Abstract

The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI) animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials.

Highlights

  • Among the early and late complications of medical implants, implant-associated infection (IAI) is one of the most serious that is associated with a high morbidity [1]

  • A frequency of 1% to 12% has been reported for methicillin resistant S. aureus (MRSA) nasal colonization [5], which is associated with a four-fold increased risk of infection [6]

  • The biofilm matrix can be composed of polysaccharide intercellular adhesin (PIA), the production of which is mediated by the ica-locus encoded enzymes, of fibronectin-binding proteins, other large proteins and extracellular DNA [12,13,14]

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Summary

Introduction

Among the early and late complications of medical implants, implant-associated infection (IAI) is one of the most serious that is associated with a high morbidity [1]. The biofilm matrix can be composed of polysaccharide intercellular adhesin (PIA), the production of which is mediated by the ica-locus encoded enzymes, of fibronectin-binding proteins, other large proteins and extracellular DNA [12,13,14] The expression of those components is governed by four major transcriptional regulators, which are the quorum sensing systems agr and luxS, as well as sarA and the stress sigma factor σB. The emergence of resistant bacteria (i.e., MRSA, vancomycin resistant S. aureus and methicillin resistant S. epidermidis) creates additional challenges, as resistance is associated with a poorer response to therapy. Despite proven efficacy of some antibiotics against adherent and metabolically inactive bacteria, antimicrobial therapy of biofilm-mediated infections alone is unsuccessful probably due to the magnitude of the formed biofilm. Depending on the question to study, different foreign body infection models can be used

General Aspects of the Subcutaneous Catheter Model
Catheter Infection Model in the Mouse
Technique
Assessment of the Host Response in the Catheter Infection Model
Assessment of Biofilm Formed by Pseudomonas aeruginosa
Tissue Cage Model in Different Animal Species
Assessment of Virulence of Bacterial Species
Assessment of Host Defense in the Tissue Cage
Assessment of Antibiotic Resistance in Vivo
Cytotoxicity of New Antimicrobial Compounds against Host Cells
Properties of Different Tissue Cage Materials
Orthopaedic Implant Infection Models
Disadvantages of Subcutaneous Animal Foreign Body Models
Findings
Conclusions
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