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3H-spiramycin penetration into fibrin vegetations in an experimental model of streptococcal endocarditis
A C Cremieux1, J M Vallois, B Maziere
1Unité 13 INSERM, Hôpital Claude Bernard, Paris, France.
Abstract:
In-vivo diffusion of labelled spiramycin into fibrin was investigated in a rabbit model of left sided subacute endocarditis caused by a nutritionally variant streptococcus that produces large fibrin vegetations. Animals received one 30 min infusion of different doses of 3H spiramycin alone (73.4 +/- 3.5 microCi and 846 microCi) or 57.5 +/- 3.5 microCi in combination with 50 mg/kg 'cold' spiramycin. Thirty minutes after the end of infusion (T30) these vegetation/blood and vegetation/muscle ratios were between 1 and 2 and the vegetation/plasma ratio was between 2 and 4 for the three doses tested. Autoradiography showed that 3H spiramycin was homogeneously distributed throughout the vegetation in comparison with some other drugs. On the other hand, there were considerable differences in antibiotic concentration among different vegetations in a single animal.
Insights
This study examined spiramycin diffusion into fibrin vegetations in rabbits with endocarditis. Spiramycin distributed homogeneously within vegetations, showing promising antibiotic penetration for treating this infection.
Area of Science:
- Pharmacology
- Infectious Diseases
- Veterinary Medicine
Background:
- Subacute bacterial endocarditis, particularly with nutritionally variant streptococci, presents challenges due to large fibrin vegetations.
- Understanding antibiotic diffusion into these vegetations is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the in-vivo diffusion of radiolabeled spiramycin into fibrin vegetations in a rabbit model of endocarditis.
- To assess the distribution and concentration of spiramycin within vegetations relative to blood, muscle, and plasma.
Main Methods:
- A rabbit model of left-sided subacute endocarditis was established using a nutritionally variant streptococcus.
- Animals received intravenous infusions of either 3H-labeled spiramycin alone or in combination with unlabeled spiramycin.
- Vegetation, blood, muscle, and plasma concentrations of 3H-spiramycin were measured at 30 minutes post-infusion using techniques including autoradiography.
Main Results:
- Vegetation/blood and vegetation/muscle concentration ratios ranged from 1 to 2, while vegetation/plasma ratios were between 2 and 4.
- Autoradiography revealed homogeneous distribution of 3H-spiramycin throughout the vegetations.
- Significant variability in antibiotic concentration was observed among different vegetations within the same animal.
Conclusions:
- Spiramycin demonstrates homogeneous diffusion into fibrin vegetations in this endocarditis model.
- The drug achieves favorable concentration ratios in vegetations compared to surrounding tissues and plasma.
- Variability in vegetation drug concentration warrants further investigation for optimizing therapeutic outcomes.