Vitreous and aqueous penetration of orally administered gatifloxacin in humans

Objective: To investigate the penetration of gatifloxacin, a novel extended-spectrum fourth-generation fluoroquinolone antibiotic, into the vitreous and aqueous humor after oral administration. Methods: A prospective, nonrandomized study of 24 consecutive patients scheduled for pars plana vitrectomy between September 2001 and May 2002 at the Cullen Eye Institute. Aqueous, vitreous, and serum samples were obtained and analyzed from 24 patients after administration of two 400-mg gatifloxacin tablets taken 12 hours apart before the operation. Assays were performed using high-performance liquid chromatography. Results: Mean±SD gatifloxacin concentrations in serum (n = 23), vitreous (n = 23), and aqueous (n = 11) were 5.14±1.36 μg/mL, 1.34±0.34 μg/mL, and 1.08±0.54 μg/mL respectively. Mean±SD sampling times after oral administration of the second gatifloxacin tablet for serum, vitreous, and aqueous were 3.2±1.0 hours, 4.0±1.0 hours, and 3.9±1.1 hours, respectively. The percentages of serum gatifloxacin concentration achieved in the vitreous and aqueous were 26.17% and 21.02%, respectively. Mean inhibitory vitreous and aqueous MIC₉₀ levels were achieved against many pathogens, including Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, Escherichia coli, Bacillus cereus, Proteus mirabilis, and other organisms. Conclusions: Orally administered gatifloxacin achieves therapeutic levels in the noninflamed human eye, and the activity spectrum appropriately encompass the bacterial species most frequently involved in the various causes of endophthalmitis. Because of its broad-spectrum coverage, low MIC₉₀ levels for the organisms of concern, and good tolerability, gatifloxacin represents a major advance in the prophylaxis or treatment of postoperative, posttraumatic, and bleb-associated bacterial endophthalmitis.