title: The antibacterial activity of levofloxacin eye drops against staphylococci using an in vitro pharmacokinetic model in the bulbar conjunctiva.
abstract: The incidence of fluoroquinolone-resistant staphylococcal isolates from the conjunctival sac is increasing. We compared pharmacological effects of levofloxacin (LVFX) against Staphylococcus epidermidis using an in vitro pharmacokinetic (PK) model simulating the concentration in the bulbar conjunctiva after applying eye drops of 0.5% and 1.5% LVFX. We used S. epidermidis conjunctival sac isolates [minimum inhibitory concentrations (MICs) of LVFX, 0.125 μg/mL]. LVFX-resistant strains were obtained from parental strains after culture with LVFX. The in vitro PK model simulated the concentration in the bulbar conjunctiva following three topical applications of 0.5% or 1.5% LVFX ophthalmic solution (0, 4, and 8 h) to rabbit eyes. Parental and LVFX-resistant strains were exposed to LVFX in the in vitro PK model, and changes in viable bacterial counts were evaluated for 12 h. The MICs of LVFX for the resistant isolates were 2-32 times higher than the parental strain, and those with MICs ≥2 ug/mL had mutations in the quinolone resistance-determining region. The PK model simulation predicts that 1.5% LVFX exerts bactericidal and bacteriostatic effects against strains with MICs of 0.125-2 and 4 μg/mL, respectively, whereas 0.5% LVFX would only be effective against strains with MICs of 0.125-1 μg/mL. The PK model predicts that the 1.5% LVFX ophthalmic solution exhibits a stronger bactericidal effect against resistant staphylococci in the bulbar conjunctiva than the 0.5% LVFX ophthalmic solution.
authors.affiliation: Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. Electronic address: t-suzuki@m.ehime-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003228:Conjunctiva / Q000378:metabolism*; D003234:Conjunctivitis, Bacterial / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D064704:Levofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus; D013212:Staphylococcus epidermidis
chemical_list: D000900:Anti-Bacterial Agents; D009883:Ophthalmic Solutions; D064704:Levofloxacin
keywords: Conjunctiva; Levofloxacin; Pharmacokinetic model; Staphylococcus epidermidis