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Published on: April 6, 2022
Treatment of rabbit corneal infections with ophthalmic gatifloxacin: a concentration dependence study
Tomoyuki Wada1, Hiroaki Naka, Hideki Tokushige
1Senju Pharmaceutical Co., Ltd. Research Laboratories, Nishiku Kobe, Hyogo, Japan.
Abstract:
This study was designed to determine the most effective dose of gatifloxacin in ophthalmic solution for control of methicillin-resistant Staphylococcus aureus (MRSA) corneal infections in rabbits. Rabbits were inoculated by injecting 9300 colony-forming units of MRSA into the corneal stroma of the eye (n=43). They were then randomly assigned to topical administration of saline, ofloxacin 0.3%, or gatifloxacin 0.02%, 0.1%, 0.3%, or 0.5% ophthalmic solutions. Infection severity 48 hours postinoculation was assessed by masked observers using standard scales. After treatment completion, viable MRSA in corneal tissue were counted, and pathologic examinations of ocular tissues were conducted. Relative to saline, treatment with gatifloxacin 0.3% or 0.5% decreased mean infection scores at every time point from 16 to 48 hours after inoculation (P < or = .012) and reduced area-under-the-curve values for infection scores by 50.3% and 54.2%, respectively (P = .00005). Rabbits treated with gatifloxacin 0.3% and 0.5% had lower area-under-the-curve values than those treated with ofloxacin 0.3% (P < or = .039). Viable MRSA in corneal tissue after gatifloxacin 0.3% or 0.5% treatment were decreased to less than 1% of those found after ofloxacin 0.3% treatment. Gram-positive colony formation and abscesses found in saline-treated corneas were distinctly alleviated by treatment with gatifloxacin 0.3% or 0.5%. No significant differences were observed between treatments with gatifloxacin 0.3% or 0.5% ophthalmic formulations and they were equally effective. Topical administration of gatifloxacin 0.3% or 0.5% ophthalmic solutions controlled MRSA corneal infections in rabbits significantly better than saline or ofloxacin 0.3%.
Insights
Gatifloxacin ophthalmic solutions at 0.3% and 0.5% effectively controlled methicillin-resistant Staphylococcus aureus (MRSA) corneal infections in rabbits. These doses significantly outperformed saline and ofloxacin treatments in reducing infection severity and bacterial load.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Pharmacology
Background:
- Corneal infections caused by methicillin-resistant Staphylococcus aureus (MRSA) pose a significant clinical challenge.
- Effective topical antimicrobial agents are crucial for managing MRSA ocular infections.
Purpose of the Study:
- To determine the optimal dose of gatifloxacin ophthalmic solution for controlling MRSA-induced corneal infections in a rabbit model.
- To compare the efficacy of different gatifloxacin concentrations against ofloxacin and saline treatments.
Main Methods:
- Rabbits with induced MRSA corneal infections were treated with topical saline, ofloxacin 0.3%, or gatifloxacin 0.02%, 0.1%, 0.3%, or 0.5%.
- Infection severity was assessed using standard scales, and viable MRSA in corneal tissue was quantified post-treatment.
- Pathologic examinations of ocular tissues were performed to evaluate treatment effects.
Main Results:
- Gatifloxacin 0.3% and 0.5% significantly reduced mean infection scores and area-under-the-curve values compared to saline.
- Higher concentrations of gatifloxacin (0.3% and 0.5%) demonstrated superior efficacy over ofloxacin 0.3% in reducing infection severity.
- Gatifloxacin 0.3% and 0.5% treatments resulted in a decrease of viable MRSA in corneal tissue to less than 1% compared to ofloxacin treatment.
Conclusions:
- Topical gatifloxacin ophthalmic solutions at 0.3% and 0.5% are highly effective in controlling MRSA corneal infections in rabbits.
- Gatifloxacin 0.3% and 0.5% demonstrate superior efficacy compared to ofloxacin 0.3% and saline.
- Both 0.3% and 0.5% gatifloxacin ophthalmic formulations were equally effective, indicating a potential therapeutic range for MRSA corneal infections.
