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Russell Tait, Richard Prankerd, Roy Robins-browne, Penelope Allen, Andrew Donohue, Dong Yang, Louise Adams, Feng Wang, Asha D'Souza, Sarah Ng; Efficacy of an Intravitreal Levofloxacin Implant in an Animal Model of Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1727.
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Bacterial endophthalmitis is a devastating ocular infection with poor visual outcome. Intravitreal injection of a bolus dose of antibiotic(s) is the preferred method of treatment. Unfortunately, a single intravitreal injection is often insufficient to treat the infection. Use of an intravitreal implant that releases an antibiotic at the appropriate dose for a sustained period may obviate the need for retreatment. We used a rabbit model of endophthalmitis to compare the efficacy of standard treatment (bolus vancomycin/ceftazidime) with a levofloxacin(LVX)-releasing implant.
Experiments were performed according to the method described by Ferrer et al. Br J Ophthalmol 2008;92:678-682. The study evaluated treatment with a LVX implant (nominally releases LVX at 100 μg per 24 h) compared with standard treatment of a bolus injection of 1% (w/v) vancomycin + 2.2% (w/v) ceftazidime, and an untreated control group. The vitreous of one eye of a New Zealand White rabbit was inoculated with S. aureus ATCC strain 29213. Treatment was administered 1 day after innoculation. On days 1, 3, 7, 10 and 14, samples of vitreous were collected for determination of the number of colony-forming units (CFUs) of S. aureus per ml and the level of LVX. The Peyman classification was used to assess the severity of endophthalmitis.
The LVX implant exhibits zero-order release of LVX over at least 30 days, regardless of geometry. LVX concentrations in vitreous matched steady-state levels predicted from pharmacokinetic calculations based on the in vitro release rate, and were well above the MIC for S. aureus for at least a 10-day period. Infection was established in all inoculated eyes. By day 3, CFUs in the vitreous of all treated eyes had fallen to below detection limits. In contrast, CFUs in the vitreous from untreated eyes increased dramatically such that by day 3 symptoms had worsened and rabbit euthanasia was required. For the implant group, mild inflammation was observed on day 3, and by day 7, symptoms of endophthalmitis had subsided. Peyman scores for the implant group were similar to or better than rabbits in the standard treatment group.
In a rabbit model of endophthalmitis the LVX implant was at least as effective as the current standard therapy of vancomycin/ceftazidime for treating infections of the vitreous cavity caused by S. aureus.
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