Efficacy and ocular penetration of sparfloxacin in experimental streptococcal endophthalmitis

Abstract

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 ...

Ciprofloxacin as Ocular Liposomal Hydrogel

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Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops

“…[1][2][3] Fluoroquinolones, as a group, have shown excellent activity against the most frequently occurring gram-positive and gram-negative ocular pathogens. [4][5][6][7][8][9] Fluoroquinolones have a unique mechanism of action: because of their strong affinity to the bacterial enzymes DNA gyrase and topoisomerase IV, they lethally interrupt bacterial replication. There appear to be fewer resistant bacterial strains against fluoroquinolones than against other antibacterials.…”

Intraocular Penetration of Orally and Intravenously Administered Fluoroquinolones in Non-Inflamed Eyes of the Patients Undergoing Vitrectomy Surgery

“…In our human study, single dose sparfloaxcin (400mg) reached vitreous humor levels of 0.71(0.05) g/ml at 12 hours after administration. Among the fluoroquinolones studied, sparfloxacin showed highest level of 0.71 g/ml at 12 hours after administration, which is above the MIC 90 of most common pathogens causing endophthalmitis in humans viz Streptococcus pyrogens, Streptococcus pneumoniae, Staphylococcus epidermidis and aureus [10]. However, this concentration may not be adequate to inhibit organisms like Pseudomonas aeuroginosa, Bacillus gragilis, Chlamydia difficile and atypical organisms like Chlamydia pneumonia etc.…”

“…Cochereau-Massin et al 1993 [10] evaluated the efficacy and ocular penetration of sparfloxacin in experimental Streptococcal endophthalmitis in rabbits. After systemic administration in rabbits, the maximum concentration of sparfloxacin in serum was 5.6 g/ml and the half-life was 7.5 hours.…”