Serratia marcescens keratitis: strain-specific corneal pathogenesis in rabbits.

PURPOSE: The purpose of this study was to develop an animal model of Serratia keratitis that is suitable to demonstrate the pathology of specific strains. METHODS: Serratia marcescens ocular strains 93-1399-1 and 94-EI-185-2, and an environmental strain (ATCC 14041) were characterized in vitro in terms of their motility, metabolic profiles, ribotypes, and protease production. The strains were then analyzed in the rabbit intrastromal injection model. Slit lamp examination (SLE) and enumeration of bacteria in the cornea was conducted every 6 hours for 30 hours post-infection. In vivo motilities were analyzed by quantification of bacteria in the peripheral and central areas of infected rabbit corneas. RESULTS: All strains were similar in their metabolic activity and production of extracellular proteases. The ocular isolates were distinct from the environmental strain in their ribotyping patterns and in their motility. Each strain grew logarithmically in the cornea up to 6 hours post-infection. SLE scores increased from 0 to 30 hours post-infection for strains ATCC 14041 and 93-1399-1, while the SLE score of strain 94-EI-185-2 reached its maximum at 18 hours post-infection. Strain-specific differences in pathology were noted from 18 to 30 hours post-infection. Strain 94-EI-185-2 produced iritis but only mild corneal changes. Strain 93-1399-1 produced a severe corneal infiltrate encompassing the entire corneal surface as well as severe conjunctival inflammation and iritis. Strain ATCC 14041 produced a localized, severe, exudative corneal abscess that contained infecting bacteria. CONCLUSIONS: A rabbit model of Serratia keratitis was developed in which bacterial growth kinetics and strain-specific ocular pathologic changes were reproducible.

Clarithromycin for experimental Staphylococcus aureus keratitis.

PURPOSE: Clarithromycin, a macrolide antibiotic not previously tested against the common causes of bacterial keratitis, was analyzed for its effectiveness in reducing the number of viable bacteria in a Staphylococcus keratitis model. An in vivo comparison of the effectiveness of clarithromycin to erythromycin, minocycline, and tetracycline for three strains of Staphylococcus aureus was done. METHODS: Rabbit eyes were intrastromally injected with 100 colony forming units of one of three strains of S. aureus. Two strains were methicillin-sensitive (ATCC 25923 and MSSA 309) and one strain methicillin-resistant (COL). Eyes were treated every 30 minutes with 0.3% clarithromycin, erythromycin, tetracycline, or minocycline from 4 to 9 hours postinfection. The number of colony forming units (CFU) per cornea in all eyes was determined at 10 hours postinfection. RESULTS: Vehicle-treated and untreated eyes (controls) contained over 6 logs of CFU per cornea, a value significantly higher than any of the antibiotic-treated eyes (P < or = 0.0001). Clarithromycin or erythromycin therapy significantly decreased the number of CFU per cornea by approximately 5 logs in the eyes infected with the methicillin-sensitive strains and by approximately 4 logs in the eyes infected with the methicillin-resistant strain. Tetracycline and minocycline were also successful in treating these strains, but overall showed less effectiveness than clarithromycin and erythromycin. CONCLUSIONS: Clarithromycin proved to be an effective ocular medication for the therapy of experimental S. aureus keratitis. The effectiveness of clarithromycin in this model and its known effectiveness for a variety of bacterial pathogens suggests a role for this drug as a useful ocular antibiotic.

Acute inflammation of the eyelid and cornea in Staphylococcus keratitis in the rabbit.

PURPOSE: The inflammatory response during Staphylococcus keratitis was analyzed biochemically and histologically to determine the source of the neutrophils infiltrating the tear film and cornea. METHODS: Rabbit eyes were swabbed and then examined by slit-lamp microscopy at 0, 5, 10, 15, 20, and 25 hours after intracorneal inoculation with Staphylococcus aureus. Bacterial colony-forming units were quantified in the cornea, eyelid, and acute inflammatory exudate. Myeloperoxidase activity of ocular swabs of acute inflammatory exudate, corneal homogenates, and eyelid homogenates was determined. Gross and microscopic examinations of corneas and eyelids were performed. RESULTS: The colony-forming units per cornea exceeded 10(7) after 10 hours, whereas no bacteria were cultured from the eyelid until 15 hours postinfection. Slit-lamp examination revealed progressive pathology, and the myeloperoxidase activities of ocular swabs, corneas, and eyelids increased markedly by 15 hours postinfection. Corneas showed a wave of neutrophils moving from the tear film toward bacteria in the central corneal stroma and early neutrophil migration from the limbus into the stroma. In the eyelid, neutrophils migrated from the stromal vessels to the tear film. CONCLUSIONS: Staphylococcus keratitis in the rabbit causes acute inflammation in the overlying eyelid. Neutrophils of the acute inflammatory exudate interact with the infected cornea, whereas neutrophils migrating through the cornea from the limbus remained distant from the site of infection.