Efficacy of sparfloxacin and autoradiographic diffusion pattern of [14C]Sparfloxacin in experimental Staphylococcus aureus joint prosthesis infection
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A C Crémieux1, A S Mghir, R Bleton
1Hôpital Bichat-Claude-Bernard, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Abstract:
Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously, twice a day). A partial knee replacement was performed with a silicone implant fitted into the intramedullary canal of the tibia, and 5 x 10(7) CFU of methicillin-susceptible S. aureus was injected into the knee. The 7-day treatment regimen was started 15 days later. The MICs and MBCs of sparfloxacin and pefloxacin were, respectively, 0.06 and 0.25 microgram/ml (MIC) and 0.25 and 1 microgram/ml (MBC). The peak levels of sparfloxacin and pefloxacin in serum were 3.6 and 21 micrograms/ml, respectively. Three weeks after the end of treatment, animals were sacrificed and tibias were removed, pulverized, and quantitatively cultured. In contrast to pefloxacin (3.61 +/- 1.64 log10 CFU/g of bone), sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log10 CFU/g of bone) (P = 0.01) in comparison with the level in controls (4.59 +/- 1.21 log10 CFU/g of bone), without selection of resistant variants. Sparfloxacin was significantly more effective than pefloxacin (P = 0.025). The autoradiographic pattern of [14C]sparfloxacin diffusion was studied in noninfected animals with prostheses and in infected animals 15 days after inoculation. Sixty minutes after completion of infusion of 250 microCi of [14C]sparfloxacin, in infected animals the highest levels of radioactivity were detected around the prosthesis, in femoral cartilage, and in articular ligaments. Radioactivity was slightly less intense in bone marrow and muscles and was very weak in compact bone. The distribution of sparfloxacin in uninfected rabbits was similar. Thus, sparfloxacin may represent a valid alternative therapy in these infections provided that it is carefully monitored for potential side effects.
Insights
Sparfloxacin significantly reduced bacterial density in a rabbit model of Staphylococcus aureus knee prosthesis infection compared to pefloxacin. This fluoroquinolone demonstrated superior efficacy without selecting for resistant strains, suggesting it as a potential therapeutic option.
Area of Science:
- Infectious Diseases
- Pharmacology
- Orthopedic Surgery
Background:
- Prosthetic joint infections caused by Staphylococcus aureus are challenging to treat.
- Antibiotic resistance is a growing concern in managing these infections.
- Evaluating novel therapeutic strategies is crucial for improving patient outcomes.
Purpose of the Study:
- To compare the efficacy of sparfloxacin and pefloxacin in a rabbit model of methicillin-susceptible Staphylococcus aureus (MSSA) knee prosthesis infection.
- To assess the distribution and penetration of sparfloxacin in infected joint tissues.
- To evaluate the potential for resistance development during treatment.
Main Methods:
- A rabbit model was established involving knee prosthesis implantation and subsequent MSSA inoculation.
- Animals were treated with either sparfloxacin or pefloxacin subcutaneously for 7 days, starting 15 days post-infection.
- Bacterial density in bone was quantified post-treatment, and [14C]sparfloxacin distribution was studied using autoradiography.
Main Results:
- Sparfloxacin significantly reduced bacterial density in bone compared to pefloxacin and controls (P = 0.01).
- Sparfloxacin demonstrated superior efficacy over pefloxacin (P = 0.025) without selecting for resistant variants.
- [14C]sparfloxacin showed good distribution around the prosthesis and in surrounding tissues, including cartilage and ligaments.
Conclusions:
- Sparfloxacin is significantly more effective than pefloxacin in treating MSSA knee prosthesis infections in this rabbit model.
- Sparfloxacin exhibits favorable tissue distribution, reaching the site of infection.
- Sparfloxacin may be a viable therapeutic alternative for such infections, warranting careful monitoring for adverse effects.