Vitreal Penetration of Topical, Oral, and Combined Dosing of Moxifloxacin in Humans

Abstract

Purpose: : To investigate the penetration of moxifloxacin, a fourth–generation fluoroquinolone antibiotic, into the vitreous humor after oral, topical, and combined administration.

Methods: : A prospective, non–randomized study of 24 consecutive patients scheduled for pars plana vitrectomy between October 2004 and June 2005 at the Medical College of Georgia and Southeast Retina Center. Patients were assigned to one of four dosing groups: Control (n =3), which received no medication; Oral (n = 8), which received a 400 mg oral dose of moxifloxacin approximately 14 hours before surgery and a second 400 mg dose 3 hours before surgery; Topical (n = 8), which received one drop of 0.5% topical moxifloxacin every 15 minutes for the hour preceding surgery (5 drops total); and Combined (n = 5), which received a 400 mg oral dose approximately 14 hours before surgery, a second oral dose 3 hours before surgery, and one drop of 0.5% topical moxifloxacin every hour for 18 hours prior to surgery (total of 19 drops). Vitreous samples were obtained from all 24 patients and analyzed using high–performance liquid chromatography.

Results: : Mean ± SD moxifloxacin concentrations in vitreous samples were below quantifiable levels (BQL) for the Control group; 1.553 ± 0.33 µg/mL for the Oral group; 0.027 µg/mL for the Topical group; and 2.219 ± 0.71 µg/mL for the Combined group. Seven of the 8 Topical patients had undetectable levels and 1 Topical patient developed post–operative endophthalmitis. Concentrations in the Oral and Combined groups exceeded the minimum inhibitory concentrations (MIC₉₀) of many common endophthalmitogenic bacteria.

Conclusions: : Orally–administered moxifloxacin achieves significant levels in the non–inflamed human vitreous. Topical moxifloxacin given during the immediate pre–operative period does not achieve significant vitreous levels while prolonged, frequent pre–operative administration may. Given its high tolerability, broad spectrum of coverage, and low MIC₉₀ levels for organisms of concern, moxifloxacin may play a role in the prophylaxis or treatment of bacterial endophthalmitis.

Keywords: endophthalmitis • vitreous • vitreoretinal surgery