PURPOSE: 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. TOLERABILITY: Six uninfected rabbits were topically treated in both eyes with 0.5% tigecycline, vehicle, or saline every 15 min for 3 h. EFFICACY: 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. TOLERABILITY: 0.5% tigecycline was graded as minimally irritating. EFFICACY: 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.
PURPOSE: 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. TOLERABILITY: Six uninfected rabbits were topically treated in both eyes with 0.5% tigecycline, vehicle, or saline every 15 min for 3 h. EFFICACY: 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. TOLERABILITY: 0.5% tigecycline was graded as minimally irritating. EFFICACY: 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: Samuel K Bouchillon; Daryl J Hoban; Brian M Johnson; Tim M Stevens; Michael J Dowzicky; David H Wu; Patricia A Bradford Journal: Diagn Microbiol Infect Dis Date: 2005-04 Impact factor: 2.803
Authors: Eric G Romanowski; Francis S Mah; Kathleen A Yates; Regis P Kowalski; Y Jerold Gordon Journal: Am J Ophthalmol Date: 2005-05 Impact factor: 5.258
Authors: Daryl J Hoban; Samuel K Bouchillon; Brian M Johnson; Jack L Johnson; Michael J Dowzicky Journal: Diagn Microbiol Infect Dis Date: 2005-07 Impact factor: 2.803
Authors: Eric G Romanowski; Francis S Mah; Regis P Kowalski; Kathleen A Yates; Y Jerold Gordon Journal: J Ocul Pharmacol Ther Date: 2008-08 Impact factor: 2.671