Effectiveness of topical taurolidine versus ciprofloxacin, ofloxacin, and fortified cefazolin in a rabbit Staphylococcus aureus keratitis model.

PURPOSE: Taurolidine is a broad-spectrum, non antibiotic antimicrobial agent, not previously tested against the common causes of bacterial keratitis. This study, employing an experimental rabbit model of Staphylococcus aureus keratitis, investigated the effectiveness of topical taurolidine in reducing the number of bacteria, and its effectiveness was compared with topical ciprofloxacin, ofloxacin, and 5% cefazolin. METHODS: The right corneas of all rabbits were intrastromally injected with 100 colony-forming units of Staphylococcus aureus ATCC strain 25923. The animals were divided into the following seven groups: Group 1 (6 rabbits) received taurolidine, group 2 (6 rabbits) received ciprofloxacin, group 3 (6 rabbits) received ofloxacin, group 4 (6 rabbits)received cefazolin, group 5 (5 rabbits) received polyvinylpyrrolidone (vehicle),group 6 (4 rabbits) received sterile water, and group 7 (4 rabbits) was left un-treated (control group). The eyes were topically treated every 30 min with the above-mentioned substances from 4 to 9 h postinjection. One hour after the last drop administration (at 10 h postinjection), signs of inflammation were scored in a masked fashion by slit-lamp examination. Then, their corneas were processed. The number of colony-forming units (cfu) per cornea in all eyes was also determined. RESULTS: All antimicrobial (taurolidine, ciprofloxacin, ofloxacin, and cefazolin) treatments significantly reduced cfu numbers and slit-lamp examination scores compared with untreated eyes, eyes that received the vehicle, or eyes with sterile water (all p values <0.05). Regarding cfu numbers, although taurolidine therapy was significantly less effective than ciprofloxacin or ofloxacin,there was no significant difference between taurolidine and cefazolin groups.However, taurolidine had similar clinical examination scores with the other antimicrobials, while it had lower scores than the vehicle, sterile water, or un-treated eyes. CONCLUSIONS: The results obtained in this study suggest that topicaltaurolidine is an effective, novel ocular chemotherapeutic agent for the therapy of rabbit experimental Staphylococcus aureus keratitis. This drug may be a useful and promising ocular antimicrobial.

Intravitreal taurolidine against experimental Staphylococcus epidermidis endophthalmitis in rabbits.

PURPOSE: Taurolidine is a broad spectrum, non-antibiotic antimicrobial agent, not previously tested against infectious endophthalmitis. The efficacy of intravitreal taurolidine in the treatment of experimental Staphylococcus epidermidis endophthalmitis was evaluated and compared with vancomycin in a rabbit model. METHODS: The right eyes of 34 albino rabbits were infected with an intravitreal inoculum of S. epidermidis (10(5) colony-forming units/0.1 ml). The right eyes of four rabbits (group 7) were not infected and served as uninfected controls. 24 hours after inoculation of bacteria the animals were divided into the following treatment groups: group 1 (7 rabbits) received intravitreal taurolidine at 24 hours and group 2 (7 rabbits) received at 48 hours. Group 3 (7 rabbits) received vancomycin at 24 hours and group 4 (7 rabbits) at 48 hours. Group 5 (3 rabbits) received polyvinylpyrrolidone at 24 hours and group 6 (3 rabbits) at 48 hours. Clinical scoring was performed at 24, 48 and 72 hours. At 72 hours post inoculation, vitreous samples were collected for quantitative microbiological studies and then, the eyes were enucleated for histopathological scorings. RESULTS: The clinical and histopathological examinations revealed significant amelioration of inflammation in eyes treated with taurolidine and vancomycin when compared with polyvinylpyrrolidone. The eyes treated with taurolidine also had significantly lower colony forming units than the eyes treated with polyvinylpyrrolidone and taurolidine rendered many eyes sterile. CONCLUSION: Taurolidine is expected to be a potential agent for treatment of S. epidermidis endophthalmitis.

A study on the toxicity of intravitreal levofloxacin in rabbits.

PURPOSE: To investigate the retinal toxicity of different doses of intravitreal injections of levofloxacin in a rabbit model, which is the levorotatory component of ofloxacin and approximately twice as potent as ofloxacin and highly active in vitro against gram-positive and -negative bacteria, and anaerobic bacteria including many ocular pathogens. METHODS: Sixteen albino rabbits were used in this study, and divided four groups. Levofloxacin in doses of 50, 100, 250 and 500 microg was injected into the midvitreous of rabbit's left eyes. The other eye served as a control and received normal saline solution. Indirect ophthalmoscopy, electroretinography (ERG) and light microscopy were used for retinal toxicity of levofloxacin. ERGs were recorded before injection and at 1(st) day, 1(st), 2(nd) and 4(th) weeks. At the end of follow-up period, the rabbits were killed and the eyes were enucleated for histologic evaluation. RESULTS: Intravitreal injections of 50, 100, 250 and 500 microg levofloxacin did not cause any deterioration of the a-wave, b-wave or oscillatory potentials of ERG throughout the follow-up period of 4 weeks. No evidence of retinal toxicity was observed by indirect ophthalmoscopy and light microscopy in any case. CONCLUSIONS: In therapeutic doses of 500 microg or less, intravitreal levofloxacin does not have retinal toxicity in rabbit eyes and this dose was well above the MIC(90) values of ocular pathogens that cause endophthalmitis. If future studies in other species confirm our findings, intravitreal levofloxacin may be a potentially important drug in the treatment and prevention of clinical bacterial endophthalmitis.