Systemic prophylaxis of experimental staphylococcal endophthalmitis: comparative efficacy of sparfloxacin, pefloxacin, imipenem, vancomycin, and amikacin.

The preventive efficacy of several antibiotics in experimental staphylococcal endophthalmitis was evaluated. Two hours before bilateral intravitreal infection with 500 cfu of Staphylococcus aureus, 18 pigmented phakic rabbits were assigned to receive a single intramuscular injection of sparfloxacin (50 mg/kg), pefloxacin (50 mg/kg), imipenem (50 mg/kg), vancomycin (30 mg/kg), amikacin (15 mg/kg), or saline and were killed 24 h after infection (6 eyes/group). Sparfloxacin, pefloxacin, and imipenem were significantly (P < .001) more effective than saline. All but 1 of the sparfloxacin-treated eyes were culture negative. To determine whether the effect persisted, an additional 24 rabbits were treated with sparfloxacin, pefloxacin, imipenem, or saline and were killed 48 h after infection (12 eyes/group). Sparfloxacin, pefloxacin, and imipenem were effective (P < .001). All sparfloxacin-treated eyes remained culture negative. These results show that systemic antibiotic administration prevents the development of experimental endophthalmitis and that further studies of sparfloxacin as a prophylactic agent are warranted.

Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits.

Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1.6, 8, or 16 mg in 0.2 ml) in the right eyes of eight rabbits was evaluated by clinical and histopathological examination. The 0.8-mg dose of pefloxacin was well tolerated. The kinetics was evaluated after a single subconjunctival injection of 0.8 mg in 18 rabbits. Animals were sacrificed at 1, 3, 5, 7, 12, or 18 h postinjection. Drug concentrations were measured by high-performance liquid chromatography. Pefloxacin was found in the cornea (maximum concentration, 18.13 micrograms/ml; half-life, 3.92 h) and in the aqueous humor (maximum concentration, 3.40 micrograms/ml; half-life, 2.14 h). Pefloxacin did not penetrate into the vitreous humor by this route. The efficacy was evaluated in an experimental model of staphylococcal corneal ulcers in eight rabbits which received two subconjunctival injections of 0.8 mg of pefloxacin at 16 and 24 h after intrastromal inoculation. The results (expressed as mean log10 CFU per milliliter +/- standard deviation) showed that pefloxacin significantly (P < 0.001) reduced the bacterial counts (4.39 +/- 0.97) compared with those in control eyes (6.46 +/- 0.69). For phakic eyes, subconjunctival pefloxacin might be of value for the treatment of corneal ulcers. Further studies are required to determine its penetration into the vitreous humor of aphakic eyes.

Kinetics and tolerability of intravitreal pefloxacin in rabbits.

In the treatment of patients with bacterial endophthalmitis, the intravitreal administration of antibiotics is suitable for induction therapy since it provides immediate high concentrations in the vitreous humor. Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend the potential routes of administration of this agent, we have assessed the kinetics and toxicity of pefloxacin in rabbit phakic eyes following intravitreal instillation. Kinetic parameters were determined for 12 albino and 12 pigmented rabbits after a single injection of 80 micrograms. Pefloxacin was undetectable in the aqueous humor but high concentrations were found in the chorioretina. The vitreal half-life was short (3 h). These results were consistent with posterior elimination via the chorioretina. Pefloxacin concentrations in the iris and chorioretina of pigmented rabbits were two-fold greater than those in albino rabbits, probably because of binding to the pigmentary apparatus. Toxicity studies, including ophthalmological and histopathological investigations, identified a maximum non-toxic dosage of 400 micrograms. Intravitreal pefloxacin may therefore be suitable for induction therapy in patients with endophthalmitis, although further studies in primates are required to confirm the efficacy and tolerability of this route of administration.

Efficacy and ocular penetration of sparfloxacin in experimental streptococcal endophthalmitis.

Gram-positive cocci are the most common pathogens in severe human eye infections. Streptococcal endophthalmitis is a devastating infection, and intravitreal antibiotic therapy is limited by retinal toxicity. Because few systemic antistreptococcal antibiotics penetrate into the vitreous, sparfloxacin, a newer quinolone with improved antistreptococcal activity, might be of interest. We therefore assessed its efficacy by the intravitreal route in a rabbit model of streptococcal endophthalmitis. The vitreal bacterial count (mean +/- standard deviation log10 CFU per milliliter) was significantly reduced after an intravitreal injection of 800 micrograms of sprafloxacin (4.9 +/- 0.7) relative to the counts in untreated control (7.1 +/- 0.7) and pefloxacin-treated (7.8 +/- 1.2) eyes. After systemic administration to rabbits, the maximum concentration of sparfloxacin in serum was 5.6 micrograms.ml-1 and the half-life was 7.5 h. Sparfloxacin exhibited very good penetration ratios in the vitreous (54%), cornea (76%), and lens (36%). In the vitreous, the levels of sparfloxacin remained greater than the MICs for most gram-positive cocci for up to 18 h. Further experimental studies are warranted to determine the efficacy of systemic sparfloxacin as adjuvant therapy in the treatment of human endophthalmitis.