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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 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 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. 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 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. 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. Results. A total of 105 patients with chronic PJI were enrolled: 64 patients in the short course group and 41 patients in the long course group. For 99 of the patients, the infection was under control during a follow-up period of at least 24 months after two-stage revision. For the short course group, the mean duration of antibiotic prophylaxis after stage II reimplantation was 20.17 days (SD 5.30) and the infection control rate was 95.3%; for the long course group these were 45.02 days (SD 15.03) and 92.7%, respectively. There was no significant difference in infection control rates between the two groups (p = 0.676). Cox regression analysis found that methicillin-resistant staphylococcus infection (p = 0.015) was an independent prognostic factor for recurrence. Conclusion. After stage II reimplantation surgery of two-stage revision for chronic PJI, extended antibiotic prophylaxis for less than one month can achieve good infection control rate. Cite this article: Bone Joint Res 2021;10(12):790–796


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 1 | Pages 60 - 67
1 Jan 2021
Bendtsen MAF Bue M Hanberg P Slater J Thomassen MB Hansen J Søballe K Öbrink-Hansen K Stilling M

Aims. Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT > MIC) for methicillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model. Methods. A total of 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every six hours during a 24-hour period. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin fT > MIC was evaluated using a low MIC target (0.5 μg/ml) and a high MIC target (2.0 μg/ml). Results. Intravenous administration resulted in longer fT > MIC (0.5 μg/ml) compared to oral administration, except for cortical bone. In Group IV, all pigs reached a concentration of 0.5 μg/ml in all compartments. The mean fT > MIC (0.5 μg/ml) was 149 minutes (95% confidence interval (CI) 119 to 179; range 68 to 323) in subcutaneous tissue and 61 minutes (95% CI 29 to 94; range 0 to 121) to 106 minutes (95% CI 76 to 136; range 71 to 154) in bone tissue. In Group PO, 0/8 pigs reached a concentration of 0.5 μg/ml in all compartments. For the high MIC target (2.0 μg/ml), fT > MIC was close to zero minutes in both groups across compartments. Conclusion. Although intravenous administration of flucloxacillin 1 g provided higher fT > MIC for the low MIC target compared to oral administration, concentrations were surprisingly low, particularly for bone tissue. Achievement of sufficient bone and soft tissue flucloxacillin concentrations may require a dose increase or continuous administration. Cite this article: Bone Joint Res 2021;10(1):60–67


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. 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.


Objectives

Irrigation is the cornerstone of treating skeletal infection by eliminating pathogens in wounds. A previous study shows that irrigation with normal saline (0.9%) and ethylenediaminetetraacetic acid (EDTA) could improve the removal of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) compared with normal saline (NS) alone. However, it is still unclear whether EDTA solution is effective against infection with drug-resistant bacteria.

Methods

We established three wound infection models (skin defect, bone-exposed, implant-exposed) by inoculating the wounds with a variety of representative drug-resistant bacteria including methicillin-resistant S. aureus (MRSA), extended spectrum beta-lactamase-producing E. coli (ESBL-EC), multidrug-resistant Pseudomonas aeruginosa (MRPA), vancomycin-resistant Enterococcus (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Enterobacter (MRE), and multidrug-resistant Proteus mirabilis (MRPM). Irrigation and debridement were repeated until the wound culture became negative. The operating times required to eliminate pathogens in wounds were compared through survival analysis.


The Bone & Joint Journal
Vol. 101-B, Issue 1_Supple_A | Pages 3 - 9
1 Jan 2019
Alamanda VK Springer BD

Aims. Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI. Materials and Methods. A search of PubMed and MEDLINE was conducted for articles published between January 1990 and February 2018 with a combination of search terms to identify studies that dealt with modifiable risk factors for reducing the rate of PJI. An evidence-based review was performed on 12 specific risk factors: glycaemic control, obesity, malnutrition, smoking, vitamin D levels, preoperative Staphylococcus aureus screening, the management of anti-rheumatic medication, perioperative antibiotic prophylaxis, presurgical skin preparation, the operating room environment, irrigant options, and anticoagulation. Results. Poor glycaemic control, obesity, malnutrition, and smoking are all associated with increased rates of PJI. Vitamin D replacement has been shown in preliminary animal studies to decrease rates of PJI. Preoperative Staphylococcus aureus screening and appropriate treatment results in decreased rates of PJI. Perioperative variables, such as timely and appropriate dosage of prophylactic antibiotics, skin preparation with chlorohexidine-based solution, and irrigation with dilute betadine at the conclusion of the operation, have all been associated with reduced rates of PJI. Similarly, aggressive anticoagulation and increased operating room traffic should be avoided to help minimize risk of PJI. Conclusion. PJI remains a serious complication of arthroplasty. Surgeons should be vigilant of the modifiable risk factors that can be addressed in an attempt to reduce the risk of PJI


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. Results. In total, eight studies which included 2738 patients were eligible for quantitative synthesis. The effect of antibiotic-loaded poly(methyl methacrylate) beads was investigated by six of these studies, and two studies evaluated the effect of local antibiotics applied without a carrier. Meta-analysis showed a significantly lower infection rate when local antibiotics were applied (4.6%; 91/1986) than in the control group receiving standard systemic prophylaxis alone (16.5%; 124/752) (p < 0.001) (odds ratio 0.30; 95% confidence interval 0.22 to 0.40). Conclusion. This meta-analysis suggests a risk reduction in FRI of 11.9% if additional local antibiotics are given prophylactically for open limb fractures. However, due to limited quality, heterogeneity, and considerable risk of bias, the pooling of data from primary studies has to be interpreted with caution. Cite this article: M. Morgenstern, A. Vallejo, M. A. McNally, T. F. Moriarty, J. Y. Ferguson, S. Nijs, WJ. Metsemakers. Bone Joint Res 2018;7:447–456. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. DOI: 10.1302/2046-3758.77.BJR-2018-0043.R1