Penetration of topical and oral ofloxacin into the aqueous and vitreous humor of inflamed rabbit eyes☆,☆☆
Introduction
Endophthalmitis is one of the most serious complications of intraocular procedures and penetrating ocular trauma. Although intravitreal antibiotics are the most important component of therapy in eradicating endophthalmitis, intravenous broad-spectrum antibiotics are commonly given to patients with penetrating ocular trauma to prevent post-traumatic endophthalmitis and are be used also as an adjunct to intravitreal antibiotics (Monk and Campoli-Richards, 1987, Osato et al., 1989, Todd and Faulds, 1991, Davis, 1996). Recent studies have shown that penetrating eye trauma and inflammation affects the ocular pharmacokinetics of certain antibiotics given intravenously, resulting in higher concentrations in traumatized (Alfaro et al., 1996) and inflamed eyes (Martin et al., 1990, Mounier et al., 1992, Meredith et al., 1995).
Ofloxacin is a fluorinated 4-quinolone antibiotic and is active against a wide spectrum of gram-positive and gram-negative organisms including various species of Staphylococcus, Streptococcus, and Pseudomonas (Auckenthaler et al., 1986, Osato et al., 1989, Todd and Faulds, 1991). It is among the fluoroquinolones considered promising for the treatment of ocular infections and shows nearly 100% bioavailability after oral administration (Monk and Campoli-Richards, 1987, Todd and Faulds, 1991). It was reported that ofloxacin penetrates the corneal and the blood-aqueous barriers and can achieve therapeutic aqueous humor levels above the minimum inhibitory concentration for many bacteria cultured in endophthalmitis in both topical and systemic administrations (Von Gunten et al., 1994, Donnenfeld et al., 1997). But higher concentrations of the antibiotic are required to inhibit Streptococcus pneumonia and Pseudomonas aeruginosa (Auckenthaler et al., 1986, Osato et al., 1989, Todd and Faulds, 1991).
Although there are several studies related to the penetration of ofloxacin into aqueous humor after topical or systemic administration (Yokota et al., 1986, Giamarellou et al., 1993, Von Gunten et al., 1994, Verbraeken et al., 1996, Başcı et al., 1997, Donnenfeld et al., 1997, Fiscella et al., 1997, Çekiç et al., 1998, Öztürk et al., 1999a), reports on penetration of systemic ofloxacin into aqueous humor and vitreous humor in inflamed eyes are limited (Mounier et al., 1992, Gatti and Panozzo, 1995, Öztürk et al., 1999a). Furthermore there are no data on penetration of topical or topical and systemic administration of ofloxacin in inflamed eyes. The purpose of the present study was to determine the aqueous and vitreous humors ofloxacin concentrations following topical instillation and oral medication in normal and inflamed eyes, and to compare the intraocular ofloxacin concentrations provided by two routes together and topical route alone.
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Materials and methods
A total of 16 mixed-gender New Zealand white rabbits weighing between 2 and 3 kg were used in accordance with the ARVO Resolution on the Use of Animals in Research. The rabbits were anaesthetised with intramuscular injection of a 50/50 mixture of xylazine hydrochloride (10 mg/kg) and ketamine hydrochloride (30 mg/kg). To further reduce discomfort, the eyes were anaesthetised using one to two drops of a oxybuprocaine (Benoxinate®, Thilo). A standardized posterior penetrating ocular trauma was
Results
The mean concentrations of ofloxacin in the aqueous and vitreous humor are listed in Table 1. The aqueous levels of ofloxacin were above the 90% minimum inhibitory concentrations (MIC90) for most of the common microorganisms causing endophthalmitis in all eyes but the vitreous levels only in the inflamed eyes of the rabbits treated both topically and orally.
In the intact eyes, oral ofloxacin supplementation increased both the aqueous and vitreous levels of ofloxacin. In the inflamed eyes, drug
Discussion
Broad-spectrum, intravenous antibiotics are commonly suggested and administered as an adjunct to intravitreal antibiotics for treatment of endophthalmitis and for prophylaxis in penetrating ocular injuries (Martin et al., 1990, Meredith et al., 1995, Alfaro et al., 1996, Davis, 1996). The combination of systemic ofloxacin and topical ofloxacin was proposed as a single-drug therapy with broad-spectrum coverage for penetrating injury, surgical prophylaxis, and, possibly, the treatment of
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2016, Progress in Retinal and Eye ResearchCitation Excerpt :In 1987, Parrish and O'Day recommended systemic antibiotic prophylaxis for the treatment of traumatic endophthalmitis even though “…we are unaware of any experimental evidence that supports the efficacy of systemic antibiotics in prophylaxis of endophthalmitis….” Some antibiotics have been shown experimentally to reach therapeutic concentrations in the vitreous of rabbits in the model of penetrating eye trauma: intravenous cefazolin (Alfaro et al., 1992), intravenous ciprofloxacin (Alfaro et al., 1996b), combined topical and oral ciprofloxacin (Ozturk et al., 1999), combined topical and oral ofloxacin (Ozturk et al., 2000), and intravenous imipenem (Engelbert et al., 2003). Although some antibiotics do reach therapeutic concentrations in the vitreous, it is a widely held opinion that the use of systemic antibiotics alone is not an effective strategy for the treatment of exogenous or endogenous bacterial endophthalmitis.
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Presented at the First Combined International Symposium on Ocular Immunology and Inflammation, Amsterdam, The Netherlands, June 27–July 1, 1998
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Proprietary interest: none