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A simple infection model using pre-colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis
M Monzón1, F García-Alvarez, A Laclériga
1CSIC-SIA, Department of Animal Health, Zaragoza, Spain.
Abstract:
Staphylococcus aureus biofilms formed on medical implants represent a serious problem, being difficult to eradicate with antibiotic therapy and leading to chronic infections. Simplified in vivo and in vitro antibiotic susceptibility assays using biofilm bacteria are needed. In this work, a novel chronic osteomyelitis infection model was developed in rats in the absence of bacterial suspension, requiring the use of only 10(6) bacteria in biofilms at the site of surgery, with a full success in reproducing infection. Stainless-steel implants pre-colonized for 12 h with a highly adherent S. aureaus isolate were introduced into the rat tibiae. In animals not submitted to antibiotic treatment, infection was found in the implants and spread to bone in all cases, indicating the high efficacy of the model to reproduce osteomyelitis. The effect of a 21-day treatment with cefuroxime, vancomycin, tobramycin or ciprofloxacin on infection was studied in this model 42 days after surgery. Bone colonization was inhibited by vancomycin and cefuroxime. Cefuroxime (the most efficient antibiotic, able to sterilize 1 out of 8 implants) reduced the number of bacteria in biofilms adhered to implants at a higher extent than vancomycin, trobramycin and ciprofloxacin. Analogous observations were made in this work in vivo and in vitro on the relative antibiotic efficacy against S. aureus biofilm bacteria. suggesting the usefulness of both tests as a potential tool to study antibiotic suceptibility, and the need for new antimicrobials against these bacteria.
Insights
Developing new treatments for Staphylococcus aureus implant infections is crucial. This study presents a novel rat model for testing antibiotic effectiveness against these challenging biofilms, showing cefuroxime and vancomycin inhibit bone colonization.
Area of Science:
- Infectious Diseases
- Biomedical Engineering
- Pharmacology
Background:
- Staphylococcus aureus biofilms on medical implants cause persistent infections, resistant to antibiotics.
- Effective antibiotic susceptibility testing for biofilm bacteria is lacking.
- Chronic osteomyelitis requires innovative infection models for research.
Purpose of the Study:
- To develop a novel, simplified in vivo rat model for chronic osteomyelitis caused by Staphylococcus aureus biofilms.
- To evaluate the efficacy of common antibiotics against S. aureus biofilms in a clinically relevant setting.
- To compare in vivo and in vitro antibiotic susceptibility of biofilm bacteria.
Main Methods:
- A chronic osteomyelitis model was created in rats using pre-colonized stainless-steel implants.
- Surgical site infection was established with 10^6 S. aureus biofilm bacteria.
- Antibiotic treatment (cefuroxime, vancomycin, tobramycin, ciprofloxacin) was administered for 21 days, with infection assessed 42 days post-surgery.
Main Results:
- The model successfully reproduced osteomyelitis in untreated animals.
- Vancomycin and cefuroxime inhibited bone colonization by S. aureus.
- Cefuroxime demonstrated the highest efficacy, reducing biofilm bacteria and sterilizing one implant.
Conclusions:
- The developed rat model is effective for studying osteomyelitis and evaluating antibiotic treatments against S. aureus biofilms.
- In vivo and in vitro antibiotic efficacy against S. aureus biofilms showed analogous results.
- New antimicrobial strategies are urgently needed to combat antibiotic-resistant S. aureus biofilms on implants.