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Successful therapy of experimental chronic foreign-body infection due to methicillin-resistant Staphylococcus aureus
C Chuard1, M Herrmann, P Vaudaux
1Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
Abstract:
We compared the efficacy of a long-duration (3-week) therapy of vancomycin, fleroxacin, fleroxacin plus rifampin, and vancomycin plus fleroxacin and rifampin in a recently developed rat model of chronic staphylococcal foreign-body infection. Subcutaneous tissue cages containing polymethylmethacrylate coverslips were infected with 1 x 10(5) to 5 x 10(5) CFU of methicillin-resistant Staphylococcus aureus. Three weeks later, a quantitative culturing of the fluid that had accumulated in the cages was done (mean, 6.72 log10 CFU/ml; n = 110) and treatment was initiated after randomization. The CFUs in the cage fluid were counted on days 11 and 22 and 1 week after the termination of treatment; in addition, a final culture of coverslips (surface-bound microorganisms) was performed. The three-drug therapy was significantly superior to the other treatments on day 11 (a 5.16 log10 decrease of bacterial counts versus a 2.12 log10 to 2.94 log10 decrease for vancomycin, fleroxacin, and fleroxacin plus rifampin; P less than 0.01). On day 22, count decreases were 4.16 log10 for vancomycin, 4.91 log10 for fleroxacin (vancomycin versus fleroxacin, not significant), 6.14 log10 for two-drug therapy, and 6.34 log10 for three-drug therapy (vancomycin-fleroxacin-rifampin versus fleroxacin-rifampin, not significant; fleroxacin-rifampin versus monotherapies, P less than 0.01); the numbers of CFU in most cage fluids were under the detection limit (20 CFU/ml) in combination groups. One week after the end of treatment, 92% of fluids and coverslips (detection limit, 1 CFU) were culture negative with tritherapy, 88% of fluids and 41% of coverslips were negative with bitherapy, and less than 12% of fluids and coverslips were negative with single drugs (for coverslips, P was <0.01 for vancomycin-fleroxacin-rifampin versus fleroxacin-rifampin and P was <0.001 for fleroxacin-rifampin versus the monotherapies). No mutants resistant to rifampin or fleroxacin were detected. In conclusion, antimicrobial combinations were highly effective and superior to single drugs in treating a chronic staphylococcal foreign-body infection for 3 weeks. The three-drug therapy decreased bacterial counts more rapidly than the two-drug therapy under study and appeared to be curative in most cases.
Insights
Combination antibiotic therapy, including a three-drug regimen, proved highly effective against chronic staphylococcal foreign-body infections in rats, significantly outperforming single-drug treatments.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Chronic foreign-body infections caused by Staphylococcus aureus are challenging to treat.
- Developing effective antimicrobial strategies for these persistent infections is crucial.
Purpose of the Study:
- To compare the efficacy of various antibiotic regimens in a rat model of chronic staphylococcal foreign-body infection.
- To evaluate long-duration (3-week) therapies including vancomycin, fleroxacin, and rifampin, alone and in combination.
Main Methods:
- A rat model was established using subcutaneous tissue cages infected with methicillin-resistant Staphylococcus aureus.
- Quantitative culturing was performed on cage fluid and coverslips before and after treatment.
- Antibiotic treatments included vancomycin, fleroxacin, fleroxacin plus rifampin, and vancomycin plus fleroxacin and rifampin for 3 weeks.
Main Results:
- The three-drug therapy (vancomycin-fleroxacin-rifampin) demonstrated superior efficacy by day 11, achieving greater bacterial count reduction.
- By day 22 and one week post-treatment, combination therapies, especially the three-drug regimen, resulted in culture-negative fluids and coverslips in a high percentage of cases.
- No resistance to fleroxacin or rifampin emerged during the study.
Conclusions:
- Antimicrobial combinations are significantly more effective than single-drug therapies for chronic staphylococcal foreign-body infections.
- The three-drug therapy showed rapid bacterial reduction and appeared curative in most instances.
- This study highlights the potential of combination antibiotic therapy for persistent staphylococcal infections.