title: Intravitreal daptomycin: a safety and efficacy study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Retina Service, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Comer
authors.forename: John B
authors.initials: JB
authors.lastname: Miller
authors.forename: Eric W
authors.initials: EW
authors.lastname: Schneider
authors.forename: Naheed W
authors.initials: NW
authors.lastname: Khan
authors.forename: David M
authors.initials: DM
authors.lastname: Reed
authors.forename: Victor M
authors.initials: VM
authors.lastname: Elner
authors.forename: David N
authors.initials: DN
authors.lastname: Zacks
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D002386:Cataract / Q000139:chemically induced; D017576:Daptomycin / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D058449:Intravitreal Injections; D008297:Male; D011817:Rabbits; D012160:Retina / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D016896:Treatment Outcome; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin