The In Vitro Evaluation of Tigecycline and the In Vivo Evaluation of RPX-978 (0.5% Tigecycline) as an 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.

In vitro comparison of combination and monotherapy for the empiric and optimal coverage of bacterial keratitis based on incidence of infection.

PURPOSE: Cefazolin/tobramycin, cefuroxime/gentamicin, and moxifloxacin were compared using bacterial keratitis isolates to determine whether empiric therapy constituted optimal antibacterial treatment. METHODS: Based on percent incidence of corneal infection, 27 Staphylococcus aureus, 16 Pseudomonas aeruginosa, 10 Serratia marcescens, 4 Moraxella lacunata, 3 Haemophilus influenzae, 9 coagulase-negative staphylococci, 7 Streptococcus viridans, 6 Streptococcus pneumoniae, 7 assorted Gram-positive isolates, and 11 assorted Gram-negative isolates were tested for minimum inhibitory concentrations to cefazolin, tobramycin, cefuroxime, gentamicin, and moxifloxacin using E-tests to determine susceptibility and potency. RESULTS: The in vitro coverage (susceptible to at least one antibiotic) of cefuroxime/gentamicin (97%) was statistically equal to cefazolin/tobramycin (93%) and moxifloxacin (92%) (P = 0.29). Double coverage (susceptible to both antibiotics) was equivalent (P = 0.77) for cefuroxime/gentamicin (42%) and cefazolin/tobramycin (40%). The susceptibilities of individual coverage were moxifloxacin (92%), gentamicin (89%), tobramycin (74%), cefazolin (58%), and cefuroxime (52%). Methicillin-resistant S. aureus was best covered by gentamicin 100% (9 of 9). Tobramycin was more potent (P = 0.00001) than gentamicin for P. aeruginosa, whereas cefazolin was more potent (P = 0.0004) than cefuroxime for S. aureus. CONCLUSIONS: Although there seems to be no in vitro empiric coverage advantage between cefazolin/tobramycin, cefuroxime/gentamicin, and moxifloxacin monotherapy, potency differences may occur and optimal treatment can best be determined with laboratory studies.