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Effect of ketorolac on Pseudomonas aeruginosa ocular infection in rabbits
E B Fraser-Smith1, T R Matthews
1Syntex Research, Department of Antimicrobial Research, Palo Alto, California.
Abstract:
Corticosteroids can exacerbate bacterial ocular infections, even in the presence of antibiotics. Ketorolac tromethamine is a new non-steroidal compound being considered as an anti-inflammatory ophthalmic drug. In this study, rabbits ocularly infected with Pseudomonas aeruginosa were treated topically with 0.4 percent tobramycin sulfate 4 times daily for 7 days to control infection. At the same times, either 0.5 percent ketorolac, 0.1 percent dexamethasone or vehicle was also given topically. Animals were scored for severity of both conjunctivitis (maximum severity rates score of 10) and corneal opacity (maximum of 4) using the Draize scale. Severity of the infection was determined by counting the number of punctate lesions which developed on the cornea. Nine days after treatment ended, the number of these lesions was the same for ketorolac as for the vehicle (respectively, 16.7 +/- 3 and 13.8 +/- 3, mean +/- SE, n = 24), indicating no exacerbation of the infection, whereas with dexamethasone these parameters increased (30.2 +/- 4, n = 24). During treatment, ketorolac reduced conjunctivitis (1.8 +/- 0.2, n = 120) when compared with the vehicle (2.9 +/- 0.2, n = 120), whereas dexamethasone did not (3.8 +/- 0.2, n V 120); neither ketorolac nor dexamethasone reduced corneal opacity (respectively, 2.3 +/- 0.05 and 2.6 +/- 0.1, n = 24) compared with vehicle (2.2 +/- 0.05, n = 24). After treatment, both conjunctivitis and corneal opacity became more severe only in dexamethasone treated eyes (respectively, 4.4 +/- 0.2, n = 120 and 3.0 +/- 0.02, n = 24). Thus, ketorolac appears to be an anti-inflammatory agent that does not worsen bacterial ocular infection.
Insights
Ketorolac tromethamine, a non-steroidal anti-inflammatory drug, did not worsen Pseudomonas aeruginosa ocular infections in rabbits, unlike dexamethasone. This suggests ketorolac is a safe anti-inflammatory for bacterial eye infections.
Area of Science:
- Ophthalmology
- Microbiology
- Pharmacology
Background:
- Corticosteroids can worsen bacterial ocular infections despite antibiotic treatment.
- Non-steroidal anti-inflammatory drugs (NSAIDs) offer an alternative for managing ocular inflammation.
Purpose of the Study:
- To evaluate the effect of ketorolac tromethamine on bacterial ocular infections.
- To compare the efficacy of ketorolac tromethamine with dexamethasone and vehicle in a rabbit model of Pseudomonas aeruginosa keratitis.
Main Methods:
- Rabbits with Pseudomonas aeruginosa ocular infections were treated with tobramycin sulfate to control infection.
- Topical ketorolac tromethamine, dexamethasone, or vehicle was administered concurrently.
- Conjunctivitis and corneal opacity were scored using the Draize scale; corneal lesions were counted to assess infection severity.
Main Results:
- Ketorolac tromethamine did not exacerbate Pseudomonas aeruginosa ocular infections, with lesion counts similar to the vehicle group post-treatment.
- Dexamethasone treatment led to a significant increase in corneal lesions, indicating exacerbation of the infection.
- Ketorolac tromethamine reduced conjunctivitis severity during treatment compared to the vehicle, while dexamethasone did not offer significant improvement and worsened inflammation post-treatment.
Conclusions:
- Ketorolac tromethamine demonstrates anti-inflammatory properties in bacterial ocular infections without worsening the infection.
- Unlike corticosteroids, ketorolac tromethamine appears to be a safe alternative for managing inflammation in bacterial eye infections.