Prevention, Diagnostic and Antibiotic Treatment of Periprosthetic Joint and Fracture Related Infection, 2nd Edition

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 11258

Special Issue Editors


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Guest Editor
Department for Joint Replacement, Rheumatoid and General Orthopaedics, Orthopaedic Clinic Markgröningen, Markgroningen, Germany
Interests: primary and revision joint arthroplasty of hip and knee; diagnostics and therapy of bone and joint infections
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Guest Editor
Center for Orthopedics and Trauma Surgery, University Hospital of Marburg, Marburg, Germany
Interests: the care of severe injuries; orthopedics and trauma surgery; special trauma surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The first Special Issue covering the topic of prevention, diagnosis and treatment of periprosthetic joint and fracture-related infections was very successful.

As such, we want to proceed with the second Special Issue on the same topic.

The aim of this Special Issue is to update the readers with new knowledge about the prevention, diagnostics, surgical and antibiotic treatment of periprosthetic joint and fracture-related infections.

Periprosthetic joint infection (PJI) and fracture-related infection (FRI) are severe complications of joint replacement and trauma surgery. Due to increasing numbers of joint replacements and revision arthroplasties, as well as fracture treatment, the number of PJIs and FRIs increase parallelly. Therefore, the prevention of this severe, expensive and resource-consuming complication is of high importance. Because no test with an accuracy of 100% exists, the diagnosis of possible infection remains a challenge. New markers and techniques are coming on the market, and research in this field of interest is important to rule out or verify these infections before surgery. The therapeutic pathways can be adapted to these differentiations.

The treatment of PJI and FRI is under continuous development and new techniques (for example, the coatings of cementless implants and local antibiotic treatment) coming on the market soon. Moreover, local and systemic antibiotic application is a significant part of successful treatment.

Therefore, we are pleased to invite you to send papers discussing a topic in the field of PJI or FRI prevention, diagnosis and treatment. Original articles or meta-analyses in the clinical field and basic research are welcome, as well as review articles that summarize up-to-date knowledge in the field of this Special Issue.

We look forward to receiving your contributions.

Website link of the first volume: https://www.mdpi.com/journal/antibiotics/special_issues/83001W58W3

Prof. Dr. Bernd Fink
Prof. Dr. Steffen Ruchholtz
Guest Editors

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Keywords

  • periprosthetic joint infection
  • fracture-related infection
  • diagnostic treatment

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Related Special Issue

Published Papers (10 papers)

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Research

9 pages, 190 KiB  
Article
Unexpected Positive Cultures During Aseptic Hip and Knee Revision Arthroplasty: Substantial Discrepancies in Laboratory Analyses
by Marius Ludwig, Michael Fuchs, Olivia Trappe, Moritz Oltmanns, Heiko Reichel and Tobias Freitag
Antibiotics 2025, 14(4), 372; https://doi.org/10.3390/antibiotics14040372 - 3 Apr 2025
Viewed by 262
Abstract
Background: Microbial analysis of tissue samples represents an important diagnostic tool in the course of revision total joint arthroplasty. Currently, unexpected positive intraoperative cultures are commonly observed during presumed aseptic revision surgery and evoke a degree of uncertainty among physicians. To date, it [...] Read more.
Background: Microbial analysis of tissue samples represents an important diagnostic tool in the course of revision total joint arthroplasty. Currently, unexpected positive intraoperative cultures are commonly observed during presumed aseptic revision surgery and evoke a degree of uncertainty among physicians. To date, it is unclear if there are deviations in pathogen detection between certified laboratories. Methods: Tissue samples of sixty consecutive patients undergoing presumably aseptic total hip and knee revision surgery were sent to two different internationally certified accredited laboratories and tested for any microbial growth as well as pathogen differentiation. Results: Each laboratory analyzed 300 samples. Laboratory 1 observed an unexpected positive culture rate of 16.7%; laboratory 2 indicated that 18.3% of all processed specimens showed pathogen growth. In comparison, a consistent microbial evaluation was only present in one patient. The kappa correlation coefficient showed a poor correlation between the two laboratories in all evaluated categories. Coagulase-negative staphylococci represented the most common pathogens of laboratory 1, while laboratory 2 predominantly observed cutibacterium acnes species. Within a mean follow-up period of 17.6 ± 18.6 months (range: 0–63 months), there was no revision due to periprosthetic joint infection. Conclusions: Unexpected positive culture results during presumed aseptic revision surgery remain a significant clinical challenge. This study is the first of its kind to evaluate the convergence of laboratory findings in the context of aseptic revision surgery. Our results suggest that even established and certified laboratories show substantial discrepancies. Thus, a careful interpretation of unexpected bacterial cultures after revision surgery is mandatory. Given the uncertainty inherent in laboratory findings, a precise clinical and histopathological evaluation of this patient cohort should be ensured. Full article
10 pages, 678 KiB  
Article
Indwelling Catheters Should Be Restricted in Primary and Revision Arthroplasty: A Retrospective Analysis After Changes to Hospital Standard Perioperative Treatment Protocol
by Matthias Schnetz, Tim Jakobi, Larissa Ewald, Alexander Klug, Matthias Münzberg and Yves Gramlich
Antibiotics 2025, 14(4), 368; https://doi.org/10.3390/antibiotics14040368 - 2 Apr 2025
Viewed by 351
Abstract
Background: Indwelling catheters are used in the perioperative management of patients treated with total joint arthroplasty (TJA) to facilitate fluid control, ease postoperative miction until patients are able to ambulate, and prevent postoperative urinary retention (POUR). However, in TJA, they may be associated [...] Read more.
Background: Indwelling catheters are used in the perioperative management of patients treated with total joint arthroplasty (TJA) to facilitate fluid control, ease postoperative miction until patients are able to ambulate, and prevent postoperative urinary retention (POUR). However, in TJA, they may be associated with a higher risk of urinary tract infections (UTIs). The aim of the study was to analyze the rates of urinary tract infections and POUR. Methods: Between 2021 and 2022, this study retrospectively identified patients before and after a change in the hospital standard perioperative treatment protocol towards a more restrictive use of indwelling catheters for TJA. In 2021, the use of indwelling catheters involved standard care, but the use was restricted in 2022. Results: A total of 1521 patients were included: 636 patients (41.8%) underwent primary arthroplasty, 646 (42.5%) underwent revision arthroplasty, and 239 (15.7%) underwent hip arthroplasty for femoral neck fractures. Standard use of indwelling catheters significantly decreased from 62.0% to 38.0% (p < 0.001), and the rate of UTI was significantly lower after the protocol change (4.7% vs. 1.2%; p < 0.001). Perioperative urine catheterization was a significant risk factor for UTI (OR = 4.22; p < 0.001), and UTI was a significant risk factor for PJI (OR = 9.99; p < 0.001). POUR increased slightly from 0.9% to 1.8%, but the difference was not significant. POUR was mostly diagnosed following the exchange of the acetabular component in revision arthroplasty (n = 11; 52.4%). Conclusions: Indwelling catheter use was associated with high rates of UTIs. Restricting perioperative use of indwelling catheters was effective in preventing UTIs while causing only a moderate increase in easily treatable postoperative urinary retention. Therefore, the use of indwelling catheters should be avoided in arthroplasty whenever possible. Full article
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10 pages, 982 KiB  
Article
Prognostic Value of C-Reactive Protein in Primary Total Hip Arthroplasty
by Moritz Mederake, Ulf Krister Hofmann and Georgios Eleftherakis
Antibiotics 2025, 14(2), 205; https://doi.org/10.3390/antibiotics14020205 - 16 Feb 2025
Viewed by 682
Abstract
Background/Objectives: Periprosthetic joint infections (PJIs) are feared complications in arthroplasty and are associated with an increased mortality rate. PJI prevention is of paramount importance since treatment is difficult. In case of an infection, it is crucial to diagnose it at an early [...] Read more.
Background/Objectives: Periprosthetic joint infections (PJIs) are feared complications in arthroplasty and are associated with an increased mortality rate. PJI prevention is of paramount importance since treatment is difficult. In case of an infection, it is crucial to diagnose it at an early stage in order to initiate adequate therapy. The Musculoskeletal Infection Society (MSIS) proposed a catalog of different major and minor diagnostic criteria in 2011 to define a PJI. They were adapted in the following years. One of these criteria is the blood level of C-reactive protein (CRP). CRP is a non-specific acute-phase protein that also increases in response to various non-infectious inflammatory responses. CRP is also routinely obtained prior to total hip arthroplasty (THA) to screen for possible contraindications for arthroplasty such as an acute infection. The validity of this approach has rarely been investigated. The aim of this study was to evaluate the diagnostic value of perioperative CRP in patients receiving a THA. Methods: A total of 239 patients were included in this study and retrospectively analyzed. CRP values were obtained preoperatively and three values postoperatively. Sensitivity, specificity, area under the curve (AUC) and optimal thresholds were calculated. Results: In the whole group, 10 patients developed a PJI. No significance was demonstrated between patients without and with later PJI in terms of preoperative CRP (p = 0.182), postoperative CRP (p = 0.167), relative CRP increase (p = 0.684) and respective CRP differences (p = 0.456). We were not able to find cut-off values with adequate sensitivity and specificity. Conclusions: Perioperative CRP values do not seem to be helpful in predicting further PJI. Rather, they should be used as a screening tool to detect ongoing infections in the individual patient prior to THA. This trial should encourage studies with more statistical power due to the small effect sizes. Full article
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13 pages, 218 KiB  
Article
Predictive Factors for Risk of Reinfection in Septic Two-Stage Revision of Total Hip and Knee Arthroplasties
by Benedikt Paul Blersch, Florian Hubert Sax, Philipp Schuster and Bernd Fink
Antibiotics 2025, 14(2), 167; https://doi.org/10.3390/antibiotics14020167 - 8 Feb 2025
Viewed by 682
Abstract
Background: The two-stage septic exchange is the most common therapy concept in the treatment of periprosthetic hip and knee infections. However, before the second-stage reimplantation can be carried out, the physician has to assess whether or not the eradication of the periprosthetic joint [...] Read more.
Background: The two-stage septic exchange is the most common therapy concept in the treatment of periprosthetic hip and knee infections. However, before the second-stage reimplantation can be carried out, the physician has to assess whether or not the eradication of the periprosthetic joint infection (PJI) has been successful. Therefore, the aim of this study was to evaluate possible predictive parameters for the successful treatment of PJI before and at the time of reimplantation. Methods: This study investigated a total of 145 patients with periprosthetic hip infection and 93 patients with periprosthetic knee infection, who all underwent a two-stage septic exchange between 2017 and 2021. In order to identify possible risk factors for reinfections, the patients underwent preoperative examination of serological inflammatory parameters, microbiological and histological examination of the periprosthetic membrane at the time of reimplantation, as well as postoperative evaluations at regular intervals for a period of at least 24 months. Results: During the follow-up period, reinfection occurred in 11.3% of cases after the two-stage septic revision. None of the serological, microbiological, or histological parameters were able to significantly predict the risk of reinfection. Risk factors associated with reinfection were BMI and previous revision surgery. Conclusions: Currently, there is no reliable predictive factor indicating the risk of reinfection at the time of reimplantation. New diagnostic methods need to be developed to evaluate the possibility and timing of endoprosthesis reimplantation. Full article
8 pages, 188 KiB  
Article
Surgical Site Preparation Using Alcohol with Chlorhexidine Compared with Povidone Iodine with Chlorhexidine Results in Similar Rate of Infection After Primary Total Joint Arthroplasty
by Stefan J. Hanish, Mateo J. Kirwan, Nuanqiu Hou, Tori J. Coble, William M. Mihalko and Christopher T. Holland
Antibiotics 2025, 14(2), 155; https://doi.org/10.3390/antibiotics14020155 - 5 Feb 2025
Viewed by 1089
Abstract
Background: Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty. A skin antiseptic solution is used to reduce the bacterial count and prevent PJI. There is no consensus in the literature on the application of antiseptic solutions. This study aims [...] Read more.
Background: Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty. A skin antiseptic solution is used to reduce the bacterial count and prevent PJI. There is no consensus in the literature on the application of antiseptic solutions. This study aims to compare the rate of infection between patients who received alcohol wash with Chloraprep to those who received povidone iodine wash with Chloraprep. Methods: A total of 607 patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) at a single institution between January 2009 and July 2023 were reviewed. Perioperative variables were collected. The infection rate was used as a primary outcome. An odds ratio was calculated to compare infection and complication rates between the groups. Results: For patients who underwent THA, no difference in the rate of complications (alcohol wash: n = 6, 4.5%; povidone wash: n = 5, 3.6%; OR: 0.796; 95% CI: 0.237–2.673) or infection (alcohol wash: n = 1, 0.7%; povidone wash: n = 2, 1.4%; OR: 1.942; 95% CI: 0.174–21.667) was found. No difference in the rate of complications (alcohol wash: n = 3, 1.9%; povidone wash: n = 2, 1.2%; OR: 0.635; 95% CI: 0.105–3.849) or infection (alcohol wash: n = 0; povidone wash: n = 1, 0.6%; OR: 0.994; 95% CI: 0.983–1.006) was found in patients who underwent TKA. Conclusions: Surgical site preparation using alcohol wash with chlorhexidine offers similar short-term benefits in preventing postoperative infection to a povidone iodine wash with chlorhexidine in primary total joint arthroplasty. The use of alcohol wash and chlorhexidine is effective, while reducing the preparation time. Full article
25 pages, 4657 KiB  
Article
Implant-Derived S. aureus Isolates Drive Strain-Specific Invasion Dynamics and Bioenergetic Alterations in Osteoblasts
by Lei Song, Lea-Sophie Schwinn, Juliane Barthel, Vanessa Ketter, Philipp Lechler, Uwe Linne, Ardawan J. Rastan, Sebastian Vogt, Steffen Ruchholtz, Jürgen R. J. Paletta and Madeline Günther
Antibiotics 2025, 14(2), 119; https://doi.org/10.3390/antibiotics14020119 - 23 Jan 2025
Viewed by 936
Abstract
Background: Implants are integral to modern orthopedic surgery. The outcomes are good, but infections remain a serious issue. Staphylococcus aureus (S. aureus), along with Staphylococcus epidermidis, are predominant pathogens responsible for implant-associated infections, as conventional antibiotic treatments often fail due [...] Read more.
Background: Implants are integral to modern orthopedic surgery. The outcomes are good, but infections remain a serious issue. Staphylococcus aureus (S. aureus), along with Staphylococcus epidermidis, are predominant pathogens responsible for implant-associated infections, as conventional antibiotic treatments often fail due to biofilm formation or the pathogens’ ability to invade cells and to persist intracellularly. Objectives: This study therefore focused on interactions of S. aureus isolates from infected implants with MG63 and SaOS2 osteoblasts by investigating the adhesion, invasion, and the impact on the bioenergetics of osteoblasts. Methods and Results: We found that the ability of S. aureus to adhere to osteoblasts depends on the isolate and was not associated with a single gene or expression pattern of characteristic adhesion proteins, and further, was not correlated with invasion. However, analysis of invasion capabilities identified better invasion conditions for S. aureus isolates with the SaOS2 osteoblastic cells. Interestingly, metabolic activity of osteoblasts remained unaffected by S. aureus infection, indicating cell survival. In contrast, respiration assays revealed an altered mitochondrial bioenergetic turnover in infected cells. While basal as well as maximal respiration in MG63 osteoblasts were not influenced statistically by S. aureus infections, we found increased non-mitochondrial respiration and enhanced glycolytic activity in the osteoblasts, which was again, more pronounced in the SaOS2 osteoblastic cells. Conclusions: Our findings highlight the complexity of S. aureus-host interactions, where both the pathogen and the host cell contribute to intracellular persistence and survival, representing a major factor for therapeutic failures. Full article
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17 pages, 2707 KiB  
Article
Tigecycline Containing Polymethylmethacrylate Cement Against MRSA, VRE, and ESBL—In Vitro Mechanical and Microbiological Investigations
by Michael Abramowicz, Andrej Trampuz and Klaus-Dieter Kühn
Antibiotics 2024, 13(11), 1102; https://doi.org/10.3390/antibiotics13111102 - 19 Nov 2024
Viewed by 1136
Abstract
Background: The use of antibiotic-loaded bone cements (ALBCs) in arthroplasty has been well established for the prevention and treatment of infections. Tigecycline (Tig), a broad-spectrum antibiotic, has shown efficacy against various pathogens, including vancomycin-resistant strains. Method: ISO and DIN mechanical and microbiological inhibition [...] Read more.
Background: The use of antibiotic-loaded bone cements (ALBCs) in arthroplasty has been well established for the prevention and treatment of infections. Tigecycline (Tig), a broad-spectrum antibiotic, has shown efficacy against various pathogens, including vancomycin-resistant strains. Method: ISO and DIN mechanical and microbiological inhibition zone tests were performed on PMMA cement with manually added Tigecycline. Results: Manually adding 0.5 and 1.0 g Tigecycline to PMMA always meets the mechanical requirements of ISO and DIN standards. Mixtures containing 0.5 g were microbiologically effective for up to 7 days and those containing 1.0 g were effective for 28–42 days. Conclusion: In revision surgery, manually adding Tigecycline in doses of 0.5–1 g to 40 g of PMMA is effective against MRSA, VRE, and ESBL without negatively affecting the cement’s properties. Full article
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11 pages, 2016 KiB  
Article
Management of Fracture-Related Infection in Conflict Zones: Lessons Learned from Medical Missions to Gaza
by Elias Nasser, Nour Alshaer, Muaaz Wajahath, Bilal Irfan, Mohammed Tahir, Mosab Nasser and Khaled J. Saleh
Antibiotics 2024, 13(11), 1020; https://doi.org/10.3390/antibiotics13111020 - 30 Oct 2024
Cited by 4 | Viewed by 2056
Abstract
Background/Objectives: Fracture-related infections (FRIs) are a significant complication in conflict zones, where limited resources and damaged infrastructure complicate orthopedic care. Methods: This study retrospectively reviews the management of FRIs during medical missions to Gaza from April to July 2024. Results: [...] Read more.
Background/Objectives: Fracture-related infections (FRIs) are a significant complication in conflict zones, where limited resources and damaged infrastructure complicate orthopedic care. Methods: This study retrospectively reviews the management of FRIs during medical missions to Gaza from April to July 2024. Results: Among 135 patients treated for war-related fractures, 30% were identified with suspected FRIs, which were primarily following explosive injuries. Contributing factors to the high incidence of infection included malnutrition, poor sanitation, and the scarcity of sterile surgical supplies. The absence of standard infection control measures further complicated treatment. Conclusions: These findings highlight the critical need for a comprehensive approach that incorporates infection prevention, sustainable healthcare planning, and quality assurance tailored to the realities of conflict zones. The study underscores the importance of international support to ensure the availability of essential medical supplies and to develop effective, context-specific strategies for infection management. By applying these insights, healthcare providers can improve patient outcomes and reduce the burden of FRIs in resource-limited settings affected by conflict. Full article
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11 pages, 251 KiB  
Article
Safety of Intraoperative Cell Salvage in Two-Stage Revision of Septic Hip Arthroplasties
by Lara Krüger, André Strahl, Eva Goedecke, Maximilian M. Delsmann, Leon-Gordian Leonhardt, Frank Timo Beil and Jan Hubert
Antibiotics 2024, 13(9), 902; https://doi.org/10.3390/antibiotics13090902 - 21 Sep 2024
Viewed by 969
Abstract
(1) Background: The aim of this study was to evaluate the safety of intraoperative cell salvage (ICS) during reimplantation in the two-stage revision of septic hip arthroplasties. (2) Methods: As part of an internal quality control study, blood cultures were taken from the [...] Read more.
(1) Background: The aim of this study was to evaluate the safety of intraoperative cell salvage (ICS) during reimplantation in the two-stage revision of septic hip arthroplasties. (2) Methods: As part of an internal quality control study, blood cultures were taken from the processed ICS blood during reimplantation and examined for possible bacterial load (study group). Due to a high rate of bacterial detection with uncertain clinical significance, consecutive ICS samples were also examined from patients undergoing aseptic revision hip arthroplasty (control group). Microbiological samples, patient and surgical characteristics and the follow-up data were analyzed retrospectively. (3) Results: 9 out of 12 (75%) patients in the study group and 5 out of 8 (63%) patients in the control group had positive ICS blood cultures. There was no significant difference between the groups (p = 0.642). The initial pathogens causing the periprosthetic joint infection (PJI) were not detected, but the bacterial spectrum resembled skin flora, with a high proportion of coagulase-negative staphylococci. No complications due to possible bloodstream-associated infections were observed. In summary, the detected pathogens were interpreted as contamination without clinical significance. (4) Conclusions: ICS in the context of reimplantation was considered a safe and recommendable procedure to optimize patient blood management. Full article
18 pages, 2360 KiB  
Article
Antimicrobial Properties and Cytotoxicity of LL-37-Derived Synthetic Peptides to Treat Orthopedic Infections
by Vincenzo Pennone, Elisa Angelini, David Sarlah and Arianna B. Lovati
Antibiotics 2024, 13(8), 764; https://doi.org/10.3390/antibiotics13080764 - 14 Aug 2024
Cited by 2 | Viewed by 2297
Abstract
Open fractures and prosthetic joints are prone to bacterial infections, especially those involving biofilms, and are worsened by antibiotic inefficacy and resistance. This highlights the need for targeted treatments against orthopedic infections. LL-37, a human cathelicidin, is known for its antimicrobial properties. This [...] Read more.
Open fractures and prosthetic joints are prone to bacterial infections, especially those involving biofilms, and are worsened by antibiotic inefficacy and resistance. This highlights the need for targeted treatments against orthopedic infections. LL-37, a human cathelicidin, is known for its antimicrobial properties. This study aimed to synthesize and evaluate LL-37-derived antimicrobial peptides (AMPs) for antibacterial efficacy and toxicity. Several truncated LL-37 analogues were created and tested against 18 bacterial strains, both ATCC and orthopedic clinical isolates, using MIC and MBC assays. Synergy with antibiotics and resistance development were also analyzed, alongside cytotoxicity on NIH-3T3 fibroblasts and hemolytic activity assessments. Six AMPs were synthesized, with FK-16 and GF-17 emerging as the most effective. The MIC values ranged from 4.69 to 18.75 µg/mL and 2.34 to 18.75 µg/mL, respectively, against S. epidermidis and S. aureus, with the MBC values matching the MIC values. Cytotoxicity tests showed no toxicity at concentrations below 75 µg/mL for GF-17 and 150 µg/mL for FK-16. Hemolytic activity was below 1% at 18.75 µg/mL for GF-17 and 75 µg/mL for FK-16. These AMPs showed no synergistic effects with antibiotics and no resistance development. FK-16 and GF-17 effectively removed biofilms, particularly against S. epidermidis. Incorporating these AMPs into surgical materials (hydrogels, cements, etc.) could enhance infection control in orthopedic procedures, warranting further in vivo studies. Full article
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