Intravitreal daptomycin: a safety and efficacy study

Retina. 2011 Jun;31(6):1199-206. doi: 10.1097/IAE.0b013e318207d1b9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Anti-Bacterial Agents
  • Daptomycin