflects open questions in the field.
Irene K. Sigmund, Marjan Wouthuyzen-Bakker, Tristan Ferry, Willem-Jan Metsemakers, Martin Clauss, Alex Soriano, Rihard Trebse, and Ricardo Sousa
J. Bone Joint Infect., 10, 139–142, https://doi.org/10.5194/jbji-10-139-2025, https://doi.org/10.5194/jbji-10-139-2025, 2025
Short summary
Short summary
This is a summary of our position paper on debridement, antimicrobial therapy, and implant retention (DAIR) procedures as a curative treatment strategy for acute periprosthetic hip and knee infections. It includes the defined indications as well as the contraindications of DAIR procedures when eradication/cure is intended, based on the currently available literature.
Irene K. Sigmund, Tristan Ferry, Ricardo Sousa, Alex Soriano, Willem-Jan Metsemakers, Martin Clauss, Rihard Trebse, and Marjan Wouthuyzen-Bakker
J. Bone Joint Infect., 10, 101–138, https://doi.org/10.5194/jbji-10-101-2025, https://doi.org/10.5194/jbji-10-101-2025, 2025
Short summary
Short summary
In this paper, we discuss the most relevant factors influencing the outcome and define indications, contraindications, and risk factors of a DAIR procedure based on the currently available literature. Furthermore, we discuss the surgical technique in combination with systemic antimicrobial therapy in patients undergoing a DAIR procedure.
Irene K. Sigmund, Marjan Wouthuyzen-Bakker, Tristan Ferry, Ricardo Sousa, Daniel Pérez-Prieto, Alex Soriano, Volker Alt, Willem J. Metsemakers, Martin Clauss, and Rihard Trebse
J. Bone Joint Infect., 11, 651–654, https://doi.org/10.5194/jbji-11-651-2026, https://doi.org/10.5194/jbji-11-651-2026, 2026
Short summary
Short summary
Sinus tracts are currently classified as present or absent in PJI definitions. Although appropriate for diagnosis, this binary approach does not reflect the considerable heterogeneity encountered in clinical practice. This Viewpoint highlights characteristics that may determine sinus tract complexity and proposes a framework for future standardized characterization to better inform surgical decision-making and treatment outcomes.
Laura Bessems, Jolien Onsea, Marjan Wouthuyzen-Bakker, Irene K. Sigmund, Tristan Ferry, Richard Kuehl, Martin Clauss, Alex Soriano, Ricardo Sousa, Annette Schuermans, and Willem-Jan Metsemakers
J. Bone Joint Infect., 11, 489–492, https://doi.org/10.5194/jbji-11-489-2026, https://doi.org/10.5194/jbji-11-489-2026, 2026
Short summary
Short summary
We examined whether patients with musculoskeletal infections need to be separated in hospital. A review of published studies found no support for routine isolation or dedicated wards for infections without multidrug-resistant organisms when standard precautions are applied. An international survey showed wide variation in clinician attitudes. These findings highlight a gap between evidence and perception and support a more risk-based approach.
Vincent K. Melemai, Ryan J. Blake, Christian Barill, Adam E. Klein, Matthew J. Dietz, and Allison M. Lastinger
J. Bone Joint Infect., 11, 331–336, https://doi.org/10.5194/jbji-11-331-2026, https://doi.org/10.5194/jbji-11-331-2026, 2026
Short summary
Short summary
Total joint arthroplasty is increasingly common in the US, with an expected rise in periprosthetic joint infection (PJI). Limited evidence exists of PJI risk in new primary arthroplasty in patients on chronic suppression for prior PJI. Due to a lack of evidence examining this population, shared decision-making must be informed by medical comorbidities and patient-related risk factors, infectious history, and the current evidence of PJI treatment and infection control measures.
Markus Luger, Martin McNally, Lukas Rabitsch, Reinhard Windhager, Richard Lass, and Irene Katharina Sigmund
J. Bone Joint Infect., 11, 305–313, https://doi.org/10.5194/jbji-11-305-2026, https://doi.org/10.5194/jbji-11-305-2026, 2026
Short summary
Short summary
Sinus tracts communicating with the prosthesis demonstrated high specificity and support their use as a confirmatory criterion for periprosthetic joint infection (PJI). Purulence also showed high specificity but may be better considered to be a suggestive criterion due to challenges in clinical differentiation. Both findings were associated with distinct microbiological patterns and less favourable outcomes, highlighting their clinical relevance.
Goran Georgievski, Nike Walter, Ronald Man Yeung Wong, Irene Katharina Sigmund, Ashok Kanuri, Christian Heiss, and Markus Rupp
J. Bone Joint Infect., 11, 219–228, https://doi.org/10.5194/jbji-11-219-2026, https://doi.org/10.5194/jbji-11-219-2026, 2026
Short summary
Short summary
This article outlines 20 common errors in the prevention, diagnosis, and management of fracture-related infection (FRI), highlighting their clinical consequences and providing practical recommendations for avoiding them. By addressing typical pitfalls and emphasizing standardized procedures and interdisciplinary collaboration, the article aims to improve patient safety and treatment outcomes.
Laura Bessems, Jolien Onsea, Baixing Chen, Marjan Wouthuyzen-Bakker, Irene K. Sigmund, Tristan Ferry, Richard Kuehl, Martin Clauss, Alex Soriano, Ricardo Sousa, Annette Schuermans, and Willem-Jan Metsemakers
J. Bone Joint Infect., 10, 489–500, https://doi.org/10.5194/jbji-10-489-2025, https://doi.org/10.5194/jbji-10-489-2025, 2025
Short summary
Short summary
Isolation of patients with musculoskeletal infections in orthopedic care is controversial. Evidence supports selective isolation for certain resistant pathogens but not for non-resistant pathogens, nor does it support the routine use of septic wards. Effective infection control depends on hospital-wide strategies and adherence to standard precautions, with specialized centres offering better care than dedicated isolation units.
Lukas Rabitsch, Markus Luger, Felix Lötsch, Peter Starzengruber, Florian Thalhammer, Reinhard Windhager, Birgit Willinger, and Irene Katharina Sigmund
J. Bone Joint Infect., 10, 437–446, https://doi.org/10.5194/jbji-10-437-2025, https://doi.org/10.5194/jbji-10-437-2025, 2025
Short summary
Short summary
The novel multiplex polymerase chain reaction (mPCR), BioFire® Joint Infection Panel (BF-JIP; bioMérieux, Marcy-l’Étoile, France), demonstrated similar diagnostic accuracy to conventional synovial fluid culture and can therefore serve as a valuable adjunct in diagnosing septic arthritis in adults, particularly in patients with prior antimicrobial therapy.
Laura K. Certain and Irene K. Sigmund
J. Bone Joint Infect., 10, 397–402, https://doi.org/10.5194/jbji-10-397-2025, https://doi.org/10.5194/jbji-10-397-2025, 2025
Short summary
Short summary
The Musculoskeletal Infection Society (MSIS) and the European Bone and Joint Infection Society (EBJIS) are comprised of experts in preventing, diagnosing, and managing orthopedic infections. In 2023, MSIS and EBJIS surveyed their membership about their approach to various clinical aspects of these challenging conditions. The results indicate that, even among experts, there remains substantial variability of practice. This variability reflects open questions in the field.
Marta Sabater-Martos, Laura Morata, Josep Maria Segur, Alex Soriano, and Juan Carlos Martínez-Pastor
J. Bone Joint Infect., 10, 237–241, https://doi.org/10.5194/jbji-10-237-2025, https://doi.org/10.5194/jbji-10-237-2025, 2025
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Short summary
This study's aim was to analyse the healing and failure rates of one-stage knee replacement in patients with positive and negative preoperative cultures and sinus presence. We concluded that culture-negative infections or the presence of a sinus tract showed similar results compared to patients that had undergone the same procedure with positive cultures or spared soft tissue.
Marta Sabater-Martos, Martin Clauss, Ana Ribau, Ricardo Sousa, and on behalf of the Leukocyte Count Synovial Fluid working group for the Unified PJI definition task force
J. Bone Joint Infect., 10, 165–184, https://doi.org/10.5194/jbji-10-165-2025, https://doi.org/10.5194/jbji-10-165-2025, 2025
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This meta-analysis evaluates synovial fluid white blood cell count and polymorphonuclear neutrophil proportion in order to diagnose chronic peri-prosthetic joint infection. Based on 74 studies, it identifies optimal thresholds, with rule-in and rule-out thresholds enhancing diagnostic precision. Confounding factors such as fractures and inflammatory arthritis are addressed. The findings support standardized diagnostic frameworks in improving accuracy and clinical consistency.
Irene K. Sigmund, Marjan Wouthuyzen-Bakker, Tristan Ferry, Willem-Jan Metsemakers, Martin Clauss, Alex Soriano, Rihard Trebse, and Ricardo Sousa
J. Bone Joint Infect., 10, 139–142, https://doi.org/10.5194/jbji-10-139-2025, https://doi.org/10.5194/jbji-10-139-2025, 2025
Short summary
Short summary
This is a summary of our position paper on debridement, antimicrobial therapy, and implant retention (DAIR) procedures as a curative treatment strategy for acute periprosthetic hip and knee infections. It includes the defined indications as well as the contraindications of DAIR procedures when eradication/cure is intended, based on the currently available literature.
Irene K. Sigmund, Tristan Ferry, Ricardo Sousa, Alex Soriano, Willem-Jan Metsemakers, Martin Clauss, Rihard Trebse, and Marjan Wouthuyzen-Bakker
J. Bone Joint Infect., 10, 101–138, https://doi.org/10.5194/jbji-10-101-2025, https://doi.org/10.5194/jbji-10-101-2025, 2025
Short summary
Short summary
In this paper, we discuss the most relevant factors influencing the outcome and define indications, contraindications, and risk factors of a DAIR procedure based on the currently available literature. Furthermore, we discuss the surgical technique in combination with systemic antimicrobial therapy in patients undergoing a DAIR procedure.
Marta Sabater-Martos, Oscar Garcia, Laia Boadas, Laura Morata, Alex Soriano, and Juan Carlos Martínez-Pastor
J. Bone Joint Infect., 10, 41–49, https://doi.org/10.5194/jbji-10-41-2025, https://doi.org/10.5194/jbji-10-41-2025, 2025
Short summary
Short summary
This is a retrospective diagnostic study in acute postoperative prosthetic joint infection in total knee arthroplasty that wants to determine diagnostic accuracy of synovial glucose and serum-to-synovial glucose ratio in acute postoperative infection. Both tests demonstrated good diagnostic potential. Notably, these biomarkers exhibited superior accuracy compared to the combination of C-reactive protein, synovial white blood cell count and polymorphonuclear percentage.
Laia Boadas-Gironès, Marta Sabater-Martos, Marc Ferrer-Banus, Àlex Soriano-Viladomiu, and Juan Carlos Martínez-Pastor
J. Bone Joint Infect., 9, 241–248, https://doi.org/10.5194/jbji-9-241-2024, https://doi.org/10.5194/jbji-9-241-2024, 2024
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When acute soft tissue defects are present after knee arthroplasty, the infection risk is high. A gastrocnemius flap is used for anterior defects, and it is not usually combined with debridement surgery unless infection is clear. We examined the benefit of combining coverage treatment with debridement surgery, DAIR, comparing the isolated traditional coverage treatment. The results suggested a higher healing rate in the combined treatment, so we recommended it.
Nicolás Cortés-Penfield, Don Bambino Geno Tai, and Angela Hewlett
J. Bone Joint Infect., 9, 161–165, https://doi.org/10.5194/jbji-9-161-2024, https://doi.org/10.5194/jbji-9-161-2024, 2024
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This survey study describes the composition of US-based orthopedic infectious diseases (Ortho ID) teams across more than a dozen large academic medical centers, finding many institutions have dedicated Ortho ID clinics or inpatient services. These teams are highly valued by both ID clinicians and surgeons for engendering strong multidisciplinary relationships and improving patient outcomes.
Marta Sabater-Martos, Marc Ferrer, Laura Morata, Alex Soriano, and Juan Carlos Martínez-Pastor
J. Bone Joint Infect., 9, 17–26, https://doi.org/10.5194/jbji-9-17-2024, https://doi.org/10.5194/jbji-9-17-2024, 2024
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This is a meta-analysis of six studies describing the cutoff values of white blood cell count and polymorphonuclear percentage in synovial fluid for the diagnosis of acute postoperative peri-prosthetic joint infection (PJI).
We found that both the WBC count and PMN percentage are good markers for diagnosis of acute postoperative PJI. However, the synovial WBC count is more powerful in diagnosing acute postoperative PJI.
We found that both the WBC count and PMN percentage are good markers for diagnosis of acute postoperative PJI. However, the synovial WBC count is more powerful in diagnosing acute postoperative PJI.
Robert A. McCulloch, Alex Martin, Bernadette C. Young, Benjamin J. Kendrick, Abtin Alvand, Lee Jeys, Jonathan Stevenson, and Antony J. Palmer
J. Bone Joint Infect., 8, 229–234, https://doi.org/10.5194/jbji-8-229-2023, https://doi.org/10.5194/jbji-8-229-2023, 2023
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Patients undergoing multiple hip and knee revision arthroplasty procedures for periprosthetic joint infection can have a changing microbiological picture, which can impact their management and outcomes. We aimed to investigate this using data from two large-volume orthopaedic centres. A total of 106 patients were identified; after six revision procedures, 90 % of patients had different organisms cultured compared with the initial revision and 53 % of the organisms were multidrug resistant.
Christen Ravn, Jeroen Neyt, Natividad Benito, Miguel Araújo Abreu, Yvonne Achermann, Svetlana Bozhkova, Liselotte Coorevits, Matteo Carlo Ferrari, Karianne Wiger Gammelsrud, Ulf-Joachim Gerlach, Efthymia Giannitsioti, Martin Gottliebsen, Nis Pedersen Jørgensen, Tomislav Madjarevic, Leonard Marais, Aditya Menon, Dirk Jan Moojen, Markus Pääkkönen, Marko Pokorn, Daniel Pérez-Prieto, Nora Renz, Jesús Saavedra-Lozano, Marta Sabater-Martos, Parham Sendi, Staffan Tevell, Charles Vogely, Alex Soriano, and the SANJO guideline group
J. Bone Joint Infect., 8, 29–37, https://doi.org/10.5194/jbji-8-29-2023, https://doi.org/10.5194/jbji-8-29-2023, 2023
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Management of septic arthritis in native joints (SANJO) is often conducted by clinicians of different specialties, experience levels, and at all hours of the day. The SANJO guideline group makes evidence-based recommendations for diagnosis, microbiological investigation, initial surgery, empirical antibiotic treatment, early mobilization, evaluation of outcomes, and treatment failure. Special considerations were made for children, tuberculosis, and SANJO after cruciate ligament reconstruction.
Nour Bouji, Sijin Wen, and Matthew J. Dietz
J. Bone Joint Infect., 7, 191–202, https://doi.org/10.5194/jbji-7-191-2022, https://doi.org/10.5194/jbji-7-191-2022, 2022
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Long antibiotic courses, including IV and oral administrations, are utilized in prosthetic joint infection (PJI) treatment. Most researchers focus on a shorter duration of the overall antibiotic course for the treatment of PJI; however, this is the first systematic review and meta-analysis to emphasize the IV component of the antibiotic course. The focus on IV treatment only is due to the burden associated with it and its prolonged utilization within the US without much evidence of practice.
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Yu, B. Z., Li, R., Li, X., Chai, W., Zhou, Y. G., and Chen, J. Y.: The relationship of C-reactive protein/interleukin-6 concentrations between serum and synovial fluid in the diagnosis of periprosthetic joint infection, J. Orthop. Surg. Res., 16, 733, https://doi.org/10.1186/s13018-021-02880-x, 2021.
Short summary
Serum C-reactive protein, fibrinogen, and interleukin-6 show the best performance among serum markers for diagnosing periprosthetic joint infection (PJI), but they lack sufficient accuracy to confirm or exclude infection reliably. These markers should be re-evaluated in future PJI definitions, as they are not suitable as stand-alone tests. Given their limitations and the superior diagnostic performance of synovial markers, the role of serum markers in PJI diagnosis should be reconsidered.
Serum C-reactive protein, fibrinogen, and interleukin-6 show the best performance among serum...
