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Keratotomy model of pseudomonas keratitis: gentamicin chemotherapy
E B Brockman1, P A Tarantino, J A Hobden
1LSU Eye Center, New Orleans 70112-2234.
Background:
Chemotherapy of bacterial keratitis requires frequent application of antibiotic drops. Collagen shields containing antibiotics could reduce the need for frequent antibiotic application. To determine the effect of gentamicin-containing collagen shields and gentamicin drops on Pseudomonas keratitis, a new keratotomy model of infection was employed.
Methods:
Model--contact lenses (58% water content) presoaked in 1% bovine serum albumin and exposed to 10(8) colony forming units per mL of Pseudomonas aeruginosa strain 27853, were found to reproducibly retain 5.9 (log base 10) colony-forming units. Rabbit corneas were scarified centrally with two perpendicular intersecting diamond knife cuts (5 mm x 5 mm x 0.2 mm), and bacteria-impregnated contact lenses were positioned and held in place for 24 hours with partial tarsorrhaphies. Treatment--Fourteen hours after lens removal (38 hours after infection), corneas were treated for 8 hours with collagen shields hydrated in saline (control), or shields impregnated with 800 micrograms gentamicin during manufacture, or one drop every 30 minutes of fortified gentamicin drops (14 mg/mL). The rabbits were killed and corneas collected for bacterial enumeration after 8 hours of treatment (46 hours after infection).
Results:
Model--Slit-lamp examination and microbiologic confirmation showed uniformity of keratitis in all eyes. Treatment--Corneas treated with saline (controls) contained 6.4 (log base 10) Pseudomonas. Corneas treated with gentamicin-impregnated collagen shields (total drug = 800 micrograms) and fortified gentamicin drops (total drug = 21 mg) showed a reduction in viable bacteria of 2 logs and 6 logs, respectively, relative to the control.
Conclusions:
In this new model of Pseudomonas keratitis, the amount of gentamicin introduced into collagen shields during manufacture effectively reduced bacterial growth in infected rabbit corneas. However, larger amounts of drug applied as fortified drops on a frequent dosing schedule were more effective by a factor of three. Treatment of keratitis with antibiotic-impregnated collagen shields may reduce the need for very frequent application of topical drops, but may be more effective with topical drop supplementation to increase the amount of drug available over the course of therapy.
Insights
Gentamicin-impregnated collagen shields effectively reduced Pseudomonas keratitis in rabbits. However, frequent fortified gentamicin drops were more effective, suggesting combination therapy may optimize treatment for bacterial keratitis.
Area of Science:
- Ophthalmology
- Microbiology
- Pharmacology
Background:
- Bacterial keratitis requires frequent antibiotic eye drops.
- Collagen shields offer a potential method to reduce application frequency.
- A novel keratotomy model was used to study Pseudomonas keratitis.
Purpose of the Study:
- To evaluate the efficacy of gentamicin-containing collagen shields and gentamicin drops.
- To compare these treatments against a control in a rabbit model of Pseudomonas keratitis.
Main Methods:
- A rabbit corneal model of Pseudomonas aeruginosa keratitis was established using impregnated contact lenses.
- Treatments included saline-hydrated collagen shields, gentamicin-impregnated collagen shields (800 µg), and frequent fortified gentamicin drops (14 mg/mL).
- Bacterial counts in corneas were enumerated after 8 hours of treatment.
Main Results:
- Gentamicin-impregnated collagen shields reduced Pseudomonas by 2 logs compared to controls.
- Fortified gentamicin drops reduced Pseudomonas by 6 logs, a three-fold greater reduction than shields.
- Both treatments demonstrated significant reduction in bacterial load.
Conclusions:
- Gentamicin collagen shields are effective in reducing bacterial growth in Pseudomonas keratitis.
- Frequent topical gentamicin drops are more potent than shields alone.
- Combining collagen shields with topical drops may enhance therapeutic efficacy for bacterial keratitis.