scholarly journals Current osteomyelitis mouse models, a systematic review

2021 ◽  
Vol 42 ◽  
pp. 334-374
Author(s):  
C Guarch-Pérez ◽  
◽  
M Riool ◽  
SAJ Zaat
Keyword(s):  
Joint Infection ◽  
Healing Process ◽  
Treatment Strategies ◽  
Antimicrobial Treatment ◽  
In Vivo Model ◽  
Bone Implant ◽  
Prosthetic Joint ◽  
Post Traumatic ◽  
Haematogenous Osteomyelitis

Osteomyelitis is an inflammatory bone disease caused by an infecting microorganism leading to a gradual bone loss. Due to the difficulty in studying osteomyelitis directly in patients, animal models allow researchers to investigate the pathogenesis of the infection and the development of novel prophylactic, anti-inflammatory and antimicrobial treatment strategies. This review is specifically focused on the in vivo mouse osteomyelitis studies available in literature. Thus, a systematic search on Web of Science and PubMed was conducted using the query “(infection) AND (mice OR mouse OR murine) AND (model OR models) AND (arthroplasty OR fracture OR (internal fixator) OR (internal fixation OR prosthesis OR implant OR osteomyelitis)”. After critical assessment of the studies according to the inclusion and exclusion criteria, 135 studies were included in the detailed analysis. Based on the model characteristics, the studies were classified into five subject groups: haematogenous osteomyelitis, post-traumatic osteomyelitis, bone-implant-related infection, peri-prosthetic joint infection, fracture-related infection. In addition, the characteristics of the mice used, such as inbred strain, age or gender, the characteristics of the pathogens used, the inoculation methods, the type of anaesthesia and analgesia used during surgery and the procedures for evaluating the pathogenicity of the infecting micro-organism were described. Overall, the mouse is an excellent first step in vivo model to study the pathogenesis, inflammation and healing process of osteomyelitis and to evaluate novel prophylaxis and treatment strategies.

scholarly journals A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model

2020 ◽  
Vol 10 ◽  
Author(s):  
John Jairo Aguilera-Correa ◽  
Amaya Garcia-Casas ◽  
Aranzazu Mediero ◽  
David Romera ◽  
Francisca Mulero ◽  
...  
Keyword(s):  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Sol Gel ◽  
In Vitro Studies ◽  
In Vivo Model ◽  
Prosthetic Joint

2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats

2021 ◽  
Vol 103-B (7 Supple B) ◽  
pp. 9-16
Author(s):  
William J. Hadden ◽  
Mazen Ibrahim ◽  
Mariam Taha ◽  
Kerstin Ure ◽  
Yun Liu ◽  
...  
Keyword(s):  
Real Time ◽  
In Vivo Imaging ◽  
Biofilm Formation ◽  
Joint Infection ◽  
Volumetric Analysis ◽  
In Vivo Model ◽  
Infection Model ◽  
Sprague Dawley ◽  
Hip Hemiarthroplasty

Aims The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16.

scholarly journals The Right Time to Safely Re-Evaluate Empirical Antimicrobial Treatment of Hip or Knee Prosthetic Joint Infections

2019 ◽  
Vol 8 (12) ◽  
pp. 2113 ◽  
Author(s):  
Deroche ◽  
Bémer ◽  
Valentin ◽  
Jolivet-Gougeon ◽  
Tandé ◽  
...  
Keyword(s):  
Joint Infection ◽  
Antimicrobial Treatment ◽  
Microbiological Diagnosis ◽  
Joint Infections ◽  
Time To Positivity ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Two Samples ◽  
The Right ◽  
Polymicrobial Infections

Currently, no guideline provides recommendations on the duration of empirical antimicrobial treatment (EAT) in prosthetic joint infection (PJI). The aim of our study was to describe the time to growth of bacteria involved in PJI, rendering possible decreased duration of EAT. Based on a French multicentre prospective cohort study, culture data from patients with confirmed hip or knee PJI were analysed. For each patient, five samples were processed. Time to positivity was defined as the first positive medium in at least one sample for virulent pathogens and as the first positive medium in at least two samples for commensals. Definitive diagnosis of polymicrobial infections was considered the day the last bacteria were identified. Among the 183 PJIs, including 28 polymicrobial infections, microbiological diagnosis was carried out between Day 1 (D1) and D5 for 96.7% of cases. There was no difference in the average time to positivity between acute and chronic PJI (p = 0.8871). Microbiological diagnosis was given earlier for monomicrobial than for polymicrobial infections (p = 0.0034). When an optimized culture of peroperative samples was carried out, almost all cases of PJI were diagnosed within five days, including polymicrobial infections. EAT can be re-evaluated at D5 according to microbiological documentation.

A 3d Histomorphometric Method for Analyses of Skeletal Tissue Mechanobiology

2007 ◽  
Author(s):  
Ryan E. Gleason ◽  
Kristy T. S. Palomares ◽  
Thomas A. Einhorn ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan
Keyword(s):  
Healing Process ◽  
Fracture Site ◽  
Cartilage Tissue ◽  
In Vivo Model ◽  
Original Form ◽  
Mechanical Stimuli ◽  
Fracture Callus ◽  
Skeletal Tissue ◽  
Form And Function

Skeletal repair and regeneration involve a dynamic interplay of biological processes that result in spatially and temporally varying patterns of tissue formation and remodeling. For example, during bone fracture healing the cartilaginous callus that is formed initially in the fracture site is subsequently mineralized and remodeled to restore the original form and function to the injured bone. During much of this healing process, the fracture callus is comprised of a heterogeneous mixture of cartilage, fibrocartilage, multipotent mesenchymal tissue, and bone. Adding to this complexity, mechanical stimuli are known to influence the rate and type of tissues formed during skeletal healing [1]. Given the growing body of evidence that controlled mechanical stimulation may be used to enhance healing, it is of substantial interest to elucidate relationships between the distributions of local stresses and strains that develop within the healing region and the distribution of tissue types that form. While histomorphometry is a well established approach for characterizing the latter, it has historically been limited to analyses of a small number of two-dimensional sections of tissue. Such 2D sampling may be inadequate for quantitative characterization of the irregular geometry and heterogeneous composition of healing tissues. In this study, we report on a 3D histomorphometric method and apply this method to an in vivo model of skeletal repair [2] in which a bending stimulus delivered to a healing bone defect results in the formation of predominantly cartilage tissue, rather than bone.

scholarly journals Immunohistological changes in skin wounds during the early periods of healing in a rat model

2012 ◽  
Vol 57 (No. 2) ◽  
pp. 77-82 ◽  
Author(s):  
F. Sabol ◽  
L. Dancakova ◽  
P. Gal ◽  
T. Vasilenko ◽  
M. Novotny ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wide Spectrum ◽  
Smooth Muscle Actin ◽  
Healing Process ◽  
Skin Wound ◽  
Hair Follicles ◽  
In Vivo Model ◽  
Wound Healing Process ◽  
Rat Skin

The complexity of the wound healing process, which is still poorly understood, prompted us to perform an immunohistochemical investigation using rat skin as an in vivo model. Fifteen Sprague-Dawley rats were included in the experiment. Two round full thickness wounds, 4 mm in diameter, were made on the backs of all rats. Haematoxylin and eosin basic staining as well as antibodies against wide spectrum keratin, keratin 10, keratin 14, α-smooth muscle actin, vimentin, fibronectin, collagens Type 1 and 3, and the transcription factor Sox-2 were applied to paraffin and frozen sections of skin wound specimens two, six and fourteen days after surgery, respectively. New hair follicles with Sox-2-positive cells were present after fourteen days; keratin/vimentin positivity was restricted to specimens of day two. Collagen-3 expression prevailed over collagen-1 expression at all evaluated time intervals, except in the uninjured part of the dermis. In conclusion, rat skin wound healing is a dynamic process which can serve as a model for studying phenomena such as cell-cell interactions and transitions in vivo.

Outcomes of repeat two-stage exchange hip arthroplasty for prosthetic joint infection

2019 ◽  
Vol 101-B (6_Supple_B) ◽  
pp. 110-115 ◽  
Author(s):  
N. Khan ◽  
D. Parmar ◽  
M. S. Ibrahim ◽  
B. Kayani ◽  
F. S. Haddad
Keyword(s):  
Hip Arthroplasty ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Antimicrobial Treatment ◽  
Successful Outcome ◽  
Two Stage ◽  
Persistent Symptoms ◽  
Prosthetic Joint ◽  
Revision Tha

Aims The increasing infection burden after total hip arthroplasty (THA) has seen a rise in the use of two-stage exchange arthroplasty and the use of increasingly powerful antibiotics at the time of this procedure. As a result, there has been an increase in the number of failed two-stage revisions during the past decade. The aim of this study was to clarify the outcome of repeat two-stage revision THA following a failed two-stage exchange due to recurrent prosthetic joint infection (PJI). Patients and Methods We identified 42 patients who underwent a two-stage revision THA having already undergone at least one previous two stage procedure for infection, between 2000 and 2015. There were 23 women and 19 men. Their mean age was 69.3 years (48 to 81). The outcome was analyzed at a minimum follow-up of two years. Results A satisfactory control of infection and successful outcome was seen in 26 patients (57%). There therefore remained persistent symptoms that either required further surgery or chronic antibiotic suppression in 16 patients (38%). One-third of patients had died by the time of two years’ follow-up. Conclusion The rate of failure and complication rate of repeat two-stage exchange THA for PJI is high and new methods of treatment including host optimization, immunomodulation, longer periods between stages, and new and more powerful forms of antimicrobial treatment should be investigated. Cite this article: Bone Joint J 2019;101-B(6 Supple B):110–115.

scholarly journals Adjunctive Rifampin Is Crucial to Optimizing Daptomycin Efficacy against Rabbit Prosthetic Joint Infection Due to Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 55 (10) ◽  
pp. 4589-4593 ◽  
Author(s):  
Azzam Saleh-Mghir ◽  
Claudette Muller-Serieys ◽  
Aurélien Dinh ◽  
Laurent Massias ◽  
Anne-Claude Crémieux
Keyword(s):  
Staphylococcus Aureus ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Detection Threshold ◽  
High Dose ◽  
Prosthesis Infection ◽  
Methicillin Resistant ◽  
Prosthetic Joint ◽  
Mutant Strains

ABSTRACTDaptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistantStaphylococcus aureus(MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 107MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Althoughin vivomean log10CFU/g of daptomycin-treated (4.23 ± 1.44;n= 12) or vancomycin-treated (4.63 ± 1.08;n= 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15;n= 9) (P< 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P< 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolatedin vivoeven without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.

Strength Retention of a New Microbial Cellulose Scaffold and Existing Collagen-Based Scaffolds After In Vivo Implantation in a Rabbit Model

2009 ◽  
Author(s):  
Michael I. Dishowitz ◽  
Miltiadis H. Zgonis ◽  
Jeremy J. Harris ◽  
Constance Ace ◽  
Louis J. Soslowsky
Keyword(s):  
Mechanical Behavior ◽  
Healing Process ◽  
Rabbit Model ◽  
In Vivo Model ◽  
Microbial Cellulose ◽  
Poor Outcomes ◽  
Over Time ◽  
Pullout Loads

Rotator cuff tendon tears often require large tensions for repair [1] and these tensions are associated with poor outcomes including rerupture [2]. To address this, repairs are often augmented with collagen-based scaffolds. Microbial cellulose, produced by A. xylinum as a laminar non-woven matrix, is another candidate for repair augmentation [3]. An ideal augmentation scaffold would shield the repair site from damaging loads as they change throughout the healing process. Although the initial mechanical properties of clinically used scaffolds have been well characterized [4–6], their mechanical behavior following implantation is not known. As a result, the role of these scaffolds throughout the healing process remains unknown. Therefore, the objective of this study is to characterize the mechanical behavior of existing collagen-based scaffolds and a new, microbial cellulose scaffold over time using an in vivo model. We hypothesize that: 1) collagen-based scaffolds will show decreased stiffness (1a) and suture pullout loads (1b) over time when compared to initial values while the microbial cellulose scaffold will not; and 2) the collagen-based scaffolds will have decreased stiffness (2a) and suture pullout loads (2b) when compared to the new, microbial cellulose scaffold at all timepoints.

2020 John Charnley Award: The antimicrobial potential of bacteriophage-derived lysin in a murine debridement, antibiotics, and implant retention model of prosthetic joint infection

2020 ◽  
Vol 102-B (7_Supple_B) ◽  
pp. 3-10 ◽  
Author(s):  
Branden R. Sosa ◽  
YingZhen Niu ◽  
Kathleen Turajane ◽  
Kevin Staats ◽  
Vincentius Suhardi ◽  
...  
Keyword(s):  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Bacterial Load ◽  
In Vitro Models ◽  
Periprosthetic Tissue ◽  
Retention Model ◽  
Prosthetic Joint ◽  
Implant Retention

Aims Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. Methods The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. Results PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. Conclusion PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3–10.

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