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Treatment of experimental foreign body infection caused by methicillin-resistant Staphylococcus aureus
J C Lucet1, M Herrmann, P Rohner
1Department of Medicine, Geneva University Hospital, Switzerland.
Abstract:
A novel model of experimental foreign body infection was developed in rats: four perforated Teflon tissue cages per animal were implanted subcutaneously and 3 to 4 weeks later were infected with 0.5 x 10(5) to 2 x 10(5) CFU of methicillin-resistant Staphylococcus aureus. After 2 weeks, the number of CFU in the cage fluid was determined [day 1 mean, (7.25 +/- 0.79) log10 CFU/ml], and treatment with vancomycin (50 mg/kg twice a day [BID]), fleroxacin (50 mg/kg BID), or fifampin (25 mg/kg BID), alone and in combination, was initiated for a duration of 6 days. Concentrations of antibiotics in cage fluids were in the range of those encountered in clinical conditions. Eighteen hours after the last injection (day 7), the number of CFU in the cage fluid was determined and the difference between day 1 and day 7 values was calculated. Rifampin, alone and in combination with fleroxacin or vancomycin, was the most effective regimen in reducing the bacterial counts in the tissue cage fluids [(1.87 +/- 1.44, 2.18 +/- 1.02, and 2.55 +/- 1.09 log10) CFU/ml, P less than 0.001, respectively]. After treatment, cage fluids and cages were analyzed for resistant bacteria. Resistance to rifampin occurred in 15 of 19 cages in animals treated with rifampin alone and in 4 of 25 in animals treated with rifampin plus vancomycin. We detected no development of resistance to rifampin in animals treated with rifampin plus fleroxacin or to fleroxacin in animals treated with this antimicrobial agent. In conclusion, regimens including rifampin alone or in combination with vancomycin or fleroxacin were an effective treatment of foreign body infection due to methicillin-resistant S. aureus in reducing bacteria counts, but rifampin monotherapy was compromised by significant emergence of resistance. The combined therapy of fleroxacin with rifampin prevent development of resistance to rifampin.
Insights
This study developed a rat model for foreign body infection. Combined therapy with fleroxacin and rifampin effectively reduced methicillin-resistant Staphylococcus aureus counts and prevented resistance development.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Foreign body infections pose significant clinical challenges.
- Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen in these infections.
- Novel therapeutic strategies are needed to combat MRSA foreign body infections.
Purpose of the Study:
- To evaluate the efficacy of vancomycin, fleroxacin, and rifampin, alone and in combination, against MRSA foreign body infections in a rat model.
- To assess the development of antibiotic resistance during treatment.
Main Methods:
- A novel rat model using Teflon tissue cages infected with MRSA was established.
- Antibiotic treatments (vancomycin, fleroxacin, rifampin) were administered for 6 days.
- Bacterial counts and antibiotic resistance were analyzed in cage fluids and cages post-treatment.
Main Results:
- Rifampin, alone and in combination with fleroxacin or vancomycin, significantly reduced MRSA bacterial counts.
- Rifampin monotherapy led to a high emergence of resistance (15/19 cages).
- Combined therapy with fleroxacin and rifampin prevented resistance development to either agent.
Conclusions:
- Regimens including rifampin effectively reduced MRSA foreign body infections.
- Rifampin monotherapy is limited by rapid resistance development.
- Combination therapy, particularly fleroxacin with rifampin, offers a promising strategy to prevent resistance and treat MRSA foreign body infections.