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Bone & Joint Open
Vol. 5, Issue 4 | Pages 367 - 373
26 Apr 2024
Reinhard J Lang S Walter N Schindler M Bärtl S Szymski D Alt V Rupp M

Aims

Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications.

Methods

In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated.


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.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 52 - 52
24 Nov 2023
Szymski D Walter N Hierl K Rupp M Alt V
Full Access

Aim

The number of periprosthetic joint infections (PJI) is increasing due to ageing population and increasing numbers of arthroplasty procedures and treatment is costly. Aim of the study was to analyze the direct healthcare costs of PJI in Europe for total hip arthroplasties (THA) and total knee arthroplasties (TKA).

Method

A systematic review in PubMed with search of direct costs of PJI in European countries was performed. Thereby the term cost* AND (infection OR PJI) AND (prosthesis OR knee OR hip OR “TKA” OR “THA” OR arthroplast*) was combined with each European country to detect relevant publications. Publications with definition of performed procedure and joint localization were included into further analysis. The mean value of direct healthcare cost was calculated for the respective joint and the respective operation performed.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 84 - 84
24 Nov 2023
Bärtl S Lovasz D Li J Alt V Rupp M
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Aim

Sepsis is a life-threatening complication of periprosthetic joint infections (PJI) that requires early and effective therapy. This study aims to investigate the epidemiology, associated risk factors, and outcome of sepsis in the context of periprosthetic joint infections (PJI).

Method

This single-center retrospective cohort study included patients treated for PJI from 2017 to 2020. Patients were classified based on the criteria of the European Bone and Joint Infection Society. The presence of sepsis was determined using the SOFA score and SIRS criteria. The cohort with PJI and sepsis (sepsis) was compared to patients with PJI without sepsis (non-sepsis). Risk factors considered were patient characteristics, affected joints, surgical therapy, microbiological findings, preexisting medical conditions, clinical symptoms, and symptom duration. Outcome parameters were mortality, length of hospital stay, and length of stay in the intensive care unit.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 19 - 19
24 Nov 2023
McNally M Alt V Wouthuyzen M Marais L Metsemakers W Zalavras C Morgenstern M
Full Access

Aim

To classify Fracture-related Infection (FRI) allowing comparison of clinical studies and to guide decision-making around the main surgical treatment concepts.

Method

An international group of FRI experts met in Lisbon, June 2022 and proposed a new FRI classification. A core group met during the EBJIS Meeting in Graz, 2022 and on-line, to determine the preconditions, purpose, primary factors for inclusion, format and the detailed description of the elements of an FRI Classification.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 5 - 5
24 Nov 2023
Szymski D Walter N Krull P Melsheimer O Grimberg A Alt V Steinbrück A Rupp M
Full Access

Aim

The aim of this investigation was to compare risk of infection in both cemented and cementless hemiarthroplasty (HA) as well as 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 cementless protheses and paired according to age, sex, body mass index (BMI), and the Elixhauser score using Mahalanobis distance matching.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 65 - 65
24 Nov 2023
Schindler M Walter N Sigmund IK Maderbacher G Alt V Rupp M
Full Access

Background

The identification of novel biomarker which is highly specific and sensitive for periprosthetic joint (PJI) have the potential to improve diagnostic accuracy and ultimately improve patient outcomes. Thus, the aim of this systemic review is to identify and evaluate novel biomarkers for the preoperative diagnostics of PJI.

Methods

MEDLINE, EMBASE, PubMed and Cochrane Library databases identified from 1st of January 2018 to 30th of September. 2022. We used “periprosthetic joint infection” OR “prosthetic joint infection” OR “periprosthetic infection” as the diagnosis of interest and the target index applied AND “marker”. To focus on novel biomarkers already used biomarkers of the established PJI diagnostic criteria of MSIS, ICM and EBJIS were not included in the analysis. These three criteria were considered the reference standard during quality assessment.


Bone & Joint Open
Vol. 4, Issue 10 | Pages 801 - 807
23 Oct 2023
Walter N Szymski D Kurtz SM Lowenberg DW Alt V Lau EC Rupp M

Aims

This work aimed at answering the following research questions: 1) What is the rate of mechanical complications, nonunion and infection for head/neck femoral fractures, intertrochanteric fractures, and subtrochanteric fractures in the elderly USA population? and 2) Which factors influence adverse outcomes?

Methods

Proximal femoral fractures occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records Data Base. The Kaplan-Meier method with Fine and Gray sub-distribution adaptation was used to determine rates for nonunion, infection, and mechanical complications. Semiparametric Cox regression model was applied incorporating 23 measures as covariates to identify risk factors.


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.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 72 - 72
11 Apr 2023
Stich T Kovářík T Křenek T Alt V Docheva D
Full Access

The goal was to analyze the cellular response, specifically the osteogenic capacity, of titanium (Ti) implants harbouring a novel laserbased-surface-structure with the overall aim: augmented osteointegration. Surface micro-/nanoproperties greatly influence cell behaviour at the tissue-implant-interface and subsequent osteointegration. We investigated Ti-materials subjected to a specially developed shifted-Laser-Surface-Texturing (sLST) technology and compared them to a standard roughening-technique (sand-blasting-acid-etching, SLA). The biological response was evaluated with hMSCs, which are naturally available at the bone-implant-interface. We hypothesized: the novel surface is beneficial for our three different (young/healthy-YH; aged/healthy-AH;aged/osteoporotic-OP) cohorts.

The sLST was performed using a SPI-G3-series laser (beam-wavelength=1064nm, pulse-duration=200ns). For the SLA surface, Ti was sandblasted, afterwards acid-etched (HCl/H2SO4). Three different hMSC cohorts were studied: YH: n=6,29±6; AH: n=5,79±5; OP: n=5,76±5 years (osteoporosis confirmed via DEXA-scan). OP hMSCs show e.g. ColI-deficient-matrix and decreased mineralization. Cells were examined for survival, cell proliferation and cytoskeleton arrangement. Osteogenic differentiation was carried out over 21 days, matrix mineralization was validated with Alizarin-Red-S-staining and quantification.

Laser-texturing generated precisely the desired microgeometry. On nanostructural level, differently-sized Ti-droplets were formed stochastically by laser-induced-Ti-plasma. Live/dead-/Actin-stainings showed comparable results for all cohorts and surfaces in terms of survival and cell shape. On Ti-materials, cell growth showed no significant difference between the 3 cohorts. Alizarin quantification revealed the highest levels on laser-textured-surfaces; highest value for YH, followed by AH, lastly OP; no significance between AH/YH, but between OP/YH (p<0.0001). However, mineralization of all cohorts cultured on laser-textured-surfaces increased significantly (p<0.0001) compared to respective SLA-group, with >20fold higher value in the OP-cohort (AH:11fold, YH:6fold).

The data proves the biocompatibility of the laser-structured-Ti for young+aged cohorts. Osteogenic differentiation was significantly augmented on laser-treated-Ti. Most intriguingly, OP-donors could reach manifold increased mineralization, suggesting the novel laser texturing can counteract the osteoporotic phenotype. As osteogenesis-enhancing capacities may be related to mechanisms controlling cellular shape/fate, further investigations referring to this are currently ongoing. In conclusion, our laser-textured-Ti-materials are safe, can have a demand-oriented designer-surface-topography and represent a great potential for development into next-generation-implants suitable for different patient-cohorts, especially osteoporosis patients.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 3 - 3
10 Feb 2023
Sundaram A Woods J Clifton L Alt V Clark R Carey Smith R
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Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany).

At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components.

Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 103 - 112
1 Feb 2023
Walter N Szymski D Kurtz SM Lowenberg DW Alt V Lau E Rupp M

Aims

The optimal choice of management for proximal humerus fractures (PHFs) has been increasingly discussed in the literature, and this work aimed to answer the following questions: 1) what are the incidence rates of PHF in the geriatric population in the USA; 2) what is the mortality rate after PHF in the elderly population, specifically for distinct treatment procedures; and 3) what factors influence the mortality rate?

Methods

PHFs occurring between 1 January 2009 and 31 December 2019 were identified from the Medicare physician service records. Incidence rates were determined, mortality rates were calculated, and semiparametric Cox regression was applied, incorporating 23 demographic, clinical, and socioeconomic covariates, to compare the mortality risk between treatments.


Aim

The aim of the present work was (i) to survey the situation of healthcare regarding the use of antibiotics in orthopaedics and trauma surgery in Germany, (ii) to determine which empiric antibiotic regimens are preferred in the treatment of periprosthethic joint infections (PJI) and (iii) to evaluate the hypothetical antibiotic adequacy of the applied empirical antibiotic therapy regimens based on a patient collective of a German university hospital.

Method

A survey on empirical and prophylactic antibiotic therapy was conducted at German university and occupational health clinics (BG clinics), each in the specialties of orthopedics and trauma surgery. A total of 71 clinics were contacted by email. The questionnaire sent included open-ended questions on systemic antibiotic prophylaxis in primary hip arthroplasty; a distinction was made between hip arthroplasty due to femoral fractures and elective hip arthroplasty. In addition, the empirical antibiotic therapy used in PJIs was surveyed. To determine the success rate of prophylaxis and therapy according to sensitivity to the antibiotics applied, the survey results were compared with previously published data on antimicrobial treatment in n=81 PJI patients treated in our department between 2017 and 2020.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 63 - 63
1 Oct 2022
Mendelsohn DH Walter N Niedermair T Alt V Brochhausen C Rupp M
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Aim

Osteomyelitis is a difficult-to-treat disease with high chronification rates. The surgical amputation of the afflicted limb sometimes remains as the patients’ last resort. Several studies suggest an increase in mitochondrial fission as a possible contributor to the accumulation of intracellular reactive oxygen species and thereby to cell death of infectious bone cells. The aim of this study is to analyze the ultrastructural impact of bacterial infection and its accompanying microenvironmental tissue hypoxia on osteocytic and osteoblastic mitochondria.

Method

19 Human bone tissue samples from patients with osteomyelitis were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their respective mitochondria were histomorphometrically analyzed. The results were compared to the control group of 5 non-infectious human bone tissue samples.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 28 - 28
1 Oct 2022
Mannala G Rupp M Alt V
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Aim

Galleria mellonella larvae is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections using small K-wire as implant material. Here, we aimed to further expand the use of G. mellonella to test other materials such as bone cement with combination of gentamicin to treat implant-associated infections.

Method

The poly methyl methacrylate (PMMA) with and without gentamicin and liquid methyl methacrylate (MMA) were kindly provided by Heraeus Medical GmbH, Wehrheim. To make the bone cement implants as cubes, Teflon plate (Karl Lettenbauer, Erlangen) with specified well size was used. The Radiopaque polymer and monomer were mixed well in a bowl, applied over on to the Teflon plate and pressed with spatula to form fine and uniform cubes. After polymerization, the bone cement implants were taken out of the Teflon well plate with the help of pin. For the infection process, bone cement cubes were pre-incubated with S. aureus EDCC 5055 culture at 5×106 CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. Survival of the larvae were observed at 37°C in an incubator. To analyze the susceptibility of the bacterial infections towards gentamicin, survival of the larvae compared with control group implanted only with bone cement. The effect of gentamicin was also measured in terms of S. aureus load in larvae on 2nd day. SEM analysis was performed to see the effect of gentamicin on biofilm formation on bone cement.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 85 - 85
1 Oct 2022
Mannala G Rupp M Alt V
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Aim

Fungal periprosthetic joint infections are difficult to treat and often associated with a limited outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules for bacteria. However, in vivo modeling of biofilm-associated fungi models are very rare. Furthermore, due to ethical restrictions, mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections with bacteria. This model organism was not used for fungi biofilm infection yet. Thus, we aimed to establish G. mellonella as in vivo model to study fungal implant infections using Candida albicans as model organism and to test anti-fungal medication.

Method

Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. For the infection process, implants were pre-incubated in specified fungal growth culture Candida albicans at 1×107 CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. To analyze the susceptibility of the implant-associated fungal infections towards anti fungal compounds, the larvae were treated with amphotericin B, fluconazole and voriconazole after 24h of implantation. The effect of anti-fungal compounds was measured in terms of survival observation for 5 days and fungal load in larvae on 2nd day. To reveal the fungal biofilm formation on implant, the implants were removed on day 3 and processed for SEM analysis.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 541 - 547
17 Aug 2022
Walter N Hierl K Brochhausen C Alt V Rupp M

Aims

This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

Methods

Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients.


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 1 | Pages 8 - 9
7 Jan 2022
Walter N Rupp M Baertl S Ziarko TP Hitzenbichler F Geis S Brochhausen C Alt V


Bone & Joint Research
Vol. 11, Issue 1 | Pages 6 - 7
3 Jan 2022
Walter N Rupp M Baertl S Alt V


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 5 - 5
1 Dec 2021
Alagboso F Mannala G Steinmann S Docheva D Rupp M Brochhausen C Alt V
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Aim

Bone regeneration following the treatment of Staphylococcal bone infection or osteomyelitis is challenging due to the ability of Staphylococcus aureus to invade and persist within bone cells, which could possibly lead to antimicrobial tolerance and incessant bone destruction.

Here, we investigated the influence of Staphylococcal bone infection on osteoblasts metabolism and function, with the underlying goal of determining whether Staphylococcus aureus-infected osteoblasts retain their ability to produce extracellular mineralized organic matrix after antibiotic treatment.

Method

Using our in vitro infection model, human osteoblasts-like Saos-2 cells were infected with high-grade Staphylococcus aureus EDCC 5055 strain, and then treated with 8 µg/ml rifampicin and osteogenic stimulators up to 21-days.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 83 - 83
1 Dec 2021
Bärtl S Gens L Zeiter S Moriarty F Alt V
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Aim

Staphylococcus aureus is the leading pathogen in fracture-related infection (FRI). Virulence factors vary between different strains, which may have a decisive influence on the course of infection. Previous in vitro experiments, in vivo testing in wax moth larvae, and genomic analysis of S. aureus isolates from FRI identified a low- and high-virulent strain. These findings correlated with the acute course of FRI induced by the high-virulent pathogen, whereas the low-virulent strain caused a chronic FRI in its human host. However, the role of bacterial virulence in FRI is not completely understood. Therefore, the present study aimed to compare the identified high- and low-virulent S. aureus isolates in a murine FRI model.

Method

Skeletally mature C57Bl/6N mice received a femoral osteotomy stabilized by titanium locking plates. FRI was established by inoculation of either high-virulent S. aureus EDCC 5458 or low-virulent S. aureus EDCC 5464 in the fracture gap. Mice were euthanized 4 and 14 days after surgery, respectively. Severity and progression of infection were assessed in terms of clinical presentation, quantitative bacteriology, semiquantitative histopathologic evaluation, and serum cytokine profile.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 25 - 25
1 Dec 2021
Walter N Bärtl S Brunotte M Engelstädter U Ehrenschwender M Hitzenbichler F Alt V Rupp M
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Aim

Fracture-related infection (FRI) is a challenging complication. This study aims to investigate (1) microbial patterns in fracture-related infection (FRI), (2) the comparison of isolated pathogens in FRI patients with early, delayed, and late onset of infection and (3) antibiotic susceptibility profiles to identify effective empiric antibiotic therapy for FRI.

Method

Patients treated for FRI from 2013 to 2020 were grouped into early (< 2 weeks), delayed (2– 10 weeks) and late (> 10 weeks) onset of infection. Pathogens detected during treatment were evaluated for pathogens. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 12 - 12
1 Dec 2021
Rupp M Henssler L Brochhausen C Zustin J Geis S Pfeifer C Alt V Kerschbaum M
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Aim

Adequate debridement of necrotic bone is of paramount importance for eradication of infection in chronic osteomyelitis. Currently, no tools are available to detect the exact amount of necrotic bone in order to optimize surgical resection. The aim of the present study was to evaluate the feasibility of an intraoperative illumination method (VELscope®) and the correlation between intraoperative and pathohistological findings in surgically treated chronic fracture related infection patients.

Method

Ten consecutive patients with chronic fracture related infections of the lower extremity were included into this prospectively performed case series. All patients had to be treated surgically for fracture related infections requiring bony debridement. An intraoperative illumination method (VELscope®) was used to intraoperatively differentiate between viable and necrotic bone. Tissue samples from the identified viable and necrotic bone areas were histopathologically examined and compared to intraoperative findings.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 76 - 76
1 Dec 2021
Mannala G Rupp M Alagboso F Docheva D Alt V
Full Access

Aim

In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules involve in biofilm. Due to ethical restrictions, the use mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections. This model organism is easy to handle, cheap and ethical restriction free and could be used for the high through put screening of antimicrobial compounds to treat biofilm. To promote the use of this model in basic research we aimed to validate this based on the typical biofilm features such as less susceptible to the antibiotics, complexity of the biofilm structure and gene expression profile of biofilms.

Method

G. mellonella larvae are maintained at 30oC on artificial diet in an incubator. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. After sterilization with 100% alcohol, these K-wires were pre-incubated in S. aureus bacterial suspension (5×106 CFU/ml) for 30 min, washed in PBS and implanted inside the larva after with help of scalpel. The larvae were incubated at 37oC for two day for the survival analysis. To analyze the less susceptibility of the biofilms towards antibiotics, the larvae were treated with gentamicin and compared survival with planktonic infection in G. mellonella. To reveal the complex structure of biofilm, the implants were removed and processed for the MALDI analysis. Whole genome-based transcriptome of biofilm was performed to explore the changes in transcriptional landscapes.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 26 - 26
1 Dec 2021
Lang S Loibl M Gläsner J Simon M Rupp M Grad S Neumann C Alt V Gessner A Hanses F
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Aim

Vertebral osteomyelitis (VO) is an infection of the spine mostly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVD) and adjacent vertebral bodies (VB) is poorly described. We aimed to investigate the connection between infection, bone- and disc-metabolism in VO patients.

Method

Fourteen patients with VO (infection group) and 14 patients with incomplete burst fractures of the spine (fracture group as controls) were included prospectively. Demographic data, treatment details, laboratory infection markers, and patient-reported outcome were assessed. Tissue biopsies from affected IVDs and adjacent VBs were analyzed for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone-metabolism by RT-qPCR.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 67 - 67
1 Dec 2021
Walter N Rupp M Hierl K Koch M Kerschbaum M Worlicek M Alt V
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Aim

We aimed to evaluate the impact of knee periprosthetic joint infection (PJI) by assessing the patients’ long-term quality of life and explicitly their psychological wellbeing after successful treatment.

Method

Thirty-six patients with achieved eradication of infection after knee PJI were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 87 - 87
1 Dec 2021
Mannala G Rupp M Walter N Brunotte M Alagboso F Docheva D Brochhausen C Alt V
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Aim

Here, we are aimed to evaluate bacteriophage (191219) to treat S. aureus implant-associated bone infections by means of testing against S. aureus during its planktonic, biofilm and intracellular growth phases and finally assessing antimicrobial effect on in vivo biofilm formed on metal K-wire in an alternative insect model Galleria mellonella.

Method

The bacteriophages (191219) were provided from D&D Pharma GmbH. These bacteriophages were tested against S. aureus EDCC 5055 (MSSA) and S. aureus DSM 21979 (MRSA) strains. To assess the activity of bacteriophages against planktonic growth phase, bacteriophages, and S. aureus EDCC 5055(1×107 CFU/ml) were co-cultured in LB media as multiplicity of infection (MOI) of 10, 1, 0.1, and 0.01 for 24 hours at 37oC and finally plated out on the LB agar plates to estimate the bacterial growth. The antimicrobial activity of bacteriophages on biofilms in vitro was measured by analysing the incubating the several fold dilutions of bacteriophages in LB media with biofilms formed on 96-well plate. The eradication of biofilm was analysed with crystal violet as well as CFU analysis methods. Later, the effect of bacteriophages on intracellular growth of S. aureus in side osteoblast was tested by treating the S. aureus infected osteoblasts at 2h, 4h and 24h time points of post treatment. In addition, we have analysed synergistic effect with gentamicin and rifampicin antibiotics to clear intracellular S. aureus. Finally, experiments are performed to prove the effect of bacteriophages to clear in vivo biofilm using alternative insect model G. mellonella as well as to detect the presence of bacteriophages inside the osteoblasts through transmission electron microscopy (TEM) analysis.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 51 - 51
1 Dec 2021
Lang S Frömming A Ehrenschwender M Neumann C Walter N Loibl M Alt V Rupp M
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Aim

Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis.

Method

We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 742 - 743
1 Nov 2021
Rupp M Walter N Baertl S Lang S Lowenberg DW Alt V


Bone & Joint Research
Vol. 10, Issue 6 | Pages 351 - 353
1 Jun 2021
Baertl S Metsemakers W Morgenstern M Alt V Richards RG Moriarty TF Young K


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.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 66 - 66
1 Dec 2020
Chu J Pfeifer C Alt V Docheva D
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Introduction

Cell-based tendon engineering is an attractive alternative therapeutic approach to established treatments of tendon injuries. Numerous cell types are promising source of tendon engineering; however, there are certain disadvantages for each cell type. Interestingly, dermal fibroblasts (DFs) are able to transdifferentiate into other cell types, they are widely distributed in dermis and easy to harvest and isolate. Furthermore, pilot clinical studies suggested a promising therapeutic potential of autologous DFs for discorded tendons (Connell et al., 2009&2011), but the underlining repair mechanisms remain unclarified. To investigate tenogenic differentiation process in great detail, we have previously established a three-dimensional (3D) cell sheet model, comprising of three consecutive step (expansion, stimulation and maturation) leading to the formation of 3D tendon-like tube (Hsieh et al., 2018; Yan et al., 2020). Hence, the aim of this study was to carry out pilot examination of the tenogenic potential of human DFs (hDFs) by implementing the 3D cell sheet model.

Methods

hDFs (company purchased, n=2), hBMSCs (human bone marrow mesenchymal stem cells, n=1) and hTSPCs (human tendon stem/progenitor cells, n=1) were used and subjected to the 3D model. In 2D culture, semi-qPCR was performed to validate the expression of DF markers in hDFs, namely NTN1, PDPN and CD26 for papillary dermis layer, and PPARG, ACTA2 and CD36 for reticular dermis layer). FACS analysis and immunofluorescence were employed to validate expression of CD73, CD90, CD105 and vimentin (mesenchyme marker), respectively. After harvesting the 3D cell sheets, wet weigh measurements, H&E and collagen type I stainings, and semi-qPCR for Scleraxis and tenomodulin were executed.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 79 - 81
1 Feb 2020
Alt V Rupp M Langer M Baumann F Trampuz A

Cite this article: Bone Joint Res. 2020;9(2):79–81.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 77 - 78
1 Feb 2020
Alt V Rupp M Langer M Baumann F Trampuz A

Cite this article: Bone Joint Res. 2020;9(2):77–78.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 62 - 62
1 Dec 2019
Rupp M Kern S Biehl C Knapp G Khassawna TE Heiß C Alt V
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Introduction

Polymicrobial infections are expected to complicate the treatment of bone and joint infections. Septic nonunions often occur after initial open fractures, which prophylactically receive broad-spectrum antibiotics. However, no data that describes frequencies of polymicrobial infections and pathogens evident in course of the treatment of septic nonunions is published. Therefore, this study aims at investigating the frequency and pathogen types in polymicrobial infections.

Methods

Surgically treated Patients with long bone septic nonunion admitted between January 2010 and March 2018 were included in the study. Following parameters were examined: age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and anatomical location of the infected nonunion. Microbiological culture data, polymerase-chain-reaction results of tissue samples, sonication, and joint fluid of the initial and follow-up revision surgeries were assessed. No exclusion criteria were determined.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 79 - 79
1 Dec 2019
Arens D Zeiter S Paulin T Ranjan N Alt V
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Aim

Silver is known for its excellent antimicrobial activity, including activity against multiresistant strains. The aim of the current study was to analyze the biocompatibility and potential influence on the fracture healing process a silver-coating technology for locking plates compared to silver-free locking plates in a rabbit model.

Methods

The implants used in this study were 7-hole titanium locking plates, and plasma electrolytic oxidation (PEO) silver coated equivalents. A total of 24 rabbits were used in this study (12 coated, 12 non-coated). An osteotomy of the midshaft of the humerus was created with an oscillating saw and the humerus stabilized with the 7 hole locking plates with a total of 6 screws. X-rays were taken on day 0, week 2, 4, 6, 8, and 10 for continuous radiographical evaluation of the fracture healing. All animals were euthanized after 10 weeks and further assessment was performed using X-rays, micro-CT, non-destructive four-point bending biomechanical testing and histology. Furthermore, silver concentration was measured in the kidney, liver, spleen and brain.


Bone & Joint Research
Vol. 8, Issue 8 | Pages 387 - 396
1 Aug 2019
Alt V Rupp M Lemberger K Bechert T Konradt T Steinrücke P Schnettler R Söder S Ascherl R

Objectives

Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study.

Methods

A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 38 - 38
1 Apr 2017
Ray S El Khassawna T Thormann U Sommer U Rhonke M Henns A Gelinsky M Hanke T Schnettler R Heiss C Alt V
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Objectives

Osteoporosis and osteomalacia lead to increased fracture risk. Previous studies documented dysregulated osteoblast and osteoclast activity, leading to a high-turnover phenotype, reduced bone mass and low bone mineral content. Osteocytes, the most abundant bone cell type, are involved in bone metabolism by enabling cell to cell interaction. Osteocytes presence and viability are crucial for bone tissue homeostasis and mechanical integrity. Osseo-integration and implant degradation are the main problems in developing biomaterials for systemically diseased bone. This study examines osteocyte localisation, morphology and on the implant surface and at the implant bone interface. Furthermore, the study investigates ECM proteins regulation correlated to osteocytes and mechanical competence in an ovariectomised rat model with a critical size metaphyseal defect.

Methodology

After induction of osteoporosis, 60 female Sprague-Dawley rats were randomised into five groups: SrCPC (n=15), CPC (n=15), ScB30 (n=15), ScB30Sr20 (n=15) and empty defect (n=15). The left femur of all animals underwent a 4mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with the above mentioned implants or left empty. After six weeks, histomorphometric analysis showed a statistically significant increase in bone formation at the tissue-implant interface in the SrCPC group compared to the other groups (p<0.01). Osteocyte morphology and networks were detected using silver and staining. ECM proteins were investigated through immunohistochemistry. Cellular populations were tested using enzyme histochemistry. Mineralisation was assessed using time of flight secondary ion mass spectrometry (TOF-SIMS). Statistical analysis was performed using Mann Whitney U test with Bonferroni correction.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 36 - 36
1 Apr 2017
Ray S Thormann U Sommer U ElKhassawna T Rhonke M Henns A Gelinsky M Hanke T Schnettler R Heiss C Alt V
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Background

Multiple Myeloma is a hematological malignancy of terminally differentiated plasma cells associated with increased osteoclast activity and decreased osteoblast functions. Systemic antiproliferative treatment includes proteasome inhibitors such as bortezomib, a clinical potent antimyeloma agent. Local delivery of biological active molecules via biomaterial composite implants to the site of the lesion has been shown to be beneficial for bone and implant-associated infections. In anticancer treatment local delivery of anticancer agents to the neoplasia via biomaterial carriers has never been reported before. The purpose of the current is to present the concepts and the first in vivo results for proteasome inhibitor composite biomaterials for local delivery of bortezomib to proliferative multiple myeloma bone lesions including concentration measurements at different anatomical regions in a rat model.

Methods

80 female Sprague-Dawley rats were randomised into five different treatment groups (n=16/group): 1) Empty (2) Xerogel-granulat: XG (3) Xerogel-granulat+100mgbortezomib [b]: XG100b (4) Xerogel-granulat+500mgb:XG500b (5) Xerogel-granulat+2500mgb:XG2500b. A 2.5 mm drill hole was then created in the metaphysis of the left femur. The defect was then either filled with the previously mentioned substitutes or left empty to serve as a control. After 4 weeks femora were harvested followed by histological, histomorphometrical and immunohistochemical (BMP2; bone-morphogenic protein 2, OPG; osteoprotegerin, RANKL; Receptor activator of nuclear factor kappa-B ligand, ASMA; alpha smooth muscle actin, ED1;CD68 antibody). TOF-SIMS was used to assess the distribution of released strontium ions. Statistical analysis was done using SPSS software. Data was not found normally distributed and hence Mann-Whitney U with bonferroni correction was used. To avoid type I errors due to unequal variances and group sizes Games-Howell test was also performed.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 543 - 543
1 Oct 2010
Alt V Donell S Eicher A Schnettler R
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The introduction of new treatments needs to be both clinically effective and cost effective. Clinicians tend to be unaware of the importance of the latter, and how health economic assessments are undertaken, especially in a public health system where the inclusion of funded treatments is made on a national basis. The purpose of this study was to determine the cost savings from a societal perspective in the use of recombinant human Bone Morphogenetic Protein -2 (rhBMP-2) in grade III A and B open tibia fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Healthcare system (direct healthcare costs) and costs for productivity losses (indirect health-care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma “BESTT study”. Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/08 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. From a societal perspective, overall savings per case of €7911 for the UK, €9270 for Germany, and €9291 were calculated. Those savings largely offset the upfront price of rhBMP-2 of €2266(£1,790) in the UK, €2970 in Germany, and €2950 in France. Total net savings can be estimated to be €9.6 million for the UK, €14.5 million for Germany, and €11.4 million for France. For all three countries reduced productivity losses are the key driver for the overall savings. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibia fractures, at a national level there are net cost-savings from a societal perspective for all three countries.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 303 - 303
1 May 2009
Alt V Bitschnau A Sewing A Wenisch S Schnettler R
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Gentamicin was described with negative effects on bone formation. Arginin-Glycin-Aspartat (RGD) sequences play a key role in the adhesion of osteoblasts and have proven to improve implant integration. We have already shown a significant reduction in infection rates by a combined gentamicin-hydroxyapatite (HA) and gentamicin-RGD-hydroxyapatite coating in a rabbit infection model for cementless joint prostheses.

The purpose of the study was to assess whether the gentamicin-HA coating had a negative effect on the implant integration and new bone formation, compared to pure HA coating, and whether this could be enhanced by additional gentamicin-RGD-HA coating.

There were 5 study groups (8 animals per group) with 5 different stainless steel K-wires: uncoated, HA coated, gentamicin-HA, RGD-coated, gentamicin-RGD-HA coated. A 2.0 mm K-wire with one type of coating was introduced into the intramedullary canal of the tibia. The tibiae were harvested after 12 weeks and standardised longitudinal and transverse sections were performed to study new bone formation around the implant and implant bone contact. New bone formation and osseointegration of the implant surface was assessed using histomorphometrical methods by computerised semi-quantitative analysis and histological methods.

There were no significant differences between the HA and the gentamicin-HA group although new bone formation and implant bone contact were always higher for the pure HA coating. Additional RGD coating on the gentamicin-RGD-HA coating did not show significant improvement of bone formation and implant integration compared to gentamicin-HA. There was a very similar histological appearance of new bone formation between all groups with very low frequency of giant cells, indicating good biocompatibility.

Gentamicin-HA coating did not have significant negative effects on bone formation and bone implant contact, compared to pure HA coating. In combination with the excellent ability to reduce infection rates, gentamicin-HA coating may have a high interest in cement-less arthroplasty.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 176 - 177
1 Mar 2009
Alt V Bitschnau A Sewing A Meissner S Wenisch S Domann E Schnettler R
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Introduction: Similar local infection prophylaxis as in cemented total joint by antibiotic-loaded bone cement has not been possible yet for cementless prostheses. In this study, a gentamicin-coating which can be brought additionally onto standard hydroxyapatite (HA) coatings of cementless prostheses is presented. It was tested whether this gentamicin-coating can reduce infection rates in a rabbit infection model with Staphylococcus aureus compared to compared to standard-HA coating. Furthermore, the biocompatibility of this gentamicin coating was investigated.

Materials and Methods: Staphylococcus aureus with a dose of 10(7) CFUs was inoculated into the intramedullary canal of the tibia of 30 rabbits followed by the implantation of standard hydroxyapatite (HA) K-wires, K-wires coated with a HA--gentamicin combination, and K-wires coated with a HA-RGD-gentamicin combination, respectively. The animals were sacrificed after 28 days and clinical, histological and microbiological assessment on the bone and on the removed K-wire itself by agar plating and DNA-pulse field gel electrophoresis were carried out to detect infection. Infection was defined as positive culture growth from the bone and/or cement samples. In another study with 40 rabbits biocompatibility of the two gentamicin-coating types was assessed after an implantation time of 12 weeks and compared to pure HA-coating and uncoated implants.

Results: Infection rates were 88% (7 of 8 animals) for the standard HA, 0% (0 of 9 animals) for the HA-gentamicin and 0% (0 of 10 animals) for the HA-RGD-gentamicin group. There was a statistically highly significant reduction of infection rates by both gentamicin-coating types compared to standard HA-coating (p < 0.001). The animals that were identified to have positive culture growth corresponded to the animals that showed clinical signs of infection. An excellent correlation between agar plating testing results of the K-wires and of the bone samples was found. Detailed histology showed cortical lysis, abcess and sequester formation in the infected animals. There were no major differences in the biocompatibility between the different groups. There were only a few giant cells and regions of bone marrow necrosis in the gentamicin-groups which was comparable to the control implants. There was a very similar histologic appearance of the gentamicin coatings and the standard HA coating.

Conclusion: Both gentamicin-coating types showed significant improvement of infection prophylaxis compared to standard HA coating. Furthermore, both gentamicin coating types revealed good biocompatibility after 12 weeks. Therefore, HA-gentamicin and HA-RGD-gentamicin coatings could help to reduce infection rates in cementless arthroplasty in all day clinical use


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 155 - 155
1 Mar 2009
Alt V Donell S Chhabra A Eicher A Schnettler R
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Introduction: The addition of recombinant human bone morphogenetic protein-2 (rhBMP-2) showed significant reduction of secondary intervention, fracture healing time and infection rates compared with intramedullary nailing alone in open tibia fractures. However, the upfront price of approx. 3000 € is a barrier to its regular use. The goal of the study was to determine potential cost savings and cost-effectiveness of rhBMP-2 in grade III open tibia fractures from the perspective of the UK National Health Service (NHS) and the German Health Care System and to derive conclusions for other European health care systems.

Materials and Methods: Clinical data from a previously published randomised controlled study with 450 patients (“BESTT study”) were used to generate total treatment costs for each patient for the control and the 1.5 mg/ml BMP-2 group based on the current German-DRG and the NHS for UK. The analysis was performed from a health care system and a societal perspective for a one year time horizon. Furthermore, assessment of the cost-effectiveness of BMP-2 was done by utility analysis.

Results: The use of BMP-2 for grade III open tibia fractures is leading to cost savings of 3183 € per case and, therefore, to net savings for the German health care system. The main driver for cost savings is faster fracture healing with faster resumption of work and reduced expenses for sickness leave payments. For the UK rhBMP-2 is a cost-effective strategy with a cost-effectiveness ratio of approx. £11,000/QALY which is well below the standard £30,000 benchmark for the NHS. From a societal perspective, rhBMP-2 is a cost-saving treatment.

Conclusions: BMP-2 leads to net savings in grade III open tibia fractures in Germany which can be expected for other European countries where sickness payments are provided by health care insurers. For countries like UK where sickness are provided by third parties BMP-2 is a cost-effective treatment strategy from a health care system perspective and a cost-saving treatment from a societal perspective.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 246 - 246
1 Sep 2005
Alt V Bechert T Steinrücke P Seidel P Dingeldein E Domann E Schnettler R
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Infections in total joint arthroplasty, particularly with multiresistant bacteria, are a serious problem. A new nanoparticulate silver cement had previously shown good biocompatibility combined with good in vitro antimicrobial activity against multiresistant bacteria.

The purpose of the current study was to evaluate the antibacterial activity of nanoparticulate silver cement against biofilm-building methicillin-resistant S. aureus (MRSA) in a rabbit model and to compare it to that of gentamicin-loaded cement.

Gentamicin cement or nanoparticulate silver bone cement was injected into the proximal half of one femur in 10 animals, respectively. Before hardening of the cement 107 or 108 colony forming units of MRSA with high gentamicin resistance were inoculated at the cement bone interface in 5 rabbits of each group. The animals were euthanized after 14 days and both the cement adjacent bone and the cement itself were studied using microbiological and histological methods. Infection was defined as positive culture growth from the bone and/or cement samples.

Infections rates were 100% for the gentamicin group (10 of 10 animals had infection) and 30% for the NanoSilver group (3 of 10 animals). Thus, nanoparticulate silver bone cement significantly reduced infection rates by 70%.

Nanoparticulate silver cement exhibited good antimicrobial activity in the prophylaxis of cement-related infections with MRSA and is therefore a promising alternative in total joint arthroplasty.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 246 - 246
1 Sep 2005
Alt V Steinrücke P Bechert T Seidel P Domann E Schnettler R
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Introduction: Deep periprosthetic infections are infrequent but devastating situations in total joint arthroplasty. During the last years the total number and the percentage of total joint infections with multiresistant bacteria has increased. The aim of this study was to investigate the antimicrobial activity of a new bone cement loaded with nanoparticulate silver against bacteria with different antibiotic resistance.

Material and Methods: An in vitro proliferation test was used to test antimicrobial properties of 1% nanoparticulate silver bone cement, gentamicin-loaded, tobramycin-loaded and plain bone cement. This in vitro testing method consisted of two incubation steps. During the first step the tested bacteria could adhere to the bone cement surface. In the second step bacteria either seeded out of vital daughter cells in case of no antimicrobial effect of the cement or were killed by the antibacterial properties of the cement. Seeding out of daughter cells was detected by a microplate reading system resulting in specific time proliferation curves. Several staphylococci and gram-negative strains with different resistance profiles against methicillin, tobramycin, and gentamicin were tested including MRSA and MRSE.

Results: 1% nanoparticulate silver bone cement showed bactericidal effect against all tested strains, including MRSA and MRSE. Gentamicin and tobramycin cement was not effective against bacteria with high resistance level against the respective antibiotic. Plain bone cement was not effective against any strain.

Conclusion: 1% nanoparticulate silver bone cement exhibited excellent antibacterial properties that could not be reached by gentamicin or tobramycin-loaded cement. Good activity against MRSA could also already be shown in a first animal trial. If further in vivo investigations confirm these promising results nanoparticulate silver bone cement is a new alternative for prophylaxis in total joint arthroplasty.