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Topical imipenem therapy of aminoglycoside-resistant Pseudomonas keratitis in rabbits
M R Sawusch1, T P O'Brien, J Valentine
1Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21205.
Abstract:
We used a rabbit model of bacterial keratitis to assess in vivo efficacy of topical imipenem, a highly potent beta-lactam antibiotic with an unusually broad spectrum of activity, including aminoglycoside-resistant Pseudomonas aeruginosa. Albino rabbits received intrastromal injections of 5 x 10(2) organisms of an aminoglycoside-resistant strain of P. aeruginosa. At five hours postinoculation, imipenem (5 mg/ml) therapy was initiated using one drop per 30 minutes for 12 hours. Corneal tissue was then excised for colony forming unit counts. Imipenem was highly effective in reducing colony forming unit counts to zero in comparison to 4.1 x 10(5) organisms for untreated controls. A second regimen beginning 24 hours postinoculation of one drop per hour for 24 hours was also successful in significantly reducing colony forming units vs controls (P less than .05). These data suggest that topical imipenem may have clinical applicability in the treatment of P. aeruginosa keratitis.
Insights
Topical imipenem effectively treated bacterial keratitis in rabbits caused by resistant Pseudomonas aeruginosa. This broad-spectrum antibiotic significantly reduced bacterial counts, showing promise for treating P. aeruginosa eye infections.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Pharmacology
Background:
- Bacterial keratitis is a serious eye infection.
- Pseudomonas aeruginosa, particularly aminoglycoside-resistant strains, poses a significant treatment challenge.
- Topical antibiotics are crucial for managing ocular infections.
Purpose of the Study:
- To evaluate the in vivo efficacy of topical imipenem against bacterial keratitis.
- To assess the effectiveness of imipenem in a rabbit model infected with aminoglycoside-resistant P. aeruginosa.
Main Methods:
- A rabbit model of bacterial keratitis was established using P. aeruginosa.
- Topical imipenem (5 mg/ml) was administered at different frequencies post-inoculation.
- Corneal tissue was analyzed for colony-forming unit (CFU) counts to determine bacterial load.
Main Results:
- Imipenem therapy reduced corneal CFU counts to zero in treated rabbits.
- Untreated control rabbits had a mean of 4.1 x 10(5) organisms.
- Both treatment regimens (intensive and less frequent) significantly reduced bacterial load compared to controls.
Conclusions:
- Topical imipenem demonstrated high efficacy in clearing P. aeruginosa from infected corneas.
- The results suggest potential clinical utility of topical imipenem for treating P. aeruginosa keratitis.
- Imipenem's broad spectrum may be beneficial against resistant bacterial strains in ocular infections.