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Intravitreal daptomycin: a safety and efficacy study
Grant M Comer1, John B Miller, Eric W Schneider
1Retina Service, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
Purpose:
To determine the ocular toxicity of intravitreally injected daptomycin, a novel antibiotic for treatment of vancomycin-resistant organisms, and its efficacy in treating intraocular infection with coagulase-negative Staphylococcus epidermidis.
Methods:
Four doses of intravitreal daptomycin were injected (75, 188, 375, and 750 μg) into 1 eye of Dutch belted rabbits (n = 3 per dose). Clinical examination, electroretinography, and histologic analysis were performed preinjection and 2 weeks after injection and compared with the fellow eye that received only intravitreal balanced salt solution. Experimental S epidermidis endophthalmitis was induced in Dutch belted rabbits (n = 24), and the ability of 200 μg of intravitreal daptomycin to result in culture-negative vitreous samples was measured at 24 hours and 48 hours.
Results:
Seventy-five micrograms and 188 μg of daptomycin demonstrated acceptable safety profiles when injected intravitreally in Dutch belted rabbits. There was a dose-dependent increase in cataract formation, electroretinogram suppression, and photoreceptor damage with higher doses. Two hundred micrograms of intravitreal daptomycin resulted in near-complete vitreous sterilization 24 hours after treatment. Vitreous sterilization was complete by 48 hours.
Conclusion:
A dose of 200 μg of intravitreal daptomycin appears to be safe and efficacious in a rabbit model of bacterial endophthalmitis. Future investigations should focus on daptomycin as a therapeutic option for treating intraocular infection caused by vancomycin-resistant organisms.
Insights
Intravitreal daptomycin at 200 μg is safe and effective for bacterial endophthalmitis in rabbits. This antibiotic shows promise for treating infections caused by vancomycin-resistant organisms.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Pharmacology
Background:
- Vancomycin-resistant organisms pose a significant challenge in treating bacterial endophthalmitis.
- Daptomycin is a lipopeptide antibiotic effective against Gram-positive bacteria, including resistant strains.
Purpose of the Study:
- To evaluate the ocular toxicity of intravitreal daptomycin.
- To assess the efficacy of intravitreal daptomycin in treating experimental bacterial endophthalmitis caused by Staphylococcus epidermidis.
Main Methods:
- Dutch belted rabbits received varying doses of intravitreal daptomycin (75-750 μg) to assess toxicity via clinical examination, electroretinography, and histology.
- Experimental endophthalmitis was induced, and the efficacy of 200 μg intravitreal daptomycin was measured by vitreous bacterial cultures at 24 and 48 hours.
Main Results:
- Doses of 75 μg and 188 μg of intravitreal daptomycin showed acceptable safety profiles.
- Higher doses led to dose-dependent cataract formation, electroretinogram suppression, and photoreceptor damage.
- 200 μg of intravitreal daptomycin achieved near-complete vitreous sterilization within 24 hours, and complete sterilization by 48 hours.
Conclusions:
- Intravitreal daptomycin at a 200 μg dose is safe and effective in a rabbit model of bacterial endophthalmitis.
- Daptomycin warrants further investigation as a treatment for intraocular infections, particularly those caused by vancomycin-resistant bacteria.
