Topical fluoroquinolones: Antimicrobial activity andin vitrocorneal epithelial toxicity

Abstract

To assess the potential of fluoroquinolones as topical antimicrobial agents, we evaluated in vitro the antimicrobial activity of five fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, and temafloxacin), as well as gentamicin, tobramycin, and cefazolin against 96 isolates of common bacterial corneal pathogens. Ciprofloxacin and temafloxacin were the most active quinolones [minimal inhibitory concentration inhibiting 90% of stains (MIC90) of 1 microgram/ml], followed by ofloxacin (MIC90 2 micrograms/ml), and norfloxacin and pefloxacin (MIC90s 4 micrograms/ml). In contrast, gentamicin and tobramycin MIC90s were 32 and 64 micrograms/ml, respectively; cefazolin MIC90 was greater than 2048 micrograms/ml. The corneal epithelial cytotoxicity of the fluoroquinolones also was evaluated utilizing an in vitro assay of 3H-thymidine uptake of rabbit corneal epithelial cell cultures. The least to greatest toxicity of the fluoroquinolones were as follows: ciprofloxacin and temafloxacin less than norfloxacin less than ofloxacin less than pefloxacin. Our study suggests that the fluoroquinolones, especially ciprofloxacin and temafloxacin, possess excellent in vitro activity against common bacterial corneal pathogens and are less toxic to the corneal epithelium than the aminoglycosides.

Effect of Ofloxacin and Netilmicin on Human Corneal and Conjunctival CellsIn Vitro

“…Therefore only 2 reports are available up to date describing a real corneal toxicity for gentamicin (but not for tobramycin) (7,12). On the other hand the data on quinolones are more consistent indicating in similar experimental models a relative high corneal toxicity (7,9,10,21). To address this debate, we tested one quinolone and one aminoglycoside in two different cell models originating from humans: the immortalized HCE-T corneal epithelial cells (27,28,30) and the continuous Wong-Kilbourne derived conjunctival cells (17,18).…”

“…It is interesting to note that other studies indicating an aminoglycoside cytotoxicity have to be carefully considered because they have been performed with very high antibiotic concentrations (.10 mg/mL) (6,8,13), or using commercial eye drops containing preservatives (11,(14)(15) whose negative influence on the cell integrity is well known (16)(17)(18)(19)(20). More consistent data are available for quinolones, indicating a relative high corneal toxicity (7,9,10,21).…”

Antibacterial Activity of Contact Lenses Bearing Surface-Immobilized Layers of Intact Liposomes Loaded With Levofloxacin

“…12,[14][15][16] However, this regimen not only is disruptive to the patient and usually necessitates hospitalization, but it has also been associated with in vitro toxicity to the corneal epithelium. 17,18 Efforts are now directed to testing new antimicrobials that better permeate the cornea and to developing delivery systems capable of prolonging the contact time between antibiotics and the corneal tissue, thereby potentially enhancing intra-corneal delivery of ophthalmic medication.…”

Quinolones: a class of antimicrobial agents

“…Topical administration to the eye shows less toxicity to the corneal epithelium than aminoglycosides (Cutarelli et al, 1991). However, ocular cataracts have been seen with prolonged use in humans (Neu, 1988).…”