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 ,ug of sparfloxacin (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 I.g. ml-l 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.The prognosis for patients with bacterial endophthalmitis remains extremely poor. Irreversible eye damage, especially to the retina, occurs during the first few hours of infection.The causative pathogens are varied: gram-positive cocci are the most frequent (11), but gram-negative bacilli can also induce fulminant endophthalmitis. The vitreous is a key compartment, since the infection can develop within it, but neither systemic nor topical antibiotics penetrate into it. Direct intravitreal injections are thus used, but they cannot be repeated because of their retinal toxicity. There is still a need for systemic antibiotics with broad antibacterial spectra of activity and good intraocular penetration.New systemic quinolones like pefloxacin, ofloxacin, and ciprofloxacin have been shown to reach high levels in the aqueous and vitreous humors (4-6, 8, 15, 18, 20, 21), but their efficacies against streptococci are limited (7, 22, 23). Sparfloxacin and temafloxacin, even newer quinolones with enhanced antistreptococcal activity in vitro (1,2,7,22), may thus be of interest in this setting.In the present study, we used an experimental rabbit model of endophthalmitis to evaluate the antistreptococcal activities of sparfloxacin and pefloxacin following direct intravitreal injection into infected eyes. We then determined the full kinetics of sparfloxacin in the ocular humors and tissues when administered by the systemic route.MATERIALS AND METHODS Antistreptococcal efficacy. Eighteen healthy pigmented rabbits (Fauve de Bourgogne) were infected in the right eye by intravitreal inoculation with 106 CFU of Streptococcus sp. strain G, a strain for which the sparfloxacin MIC is 0.5 ,ug. ml-'. The animals were anesthetized by intramuscular injection of ketamine ...
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.
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