Does PGE₁ vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model

PLoS One. 2014 Apr 9;9(4):e94758. doi: 10.1371/journal.pone.0094758. eCollection 2014.

Abstract

Background: Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated.

Methodology: A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses.

Results: The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment.

Conclusions: The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprostadil / pharmacology
  • Alprostadil / therapeutic use*
  • Animals
  • Bacterial Load / drug effects
  • Body Weight
  • Bone Density / drug effects
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / microbiology
  • Bone and Bones / pathology
  • Bone and Bones / physiopathology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications*
  • Disease Models, Animal
  • Female
  • Joints / pathology
  • Joints / physiopathology
  • Mice, Inbred NOD
  • Orthopedics*
  • Prosthesis-Related Infections / blood
  • Prosthesis-Related Infections / complications
  • Prosthesis-Related Infections / drug therapy*
  • Prosthesis-Related Infections / prevention & control*
  • Staphylococcus aureus / physiology
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*
  • X-Ray Microtomography

Substances

  • Vasodilator Agents
  • Alprostadil

Grants and funding

The entire work was funded by the Italian Ministry of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.