title: The In Vitro Evaluation of Tigecycline and the In Vivo Evaluation of RPX-978 (0.5% Tigecycline) as an Ocular Antibiotic.
abstract: OBJECTIVE
  The goals of the current study were to determine the in vitro antibacterial activity of tigecycline against multiple clinically relevant ocular pathogens and to evaluate the in vivo ocular tolerability and efficacy of 0.5% tigecycline in a methicillin-resistant Staphylococcus aureus (MRSA) keratitis model.
  
  
  METHODS
  In vitro: Minimum inhibitory concentrations (MICs) were determined for 110 clinical conjunctivitis isolates, 26 keratitis isolates of Pseudomonas aeruginosa, and 10 endophthalmitis isolates each of MRSA, methicillin-susceptible S. aureus (MSSA), MR, and MS coagulase-negative Staphylococcus.
  
  
  RESULTS
  Six uninfected rabbits were topically treated in both eyes with 0.5% tigecycline, vehicle, or saline every 15 min for 3 h.
  
  
  RESULTS
  Thirty-two rabbits were intrastromally injected with 700 Colony Forming Units (CFU) of MRSA in both eyes and were separated into 4 groups (n = 8): tigecycline 0.5%; vancomycin 5%; saline; and no treatment (euthanized before treatment for baseline CFU). Four hours after MRSA challenge, topical treatment of 1 drop every 15 min for 5 h was initiated. One hour after treatment, the corneas were harvested for CFU. The data were analyzed nonparametrically.
  
  
  RESULTS
  In vitro: Tigecycline demonstrated lower MICs than the other tested antibiotics against gram-positive organisms, especially MRSA, while MICs against gram-negative pathogens, including fluoroquinolone-resistant P. aeruginosa, appeared to be in the treatable range with aggressive topical therapy.
  
  
  RESULTS
  0.5% tigecycline was graded as minimally irritating.
  
  
  RESULTS
  0.5% tigecycline and vancomycin produced similar reductions in CFU and were less than saline (P < 0.05). Tigecycline and vancomycin demonstrated 99.9% reductions compared with baseline CFU.
  
  
  CONCLUSIONS
  Tigecycline is a potential candidate for a topical ocular antibiotic.
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Romanowski
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kowalski
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: O'Connor
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Yates
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Francis S
authors.initials: FS
authors.lastname: Mah
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
authors.affiliation: Department of Ophthalmology, The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh Medical Center and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Regis P
authors.initials: RP
authors.lastname: Kowalski
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D066298:In Vitro Techniques; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline