In vivo toxicity of netilmicin and ofloxacin on intact and mechanically damaged eyes of rabbit.

PURPOSE: To evaluate the in vivo toxicity of netilmicin and ofloxacin using both normal and mechanically damaged eyes of rabbit. METHODS: Male albino New Zealand rabbits were given either 0.3% netilmicin, 0.3% ofloxacin, or 0.9% sodium chloride solution by topical instillation (50 microL) into the conjunctival sac 6 times daily for 5 days. In some animals a 6-mm-diameter epithelial wound was mechanically made to the center of the cornea. Ocular toxicity on normal eyes was evaluated by impression cytology of the conjunctiva, histology of the entire globes, and scanning electron microscopy (SEM) of the cornea. Analysis of toxicity and reepithelialization on wounded corneas was evaluated by SEM with observations being made 48 and 72 hours after induction of the wound. RESULTS: Cytologic, histopathologic, and SEM analyses of normal healthy eyes following netilmicin treatment revealed no signs of toxicity, whereas those treated with ofloxacin revealed alterations in the cornea (stromal swelling) and conjunctiva (infiltration of polymorphonuclear cells) with reduced goblet cell numbers. Wounded corneas treated with netilmicin exhibited normal morphology and reepithelialization, whereas the administration of ofloxacin resulted in disordered cellular organisation and slower rates of epithelial recovery. CONCLUSIONS: Netilmicin, an antibacterial aminoglycoside, is well tolerated even in an experimental wound-healing model where the integrity of the ocular surface is compromised, whereas ofloxacin, a fluoroquinolone, appears to provoke an inflammatory response in the normal eye and a clear alteration of reepithelialization in the wounded eye. These findings suggest that netilmicin may offer a superior toxicological profile in both normal eyes and clinical situations where the integrity of the ocular epithelium is suspect.

Effects on adhesiveness and hydrophobicity of sub-inhibitory concentrations of netilmicin.

The effect of sub-inhibitory concentrations (SICs) of netilmicin on bacterial hydrophobicity and adhesiveness to conjunctival cells was investigated. One strain each of Pseudomonas aeruginosa, Pseudomonas spp., Staphylococcus aureus and S. epidermidis was investigated for its susceptibility to netilmicin, its adherence to conjunctival cells and to the effect of hydrocarbon hexadecane before and after treatment with SIC of netilmicin. All of the bacteria tested were susceptible to netilmicin except for Pseudomonas spp. which showed intermediate resistance. Netilmicin-treated Pseudomonas strains exhibited a lower level of hydrophobicity towards n-hexadecane compared with non-treated strains, while netilmicin-treated S. epidermidis and S. aureus showed a slight increase of hydrophobicity. Adherence of the two Pseudomonas strains to conjunctival cells was significantly reduced after growth in the presence of netilmicin, while the adherence of the two staphylococci was only slightly reduced.

In vitro toxicity of netilmicin and ofloxacin on corneal epithelial cells.

PURPOSE: To evaluate the in vitro cytotoxic effect of the aminoglycoside antibiotic netilmicin on rabbit corneal epithelial cells (SIRC) compared with ofloxacin, a commonly used fluoroquinolone ocular antibiotic. METHODS: SIRC cell cultures were incubated for 8 to 72 h in the presence and absence of netilmicin (1.5, 3, and 6 mg/mL) and equal concentrations of ofloxacin. Cell viability in treated and untreated SIRC cells was measured by both neutral red and MTT colorimetric assays at 8, 24, and 72 h, whereas changes in cell morphology were examined at 8, 24, 48, and 72 hours by the use of phase-contrast microscopy. RESULTS: Netilmicin, at all tested concentrations, failed to alter SIRC cell viability or morphology. In contrast, all concentrations of ofloxacin caused statistically significant dose- and time-dependent reductions in cell viability even after 8 h. After 72 h there was complete loss of cell viability. Morphologic examination of SIRC cells after 8 h of incubation with ofloxacin revealed that the fluoroquinolone antibiotic, at all concentrations, produced large numbers of dead cells, compromised intercellular contacts, and altered general morphology. After 48 h the cell monolayer was observed to be completely destroyed. CONCLUSION: Netilmicin, at the concentrations used, is an antibiotic devoid of obvious cellular toxicity and may also be considered as a suitable first-choice drug in the treatment of those pathologies that compromise the integrity of the ocular surface.

Treatment of acute bacterial conjunctivitis with topical netilmicin.

PURPOSE: This study compares the clinical and microbiologic value of topical netilmicin with that of gentamicin in the treatment of acute bacterial conjunctivitis. METHODS: A double-blind, randomized, prospective, controlled study was performed in 209 patients. One to two drop(s) of either antibiotic was applied to the affected eye(s) four times a day for up to 10 days. Patients were examined at the time of diagnosis and after 3, 5, and 10 days. Clinical efficacy was measured as the cumulative sum score (CSS) of the key signs and symptoms of acute bacterial ocular infection. Sensitivity/resistance was evaluated using the disk diffusion method. RESULTS: Drug efficacy assessment was restricted only to patients with positive baseline culture results (n = 121). Of the isolated organisms, 96.9% were sensitive to netilmicin, whereas only 75.0% were sensitive to gentamicin (p = 0.00001). Netilmicin provided a broad-spectrum coverage comparable with that of ciprofloxacin, ofloxacin, and norfloxacin. Netilmicin also was more effective than gentamicin in eradicating infections (p = 0.001 at day 5 and p = 0.037 at day 10) and in ameliorating the CSS (p = 0.037 at day 3, p = 0.001 at both day 5 and day 10). Only minor adverse events occurred in patients treated with either netilmicin or gentamicin. CONCLUSIONS: This study demonstrates that netilmicin is a safe and effective antibiotic that can be used as first-line therapy for the treatment of acute bacterial conjunctivitis.

Residence time of netilmicin in tears.

PURPOSE: To determine the concentration of netilmicin in tears after eye drop administration. METHODS: A clinical study was carried out on 32 healthy volunteers. Subjects were divided into four groups and underwent tear collection at 5, 10, 20, and 60-minutes after drug administration, respectively. Tear samples were collected through capillary suction from the inferior conjunctival "cul-de-sac" and analyzed by high-pressure liquid chromatography (HPLC). RESULTS: Netilmicin concentration in tears decreased after a first order kinetics, a best-fit curve was drawn and the minimum inhibitory concentration (MIC90) intersection for the most common ocular pathogens was calculated. CONCLUSIONS: The extrapolation of the curve shows that the concentration of netilmicin on the ocular surface can be effective against microorganisms more than 120 minutes after eye drop instillation.