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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. Results. Escherichia coli was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated E. coli from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups. Conclusion. IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use. Cite this article: Bone Joint Res 2024;13(10):546–558


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.


Aims. This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). Methods. A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. Results. The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Conclusion. Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics. Cite this article: Bone Joint Res 2024;13(9):441–451


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. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 629 - 638
1 Sep 2022
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Aims

Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms.

Methods

Mature biofilms of S. aureus (ATCC 29213) were grown on titanium alloy (Ti6Al4V) coupons for seven days and were subjected to the following treatments or their combinations: antibiotics, mechanical cleaning, or heat shock by induction heating of 60°C for one minute. Experiments were repeated at least five times.


Bone & Joint Research
Vol. 11, Issue 5 | Pages 327 - 341
23 May 2022
Alagboso FI Mannala GK Walter N Docheva D Brochhausen C Alt V Rupp M

Aims

Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy.

Methods

The human osteoblast-like Saos-2 cells infected with S. aureus EDCC 5055 strain and treated with 8 µg/ml RMP underwent osteogenic stimulation for up to 21 days. Test groups were Saos-2 cells + S. aureus and Saos-2 cells + S. aureus + 8 µg/ml RMP, and control groups were uninfected untreated Saos-2 cells and uninfected Saos-2 cells + 8 µg/ml RMP.


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.


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. 9, Issue 11 | Pages 778 - 788
1 Nov 2020
Xu H Yang J Xie J Huang Z Huang Q Cao G Pei F

Aims

The efficacy and safety of intrawound vancomycin for preventing surgical site infection in primary hip and knee arthroplasty is uncertain.

Methods

A systematic review of the literature was conducted, indexed from inception to March 2020 in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases. All studies evaluating the efficacy and/or safety of intrawound vancomycin in patients who underwent primary hip and knee arthroplasty were included. Incidence of periprosthetic joint infection (PJI), superficial infection, aseptic wound complications, acute kidney injury, anaphylactic reaction, and ototoxicity were meta-analyzed. Results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). The quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool.


Bone & Joint Research
Vol. 9, Issue 5 | Pages 211 - 218
1 May 2020
Hashimoto A Miyamoto H Kobatake T Nakashima T Shobuike T Ueno M Murakami T Noda I Sonohata M Mawatari M

Aims

Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation.

Methods

Pure titanium discs (Ti discs), Ti discs coated with HA (HA discs), and 3% Ag-HA discs developed using a thermal spraying were inoculated with MRSA suspensions containing a mean in vitro 4.3 (SD 0.8) x 106 or 43.0 (SD 8.4) x 105 colony-forming units (CFUs). Immediately after MRSA inoculation, sterile phosphate-buffered saline or VCM (20 µg/ml) was added, and the discs were incubated for 24 hours at 37°C. Viable cell counting, 3D confocal laser scanning microscopy with Airyscan, and scanning electron microscopy were then performed. HA discs and Ag HA discs were implanted subcutaneously in vivo in the dorsum of rats, and MRSA suspensions containing a mean in vivo 7.2 (SD 0.4) x 106  or 72.0 (SD 4.2) x 105  CFUs were inoculated on the discs. VCM was injected subcutaneously daily every 12 hours followed by viable cell counting.


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. Results. For the young biofilm, total eradication was observed at 65°C or higher for 3.5 minutes followed by 24 hours of vancomycin 10 mg/l and rifampicin 1 mg/l. For the mature biofilm, total eradication was observed at 60°C for 3.5 minutes followed by 24 hours of vancomycin 10 mg/l and rifampicin 1 mg/l. Total eradication was also observed at 60°C for 3.5 minutes followed by 24 hours of vancomycin 1 mg/l and rifampicin 1 mg/l followed by another thermal shock of 60°C for 3.5 minutes (two thermal shocks). Conclusion. Induction heating of Ti6Al4V coupons is effective in reducing bacterial load in vitro for S. epidermidis biofilms. Induction heating and antibiotics have a synergistic effect resulting in total eradication of the biofilm at 60°C or higher for clinically relevant concentrations of vancomycin and rifampicin. Cite this article:Bone Joint Res. 2020;9(4):192–199


Bone & Joint Research
Vol. 9, Issue 2 | Pages 49 - 59
1 Feb 2020
Yu K Song L Kang HP Kwon H Back J Lee FY

Aims

To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone.

Methods

Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation.


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 1 | Pages 3 - 10
1 Jan 2019
Hernandez P Sager B Fa A Liang T Lozano C Khazzam M

Objectives

The purpose of this study was to examine the bactericidal efficacy of hydrogen peroxide (H2O2) on Cutibacterium acnes (C. acnes). We hypothesize that H2O2 reduces the bacterial burden of C. acnes.

Methods

The effect of H2O2 was assessed by testing bactericidal effect, time course analysis, growth inhibition, and minimum bactericidal concentration. To assess the bactericidal effect, bacteria were treated for 30 minutes with 0%, 1%, 3%, 4%, 6%, 8%, or 10% H2O2 in saline or water and compared with 3% topical H2O2 solution. For time course analysis, bacteria were treated with water or saline (controls), 3% H2O2 in water, 3% H2O2 in saline, or 3% topical solution for 5, 10, 15, 20, and 30 minutes. Results were analyzed with a two-way analysis of variance (ANOVA) (p < 0.05).


Bone & Joint Research
Vol. 7, Issue 11 | Pages 609 - 619
1 Nov 2018
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Objectives. Prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Non-contact induction heating of metal implants is a new and emerging treatment for PJI. However, there may be concerns for potential tissue necrosis. It is thought that segmental induction heating can be used to control the thermal dose and to limit collateral thermal injury to the bone and surrounding tissues. The purpose of this study was to determine the thermal dose, for commonly used metal implants in orthopaedic surgery, at various distances from the heating centre (HC). Methods. Commonly used metal orthopaedic implants (hip stem, intramedullary nail, and locking compression plate (LCP)) were heated segmentally using an induction heater. The thermal dose was expressed in cumulative equivalent minutes at 43°C (CEM43) and measured with a thermal camera at several different distances from the HC. A value of 16 CEM43 was used as the threshold for thermal damage in bone. Results. Despite high thermal doses at the HC (7161 CEM43 to 66 640 CEM43), the thermal dose at various distances from the HC was lower than 16 CEM43 for the hip stem and nail. For the fracture plate without corresponding metal screws, doses higher than 16 CEM43 were measured up to 5 mm from the HC. Conclusion. Segmental induction heating concentrates the thermal dose at the targeted metal implant areas and minimizes collateral thermal injury by using the non-heated metal as a heat sink. Implant type and geometry are important factors to consider, as they influence dissipation of heat and associated collateral thermal injury. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Segmental induction heating of orthopaedic metal implants. Bone Joint Res 2018;7:609–619. DOI: 10.1302/2046-3758.711.BJR-2018-0080.R1


Bone & Joint Research
Vol. 7, Issue 8 | Pages 517 - 523
1 Aug 2018
Tsang STJ Gwynne PJ Gallagher MP Simpson AHRW

Objectives

Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time.

Materials and Methods

Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 minutes, 180 minutes, and 24 hours.


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.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 457 - 467
1 Jul 2018
Smith IDM Milto KM Doherty CJ Amyes SGB Simpson AHRW Hall AC

Objectives. Staphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability. Methods. Bovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy. Results. Hla-producing mutants caused substantial chondrocyte death compared with the toxin-deficient control (Hla-Hlb-Hlg-), whilst mutants producing Hlb and Hlg in the absence of Hla induced minimal chondrocyte death. Coronal studies established that Hla-induced chondrocyte death started in the superficial zone of cartilage and spread to deeper layers, whereas Hlb and Hlg toxins were without significant effect. Conclusion. This study identified Hla as a highly potent S. aureus toxin that caused rapid chondrocyte death in bovine cartilage, with other toxins or metabolic products produced by the bacteria playing a minor role. The identification of Hla in mediating chondrocyte death may assist in the development of therapeutic strategies aimed at reducing the extent of cartilage damage during and after an episode of septic arthritis. Cite this article: I. D. M. Smith, K. M. Milto, C. J. Doherty, S. G. B. Amyes, A. H. R. W. Simpson, A. C. Hall. A potential key role for alpha-haemolysin of Staphylococcus aureus in mediating chondrocyte death in septic arthritis. Bone Joint Res 2018;7:457–467. DOI: 10.1302/2046-3758.77.BJR-2017-0165.R1


Bone & Joint Research
Vol. 7, Issue 1 | Pages 46 - 57
1 Jan 2018
Zhou J Zhou XG Wang JW Zhou H Dong J

Objective

In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits.

Methods

The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects.