Experimental reproduction of periprosthetic joint infection: Developing a representative animal model

López-Torres, Irene Isabel; Sanz-Ruíz, Pablo; Navarro‐García, Federico; León-Román, Víctor Estuardo; Vaquero-Martín, Javier

doi:10.1016/j.knee.2019.12.012

Cited by 5 publications

(21 citation statements)

References 21 publications

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“…All animals had their proximal tibial metaphysis replaced by a stainless steel insert designed by 3D printing according to the technique described in another study [19]. After implantation and closure of the arthrotomy, 1 mL of 10 5 CFU from the methicillin-sensitive Staphylococcus aureus strain ATCC® 29,213™ was inoculated by intraarticular injection [20]. One week after the inoculation, the animals were re-anaesthetised to carry out the first stage of prosthetic replacement, intra-operative samples were taken to verify the presence of infection, the stainless steel insert was removed, and a cement spacer was fitted.…”

Section: Animals and Surgical Proceduresmentioning

confidence: 99%

“…1B). The diagnostic criteria for infection are summarised in Table 1 [20]. The evolution of the inflammatory parameters was defined according to variations in ESR, leukocyte count, platelet count, and percentage of serum lymphocytes.…”

Section: Analytical Determinationsmentioning

confidence: 99%

“…The spacers were also removed, sonicated, and washed three times with sterile saline solution to eliminate planktonic bacteria. All these samples were treated using a previously described procedure [20] in order to obtain final microbiological culture samples.…”

Section: Analytical Determinationsmentioning

confidence: 99%

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The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

López-Torres

Vaquero-Martín

Torres-Suárez

et al. 2022

International Orthopaedics (SICOT)

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Purpose Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. Methods An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. Results The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. Conclusion The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

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Section: Animals and Surgical Proceduresmentioning

confidence: 99%

Section: Analytical Determinationsmentioning

confidence: 99%

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The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

López-Torres

Vaquero-Martín

Torres-Suárez

et al. 2022

International Orthopaedics (SICOT)

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“…An excessively large inoculum can cause sepsis and death while an insufficient inoculum will quickly be cleared. 34,163,164 The duration of time following the inoculation of the pathogen in which the infection is established in the model must also be considered since this is dependent upon the species used in the model and differs from clinical presentation. 31 Additionally, the virulence of the bacterial strain used in the model and the culture conditions (i.e., log phase versus stationary phase growth) impact the concentration of the inoculum required to establish an infection.…”

Section: Considerations In Establishing Clinically Relevant Preclinic...mentioning

confidence: 99%

“…32,33 Technological advancements (e.g., 3Dprinting, bacterial genomic sequencing, etc. 33,34 ) have enabled the development of more clinically relevant and reproducible in vivo models that may facilitate and improve understanding of the development and treatment of implant-associated infections moving forward. Furthermore, advances in realtime in vivo imaging modalities (e.g., positron emission tomography (PET), fluorescence) and radioactive tracers and probes offer the potential to monitor the efficacy of antimicrobial orthopedic materials and progression of infection and inflammation noninvasively.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

et al. 2021

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While orthopedic implant-associated infections are rare, revision surgeries resulting from infections incur considerable healthcare costs and represent a substantial research area clinically, in academia, and in industry. In recent years, there have been numerous advances in the development of antimicrobial strategies for the prevention and treatment of orthopedic implant-associated infections which offer promise to improve the limitations of existing delivery systems through local and controlled release of antimicrobial agents. Prior to translation to in vivo orthopedic implant-associated infection models, the properties (e.g., degradation, antimicrobial activity, biocompatibility) of the antimicrobial materials can be evaluated in subcutaneous implant in vivo models. The antimicrobial materials are then incorporated into in vivo implant models to evaluate the efficacy of using the material to prevent or treat implant-associated infections. Recent technological advances such as 3D-printing, bacterial genomic sequencing, and real-time in vivo imaging of infection and inflammation have contributed to the development of preclinical implant-associated infection models that more effectively recapitulate the clinical presentation of infections and improve the evaluation of antimicrobial materials. This Review highlights the advantages and limitations of antimicrobial materials used in conjunction with orthopedic implants for the prevention and treatment of orthopedic implant-associated infections and discusses how these materials are evaluated in preclinical in vivo models. This analysis serves as a resource for biomaterial researchers in the selection of an appropriate orthopedic implant-associated infection preclinical model to evaluate novel antimicrobial materials.

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Development of an innovative in vivo model of PJI treated with DAIR

Poilvache

Bambeke²

2022

Front. Med.

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IntroductionProsthetic Joint Infection (PJI) are catastrophic complications of joint replacement. Debridement, implant retention, and antibiotic therapy (DAIR) is the usual strategy in acute infections but fails in 45% of MRSA infections. We describe the development of a model of infected arthroplasty in rabbits, treated with debridement and a course of vancomycin with clinically relevant dosage.Materials and methodsA total of 15 rabbits were assigned to three groups: vancomycin pharmacokinetics (A), infection (B), and DAIR (C). All groups received a tibial arthroplasty using a Ti-6Al-4V implant. Groups B and C were infected per-operatively with a 5.5 log10 MRSA inoculum. After 1 week, groups C infected knees were surgically debrided. Groups A and C received 1 week of vancomycin. Pharmacokinetic profiles were obtained in group A following 1st and 5th injections. Animals were euthanized 2 weeks after the arthroplasty. Implants and tissue samples were processed for bacterial counts and histology.ResultsAverage vancomycin AUC0–12 h were 213.0 mg*h/L (1st injection) and 207.8 mg*h/L (5th injection), reaching clinical targets. All inoculated animals were infected. CFUs were reproducible in groups B. A sharp decrease in CFU was observed in groups C. Serum markers and leukocytes counts increased significantly in infected groups.ConclusionWe developed a reproducible rabbit model of PJI treated with DAIR, using vancomycin at clinically relevant concentrations.

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Experimental reproduction of periprosthetic joint infection: Developing a representative animal model

Cited by 5 publications

References 21 publications

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

Development of an innovative in vivo model of PJI treated with DAIR

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