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Bone & Joint Research
Vol. 13, Issue 10 | Pages 535 - 545
2 Oct 2024
Zou C Guo W Mu W Wahafu T Li Y Hua L Xu B Cao L

Aims. We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach. Methods. We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography. Results. The peak concentrations of vancomycin and meropenem in the joint cavity were observed at one hour post-injection, with mean values of 14,933.9 µg/ml (SD 10,176.3) and 5,819.1 µg/ml (SD 6,029.8), respectively. The trough concentrations at 24 hours were 5,495.0 µg/ml (SD 2,360.5) for vancomycin and 186.4 µg/ml (SD 254.3) for meropenem. The half-life of vancomycin was 6 hours, while that of meropenem ranged between 2 and 3.5 hours. No significant adverse events related to the antibiotic administration were observed. Conclusion. This method can achieve sustained high antibiotic concentrations within the joint space, exceeding the reported minimum biofilm eradication concentration. Our study highlights the remarkable effectiveness of intra-articular antibiotic infusion in delivering high intra-articular concentrations of antibiotics. The method provided sustained high antibiotic concentrations within the joint cavity, and no severe side-effects were observed. These findings offer evidence to improve clinical treatment strategies. However, further validation is required through studies with larger sample sizes and higher levels of evidence. Cite this article: Bone Joint Res 2024;13(10):535–545


Bone & Joint Research
Vol. 11, Issue 2 | Pages 112 - 120
16 Feb 2022
Vittrup SØ Hanberg P Knudsen MB Tøstesen SK Kipp JO Hansen J Jørgensen NP Stilling M Bue M

Aims. Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem. Methods. Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results. Across the targeted ECOFF values, vancomycin displayed longer T > MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T > MIC. For the low MIC targets and across compartments, mean T > MIC ranged between 208 and 449 minutes (46% to 100%) for vancomycin and between 189 and 406 minutes (42% to 90%) for meropenem. For the high MIC targets, mean T > MIC ranged between 30 and 446 minutes (7% to 99%) for vancomycin and between 45 and 181 minutes (10% to 40%) for meropenem. Conclusion. The differences in the T > MIC between the low and high targets illustrate how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contamination, or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T > MIC in all the exposed tissues, and thereby lower the risk of acquiring an infection after open tibial fractures. Cite this article: Bone Joint Res 2022;11(2):112–120


Bone & Joint Research
Vol. 10, Issue 5 | Pages 321 - 327
3 May 2021
Walter N Rupp M Hierl K Pfeifer C Kerschbaum M Hinterberger T Alt V

Aims. We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results. With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion. Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients. Cite this article: Bone Joint Res 2021;10(5):321–327


Bone & Joint Research
Vol. 12, Issue 10 | Pages 644 - 653
10 Oct 2023
Hinz N Butscheidt S Jandl NM Rohde H Keller J Beil FT Hubert J Rolvien T

Aims

The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Methods

Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20).


Bone & Joint Research
Vol. 13, Issue 8 | Pages 383 - 391
2 Aug 2024
Mannala GK Rupp M Walter N Youf R Bärtl S Riool M Alt V

Aims

Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella.

Methods

For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 525 - 534
1 Oct 2024
Mu W Xu B Wang F Maimaitiaimaier Y Zou C Cao L

Aims

This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

Methods

We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 353 - 361
10 Jul 2024
Gardete-Hartmann S Mitterer JA Sebastian S Frank BJH Simon S Huber S Löw M Sommer I Prinz M Halabi M Hofstaetter JG

Aims

This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool.

Methods

Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 695 - 702
1 Dec 2024
Cordero García-Galán E Medel-Plaza M Pozo-Kreilinger JJ Sarnago H Lucía Ó Rico-Nieto A Esteban J Gomez-Barrena E

Aims

Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.

Methods

Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Staphylococcus aureus biofilm. Sacrifice and sample collection were performed 24, 48, or 96 hours postoperatively. Retrieved screws were sonicated, and adhered bacteria were estimated via drop-plate. Width of bone necrosis in retrieved femora was assessed through microscopic examination. Analysis was performed using non-parametric tests with significance fixed at p ≤ 0.05.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 127 - 135
22 Mar 2024
Puetzler J Vallejo Diaz A Gosheger G Schulze M Arens D Zeiter S Siverino C Richards RG Moriarty TF

Aims

Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

Methods

Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST).


Bone & Joint Research
Vol. 13, Issue 3 | Pages 101 - 109
4 Mar 2024
Higashihira S Simpson SJ Morita A Suryavanshi JR Arnold CJ Natoli RM Greenfield EM

Aims

Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone.

Methods

S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs).


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Methods

A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 306 - 314
19 Jun 2024
Wu B Su J Zhang Z Zeng J Fang X Li W Zhang W Huang Z

Aims

To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).

Methods

A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001).


Bone & Joint Research
Vol. 13, Issue 8 | Pages 401 - 410
15 Aug 2024
Hu H Ding H Lyu J Chen Y Huang C Zhang C Li W Fang X Zhang W

Aims

This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.

Methods

A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 321 - 330
9 May 2023
Lenguerrand E Whitehouse MR Beswick AD Kunutsor SK Webb JCJ Mehendale S Porter M Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 40 - 51
11 Jan 2024
Lin J Suo J Bao B Wei H Gao T Zhu H Zheng X

Aims

To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

Methods

EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 72 - 79
18 Jan 2023
Welling MM Warbroek K Khurshid C van Oosterom MN Rietbergen DDD de Boer MGJ Nelissen RGHH van Leeuwen FWB Pijls BG Buckle T

Aims

Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods.

Methods

99mTc-UBI29-41-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 19 - 27
5 Jan 2024
Baertl S Rupp M Kerschbaum M Morgenstern M Baumann F Pfeifer C Worlicek M Popp D Amanatullah DF Alt V

Aims

This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated.

Methods

A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss’ kappa and Cohen’s kappa were calculated for interobserver and intraobserver reliability, respectively.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 331 - 338
16 May 2023
Szymski D Walter N Krull P Melsheimer O Grimberg A Alt V Steinbrueck A Rupp M

Aims

The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture.

Methods

Data collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Methods

A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 690 - 699
4 Oct 2022
Lenguerrand E Whitehouse MR Kunutsor SK Beswick AD Baker RP Rolfson O Reed MR Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage revision surgery and single-stage revision surgery among patients with infected primary knee arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary knee arthroplasty, initially revised with a single-stage or a two-stage procedure in England and Wales between 2003 and 2014, were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HR) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


The Bone & Joint Journal
Vol. 101-B, Issue 1_Supple_A | Pages 19 - 24
1 Jan 2019
Thakrar RR Horriat S Kayani B Haddad FS

Aims. Prosthetic joint infections (PJIs) of the hip and knee are associated with significant morbidity and socioeconomic burden. We undertook a systematic review of the current literature with the aim of proposing criteria for the selection of patients for a single-stage exchange arthroplasty in the management of a PJI. Material and Methods. A comprehensive review of the current literature was performed using the OVID-MEDLINE, EMBASE, and Cochrane Library databases and the search terms: infection and knee arthroplasty OR knee revision OR hip arthroplasty OR hip revision, and one stage OR single stage OR direct exchange. All studies involving fewer than ten patients and follow-up of less than two years in the study group were excluded as also were systematic reviews, surgical techniques, and expert opinions. Results. The initial search revealed 875 potential articles of which 22 fulfilled the inclusion and exclusion criteria. There were 16 case series and six comparative studies; five were prospective and 14 were retrospective. The studies included 962 patients who underwent single stage revision arthroplasty of an infected hip or knee joint. The rate of recurrent infection ranged from 0% to 18%, at a minimum of two years’ follow-up. The rate was lower in patients who were selected on the basis of factors relating to the patient and the local soft-tissue and bony conditions. . Conclusion. We conclude that single-stage revision is an acceptable form of surgical treatment for the management of a PJI in selected patients. The indications for this approach include the absence of severe immunocompromise and significant soft-tissue or bony compromise and concurrent acute sepsis. We suggest that a two-stage approach should be used in patients with multidrug resistant or atypical organisms such as fungus


Aims

Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

Methods

Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 398 - 408
22 Jun 2022
Xu T Zeng Y Yang X Liu G Lv T Yang H Jiang F Chen Y

Aims

We aimed to evaluate the utility of 68Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with 99mTc-methylene bisphosphonates (99mTc-MDP) bone scan.

Methods

We studied 39 patients with suspected PJI or AL. These patients underwent 68Ga-citrate PET/CT, 99mTc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 73 - 81
22 Feb 2022
Gao T Lin J Wei H Bao B Zhu H Zheng X

Aims

Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive.

Methods

We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli.


Bone & Joint Research
Vol. 11, Issue 3 | Pages 143 - 151
1 Mar 2022
Goetz J Keyssner V Hanses F Greimel F Leiß F Schwarz T Springorum H Grifka J Schaumburger J

Aims

Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA.

Methods

For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 49 - 60
1 Feb 2022
Li J Wong RMY Chung YL Leung SSY Chow SK Ip M Cheung W

Aims

With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

Methods

A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 104 colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 790 - 796
1 Dec 2021
Fang X Wang Q Yang X Zhang F Huang C Huang Z Shen H Zhang W

Aims

To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI).

Methods

This study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 156 - 165
1 Mar 2021
Yagi H Kihara S Mittwede PN Maher PL Rothenberg AC Falcione ADCM Chen A Urish KL Tuan RS Alexander PG

Aims

Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur.

Methods

Fresh suspensions of Staphylococcus aureus (ATCC 25923) were prepared in phosphate-buffered saline (PBS) (1 × 109 colony-forming units (CFUs)/ml). Periprosthetic osteomyelitis in female New Zealand white rabbits was induced by intraosseous injection of planktonic bacterial suspension into a predrilled bone tunnel prior to implant screw placement, examined at five and 28 days (n = 5/group) after surgery, and compared to a control aseptic screw group. Radiographs were obtained weekly, and blood was collected to measure ESR, CRP, and white blood cell (WBC) counts. Bone samples and implanted screws were harvested on day 28, and processed for histological analysis and viability assay of bacteria, respectively.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 149 - 155
16 Feb 2021
Shiels SM Sgromolo NM Wenke JC

Aims

High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder.

Methods

Complex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 77 - 84
1 Jan 2021
Milstrey A Rosslenbroich S Everding J Raschke MJ Richards RG Moriarty TF Puetzler J

Aims

Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents.

Methods

S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 848 - 856
1 Dec 2020
Ramalhete R Brown R Blunn G Skinner J Coathup M Graney I Sanghani-Kerai A

Aims

Periprosthetic joint infection (PJI) is a debilitating condition with a substantial socioeconomic burden. A novel autologous blood glue (ABG) has been developed, which can be prepared during surgery and sprayed onto prostheses at the time of implantation. The ABG can potentially provide an antimicrobial coating which will be effective in preventing PJI, not only by providing a physical barrier but also by eluting a well-known antibiotic. Hence, this study aimed to assess the antimicrobial effectiveness of ABG when impregnated with gentamicin and stem cells.

Methods

Gentamicin elution from the ABG matrix was analyzed and quantified in a time-dependent manner. The combined efficiency of gentamicin and ABG as an anti-biofilm coating was investigated on titanium disks.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 635 - 644
1 Oct 2020
Lemaignen A Grammatico-Guillon L Astagneau P Marmor S Ferry T Jolivet-Gougeon A Senneville E Bernard L

Aims

The French registry for complex bone and joint infections (C-BJIs) was created in 2012 in order to facilitate a homogeneous management of patients presented for multidisciplinary advice in referral centres for C-BJI, to monitor their activity and to produce epidemiological data. We aimed here to present the genesis and characteristics of this national registry and provide the analysis of its data quality.

Methods

A centralized online secured database gathering the electronic case report forms (eCRFs) was filled for every patient presented in multidisciplinary meetings (MM) among the 24 French referral centres. Metrics of this registry were described between 2012 and 2016. Data quality was assessed by comparing essential items from the registry with a controlled dataset extracted from medical charts of a random sample of patients from each centre. Internal completeness and consistency were calculated.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 450 - 456
1 Aug 2020
Zhang Z Cai Y Bai G Zhang C Li W Yang B Zhang W

Aims

This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) .

Methods

A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 587 - 592
5 Sep 2020
Qin L Li X Wang J Gong X Hu N Huang W

Aims

This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI.

Methods

Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 440 - 449
1 Jul 2020
Huang Z Li W Lee G Fang X Xing L Yang B Lin J Zhang W

Aims

The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients.

Methods

A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture.


Bone & Joint Research
Vol. 9, Issue 5 | Pages 219 - 224
1 May 2020
Yang B Fang X Cai Y Yu Z Li W Zhang C Huang Z Zhang W

Aims

Preoperative diagnosis is important for revision surgery after prosthetic joint infection (PJI). The purpose of our study was to determine whether reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is used to detect bacterial ribosomal RNA (rRNA) preoperatively, can reveal PJI in low volumes of aspirated fluid.

Methods

We acquired joint fluid samples (JFSs) by preoperative aspiration from patients who were suspected of having a PJI and failed arthroplasty; patients with preoperative JFS volumes less than 5 ml were enrolled. RNA-based polymerase chain reaction (PCR) and bacterial culture were performed, and diagnostic efficiency was compared between the two methods.According to established Musculoskeletal Infection Society (MSIS) criteria, 21 of the 33 included patients were diagnosed with PJI.


Bone & Joint Research
Vol. 9, Issue 4 | Pages 192 - 199
1 Apr 2020
Pijls BG Sanders IMJG Kujiper EJ Nelissen RGHH

Aims

Induction heating is a noninvasive, nonantibiotic treatment modality that can potentially be used to cause thermal damage to the bacterial biofilm on the metal implant surface. The purpose of this study was to determine the effectiveness of induction heating on killing Staphylococcus epidermidis from biofilm and to determine the possible synergistic effect of induction heating and antibiotics.

Methods

S. epidermidis biofilms were grown on titanium alloy (Ti6Al4V) coupons for 24 hours (young biofilm) and seven days (mature biofilm). These coupons with biofilm were heated to temperatures of 50°C, 55°C, 60°C, 65°C, 70°C, 80°C, and 90°C for 3.5 minutes and subsequently exposed to vancomycin and rifampicin at clinically relevant concentrations.


Aims

Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown.

Methods

Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 71 - 76
1 Feb 2020
Gao T Lin J Zhang C Zhu H Zheng X

Aims

The purpose of this study was to determine whether intracellular Staphylococcus aureus is associated with recurrent infection in a rat model of open fracture.

Methods

After stabilizing with Kirschner wire, we created a midshaft femur fracture in Sprague-Dawley rats and infected the wound with green fluorescent protein (GFP)-tagged S. aureus. After repeated debridement and negative swab culture was achieved, the isolation of GFP-containing cells from skin, bone marrow, and muscle was then performed. The composition and viability of intracellular S. aureus in isolated GFP-positive cells was assessed. We suppressed the host immune system and observed whether recurrent infection would occur. Finally, rats were assigned to one of six treatment groups (a combination of antibiotic treatment and implant removal/retention). The proportion of successful eradication was determined.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 459 - 468
1 Oct 2019
Hotchen AJ Dudareva M Ferguson JY Sendi P McNally MA

Objectives

The aim of this study was to assess the clinical application of, and optimize the variables used in, the BACH classification of long-bone osteomyelitis.

Methods

A total of 30 clinicians from a variety of specialities classified 20 anonymized cases of long-bone osteomyelitis using BACH. Cases were derived from patients who presented to specialist centres in the United Kingdom between October 2016 and April 2017. Accuracy and Fleiss’ kappa (Fκ) were calculated for each variable. Bone involvement (B-variable) was assessed further by nine clinicians who classified ten additional cases of long bone osteomyelitis using a 3D clinical imaging package. Thresholds for defining multidrug-resistant (MDR) isolates were optimized using results from a further analysis of 253 long bone osteomyelitis cases.


Bone & Joint Research
Vol. 8, Issue 8 | Pages 367 - 377
1 Aug 2019
Chen M Chang C Chiang-Ni C Hsieh P Shih H Ueng SWN Chang Y

Objectives

Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI.

Methods

We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing.


Bone & Joint Research
Vol. 8, Issue 5 | Pages 199 - 206
1 May 2019
Romanò CL Tsuchiya H Morelli I Battaglia AG Drago L

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma.

Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.


Bone & Joint Research
Vol. 8, Issue 4 | Pages 179 - 188
1 Apr 2019
Chen M Chang C Yang L Hsieh P Shih H Ueng SWN Chang Y

Objectives

Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis.

Methods

We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 49 - 54
1 Feb 2019
Stravinskas M Nilsson M Vitkauskiene A Tarasevicius S Lidgren L

Objectives

The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month.

Methods

Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 447 - 456
1 Jul 2018
Morgenstern M Vallejo A McNally MA Moriarty TF Ferguson JY Nijs S Metsemakers W

Objectives

As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures.

Methods

A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis.