Intravitreal daptomycin: a safety and efficacy study

• Published in: Retina (Philadelphia, Pa.) Vol. 31; no. 6; pp. 1199 - 1206
• Main Authors: Comer, Grant M, Miller, John B, Schneider, Eric W, Khan, Naheed W, Reed, David M, Elner, Victor M, Zacks, David N
• Format: Journal Article
• Language: English
• Published: United States 01-06-2011
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - toxicity; Cataract - chemically induced; Daptomycin - administration & dosage; Daptomycin - toxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Electroretinography - drug effects; Endophthalmitis - drug therapy; Endophthalmitis - microbiology; Eye Infections, Bacterial - drug therapy; Eye Infections, Bacterial - microbiology; Intravitreal Injections; Male; Rabbits; Retina - drug effects; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus epidermidis - drug effects; Treatment Outcome; Vancomycin Resistance
• ISSN: 0275-004X; 1539-2864
• DOI: 10.1097/IAE.0b013e318207d1b9

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.
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.
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.
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.