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Maher Saleh, Sophie Lefevre, Tristan Bourcier, Gilles Prevost, David Gaucher, Claude Speeg-schatz, Francois Jehl; Effects Of Intravitreal Injection Of Daptomycin In An Experimental Rabbit Model Of Staphylococcus Aureus Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6202.
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To evaluate the effects of intravitreal daptomycin in an experimental rabbit model of Staphylococcus aureus endophthalmitis.
Right eyes of 28 rabbits weighing 3 to 4kg were used. Five hundred colony-forming units (CFU) of S. aureus, diluted in 0.1 ml of a saline solution, were inoculated into the vitreous cavity. Eyes were randomly assigned to one of the three treatment groups of 8, equally. Twenty-four hours after the inoculation of S. aureus, group 1 received 0.2 mg of daptomycin (DAP 0.2 group) and group 2 received 1mg (DAP 1 group). Group 3 received 1mg of vancomycin (VAN 1 group), while group 4 (n=4) served as a control group receiving a sterile saline solution in place of the antibiotic. Clinical examination (score of Nussenblatt) was performed daily. Vitreous aspirates were obtained 1, 3, 5, and 8 days after the bacterial inoculation for microbiological analysis. Vitreal concentrations of daptomycin were measured by high performance liquid chromatography. Animals were humanely killed at day 8 before being enucleated for histopathological examination. Statistical analysis was performed using Kruskal-Wallis tests.
At day 5, 62.5% of the infected eyes in the DAP 0.2 group were sterilized, against 87.5 % in the VAN 1 group. All eyes in the DAP 1 group were sterilized. Bacterial counts (log10 CFU/mL) were 6.82 ± 1.0, 1.59 ± 1.66, 2.16 ± 1.74, 1.0 ± 0.0 in the BSS, VAN 1, DAP 0.2 and DAP 1 groups, respectively (p < 0.001). Daptomycin vitreal elimination half-times were 30 and 39 hours in the DAP 0.2 and DAP 1 groups, respectively. The ratios area underthe concentration-time-curve for 0-24 h and maximum peak concentration (Cmax) reached 19 and 20 mgh/L. The 1 mg daptomycin dose was superior to other regimens in limiting ocular inflammation and preserving the ocular structures.
Intravitreal injection of 1mg of daptomycin was effective in treating S. aureus endophthalmitis. Further studies in humans are needed to confirm these results and to determine the toxicity of daptomycin to ocular structures.
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