The antibacterial activity of levofloxacin eye drops against staphylococci using an invitro 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 invitro 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, 0.125μg/mL]. LVFX-resistant strains were obtained from parental strains after culture with LVFX. The invitro 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 8h) to rabbit eyes. Parental and LVFX-resistant strains were exposed to LVFX in the invitro PK model, and changes in viable bacterial counts were evaluated for 12h. The MICs of LVFX for the resistant isolates were 2-32 times higher than the parental strain, and those with MICs ≥2ug/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 4μg/mL, respectively, whereas 0.5% LVFX would only be effective against strains with MICs of 0.125-1μg/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.